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Archive for the ‘Dental Stem Cells’ Category

Global Tooth Regeneration Market: Industry Analysis and Forecast (2020-2027)-by Type, Application, Population Demographics and Region – re:Jerusalem

Saturday, October 10th, 2020

Global Tooth Regeneration Market was valued US$ XX Mn in 2019 and is expected to reach US$ XX Mn by 2027, at a CAGR of 6.5% during a forecast period 2020-2027.

Market Dynamics

The Research Report gives a comprehensive account of the drivers and restraints in the tooth regeneration.Somatic stem cells are composed and reprogrammed to induced pluripotent stem cells which can be placed in the dental lamina directly or placed in an absorbable biopolymer in the shape of the new tooth, which is a main source of the novel bioengineered teeth. Tooth replacement therapy is pondered to be a greatly attractive concept for the next generation bioengineered organ replacement.The report study has analyzed revenue impact of covid-19 pandemic on the sales revenue of market leaders, market followers and disrupters in the report and same is reflected in our analysis.

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The global tooth regeneration market is mainly compelled by the high occurrence of dental problems with the new research and development activities. According to WHO, the Global Burden of Disease Study 2017 estimated that oral diseases affect close to 3.5 billion people worldwide, with caries of permanent teeth being the most common condition. Globally, it is likely that 2.3 billion people suffer from caries of permanent teeth and more than 530 million children suffer from caries of primary teeth. Additionally, positive refund policies for instance coverage of Medicaid insurance for dental loss treatment and emergence of new technologies like laser tooth generation techniques are projected to enhance the global tooth generation market throughout the estimated period.

Different researches are carried out by several academies and corporations to understand the possibility of stem cell-based regenerative medicines tooth regeneration. Though stem cell is the protuberant technology in research for tooth regeneration, several organizations are also leveraging laser, drug, and gel as mediums to regenerate teeth. For example, the Wyss Institute at Harvard University is engaged in research related to tooth regeneration using lasers. Tooth generation using stem cells is now under research through the globe. There are some key stem cells on which research are carried out such as stem cells from human exfoliated deciduous teeth (SHEDs), dental pulp stem cells, dental follicle progenitor cells (DFPCs), periodontal ligament stem cells (PDLSCs), and stem cells from apical papilla (SCAPs).A 2009 nationwide survey by the Nova South-eastern University in the U.S. publicized that around 96% of dentists expect stem cell regeneration to lead the future of the dentistry industry.However, occurrence rates are growing in low and middle-income countries. Though, some factors like the preference for endodontic treatment over tooth regeneration products in key dental surgeries and local inflammatory activity, which results in chronic complications to dental replacements, is anticipated to hamper the market throughout the forecast period.

Global Tooth Regeneration Market Segment analysis

Based on population demographics, the geriatric segment is expected to grow at a CAGR of XX% during the forecast period. According to NIH, the geriatric population has an average 18.9 remaining teeth. About 23% of the geriatric population has no teeth, making a positive market situation for manufacturing companies. The above 18 million dental procedures are anticipated to be carried out amongst the geriatric population between 2019 and 2027. Commercialization of tooth regeneration is expected to create lucrative market opportunities for industry players.Based on Type, the dentin segment accounted for a projecting share of the global tooth regeneration market in 2019, owing to the growing occurrence of dental surgery and the uprising demand for tooth regeneration in cosmetic surgery, particularly from developing economies like India, China, and Brazil.

Global Tooth Regeneration Market Regional analysis

The Asia Pacific is projected to dominate the global tooth regeneration market throughout the forecast period. Tooth regeneration addressable market is likely to be highest in the Asia Pacific, with China and India located as the major growth engines. The occurrence of tooth regeneration is projected to capture this market. Also, the number of dental procedures is anticipated to grow at the highest CAGR of ~10.8% in the Asia Pacific between 2019 and 2027. Besides, the growing incidence of dental cavities & periodontics, particularly in emerging countries like China and India has led to the rising demand for orthopedic & dental surgery.North America and Europe are estimated to collectively account for the major share of global procedures during the forecast period.

Key Developments

In June 2018, Datum Dental Ltd., the prominent provider of OSSIX brand innovative solutions for bone and tissue regeneration for dentistry, announced clearances for OSSIX Bone with Health Canada and CE Mark approval in Europe. OSSIX Bone received FDA clearance in July 2017 and was launched commercially in the USA. In April 2018, Datum Dental, the leading provider of OSSIX brand innovative solutions for bone and tissue regeneration for dentistry, announced the expansion of its global distribution network. In the USA, Dentsply Sirona Implants is now promoting the full OSSIX line.

The objective of the report is to present a comprehensive analysis of the Global Tooth Regeneration Market including all the stakeholders of the industry. The past and current status of the industry with forecasted market size and trends are presented in the report with the analysis of complicated data in simple language. The report covers all the aspects of the industry with a dedicated study of key players that includes market leaders, followers and new entrants. PORTER, SVOR, PESTEL analysis with the potential impact of micro-economic factors of the market has been presented in the report. External as well as internal factors that are supposed to affect the business positively or negatively have been analysed, which will give a clear futuristic view of the industry to the decision-makers.

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The report also helps in understanding Global Tooth Regeneration Market dynamics, structure by analysing the market segments and projects the Global Tooth Regeneration Market size. Clear representation of competitive analysis of key players by Application, price, financial position, Product portfolio, growth strategies, and regional presence in the Global Tooth Regeneration Market make the report investors guide.Scope of the Global Tooth Regeneration Market

Global Tooth Regeneration Market, By Type

Dentin Dental Pulp Tooth EnamelGlobal Tooth Regeneration Market, By Applications

Hospitals Dental Clinics OthersGlobal Tooth Regeneration Market, By Population Demographics

Geriatric Middle-aged Adults OthersGlobal Tooth Regeneration Market, By Regions

North America Europe Asia-Pacific South America Middle East and Africa (MEA)Key Players operating the Global Tooth Regeneration Market

Unilever Straumann Dentsply Sirona 3M Zimmer Biomet Ocata Therapeutics Integra LifeSciences Datum Dental CryoLife BioMimetic Therapeutic Cook Medical

MAJOR TOC OF THE REPORT

Chapter One: Tooth Regeneration Market Overview

Chapter Two: Manufacturers Profiles

Chapter Three: Global Tooth Regeneration Market Competition, by Players

Chapter Four: Global Tooth Regeneration Market Size by Regions

Chapter Five: North America Tooth Regeneration Revenue by Countries

Chapter Six: Europe Tooth Regeneration Revenue by Countries

Chapter Seven: Asia-Pacific Tooth Regeneration Revenue by Countries

Chapter Eight: South America Tooth Regeneration Revenue by Countries

Chapter Nine: Middle East and Africa Revenue Tooth Regeneration by Countries

Chapter Ten: Global Tooth Regeneration Market Segment by Type

Chapter Eleven: Global Tooth Regeneration Market Segment by Application

Chapter Twelve: Global Tooth Regeneration Market Size Forecast (2019-2026)

Browse Full Report with Facts and Figures of Tooth Regeneration Market Report at: https://www.maximizemarketresearch.com/market-report/global-tooth-regeneration-market/55424/

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Global Tooth Regeneration Market: Industry Analysis and Forecast (2020-2027)-by Type, Application, Population Demographics and Region - re:Jerusalem

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The global regenerative medicine market is projected to reach USD 17.9 billion by 2025 from USD 8.5 billion in 2020, at a CAGR of 15.9% – Yahoo…

Saturday, October 10th, 2020

during the forecast period. Market growth is driven by the rising prevalence of chronic diseases, genetic disorders, and cancer; rising investments in regenerative medicine research; and the growing pipeline of regenerative medicine products.

New York, Oct. 08, 2020 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Regenerative Medicine Market by Product, Application, Geography - Global Forecast to 2025" - https://www.reportlinker.com/p04700208/?utm_source=GNW However, the high cost of cell and gene therapies and ethical concerns related to the use of embryonic stem cells in research and development are expected to restrain the growth of this market during the forecast period.The cell therapies segment accounted for the highest growth rate in the regenerative medicine market, by product, during the forecast periodBased on products, the regenerative medicine market is segmented into tissue-engineered products, cell therapies, gene therapies, and progenitor and stem cell therapies.The cell therapies segment accounted for the highest growth rate in the regenerative medicine market in 2019.

The increasing adoption of tissue-engineered products for the treatment of chronic wounds and musculoskeletal disorders and the rising funding for the R&D of regenerative medicine products and therapies are the major factors driving the growth of this segment.

Oncology segment accounted for highest CAGRBased on applications, the regenerative medicine market is segmented into musculoskeletal disorders, wound care, oncology, ocular disorders, dental, and other applications.In 2019, the oncology segment accounted for the highest growth rate.

This can be attributed to the rising prevalence of orthopedic diseases, growing geriatric population, increasing number of stem cell research projects, growing number of clinical researches/trials, and the rich pipeline of stem cell products for the treatment of musculoskeletal disorders.

Europe: The fastest-growing region regenerative medicine marketThe global regenerative medicine market is segmented into North America, Europe, the Asia Pacific, and Rest of the World.The North America region is projected to grow at the highest CAGR during the forecast period in 2019.

The growth in the North American regenerative medicine market can be attributed to rising stem cell banking, tissue engineering, and drug discovery in the region; expansion of the healthcare sector; and the high adoption of stem cell therapy and cell immunotherapies for the treatment of cancer and chronic diseases.

The primary interviews conducted for this report can be categorized as follows: By Company Type: Tier 1 - 20%, Tier 2 - 45%, and Tier 3 - 35% By Designation: C-level - 30%, D-level - 20%, and Others - 50% By Region: North America - 36%, Europe - 25%, Asia Pacific - 27%, and Rest of the World 12%

Lits of companies Profiled in the Report: 3M (US) Allergan plc (Ireland) Amgen, Inc. (US) Aspect Biosystems (Canada) bluebird bio (US) Kite Pharma (US) Integra LifeSciences Holdings Corporation (US) MEDIPOST Co., Ltd. (South Korea) Medtronic plc (Ireland) Anterogen Co., Ltd. (South Korea) MiMedx Group (US) Misonix (US) Novartis AG (Switzerland) Organogenesis Inc. (US) Orthocell Limited (Australia) Corestem, Inc. (South Korea) Spark Therapeutics (US) APAC Biotech (India) Shenzhen Sibiono GeneTech Co., Ltd. (China) Smith & Nephew plc (UK) Stryker Corporation (US) Takeda Pharmaceutical Company Limited (Japan) Tego Science (South Korea) Vericel Corporation (US) Zimmer Biomet (US)

Research Coverage:This report provides a detailed picture of the global regenerative medicine market.It aims at estimating the size and future growth potential of the market across different segments, such as product, application, and region.

The report also includes an in-depth competitive analysis of the key market players, along with their company profiles, recent developments, and key market strategies.

Key Benefits of Buying the Report:The report will help market leaders/new entrants by providing them with the closest approximations of the revenue numbers for the overall regenerative medicine market and its subsegments.It will also help stakeholders better understand the competitive landscape and gain more insights to position their business better and make suitable go-to-market strategies.

This report will enable stakeholders to understand the pulse of the market and provide them with information on the key market drivers, restraints, opportunities, and trends.

Read the full report: https://www.reportlinker.com/p04700208/?utm_source=GNW

About ReportlinkerReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.

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Original post:
The global regenerative medicine market is projected to reach USD 17.9 billion by 2025 from USD 8.5 billion in 2020, at a CAGR of 15.9% - Yahoo...

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The end-use Industries to Help the Tooth Regenerations market stand in a good stead between 2018 and 2026 – The Daily Chronicle

Friday, September 18th, 2020

The tooth is a biological organ and consists of multiple tissues including the cementum, dentin, enamel, and pulp. Dental caries, Periodontal disease, and tooth fracture are the three main factor for tooth loss. Tooth Regeneration is the specialty concerned with the treatment of dental diseases such as a cavity, periodontal disease and fracture of the tooth. Dental caries is also known as tooth decay is the main oral health problems in most of the industrialized countries. Facial trauma also the major cause of tooth loss. Tooth loss leads to people mentally and physically disturb and it also affect the self-confidence and quality of life. Tooth regeneration is the process of individual tissue and the whole tooth development. Basically, it is the process of restoring the loss of natural teeth. Tooth regeneration is stem cell-based regenerative medical procedure which is used in stem cell biology sector and tissue engineering. There are two approaches used in the build of new whole teeth, in vivo implantation of tooth germ cells which were previously generated from stem cells and grow in vitro cells and another organotypic culture is an appropriate technique for the generation of teeth. The process of tooth regeneration imitates the natural tooth development using stem cells. In another way instead of whole teeth regeneration, Different part of the teeth regenerates such as Enamel regeneration, Dentin regeneration, Pulp regeneration, and periodontal regeneration.

Globally increasing incidence and prevalence of dental problems such as a cavity, periodontal disease, and tooth fracture are the major factors driving the growth of the Tooth Regenerations market. Innovative new techniques in Tooth regeneration such as cell homing, cell transplantation is expected to increase the acceptance of Tooth Regenerations. Tooth regeneration not only regrowth the entire tooth but also the restoration of individual components of the tooth such as dentin, cementum, enamel and dental pulp and these individual regeneration process is anticipate the boost the market growth of tooth regeneration market. Dental implantation also increases the growth of tooth regeneration market. People are very keen interested in the tooth regeneration and they are also giving more importance to the aesthetic aspects of dental products, which is expected to increase the Tooth Regenerations and dental market over the forecast period. The increasing demand for a customized Tooth Regeneration with the specifications and other dental decorative installations is the key factor anticipated to propel the demand for Tooth Regenerations worldwide.

To remain ahead of your competitors, request for a sample [emailprotected]

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The Global Tooth Regenerations market is segmented on the basis of application, Demographics, technique and by End user

Based on the Application type Tooth Regenerations market is segmented as:

Based on the Demographic Tooth Regenerations market is segmented as:

Based on the Technique, Tooth Regenerations market is segmented as:

Based on the end user Tooth Regenerations market is segmented as:

According to WHO, approx.30% the geriatric population is affected by the complete loss of teeth. Rapidly increasing Dental cavities and periodontal diseases are the major drivers in the Tooth Regenerations market. The global Tooth Regenerations market by application is expected to be dominated the market of Tooth Regenerations, out of which Enamel segment is expected to generate maximum revenue share over the forecast period. By end user, Tooth Regenerations market is expected to be dominated by dental clinics and hospitals. The manufacturers in the concerned market are focusing on manufacturing advanced products for better patient compliance and make the procedure easier. The market of tooth regeneration is anticipated to boost by stem cell regeneration technology

To receive extensive list of important regions, Request Methodology here @

https://www.persistencemarketresearch.com/methodology/26263

The global Tooth Regenerations market is expected to be dominated by North America due to higher adoption and significant geriatrics population which also increase the demand for dental service for Dental caries and Periodontal disease. Europe is expected to be the second most lucrative Tooth Regenerations market due to rising funds for research for the growing patient population. Asia-Pacific is expected to be the fastest growing Tooth Regenerations market due to rapidly increasing incidence of dental surgery, general prosthetic fixation. Latin America and Middle East & Africa are expected to be the least lucrative market due to Low awareness regarding the use of Tooth Regenerations technology and comparatively less developed healthcare infrastructure in major regions.

Examples of some of the market participants in the global Tooth Regenerations market identified are DENTSPLY Implant, Unilever, Datum Dental, Institut Straumann AG, Keystone Dental, Inc., Zimmer Biomet, Wright Medical Group N.V., Integra LifeSciences, CryoLife, Inc, BioMimetic Therapeutics, Inc, Cook Group and among others.

The report is a compilation of first-hand information, qualitative and quantitative assessment by industry analysts, inputs from industry experts and industry participants across the value chain. The report provides in-depth analysis of parent market trends, macro-economic indicators and governing factors along with market attractiveness as per segments. The report also maps the qualitative impact of various market factors on market segments and geographies.

You Can Request for TOC Here @https://www.persistencemarketresearch.com/toc/26263

Explore Extensive Coverage of PMR`s

Life Sciences & Transformational HealthLandscape

About us:

Persistence Market Research (PMR) is a third-platform research firm. Our research model is a unique collaboration of data analytics andmarket research methodologyto help businesses achieve optimal performance.

To support companies in overcoming complex business challenges, we follow a multi-disciplinary approach. At PMR, we unite various data streams from multi-dimensional sources. By deploying real-time data collection, big data, and customer experience analytics, we deliver business intelligence for organizations of all sizes.

Our client success stories feature a range of clients from Fortune 500 companies to fast-growing startups. PMRs collaborative environment is committed to building industry-specific solutions by transforming data from multiple streams into a strategic asset.

Contact us:

Naved BegPersistence Market ResearchAddress 305 Broadway, 7th Floor, New York City,NY 10007 United StatesU.S. Ph. +1-646-568-7751USA-Canada Toll-free +1 800-961-0353Sales[emailprotected]Websitehttps://www.persistencemarketresearch.com

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The end-use Industries to Help the Tooth Regenerations market stand in a good stead between 2018 and 2026 - The Daily Chronicle

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Increase in Frequency of Product Innovations to Drive the Tooth Regenerations Market from 2018 to 2026 – Lake Shore Gazette

Tuesday, September 15th, 2020

The tooth is a biological organ and consists of multiple tissues including the cementum, dentin, enamel, and pulp. Dental caries, Periodontal disease, and tooth fracture are the three main factor for tooth loss. Tooth Regeneration is the specialty concerned with the treatment of dental diseases such as a cavity, periodontal disease and fracture of the tooth. Dental caries is also known as tooth decay is the main oral health problems in most of the industrialized countries. Facial trauma also the major cause of tooth loss. Tooth loss leads to people mentally and physically disturb and it also affect the self-confidence and quality of life. Tooth regeneration is the process of individual tissue and the whole tooth development. Basically, it is the process of restoring the loss of natural teeth. Tooth regeneration is stem cell-based regenerative medical procedure which is used in stem cell biology sector and tissue engineering. There are two approaches used in the build of new whole teeth, in vivo implantation of tooth germ cells which were previously generated from stem cells and grow in vitro cells and another organotypic culture is an appropriate technique for the generation of teeth. The process of tooth regeneration imitates the natural tooth development using stem cells. In another way instead of whole teeth regeneration, Different part of the teeth regenerates such as Enamel regeneration, Dentin regeneration, Pulp regeneration, and periodontal regeneration.

Globally increasing incidence and prevalence of dental problems such as a cavity, periodontal disease, and tooth fracture are the major factors driving the growth of the Tooth Regenerations market. Innovative new techniques in Tooth regeneration such as cell homing, cell transplantation is expected to increase the acceptance of Tooth Regenerations. Tooth regeneration not only regrowth the entire tooth but also the restoration of individual components of the tooth such as dentin, cementum, enamel and dental pulp and these individual regeneration process is anticipate the boost the market growth of tooth regeneration market. Dental implantation also increases the growth of tooth regeneration market. People are very keen interested in the tooth regeneration and they are also giving more importance to the aesthetic aspects of dental products, which is expected to increase the Tooth Regenerations and dental market over the forecast period. The increasing demand for a customized Tooth Regeneration with the specifications and other dental decorative installations is the key factor anticipated to propel the demand for Tooth Regenerations worldwide.

To remain ahead of your competitors, request for a sample here@

https://www.persistencemarketresearch.com/samples/26263

The Global Tooth Regenerations market is segmented on the basis of application, Demographics, technique and by End user

Based on the Application type Tooth Regenerations market is segmented as:

Based on the Demographic Tooth Regenerations market is segmented as:

Based on the Technique, Tooth Regenerations market is segmented as:

Based on the end user Tooth Regenerations market is segmented as:

According to WHO, approx.30% the geriatric population is affected by the complete loss of teeth. Rapidly increasing Dental cavities and periodontal diseases are the major drivers in the Tooth Regenerations market. The global Tooth Regenerations market by application is expected to be dominated the market of Tooth Regenerations, out of which Enamel segment is expected to generate maximum revenue share over the forecast period. By end user, Tooth Regenerations market is expected to be dominated by dental clinics and hospitals. The manufacturers in the concerned market are focusing on manufacturing advanced products for better patient compliance and make the procedure easier. The market of tooth regeneration is anticipated to boost by stem cell regeneration technology

To receive extensive list of important regions, Request Methodology here @

https://www.persistencemarketresearch.com/methodology/26263

The global Tooth Regenerations market is expected to be dominated by North America due to higher adoption and significant geriatrics population which also increase the demand for dental service for Dental caries and Periodontal disease. Europe is expected to be the second most lucrative Tooth Regenerations market due to rising funds for research for the growing patient population. Asia-Pacific is expected to be the fastest growing Tooth Regenerations market due to rapidly increasing incidence of dental surgery, general prosthetic fixation. Latin America and Middle East & Africa are expected to be the least lucrative market due to Low awareness regarding the use of Tooth Regenerations technology and comparatively less developed healthcare infrastructure in major regions.

Examples of some of the market participants in the global Tooth Regenerations market identified are DENTSPLY Implant, Unilever, Datum Dental, Institut Straumann AG, Keystone Dental, Inc., Zimmer Biomet, Wright Medical Group N.V., Integra LifeSciences, CryoLife, Inc, BioMimetic Therapeutics, Inc, Cook Group and among others.

The report is a compilation of first-hand information, qualitative and quantitative assessment by industry analysts, inputs from industry experts and industry participants across the value chain. The report provides in-depth analysis of parent market trends, macro-economic indicators and governing factors along with market attractiveness as per segments. The report also maps the qualitative impact of various market factors on market segments and geographies.

You Can Request for TOC Here @https://www.persistencemarketresearch.com/toc/26263

Explore Extensive Coverage of PMR`s

Life Sciences & Transformational HealthLandscape

About us:

Persistence Market Research (PMR) is a third-platform research firm. Our research model is a unique collaboration of data analytics andmarket research methodologyto help businesses achieve optimal performance.

To support companies in overcoming complex business challenges, we follow a multi-disciplinary approach. At PMR, we unite various data streams from multi-dimensional sources. By deploying real-time data collection, big data, and customer experience analytics, we deliver business intelligence for organizations of all sizes.

Our client success stories feature a range of clients from Fortune 500 companies to fast-growing startups. PMRs collaborative environment is committed to building industry-specific solutions by transforming data from multiple streams into a strategic asset.

Contact us:

Naved BegPersistence Market ResearchAddress 305 Broadway, 7th Floor, New York City,NY 10007 United StatesU.S. Ph. +1-646-568-7751USA-Canada Toll-free +1 800-961-0353Salessales@persistencemarketresearch.comWebsitehttps://www.persistencemarketresearch.com

See the original post here:
Increase in Frequency of Product Innovations to Drive the Tooth Regenerations Market from 2018 to 2026 - Lake Shore Gazette

Read More...

Incremental Sales to Drive the Tooth Regenerations Market from 2018 to 2026 – Lake Shore Gazette

Tuesday, September 15th, 2020

The tooth is a biological organ and consists of multiple tissues including the cementum, dentin, enamel, and pulp. Dental caries, Periodontal disease, and tooth fracture are the three main factor for tooth loss. Tooth Regeneration is the specialty concerned with the treatment of dental diseases such as a cavity, periodontal disease and fracture of the tooth. Dental caries is also known as tooth decay is the main oral health problems in most of the industrialized countries. Facial trauma also the major cause of tooth loss. Tooth loss leads to people mentally and physically disturb and it also affect the self-confidence and quality of life. Tooth regeneration is the process of individual tissue and the whole tooth development. Basically, it is the process of restoring the loss of natural teeth. Tooth regeneration is stem cell-based regenerative medical procedure which is used in stem cell biology sector and tissue engineering. There are two approaches used in the build of new whole teeth, in vivo implantation of tooth germ cells which were previously generated from stem cells and grow in vitro cells and another organotypic culture is an appropriate technique for the generation of teeth. The process of tooth regeneration imitates the natural tooth development using stem cells. In another way instead of whole teeth regeneration, Different part of the teeth regenerates such as Enamel regeneration, Dentin regeneration, Pulp regeneration, and periodontal regeneration.

Globally increasing incidence and prevalence of dental problems such as a cavity, periodontal disease, and tooth fracture are the major factors driving the growth of the Tooth Regenerations market. Innovative new techniques in Tooth regeneration such as cell homing, cell transplantation is expected to increase the acceptance of Tooth Regenerations. Tooth regeneration not only regrowth the entire tooth but also the restoration of individual components of the tooth such as dentin, cementum, enamel and dental pulp and these individual regeneration process is anticipate the boost the market growth of tooth regeneration market. Dental implantation also increases the growth of tooth regeneration market. People are very keen interested in the tooth regeneration and they are also giving more importance to the aesthetic aspects of dental products, which is expected to increase the Tooth Regenerations and dental market over the forecast period. The increasing demand for a customized Tooth Regeneration with the specifications and other dental decorative installations is the key factor anticipated to propel the demand for Tooth Regenerations worldwide.

To remain ahead of your competitors, request for a sample here@

https://www.persistencemarketresearch.com/samples/26263

The Global Tooth Regenerations market is segmented on the basis of application, Demographics, technique and by End user

Based on the Application type Tooth Regenerations market is segmented as:

Based on the Demographic Tooth Regenerations market is segmented as:

Based on the Technique, Tooth Regenerations market is segmented as:

Based on the end user Tooth Regenerations market is segmented as:

According to WHO, approx.30% the geriatric population is affected by the complete loss of teeth. Rapidly increasing Dental cavities and periodontal diseases are the major drivers in the Tooth Regenerations market. The global Tooth Regenerations market by application is expected to be dominated the market of Tooth Regenerations, out of which Enamel segment is expected to generate maximum revenue share over the forecast period. By end user, Tooth Regenerations market is expected to be dominated by dental clinics and hospitals. The manufacturers in the concerned market are focusing on manufacturing advanced products for better patient compliance and make the procedure easier. The market of tooth regeneration is anticipated to boost by stem cell regeneration technology

To receive extensive list of important regions, Request Methodology here @

https://www.persistencemarketresearch.com/methodology/26263

The global Tooth Regenerations market is expected to be dominated by North America due to higher adoption and significant geriatrics population which also increase the demand for dental service for Dental caries and Periodontal disease. Europe is expected to be the second most lucrative Tooth Regenerations market due to rising funds for research for the growing patient population. Asia-Pacific is expected to be the fastest growing Tooth Regenerations market due to rapidly increasing incidence of dental surgery, general prosthetic fixation. Latin America and Middle East & Africa are expected to be the least lucrative market due to Low awareness regarding the use of Tooth Regenerations technology and comparatively less developed healthcare infrastructure in major regions.

Examples of some of the market participants in the global Tooth Regenerations market identified are DENTSPLY Implant, Unilever, Datum Dental, Institut Straumann AG, Keystone Dental, Inc., Zimmer Biomet, Wright Medical Group N.V., Integra LifeSciences, CryoLife, Inc, BioMimetic Therapeutics, Inc, Cook Group and among others.

The report is a compilation of first-hand information, qualitative and quantitative assessment by industry analysts, inputs from industry experts and industry participants across the value chain. The report provides in-depth analysis of parent market trends, macro-economic indicators and governing factors along with market attractiveness as per segments. The report also maps the qualitative impact of various market factors on market segments and geographies.

You Can Request for TOC Here @https://www.persistencemarketresearch.com/toc/26263

Explore Extensive Coverage of PMR`s

Life Sciences & Transformational HealthLandscape

About us:

Persistence Market Research (PMR) is a third-platform research firm. Our research model is a unique collaboration of data analytics andmarket research methodologyto help businesses achieve optimal performance.

To support companies in overcoming complex business challenges, we follow a multi-disciplinary approach. At PMR, we unite various data streams from multi-dimensional sources. By deploying real-time data collection, big data, and customer experience analytics, we deliver business intelligence for organizations of all sizes.

Our client success stories feature a range of clients from Fortune 500 companies to fast-growing startups. PMRs collaborative environment is committed to building industry-specific solutions by transforming data from multiple streams into a strategic asset.

Contact us:

Naved BegPersistence Market ResearchAddress 305 Broadway, 7th Floor, New York City,NY 10007 United StatesU.S. Ph. +1-646-568-7751USA-Canada Toll-free +1 800-961-0353Salessales@persistencemarketresearch.comWebsitehttps://www.persistencemarketresearch.com

Link:
Incremental Sales to Drive the Tooth Regenerations Market from 2018 to 2026 - Lake Shore Gazette

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Parents plea for stem cell help to save life of daughter with rare blood disorder – Mirror Online

Wednesday, September 2nd, 2020

The parents of a girl battling a deadly blood disorder are begging people to join the stem cell donor register to save her life after her only match in the world pulled out at the last minute.

Evie Hodgson, eight, who suffers from aplastic anaemia, was due to have a bone marrow transplant this month but her donor backed out at the last possible moment.

Her mum, Tina, says the chances of finding another donor are so slim that doctors are now planning a different course of treatment. But, in future, a stem call transplant is Evies best hope of being cured.

The schoolgirl, from Whitby, North Yorks, was first taken to hospital with a rash and was diagnosed with aplastic anaemia in May.

After a global donor search was launched, a 10/10 match was found and the anonymous donor agreed to the procedure. In preparation, Evie had to have dental work and one of her ovaries was removed. But on August 14 the donor pulled out.

Tina, 37, who works at RAF Flyingdales, in Pickering, North Yorks, said: We were devastated, it was a huge blow. We have no idea why the donor changed their mind. Evie has already been through so much. She thought she had a donor and now she doesnt.

The donor pulling out is quite hard-hitting, but we want to raise awareness of the stem cell register. Its so easy to be a donor. Its just like giving blood, but you could save a childs life. Its so easy to join but only 1% of the UK population is registered.

Evie said: I need this transplant to save my life. Please sign the register to help.

Tina added: The condition Evie has is life-threatening. She wont survive without a transplant. We are desperately appealing for people to sign the stem cell register.

Evie was diagnosed with the condition after she developed a pin-prick rash on her back, which didnt fade. Tests revealed she had low blood platelet levels and she was told she needed a bone marrow transplant.

Aplastic anaemia is a rare life-threatening condition where the bone marrow fails to produce enough blood cells. Around 100-150 people are diagnosed in the UK each year.

Treatment can include immunosuppressants, chemotherapy, blood transfusions, or blood and bone marrow transplants.

Neither Tina, dad Andy, 49, or brother William, five, were a match and so an international search was launched.

Tina said: Our world crumbled when Evie was diagnosed. Evie knew shed need chemotherapy. She donated her hair to The Little Princess Trust, after making friends with poorly children who have lost all their hair.

Evie will be treated with immunosuppressants while the search for a donor continues.

Blood cancer charity Anthony Nolan is looking for stem cell donors between the ages of 16-30.

Research shows that younger donors result in better outcomes for patients.

To find out how to donate click here.

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Parents plea for stem cell help to save life of daughter with rare blood disorder - Mirror Online

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Unraveling the use of CBD in veterinary medicine – Jill Lopez

Wednesday, September 2nd, 2020

It was about the 3rd week into Bastions recovery from his TPLO surgery and he was already having a rough time. Bastion was a gregarious yellow Labrador who had his injured stifle about 25 days ago. Fortunately, his family elected for him to have his stifle surgically reconstructed. Initially, he had recovered well from surgery. But one day in particular, he presented to the hospital because he had a brief setback. He was limping far more severely than what would be normally expected at this stage of recovery.

The osteotomy from his surgery had not yet completely healed and he was still in the middle of his prescribed 5 weeks of exercise strict restriction. His family was trying their best but Bastion wasnt having it. He was too active at home and his humans were growing frustrated. Anti-anxiety medications had been dispensed but they were not given. Instead, his family had decided to give him CBD oil at home. When I asked why the prescribed medications had not been given, the client responded, I found CBD oil at the local farmers market and I figured it would work just as well.

Like Bastion, an increasing number of pets are receiving cannabidiol (CBD) supplements. The popularity of CBD continues to rise and many clients are incorporating CBD as part of the medication protocol for their pets, either as an adjunct or, as alternative treatment option.

Perhaps the initial interest in the benefits of CBD can be traced back to 1998, or possibly earlier, when scientists at the National Institutes of Health discovered that CBD could protect cells from oxidative stress. These findings fueled interest in the human medical field and, in large part, that appeal has been transmuted into veterinary medicine. The regard for this molecule has risen to such levels that in many homes, CBD is being used as the sole treatment option for a variety of medical conditions.

Veterinarians are becoming more fluent in the fascinating pharmacology regarding the use of this phytocannabinoid. A recent survey indicated that most veterinarians (61.5%) felt comfortable discussing the use of CBD with their colleagues, but only 45.5% felt comfortable discussing this topic with clients.1 Furthermore, veterinarians and clients in states with legalized recreational marijuana were more likely to talk about the use of CBD products to treat canine ailments than those in other states.2 Lastly, CBD was most frequently discussed as a potential treatment for pain management, anxiety and seizures.1 At first glance, the use of CBD has tangential or limited relevance in the world of veterinary surgery. However, as one takes a closer look at the putative, and proven benefits, it is clear that we are just scratching the surface of its therapeutic benefits. This article takes a brief dive into the world of CBD and its promise in the field of veterinary surgery.

Pain

Whether you perform surgery within a specialty discipline (oncology, orthopedics, neurology, soft tissue surgery, mixed animal, oral/dental, etc), or surgery is only a small part of your general practice, every veterinarian endeavors to aggressively manage pain. The first choice for pain relief among many clinicians are the medications that have been more extensively studied including, but not limited to, anti-inflammatories, gabapentinoids, opioids, local anesthetics, and other analgesics (acetaminophen, amantadine, cerenia etc). These medications or a combination thereof, have been prescribed to treat pain from orthopedic surgery, soft tissue surgery, surgical neuropathic conditions, pain from intestinal surgery, to name just a few. In the most basic schema, pain is divided into four categories: nociceptive pain (a response to damaged tissue), neuropathic pain (a response to directly-damaged sensory or spinal nerves), centralized pain (the result of pain signals being improperly amplified), and inflammatory pain.1 Cannabinoids may have a role to play in mediating all four of these types of pain states. When tissue is damaged, histamine, serotonin, TNF-alpha, IL-1-beta, IL-6, and Il -17 6, and interleukin 17 are released.2 Cannabinoids bind to the CB1 receptors and attenuate the pain signal by slowing down the release of those neurotransmitters.3 This process can take place locally or in the central nervous system.3 Cannabinoids have also been shown to inhibit the release of GABA, a well known neurotransmitter associated with pain.3 Although there is a paucity of clinical research on the use of CBD to treat postoperative pain in the veterinary medical setting, there has been heartening research conducted in humans. Indeed, National Academies of Sciences, Engineering, and Medicine concluded that there is, substantial evidence that cannabis is an effective treatment for chronic pain in adults.

Opioids have long been the go to option, or cornerstone of pain management, however, the potential for the adverse events associated with the use of opioids in veterinary patients is universally accepted.38 I have seen how distressing it can be for a family to see their pet experiencing any of the unpleasurable side effects of opioids including urine retention, delayed bowel movements, whining, panting, disorientation, or other manifestations of dysphoria. Those are just some of the challenges that clinicians face when using opioids for chronic pain management. Considering the ongoing consequences of the opioid epidemic, there is a search for pain management solutions that are innovative, prone to less adverse events, and are more effective. As the scientific community begins to evaluate the evidence for use of CBD , it is clear that more research is needed.

Anecdotal reports of CBDs efficacy as a pain reliever are ubiquitous but more are turning to scientific data for evidence of CBDs efficacy. A study in 2020 evaluating effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients found that over half of chronic pain patients (53%) reduced or eliminated their opioids within 8 weeks after adding CBD-rich hemp extract to their regimens.5 Almost all CBD users (94%) reported quality of life improvements.5 And in a recent study evaluating orally consumed cannabinoids for long-lasting relief of allodynia in a mouse model, found that cannabinoids reduced hyperalgesia and a similar effect was not found with morphine.4 Mouse vocalizations were recorded throughout the experiment, and mice showed a large increase in ultrasonic, broadband clicks after sciatic nerve injury, which was reversed by THC, CBD, and morphine.4 The study demonstrated that cannabinoids provide long-term relief of chronic pain states.4 If research shows that use of cannabinoids in animals, specifically, CBD, can help to decrease the use of opioids for pain management, that would help make more animals comfortable and potentially help to fight the tragic epidemic of human prescription opioid abuse. Further research is needed in a variety of species, specifically, both the canine and feline species.

Bone Healing

Both general veterinary practitioners and veterinary surgeons commonly diagnose and treat fractures. A large retrospective study of fracture incidence in dogs in North America has not been published since 1994; however, the findings from that study are still informative regarding the frequency of bone injuries. That study demonstrated that approximately 24% of all patients in the population studied over a 10 year period were affected by a disorder of the musculoskeletal system, with fractures contributing the largest proportion (over 29%) of all of the diagnosis of the appendicular skeletal system.7 Although that research is dated, the conclusions from this study - at the very least, indicate that fractures are commonplace in the clinical veterinary setting.7 Fracture repair has gradually become more straightforward due to improvements in technology. Because of these innovations, speciality surgeons and general practitioners who repair fractures have begun to see better surgical outcomes. So whether you primarily stabilize fractures with implants, or if external coaptation of fractures with the intention to refer (or perhaps as the primary means of fixation) is your treatment of choice, all veterinary practitioners aim to help fractured bones heal quickly. Despite these technological improvements, bone healing can be protracted or non existent with some fractures. There are a variety of options at a veterinarians disposal to kick-start the healing process but perhaps in the near future, CBD may be added to that armamentarium. The effect of CBD in fracture healing has been investigated evaluating bone callus formation in femur fractures in a rat model.8 The findings demonstrated enhanced biomechanical properties of healing fractures in those given CBD compared with a control group.8 This effect was not found in those only given 9-THC. Moreover, the bone forming effects (osteogenic) of CBD were weakened when test subjects were given equal amounts of CBD and 9-THC.6 Another in vivo research study indicated that when CBD is incorporated into a surface that promotes bone growth (osteoconductive scaffold) it can stimulate stem cell migration and osteogenic differentiation.9 Further studies are needed to better evaluate the role of CBD in healing and bone metabolism of companion animals so that these findings can be applied in the clinical setting.

Additionally, cannabis has been shown to be a useful addition in treatment plans optimized to improve bone health in laboratory studies. A study endeavored to more closely understand the role of CB2 receptors in maintaining bone health. CB2 receptors in bone cells have been linked to maintaining bone density and stimulating growth, and may therefore have a part in reversing the effects of osteoporosis.10 One study evaluating role of CB2 receptors, found that in mice whose genes had been altered to remove the CB1 or CB2 receptors, those that developed signs of bone weakness that were far more pronounced than those in the control group.12 Another study in 2009, investigated the relationship between CB2 expression and bone disease in humans. The study found that people with dysfunctional CB2 receptors to have significantly weaker hand bones.11

Arthritis

Osteoarthritis (OA) affects many dogs, large and small. Most often, OA is the consequence of a developmental orthopedic disease that often affects a single joint or a pair of joints, and, less often, affects multiple joints. It is axiomatic that Mother Nature likes symmetry thus developmental orthopedic diseases frequently affect both left and right joints. For example, hip dysplasia is reportedly bilateral in >60% of affected dog,s13 and elbow dysplasia is bilateral in approximately 50% of affected dogs.14 Osteoarthritis occurs secondary to a myriad of primary orthopedic conditions that affect a variety of joints including: the hip (most common causes of OA in the hip: hip dysplasia, Perthes disease); stifle (patellar luxation, cranial cruciate ligament disease, osteochondritis dissecans [OCD]); elbow (elbow dysplasia, elbow OCD, fragmentation of the medial coronoid process, incomplete ossification of the humeral condyle); shoulder (shoulder OCD, developmental shoulder subluxation); tarsus (OCD of the talus), and carpus (carpal laxity, carpal subluxation secondary to chondrodystrophy); and metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joint degenerative osteoarthritis (digital osteoarthritis) .

Cannabinoids were found to treat pain secondary to inflammation in a variety of studies on humans. Some of the most compelling research has shown that cannabis can reduce the inflammation in the joint caused in human patients diagnosed with immune mediated arthritis.15 One study found that cannabinoids could simultaneously reduce the secretion of cytokines involved in inflammation from one type of TH immune cells, which were being under-produced, while also increasing their numbers to correct their scarcity.15 Furthermore in a study in 2003, researchers found that plant-based cannabinoids could suppress the expression of interleukin-1betaone of the most prominent markers for inflammation in patients with rheumatoid arthritisby as much as 50%.16 And finally, in 2006, transdermal applications of CBD were shown to decrease biomarkers that can contribute to neurogenic inflammation in a sample of arthritic rats. 17

A report published in the journal of PAIN, lead by researchers at Baylor College of Medicine revealed the results of a large, double blinded, placebo controlled study on the positive effects CBD had in the fight against osteoarthritis.18 The study was designed with two main goals: The first portion of the research studied the effect CBD had on the inflammatory molecules and cells in mice.18 The second portion of the study, investigated whether CBD improved the quality of life in dogs diagnosed with osteoarthritis. In lab tests and in mouse models, CBD significantly decreased the production of natural chemicals that promote inflammation and it increased the natural chemicals that fight inflammation.18 Essentially, what they saw was a drop in proinflammatory cytokines and an increase in anti-inflammatory cytokines. 18 For dogs with osteoarthritis, CBD significantly decreased pain and increased mobility in a dose-dependent fashion. Importantly, A lower dose of liposomal CBD was as effective as the highest dose of nonliposomal CBD, indicating that the effect of CBD was quicker and more effective when CBD was delivered encapsulated in liposomes than without.18 Blood samples indicated no significant harmful side effects, or adverse events, over the 4-week analysis period.18 Although this study is very promising and it supports the safety and therapeutic potential of hemp-derived CBD for relieving arthritic pain in dogs, it is important to consult with your pets veterinarian before giving any supplement or medication.

In the veterinary population, use of cannabidiol and other alternative treatments may have the potential to obviate the need for other medications, and thus spare patients from adverse effects associated with their use. More likely, the use of cannabinoids could be additive or synergistic in a multimodal treatment strategy and could increase quality-of-life issues associated with painful arthritic conditions.

Intervertebral Disk Disease

As our patients age, discs in the spine also undergo degenerative changes. Thus, degeneration of intervertebral discs is evitable. This process of degeneration is multifactorial process and it involves hypoxia, inflammation, neoinnervation, accelerated catabolism, and reduction in water and glycosaminoglycan content.39 The magnitude and severity of disc degeneration can vary widely between patients. The most common locations of clinically relevant disc disease are located in the cervical spine, thoracolumbar spine, and the lumbosacral spine.40 Although there are various manifestations of disc disease, broad classifications of Hansen Type I and Type II are typically used to describe the condition. In short, disc material may either extrude (acute herniations) or protrude (chronic herniations), both of which compress the spinal cord which ultimately can cause pain, paresis, paralysis and other neurological deficits.40 The prevalence of thoracolumbar disc disease dogs has been estimated at 3.5%.40 Depending on the neurologic examination, diagnosis, severity, prognosis, and other factors, surgery may be recommended to decompress the spinal cord.

After surgical decompression, there are a host of challenges that the the patient, the family, and the surgeon, may have to work through including a potentially protracted recovery, recurrence of neurological signs, post surgical pain, spinal instability, urinary disorders, (cystitis, urinary tract infection, urinary retention, micturition disorders), ascending myelomalacia, and others.41 Could CBD play a part in helping to improve those affected by disc disease pre-, intra-, or post-operatively and what types of spinal disorders could benefit from CBD? A study conducted on the use of CBD in mice with degenerative disc disease showed promise in mitigating the effect of disc damage and wear.19 Instead of being ingested orally, CBD was injected at the site of the disc. Researchers investigated the effects of cannabidiol intradiscal injection using a combination of MRI and histological analyses.19 A puncture was created in the disc and then CBD was injected into the disc (30, 60 or 120 nmol) shortly after.19 The effects of intradiscal injection of cannabidiol were analyzed within 2 days by MRI.17 Fifteen days later, the group that received cannabidiol 120 nmol was resubmitted to MRI examination and then to histological analyses after the cannabidiol injection.19 What they found was that cannabidiol significantly decreased the effects of disc injury induced by the needle puncture.19 These results suggest that this compound could be useful in the treatment of intervertebral disc degeneration perhaps using a novel route of administration.

Unfortunately, the exact mechanism for how CBD oil helped protect disc damage is still being investigated. The hope is that the neuroprotective properties of cannabidiol can also be found in the study of canine and feline disc disease to ultimately improve functional recovery.

References:

Kogan L, Schoenfeld-Tacher R, et al. US Veterinarians' Knowledge, Experience, and Perception Regarding the Use of Cannabidiol for Canine Medical Conditions. Front Vet Sci. 2018;5:338.

Abd-Elsayed A., Deer T.R. (2019) Different Types of Pain. In: Abd-Elsayed A. (eds) Pain. Springer, Cham. https://doi.org/10.1007/978-3-319-99124-5_3

Manzanares J, Julian MD, Carrascosa A. Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes Curr Neuropharmacol. 2006 Jul; 4(3): 239257.

Abraham AD, Leung EJ, Brenden A, Wong BA, Rivera ZM, Kruse LC, et al. Orally consumed cannabinoids provide long-lasting relief of allodynia in a mouse model of chronic neuropathic pain. 2020 Jun;45(7):1105-1114. doi: 10.1038/s41386-019-0585-3. Epub 2019 Dec 7.

Capano A, Weaver R, Burkman E. Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: a prospective cohort study. Postgrad Med. 2020 Jan;132(1):56-61. doi:10.1080/00325481.2019.1685298. Epub 2019 Nov 12.

Abraham AD, Leung EJ, Wong BA, Rivera ZM, Kruse LC, Clark JJ, Land BB. Orally consumed cannabinoids provide long-lasting relief of allodynia in a mouse model of chronic neuropathic pain. Neuropsychopharmacology. 2020: 45:11051114.

Johnson, J., Austin, C., & Breur, G. Incidence of Canine Appendicular Musculoskeletal Disorders in 16 Veterinary Teaching Hospitals from 1980 through 1989. Veterinary and Comparative Orthopaedics and Traumatology, 07(02), 5669. (1994). doi:10.1055/s-0038-1633097

Kogan NM, Melamed E, Wasserman E. Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts J Bone Miner Re. 2015 Oct;30(10):1905-13. doi: 10.1002/jbmr.2513. Epub 2015 May 10.

Kamali, A., Oryan, A., Hosseini, S., Ghanian, M. H., Alizadeh, M., Baghaban Eslaminejad, M., & Baharvand, H. Cannabidiol-loaded microspheres incorporated into osteoconductive scaffold enhance mesenchymal stem cell recruitment and regeneration of critical-sized bone defects. Materials Science and Engineering: (2019). C, 101, 6475. doi:10.1016/j.msec.2019.03.070

Bab I, Zimmer A. Cannabinoid Receptors and the Regulation of Bone Mass. British Journal of Pharmacology. 2007 153:182-188 doi:10.1038/sj.bjp.0707593

I. Idris, A. Cannabinoid Receptors as Target for Treatment of Osteoporosis: A Tale of Two Therapies. Current Neuropharmacology. 2010. 8(3), 243253. doi:10.2174/157015910792246173

Meliha Karsak et al. The Cannabinoid Receptor Type 2 (CNR2) Gene Is Associated with Hand Bone Strength Phenotypes in an Ethnically Homogeneous Family Sample. Human Genetics. 2009. 5:629-36 doi:10.1007/s00439-009-0708-8.

Loder, R. T., & Todhunter, R. J. The Demographics of Canine Hip Dysplasia in the United States and Canada. Journal of Veterinary Medicine. 2017 115. doi:10.1155/2017/5723476

ONeill DG, Brodbelt DC, Hodge R,. Church DB, Meeson RL. Epidemiology and clinical management of elbow joint disease in dogs under primary veterinary care in the UK. Canine Medicine and Genetics. 2020 volume 7:1

Susan H. Pross et al. Differential Suppression of T-cell Subpopulations by THC (delta-9- tetrahydrocannabinol). International Journal of Immunopharmacology 12, no. 5 (1990): 539-44. doi:10.1016/0192-0561(90)90118-7

Robert B. Zurier et al. Suppression of Human Monocyte Interleukin-1 Production by Ajulemic Acid, a Nonpsychoactive Cannabinoid. Biochemical Pharmacology. 2003 4:649-55. doi:10.1016/s0006-2952(02)01604-0.

D.c. Hammell et al. Transdermal Cannabidiol Reduces Inflammation and Pain-related Behaviours in a Rat Model of Arthritis. European Journal of Pain. 2015 6:936-48. doi:10.1002/ejp.818

Verrico, C. D., Wesson, S., Konduri, V., Hofferek, C. J., Vazquez-Perez, J., Blair, E., Halpert, M. M. A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain. 2020. Pain. doi:10.1097/j.pain.0000000000001896

Silveira, J. W., Issy, A. C., Castania, V. A., Salmon, C. E. G., Nogueira-Barbosa, M. H., Guimares, et al. Protective Effects of Cannabidiol on Lesion-Induced Intervertebral Disc Degeneration. 2014. PLoS ONE 9:12 doi:10.1371/journal.pone.0113161

Yam, M., Loh, Y., Tan, C., Khadijah Adam, S., Abdul Manan, N., & Basir, R. . General Pathways of Pain Sensation and the Major Neurotransmitters Involved in Pain Regulation. International Journal of Molecular Sciences. 2018 19(8), 2164. doi:10.3390/ijms19082164

Costigan, M., Scholz, J., & Woolf, C. J. Neuropathic Pain: A Maladaptive Response of the Nervous System to Damage. Annual Review of Neuroscience. 2009 32(1), 132. doi:10.1146/annurev.neuro.051508.135531

Arora A, Taliyan R, Sharma PL. Ameliorative Potential of Cannabis Sativa Extract on Diabetes Induced Neuropathic Pain in Rats. International Journal of Pharmaceutical Sciences and Research 1. 2010 https://www.researchgate.net/publication/216536386_Ameliorative_potential_of_cannabis_sativa_extract_

Mark S. Wallace et al., Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy. 2015. Pain 16(7): 616-27 doi:10.1016/j.jpain.2015.03.008.

Gruen, M. E., Roe, S. C., Griffith, E., Hamilton, A., & Sherman, B. L.. Use of trazodone to facilitate postsurgical confinement in dogs. Journal of the American Veterinary Medical Association. (2014) 245(3), 296301. doi:10.2460/javma.245.3.296

Serra, G., & Fratta, W. A possible role for the endocannabinoid system in the neurobiology of depression. Clinical Practice and Epidemiology in Mental Health. 2007. 3(1), 25. doi:10.1186/1745-0179-3-25

Kim, E. J., Pellman, B., & Kim, J. J. Stress effects on the hippocampus: a critical review. Learning & Memory. 2015. 22(9), 411416. doi:10.1101/lm.037291.114

Demirakca, T., Sartorius, A., Ende, G., et al. Diminished gray matter in the hippocampus of cannabis users: Possible protective effects of cannabidiol. 2010. Drug and Alcohol Dependence. doi:10.1016/j.drugalcdep.2010.09.020

Mateus M. Bergamaschi et al. Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Nave Social Phobia Patients. Neuropsychopharmacology. 2011 36(6):1219-26 doi:10.1038/npp.2011.6.

Jos Alexandre S Crippa et al. Neural Basis of Anxiolytic Effects of Cannabidiol (CBD) in Generalized Social Anxiety Disorder: A Preliminary Report. Journal of Psychopharmacology. 2010. 25: 1doi:10.1177/0269881110379283.

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Zieba, J., Sinclair, D., Sebree, T., Bonn-Miller, M., Cannabidiol (CBD) reduces anxiety-related behavior in mice via an FMRP1-independent mechanism. Pharmacology Biochemistry and Behavior. 2019. doi:10.1016/j.pbb.2019.05.002

Pamplona, F. A., da Silva, L. R., & Coan, A. C. Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis. 2018. Frontiers in Neurology, 9. doi:10.3389/fneur.2018.00759

Palmieri B, Laurino C, Vadal M. A therapeutic effect of cbd-enriched ointment in inflammatory skin diseases and cutaneous scars. Mar-Apr 2019;170(2):e93-e99. doi: 10.7417/CT.2019.2116.

Sangiovanni, E., Fumagalli, M., Pacchetti, B., Piazza, S., et al.. Cannabis sativa L. extract and cannabidiol inhibit in vitro mediators of skin inflammation and wound injury. (2019). Phytotherapy Research. doi:10.1002/ptr.6400

B. Van Klingeren and M. Ten Ham. Antibacterial Activity of 9-tetrahydrocannabinol and Cannabidiol. 1976. 42(1-2): 9-12 doi:10.1007/bf00399444.

Giovanni Appendino et al. Antibacterial Cannabinoids From Cannabis Sativa: A StructureActivity Study. 2008. Journal of Natural Products 71(8):1427-430, doi:10.1021/np8002673

McIver, V., Tsang, A., Symonds, N., Perkins, N., et al. Effects of topical treatment of cannabidiol extract in a unique manuka factor 5 manuka honey carrier on second intention wound healing on equine distal limb wounds: a preliminary study. 2020. Australian Veterinary Journal. doi:10.1111/avj.12932

White, D. M., Mair, A. R., & Martinez-Taboada, F. Opioid-free anaesthesia in three dogs. Open Veterinary Journal. 2017 7(2), 104. doi:10.4314/ovj.v7i2.5

Hansen T, Smolders LA, Tryfonidou MA, et al: The Myth of Fibroid Degeneration in the Canine Intervertebral Disc: A Histopathological Comparison of Intervertebral Disc Degeneration in Chondrodystrophic and Nonchondrodystrophic Dogs. Vet Pathol 2017 Vol 54 (6) pp. 945-952.

40. Jeffery ND, Levine JM, Olby NJ, et al: Intervertebral disk degeneration in dogs: consequences, diagnosis, treatment, and future directions. J Vet Intern Med 2013 Vol 27 (6) pp. 1318-33.

41. Balducci F, Canal S, Contiero B, et al: Prevalence and Risk Factors for Presumptive Ascending/Descending Myelomalacia in Dogs after Thoracolumbar Intervertebral Disk Herniation. J Vet Intern Med 2017 Vol 31 (2) pp. 498-504.

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Unraveling the use of CBD in veterinary medicine - Jill Lopez

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Global Stem Cell Banking Market with Covid-19 Effect Analysis, Growth, Research Findings, Type, Application, Element Global Trends and Forecast to…

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Placental Stem Cells (PSCs)Human Embryo-derived Stem Cells (HESCs)Bone Marrow-derived Stem Cells (BMSCs)Adipose Tissue-derived Stem Cells (ADSCs)Dental Pulp-derived Stem Cells (DPSCs)Other Stem Cell Sources

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Table ofContents

Global Stem Cell Banking Market Research Report 2020-2026

Chapter 1 Stem Cell Banking Market Overview

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Chapter 8 Marketing Strategy Analysis, Traders

Chapter 9 Stem Cell Banking Market Factors Analysis

Chapter 10 Global Stem Cell Banking Market Forecast up to 2026

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Global Stem Cell Banking Market with Covid-19 Effect Analysis, Growth, Research Findings, Type, Application, Element Global Trends and Forecast to...

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Plasma Therapy Market Overview with Detailed Analysis, Competitive landscape, Forecast to 2025 – StartupNG

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Plasma Therapy Regional Market Analysis

Plasma Therapy Segment Market Analysis (by Type)

Plasma Therapy Segment Market Analysis (by Application)

Plasma Therapy Major Manufacturers Analysis

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Active Data Warehousing Market to Witness Robust Expansion Throughout the Forecast Period 2020 2025 – The Daily Chronicle

Thursday, August 20th, 2020

Market Study Report, LLC, provides a research on the Active Data Warehousing market which offers a concise summary pertaining to industry valuation, SWOT Analysis, market size, revenue estimation and geographical outlook of the business vertical. The study descriptively draws out the competitive backdrop of eminent players driving the Active Data Warehousing market, including their product offerings and growth plans.

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The study underlines the major industry trends while analyzing the growth avenues, market size, sales volume, and revenue predictions. Significant information concerning the growth opportunities as well as the numerous market segmentations are enlisted.

Also, the report measures the effect of COVID-19 pandemic on the profit graph of the Active Data Warehousing market.

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The document delivers a comprehensive assessment of the geographical terrain of the Active Data Warehousing market and splits the same into North America, Europe, Asia-Pacific, Middle East & Africa and South America.

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Reserach Objectiveof this report are:

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This research report represents a 360-degree overview of the competitive landscape of the Global Active Data Warehousing Market. Furthermore, it offers massive data relating to the recent trends, technological advancements, tools, and methodologies. The research report analyzes the Global Active Data Warehousing Market in a detailed and concise manner for better insights into the businesses.

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3D bioprinting spatiotemporally defined patterns of growth factors to tightly control tissue regeneration – Science Advances

Thursday, August 20th, 2020

INTRODUCTION

In recent years, a number of growth factors have been tested in clinical trials for a variety of therapeutic applications including bone regeneration and neovascularization of ischemic tissues. Despite early promising results, the results obtained in larger phase 2 trials have often not shown the expected benefit to patients (1, 2), with some having marked adverse effects (35). The Infuse bone graft, which consists of recombinant human bone morphogenetic protein-2 (rhBMP-2) soaked onto a collagen sponge at a dosage of 1.5 mg/ml, has received Food and Drug Administration approval for certain spinal, dental, and trauma indications and is in widespread clinical use. However, major complications and adverse effects have increasingly been attributed because of the off-label use of the product (3, 4). Clinically, the current delivery vehicle for BMP-2 is a collagen powder or sponge that has been shown to result in a large initial burst release, which contrasts with the expression profile observed during normal fracture repair where BMP expression increases until day 21, suggesting a need for slower and more sustained growth factor release profile (6, 7). Furthermore, because of the short half-life of the growth factor and the harsh fracture environment (5), supraphysiological dosages of BMP-2 are being delivered to elicit bone regeneration, which has been linked to adverse effects such as heterotopic ossification. Therefore, there is a clear clinical need to develop alternative strategies to deliver single or multiple growth factors to the site of injury with sustainable and physiologically relevant dosages such that repair is induced without these adverse effects.

A number of growth factors have been shown to be expressed at different phases of fracture healing, including vascular endothelial growth factor (VEGF) and BMPs. The coupled relationship in bone healing, both physical and biochemical, between blood vessels and bone cells has long been recognized (8, 9). During fracture healing, VEGF is released directly after injury and predominately drives the formation of the fracture hematoma (9). Inhibition of VEGF has been shown to disrupt the repair of fractures and large bone defects (1012). Despite this, VEGF delivery alone is often not sufficient to heal critically sized bone defects, which may be due to suboptimal dosing or the timing of VEGF release. Furthermore, VEGF does not appear to drive progenitor cell differentiation toward the chondrogenic or osteogenic lineage; therefore, combination therapies with BMPs have been developed in an attempt to accelerate the regeneration of large bone defects (9, 1318). During normal fracture healing, VEGF expression peaks around day 5/10 (19, 20) and then decreases, whereas BMP-2 expression increases constantly until day 21, suggesting a need for delivery systems that support the early release of VEGF and the sustained release of BMP-2 (6, 7, 19, 20). To this end, composite polymer systems have been used to deliver VEGF and BMP-2 in a sequential fashion (1518). The timed release of VEGF/BMP-2 was found to enhance ectopic bone formation (1618); however, in an orthotopic defect, no significant benefit was observed (17, 18). This may be due to the high dose of VEGF used in these studies (18), which has previously been shown to disrupt osteogenesis as a result of abnormal angiogenesis and vascular structure (8), or due to suboptimal growth factor release profiles from these constructs. This suggests that novel strategies are required for delivering low-dosage VEGF and BMP-2, with tight temporal control, to enhance vascularization and subsequent bone formation in orthotopic defects. Nanoparticles such as hydroxyapatite (HA) and laponite are known to be osteoinductive and have previously been shown to facilitate the adsorption and immobilization of proteins such as VEGF and BMP-2 because of the strong attraction between the nanoparticles and the growth factor (2123). This motivates the integration of these nanoparticles into regenerative implants to enable tight temporal control over the rate at which encapsulated growth factors are released into damaged tissue.

Processes such as angiogenesis are regulated not only by the temporal presentation of growth factors but also by spatial gradients of morphogens that regulate chemotactic cell migration. Using microfluidic devices (24, 25) or three-dimensional (3D) culture models (26, 27), it has been demonstrated that endothelial cell migration is mediated by gradients in VEGF. However, it is unclear whether incorporating gradients of VEGF into tissue-engineered scaffolds will enhance angiogenesis in vivo. Here, we used emerging multiple-tool biofabrication techniques (28) to deliver VEGF and BMP-2 with distinct spatiotemporal release profiles to enhance the regeneration of critically sized bone defects. To tune the temporal release of these morphogens from 3D printed constructs, we functionalized alginate-based bioinks with different nanoparticles known to bind these regulatory factors. Both the spatial position and temporal release of growth factor from the 3D printed implant determined its therapeutic potential. By slowing the release of BMP-2, it was possible to enhance bone formation in vivo within predefined positions of the implant. Furthermore, introducing spatial gradients of VEGF into 3D printed implants enhanced vascularization in vivo compared to controls homogenously loaded with the same total amount of growth factor. We also demonstrate accelerated large bone defect healing, with minimal ectopic bone formation, using 3D printed implants containing a spatial gradient of VEGF and spatially localized BMP-2.

To produce a printable bioink, various weight concentrations of methylcellulose were first added to RGD -irradiated alginate. Print fidelity (as measured by the filament spreading ratio) improved by increasing the methylcellulose content [see fig. S1 (A and B)]; however, the capacity to print multiple layers of material worsens because of the overly adhesive nature of the ink. For these reasons, a weight concentration of 2:1 (w/w) alginate to methylcellulose was chosen for all bioinks, as it substantially increased the print fidelity while allowing multiple layers of material to be accurately deposited.

To tune the temporal release profile of growth factor (here, VEGF), clay nanoparticles (22, 23, 29) or hydroxyapatite nanoparticles (nHA) (21) were added to the alginate-methylcellulose bioink. Adding methylcellulose to the alginate to produce a printable ink significantly increased the release of VEGF compared to that observed from alginate only [see fig. S1 (C and D)]. The addition of laponite, a clay-based nanoparticle, markedly slowed the release of VEGF (see fig. S1C), while the incorporation of nHA only had a small effect on growth factor release, producing a slightly more gradual release profile (see fig. S1D). This blend (alginate, methylcellulose, and nHA) will hereafter be referred to as the vascular bioink, as it allowed for the near complete release of VEGF over 10 days, mimicking that observed during normal fracture healing (19, 20). No laponite was included in this vascular bioink.

To demonstrate the utility of this vascular bioink, two strategies were compared to print implants containing a spatial gradient of VEGF (see fig. S1E). In the first, VEGF (100 ng/ml) was printed into the central 5-mm core of constructs 8 mm in diameter and 4 mm high, with a VEGF-free bioink used to print the periphery of the construct. In the second, VEGF (80 ng/ml) was printed into the center of the construct, and VEGF (20 ng/ml) was printed around the periphery of the implant. Control constructs containing a homogenous distribution of VEGF were also printed. One hour after printing, clear spatial differences in VEGF localization were observed in both gradient constructs, while roughly the same amount of protein was detected in the core and periphery of the homogenous VEGF control (see fig. S1F). Fourteen days after printing, a spatial gradient still existed in the construct that initially had all VEGF loaded into its central region, with no gradient observed in the other groups (see fig. S1G). This demonstrates that spatial gradients of growth factor can be maintained within constructs for at least 14 days after printing.

We next sought to assess whether depositing spatial gradients of VEGF within 3D printed polycaprolactone (PCL) implants would accelerate vascularization of the constructs in vivo. To this end, Homogenous VEGF, Gradient VEGF, and No VEGF constructs were implanted subcutaneously in the back of mice (see Fig. 1A), where the total amount of growth factor (25 ng) within the two VEGF-containing implants was constant. Two weeks after implantation, histological analysis of hematoxylin and eosin (H&E)stained samples revealed the presence of vessels in the Homogenous VEGF and Gradient VEGF groups; however, there were no obvious vessels present in the No VEGF group (see Fig. 1B). These vessels appeared mature, complete with smooth muscle actin (-SMA) and von Willebrand factor (vWF)stained walls and perfused with erythrocytes (see fig. S2A). The Homogenous VEGF constructs had vessels predominantly located in the periphery of the scaffold, with little to none present within the center of the scaffold. On the other hand, vessels were present both in the periphery and in the center of the Gradient VEGF group. Four weeks after implantation, all three experimental groups had mature vessels present (see Fig. 1C and fig. S2B). Similar to the Homogeneous VEGF group, the No VEGF group had vessels predominantly located in the periphery of the constructs, with little to none present within the center of the construct. When quantified, at both 2 and 4 weeks, there were significantly more vessels present in the Gradient VEGF group compared to both the Homogenous VEGF and No VEGF group (see Fig. 1D). There was significantly more vessels present in the periphery of the Gradient VEGF constructs at both 2 and 4 weeks in vivo compared to the other two experimental groups [see Fig. 1 (E and F)]. There was also a trend toward a larger number of vessels present in the center of the Gradient VEGF construct at 4 weeks compared to No VEGF (P = 0.09) and Homogenous VEGF (P = 0.1) groups (see Fig. 1F).

(A) Schematic of the 3D printed scaffold and experimental groups. Construct design (4 mm in diameter, 5 mm in height). H&E-stained sections of the three experimental groups at (B) 2 and (C) 4 weeks in vivo. Images were taken at 20. Arrows denote vessels. (D) Total number of vessels of the experimental groups at 2 and 4 weeks in vivo. Number of vessels present in the center versus the periphery at (E) 2 and (F) 4 weeks in vivo. **P < 0.01. Error bars denote SDs (n = 8 animals; n = 5 slices per animal). FBS, fetal bovine serum; pen/strep, penicillin/streptomycin.

Recognizing that a slower and more sustained release of BMP-2 could be beneficial for promoting osteogenesis (6, 7), we next sought to compare bone formation in vivo within implants with temporally distinct growth factor release profiles. To the base alginate-methylcellulose bioink (here termed the Fast BMP-2 Release bioink), laponite at varying w/w ratios of laponite to alginate were compared to determine the optimum ratio to generate a Slow BMP-2 Release bioink (see fig. S3). As there was little difference in the growth factor release profile from the different groups, a 6:1 alginate:laponite w/w ratio was chosen to minimize the amount of laponite in the bioink. The addition of laponite markedly slowed the in vitro release of BMP-2 from the bioink, resulting in a reasonable constant release of growth factor from day 7 to day 35 (see Fig. 2C). The addition of laponite also had no significant effect on the degradation rate of the bioink (Fig. 2B).

(A) Schematic of the experimental groups. Construct design (4 mm in diameter, 5 mm in height). MEM, alpha minimum essential medium. (B) Degradation of the two bioinks. (C) Cumulative release of BMP-2 of the fast release bioink versus the slow release bioink. (D) 3D reconstructions of the CT data for each group at 8 weeks. (E) CT analysis on total mineral deposition of each of the groups after 8 weeks in vivo. (F) CT analysis on the location of mineral deposition of each of the groups after 8 weeks in vivo. ***P < 0.001; error bars denote SDs (n = 8 animals). (G) Goldners trichromestained sections of both groups after 8 weeks in vivo. Images were taken at 20. White arrows denote developing bone tissue, and black arrows denote blood vessels. (H) Quantification of the amount of new bone formation per total area. Error bars denote SDs; **P < 0.01 (n = 8 animals, n = 6 slices per animal).

To assess whether slow and sustained release of BMP-2 would enhance ectopic bone formation in vivo, Fast BMP-2 Release (laponite) and Slow BMP-2 Release (+laponite) bioinks were mixed with bone marrowderived mesenchymal stem cells (BMSCs), deposited within 3D printed scaffolds, and then implanted subcutaneously in the back of mice (see Fig. 2A). Seeding these bioinks with MSCs was used to test their potential for promoting osteogenesis in an ectopic location. BMP-2 was specifically localized around the periphery of the implant. This pattern of growth factor presentation was chosen to test the capacity of the printed implants to spatially localize bone formation in vivo (note that the geometry of the implant is the same as that which will be used in the segmental defect study below, with the BMP-2 localized to the periphery of the implant such that bone would only form along the cortical shaft of the damaged limb rather than throughout). Eight weeks after implantation, there was significantly more mineral within the Slow BMP-2 Release group compared to the Fast BMP-2 Release group [see Fig. 2 (D and E)]. Microcomputed tomography (CT) reconstructions revealed that the mineral was preferentially deposited around the periphery of the constructs where the BMP-2 was localized [see Fig. 2 (D and F)]. Histological staining further verified this finding, with positive staining for new bone seen predominantly in the periphery of both groups (see Fig. 2G, denoted by white arrows). Quantification revealed that the Slow BMP-2 Release constructs had significantly more new bone formation per total area of construct (see Fig. 2H).

We next sought to assess whether the delayed release of BMP-2 from printed constructs containing spatial gradients in VEGF would enhance angiogenesis and bone formation within critically sized bone defects. To this end, VEGF gradient only, BMP-2 gradient only, and Composite (VEGF+BMP-2 gradient) constructs were printed and implanted in a 5-mm rat femoral defect (see Fig. 3A) and compared to an empty defect.

(A) Schematic of the 3D printed experimental groups including key features of the developed bioinks and the segmental defect procedure. Construct design (4 mm in diameter, 5 mm in height). (B) CT angiography representative images of vessel diameter. Red arrows denote leaky blood vessels denoted by pools of contrast agent. Quantification on (C) total vessel volume, (D) average vessel diameter, and (E) connectivity for all groups after 2 weeks in vivo. *P < 0.05 and **P < 0.01; error bars denote SDs (n = 9 animals). (F) Immunohistochemical staining of nuclei (blue), vWF (red), and SMA (green) of the experimental groups at 2 weeks after implantation. Images were taken at 40 and 63. Yellow arrows denote vessels with SMA and vWF dual staining; white arrows denote slightly less mature vessels with only vWF positive staining.

Two weeks after implantation, CT angiography was used to quantify and visualize the early vascular network that had formed within the defect site. 3D reconstructions revealed that vascular networks had formed in all four experimental groups (see Fig. 3B). When quantified, there was a significant increase in vessel volume in the Composite group compared to the VEGF gradient group (see Fig. 3C). There was also a significant increase in average vessel thickness in the BMP-2 gradient and Composite groups compared to the VEGF gradient group (see Fig. 3D). Although there was no significant difference in the connectivity of the vessels, there was a trend (P = 0.1) toward increased connectivity in the Composite group compared to the VEGF gradient group (see Fig. 3E). 3D reconstructions also revealed the presence of primitive immature blood vessels depicted by large globules of contrast agent (denoted by the red arrows in Fig. 3B). There appeared to be fewer primitive blood vessels present in the Composite group than the other three experimental groups. This was further verified by SMA and vWF staining, which revealed a larger number of vessels with only positive vWF-stained walls in the Empty and VEGF gradient groups (see Fig. 3F, denoted by white arrows). On the other hand, there were predominately more mature vessels with SMA and vWF-stained walls in both the BMP-2 gradient and Composite groups (see Fig. 3F, denoted by yellow arrows). Note that the differences in angiogenesis seen between the VEGF gradient and Composite groups (same amount of VEGF in both groups) could at least partially be explained by looking at the VEGF release profile from both groups (see fig. S4). The addition of the osteoinductive ink around the implant periphery significantly reduced the VEGF release rate from construct into the media, with a more linear release of growth factor over time.

Two weeks after surgery, defects within the Empty group were filled with a fibrous tissue (see Fig. 4A). In contrast, positive staining for cartilage and new bone deposition was observed in the BMP-2 gradient and Composite groups, suggesting that new bone was forming at least partially via endochondral ossification. When quantified, there was a trend toward increased cartilage development (red staining in Safranin O images) in both the BMP-2 gradient (P = 0.12) and Composite (P = 0.18) groups compared to the Empty (see Fig. 4B). No significant differences in bone formation was observed between any of the groups at week 2; however, the CT reconstructions showed mineralized calluses beginning to form in the BMP-2 gradient and Composite groups, which was less evident in the Empty and VEGF gradient groups [see Fig. 4 (C and D)].

(A) H&E- and Safranin Ostained sections of all groups after 2 weeks in vivo. Images were taken at 20. DB denotes cartilage undergoing endochondral ossification to become developing bone, and B denotes positive new bone tissue. Quantification of the amount of (B) bone formation and (C) developing bone per total area. Error bars denote SDs (n = 9 animals). (D) CT reconstructed images of the defect site.

Next, CT analysis was used to visualize and quantify bone formation within the defects at 4, 8, 10, and 12 weeks after implantation. Compared to the Empty group, there were significantly higher levels of new bone formation in the Composite group as early as 8 weeks after implantation [see Fig. 5 (A and B)]. A consistent pattern of healing was observed in the Composite group, with bone forming down through the PCL scaffold framework (see Fig. 5A and fig. S5). After 10 weeks of implantation, significantly higher levels of bone formation was observed in the BMP-2 gradient and Composite groups compared to the Empty group. By 12 weeks, all three experimental groups contained significantly higher levels of new bone compared to the Empty group. Twelve weeks after implantation, bone density mapping revealed that the new bone formed in the experimental groups consisted of a dense cortical-like bone present around the periphery of defect, comparable to the adjacent native bone (1200 mg HA/cm3) (see Fig. 5C). Quantitative densitometry analysis revealed no significant difference in the average density (mg HA/cm3) of the new bone that did form between any of the groups over the 12 weeks (see Fig. 5D).

(A) Reconstructed in vivo CT analysis of bone formation in the defects. (B) Quantification of total bone volume (mm3) in the defects at each time point. (C) Representative images of CT bone densities in the defects at 12 weeks halfway through the defect (scale bar, 1 mm throughout). (D) Average bone density (mg HA/cm3) in the defects at each time point. (E) Outline of ROI bone volume analysis including definitions of core, annulus, and heterotopic regions. (F) Total bone volume (mm3) in each region at 12 weeks. **P < 0.01, ***P < 0.001, and ****P < 0.0001; error bars denote SDs (n = 9 animals).

To assess the levels of heterotopic bone formation, region of interest (ROI) bone volume analysis was performed on the week 12 reconstructions. The total bone volume was quantified in the core, annulus, and heterotopic regions of the defect (see Fig. 5E). In all three experimental groups, bone preferentially formed in the annulus of the defect, with little ectopic bone formation (see Fig. 5F). All three experimental groups had significantly higher total bone volume in the annulus of the defect compared to the Empty annulus, with the highest total bone volume present in the Composite group.

We next sought to assess the nature of new bone tissue being formed using histological staining. Goldners trichrome staining revealed predominantly fibrous tissue formation, similar to what was seen previously at 2 weeks, in the Empty group (see Fig. 6A). There was positive staining for new bone, complete with marrow cavities, in all three experimental groups at 12 weeks after implantation. When quantified, there was significantly more bone found in all three experimental groups compared to the Empty group (see Fig. 6B). There were also significantly higher amounts of bone marrow present in the Composite group compared to the Empty group (see Fig. 6C). As observed in the CT 3D reconstructions, it is clear that the bone is forming down through the PCL scaffold framework, specifically in the Composite group. Safranin O staining revealed the presence of cartilage in all three experimental groups after 12 weeks, demonstrating that bone is continuing to develop via endochondral ossification. When quantified, there was significantly more cartilage present in the Composite group compared to all other groups at this time point (see Fig. 6D).

(A) Goldners trichrome and Safranin Ostained sections of all groups after 12 weeks in vivo. Images were taken at 20. BM denotes bone marrow. PCL denotes areas where the PCL frame was. DB denotes cartilage undergoing endochondral ossification to become new bone, and B denotes positive bone tissue. Quantification of the amount of (B) bone formation, (C) bone marrow, and (D) developing bone per total area. Error bars denote SDs. *P < 0.05, **P < 0.01, and ****P < 0.0001 (n = 9 animals).

Despite the tremendous potential of growth factor delivery, the results obtained in larger clinical trials have not always shown the expected benefit to patients (2), with some studies reporting marked adverse effects (35). The reasons for this are multifaceted, from the delivery methods to the supraphysiological dosages needed to elicit a therapeutic effect and the costs and adverse effects attached to these high doses. This study presents a novel alternative approach for spatiotemporally controlled delivery of growth factors. We developed a range of nanoparticle-functionalized bioinks to precisely control the temporal release of growth factors from 3D printed implants. Using multiple tool biofabrication techniques, we were able to print constructs containing spatiotemporal gradients of growth factors, which allowed for controlled tissue regeneration without the need for supraphysiological dosages. Specifically, the appropriate patterning of VEGF enhanced angiogenesis in vivo and, when coupled with defined BMP-2 localization and release kinetics, enhanced large bone defect healing with little heterotopic bone formation.

Alginate hydrogels are commonly used for bone tissue engineering, with a number of studies demonstrating the bone regeneration potential of RGD functionalized and -irradiated alginate (3033), making it a promising base bioink for the 3D bioprinting of osteogenic implants. However, one drawback to using RGD -irradiated alginate as a bioink is its low viscosity. It is imperative when printing multilayered structures that the bioink have appropriate rheological properties to prevent collapsing or sagging of the printed structure. The addition of methylcellulose to alginate-based bioinks was found to have a significant effect on both printability and the rate of growth factor release. The addition of methylcellulose has previously been shown to substantially increase the print fidelity of an alginate base bioink (22, 34, 35), although typically using higher concentrations than the one used in this study. Adding methylcellulose also accelerated the rate of growth factor release. This was previously seen with albumin release from alginate-methylcellulose beads (36). Such a polymeric network is at least partially defined by physical entanglements between the alginate or methylcellulose chains. As methylcellulose is characterized by high swellability, when the alginate/methylcellulose bioink is exposed to the medium, it swells rapidly, resulting in accelerated growth factor release from the bioink. The addition of methylcellulose may also have neutralized the charge on the alginate, which would also influence growth factor release kinetics. In contrast, the addition of nanoparticles, and, in particular, laponite, slowed the release of growth factor from the inks. Both nHA and laponite have previously been shown to facilitate with the adsorption and immobilization of VEGF within a hydrogel due to the strong attraction between the nanoparticles and the growth factor (2123). The stronger association between growth factors and laponite can be linked to the physiochemical properties of these particles (22, 29). These disc-shaped particles [typically 25 nm in diameter and 1 nm in thickness (37)] are characterized by a highly negatively charged face and a positively charged rim (22), with a zeta potential of 61 mV (as determined by the manufacturer). This allowed the positively charged growth factors such as VEGF to form strong electrostatic bonds with the negatively charged face of the nanoparticles (22). In contrast, the nHA nanoparticles used in this study, which we have previously shown to have a zeta potential of around 5 mV (38), would form a slightly weaker electrostatic bond with the VEGF. The addition of laponite to bioinks has also previously been shown to influence their mechanical properties (37). While we did not directly assess whether the addition of laponite influenced the stiffness of our ink, we did observe that it had no effect on their degradability, and on the basis of w/w ratio used in this study, we do not believe it had marked effects on mechanical properties such as matrix stiffness. Previous studies have shown that when using high concentrations of alginate (similar to that used in this study), the addition of laponite does not markedly affect the rheological properties of the bioink (37). However, future studies should investigate the overall mechanical properties of a bioink, as this may also influence its osteogenic potential (39). A potential limitation of laponite is that the strong electrostatic bond can limit the amount of growth factor released from a delivery system in the short-medium term (22). In this study, by tuning the ratio of laponite to alginate, it was possible to engineer bioinks that released most of their loaded protein over 35 days. Therefore, using specifically selected nanoparticles, it is possible to develop bioinks that support growth factor release profiles spanning days to weeks.

Using multiple-tool biofabrication, we demonstrated that distinct growth factor gradients can be established and maintained over time and that incorporating these gradients into printed implants can enhance sprouting angiogenesis in vivo. The process of sprouting angiogenesis begins with the selection of a distinct site on the mother vessel where sprout formation is initiated. This distinct site is referred to as the tip cell, and as the new sprout elongates, branches, and connects with other sprouts, the selection process for the tip cell is constantly reiterated (40). Previous studies have shown in the early postnatal retinas that tip cell migration depends on a gradient of VEGF-A and its proliferation is regulated by its concentration (40, 41). Therefore, the increase in vessel infiltration observed in VEGF gradient implants can possibly be attributed to tip cell migration and proliferation toward the areas of high VEGF concentration (40, 41). In contrast, when VEGF was homogenously distributed within the implant, there was less of a chemotactic effect, resulting in lower levels of vessel infiltration into the center of the construct.

When this bioprinting strategy was used to deliver both growth factors within a large bone defect, there was a significant increase in vessel infiltration within implants containing both a VEGF gradient and BMP-2 compared to those containing VEGF alone. Although it has been shown that delivery of BMP-2 alone can enhance new blood vessel formation within bone defects (42, 43), previous studies have not reported a benefit to delivering both growth factors to the defect site (17, 18). The finding that the laponite-functionalized bioink around the periphery of the implant was slowing the release of VEGF from the implant may partially explain the higher levels of vessel infiltration observed within the composite implant, with the slower VEGF release profile being perhaps more conducive to angiogenesis within the orthotopic environment. Somewhat unexpectedly, despite enhancing overall levels of bone formation, VEGF delivery alone did not increase early vessel infiltration into the implant. Note that orthotopic hematomas, generated by the surgical procedure, would have provided all defects with a source of endogenous chemotactic, angiogenic, and mitogenic growth factors (17). This may have mitigated the effect that an implant containing a VEGF gradient alone had on early angiogenesis.

3D printed implants containing spatial gradients of VEGF, coupled with defined BMP-2 localization, enhanced large bone defect healing with little heterotopic bone formation. Critically, this increase in bone healing was achieved using very low concentrations of exogenous growth factors. The concentration of VEGF used in this study was substantially less (80 to 160 times less) than previous studies (17, 18). Achieving therapeutic benefits with these low concentrations of growth factors is important for multiple reasons, not least of which is the observation that high concentrations of VEGF have been previously shown to disrupt osteogenesis as the result of abnormal angiogenesis and vascular structure (8). Furthermore, the concentrations of BMP-2 used here are at least an order of magnitude lower than that used previously to repair similar sized defects in a rat femoral defect model (28, 31). Repair in these studies is typically associated with a substantial amount of heterotopic bone formation (28, 31). Directly comparing to previous work in our lab, which used a clinically relevant BMP-2 dose in the same defect model (28), the results from this study exhibited substantially less heterotrophic bone formation [10% versus 50% (28) of total bone volume]. Although we did not observe full bone bridging after 12 weeks, new bone was still being formed via the process of endochondral ossification at 12 weeks, suggesting that regeneration was still proceeding. Allowing some level of physiological loading earlier in the healing process would likely have further accelerated regeneration (44). Together, the results from this study demonstrate the potential of 3D printing morphogen gradients for controlled tissue regeneration (with minimal heterotopic bone formation) without the need of supraphysiological dosages.

The translation of tissue engineering concepts from bench to bedside is a challenging, expensive, and time-consuming process. Numerous products have not made it past phase 2 trials, as they have not shown the expected benefit in patients (1, 2), while others have been associated with marked adverse effects (35). Here, we describe a previously unidentified approach for spatiotemporally defined growth factor delivery and demonstrate a potential clinical utility in the regeneration of large bone defects or the increased vascularization of any 3D printed construct. Proof-of-concept studies in small animals established the potential of these growth factor loaded bioinks for inducing enhanced angiogenesis and bone regeneration without the need for supraphysiological dosages. The benefit of this precise localization of growth factors in both time and space is that it allows for tightly controlled angiogenesis and new tissue formation, thereby reducing off-target effects. It is envisioned that this platform technology could be applied to the controlled regeneration of numerous different tissue types.

This study was designed to test whether the delayed release of BMP-2 from bioprinted constructs containing spatial gradients in VEGF will first enhance vascularization and sequentially enhance orthotopic bone regeneration. All animal experiments were conducted in accordance with the recommendations and guidelines of The Health Products Regulatory Authority, the competent authority in Ireland responsible for the implementation of Directive 2010/63/EU on the protection of animals used for scientific purposes in accordance with the requirements of the Statutory Instrument no. 543 of 2012. Subcutaneous mouse experiments were carried out under license (AE 19136/P069), and the rat femoral defect experiments were carried out under license (AE19136/P087) approved by The Health Products Regulatory Authority and in accordance with protocols approved by the Trinity College Dublin Animal Research Ethics Committee. The n for rodent models were based on the predicted variance in the model and was powered to detect 0.05 significance. For the subcutaneous surgeries, constructs were implanted in a balanced manner, such that each group contained an implant placed at each of the subcutaneous locations and samples for both surgical procedures were randomly distributed across the operated animals. For the rat surgeries, three rats from the empty group died from unforeseen complications and so were removed from the n number at the 12-week time point. One rat from the BMP-2 gradient group at 12-week time point was also removed, as it was deemed a statistical outlier using the Grubbs test.

Lowmolecular weight sodium alginate (58,000 g/mol) was prepared by irradiating sodium alginate (196, 000 g/mol; Protanal LF 20/40, Pronova Biopolymers, Oslo, Norway) at a gamma dose of 50,000 gray, as previously described (45). RGD-modified alginate was prepared by coupling the GGGGRGDSP to the alginate using standard carbodiimide chemistry. All bioinks were prepared by dissolving the RGD -irradiated alginate in growth medium, which consisted of alpha minimum essential medium (MEM) (GlutaMAX; Gibco, Biosciences, Ireland), 10% fetal bovine serum (FBS) (EU Thermo Fisher Scientific), penicillin (100 U/ml; Sigma-Aldrich), and streptomycin (100 g/ml; Sigma-Aldrich) (pen-strep) to make up a final concentration of 3.5% (w/v).

3D bioplotter from RegenHU (3DDiscovery) was used to evaluate the printability of the generated bioinks. The printability of varying the w/w ratio (2:1, 1:1, and 1:2) of methylcellulose to alginate was evaluated by measuring the spreading ratio as previously described (39)Spreading Ratio=Printed Filament DiameterActual Needle Diameter

To establish whether increasing the viscosity of the bioink influences growth factor release, methylcellulose (Sigma-Aldrich) was also added at ratio of 1:2 (w/w) to a 3.5% alginate solution of RGD -irradiated alginate. To establish whether the addition of clay-based particles to the bioink could further tailor the growth factor release profile of the bioinks, a 3.5% RGD -irradiated alginate solution was made, and either methylcellulose (2:1) (w/w) or a combination of both methylcellulose and laponite (Laponite XLG, BYK Additives & Instruments, UK) (6:3:1) (w/w) was added.

To establish whether the addition of nHA to the alginate would facilitate the adsorption and immobilization of growth factors within the hydrogel due to their strong electrostatic attraction between nHAs, three bioinks were tested (21). nHAs were prepared following a previously described protocol (46). A 3.5% RGD -irradiated alginate solution was made, and either methylcellulose (1:2) (w/w) or a combination of methylcellulose and nHA (2:1:2) (w/w) particles was added.

For all the growth factor release studies, VEGF (100 ng/ml; Gibco Life Technologies, Gaithersburg, MD, USA) was added to the solutions using dual-syringe approach, before precross-linking with 60 mM CaSO4 to make the bioinks as previously described (39). All constructs were cultured in growth medium in normoxic conditions, and media from each sample were changed bi-weekly. For VEGF release study, medium samples were taken (days 0, 3, 5, and 10) and snap-frozen at 80C. Hydrogels were also snap-frozen at 80C on day 0 to quantify the concentration of growth factor present in the constructs directly after printing.

To demonstrate the utility of the vascular bioink, two strategies were compared to print implants containing a spatial gradient of VEGF. The vascular bioink was prepared, cross-linked with 60 mM CaSO4, and printed to generate three experimental groups: (i) Homogenous VEGF. Bioink loaded with VEGF (100 ng/ml) was used to print constructs 8 mm in diameter and 4 mm high. (ii) Gradient 1. Bioink loaded with VEGF (100 ng/ml) was used to print a central 5-mm core with a VEGF-free bioink printed around the periphery of the 8-mm-diameter construct. (iii) Gradient 2. VEGF (80 ng/ml) was printed into the core, and VEGF (20 ng/ml) was printed into the periphery. Postprinting constructs were cross-linked again in a bath of 100 mM CaCl2 for 1 min. Constructs were cultured in growth medium in normoxic conditions for 14 days in vitro. The center and periphery of each construct were separated by coring out the center from the periphery of the scaffold and then snap-frozen at 80C, 1 hour after printing, and after 14 days in vitro.

To investigate whether the addition of laponite can tailor the growth factor release profile over a long culture period, a base bioink (Fast BMP-2 Release) and a laponite bioink (Slow BMP-2 Release) were compared. For both growth factor release profiles, a dual-syringe approach was used to deliver BMP-2 (200 ng/ml; PeproTech, UK) to the solutions before precross-linking with 60 mM CaSO4 to make the bioinks. These were printed into a 100 mM CaCl2 soak agarose mold to generate final constructs of 6 mm by 6 mm high. In addition to comparing the growth factor release profile of the two bioinks, the degradation rate of the bioinks was also investigated. These scaffolds were cultured in normoxic conditions for up to 35 days and media from each sample were changed weekly. For BMP-2 release study, medium samples were taken (days 0, 5, 7, 14, 21, and 35) and snap-frozen at 80C. Printed hydrogels were also snap-frozen at 80C on day 0 to quantify the concentration of growth factor present in the constructs directly after printing. For the degradation study, samples were washed and snap-frozen at 80C and each time point (days 0, 5, 7, 14, and 21). Samples were lyophilized by placing the samples in a freeze dryer (FreeZone Triad, Labconco, Kansas City, USA). Each sample was then weighed using an analytical balance (Mettler Toledo, XS205).

An enzyme-linked immunosorbent assay was used to quantify the levels of VEGF and BMP-2 (Bio-Techne, MN, USA) released by the alginates. The alginate samples were depolymerized with 1 ml of citrate buffer (150 mM sodium chloride, 55 mM sodium citrate, and 20 mM EDTA in H2O) for 15 min at 37C. The cell culture media and depolymerized alginate samples were analyzed at the specific time points detailed above. Assays were carried out as per the manufacturers protocol and analyzed on a microplate reader at a wavelength of 450 nm.

BMSCs were obtained from the femur of a 4-month-old porcine donor as previously described (47). All expansion was conducted in normoxic conditions, expanded in growth medium where the medium was changed twice weekly. Cells were used at the end of passage 3.

A 3D bioplotter from RegenHU (3DDiscovery) was used to print all of the scaffolds. Using a 30-gauge needle, constructs of 4 mm 5 mm high with both lateral and horizontal porosity and a fiber spacing of 1.2 mm were printed with PCL (Cappa, Perstop). The printing parameters of the PCL were as follows: temperature of thermopolymer tank (69C), temperature of thermopolymer head (72C), pressure (1 bar), screw speed (30 rpm), and feed rate (3 mm/s). Scaffolds were sterilized using ethylene oxide sterilization before hydrogel printing.

For the VEGF gradient study, the vascular bioink was prepared, cross-linked with 60 mM CaSO4, and printed within the PCL framework to generate three experimental groups: (i) No VEGF, bioink not loaded with VEGF; (ii) Homogenous, bioink loaded with VEGF (100 ng/ml) deposited (25 ng per construct) throughout the construct; and (iii) Gradient, bioink loaded with VEGF (500 ng/ml) deposited in the center (25 ng per construct) and VEGF-free bioink deposited on the outside (see Fig. 1A). Postprinting constructs were cross-linked again in a bath of 100 mM CaCl2 for 1 min.

For the BMP-2 release study, both a fast and slow release bioink were prepared and using the dual syringe approach, porcine MSCs were (2 106/ml) mixed to both bioinks to have an overall seeding density of 500 105 porcine MSCs/construct before being cross-linked with 60 mM CaSO4. Both bioinks were printed within the PCL framework to generate two experimental groups: (i) Fast release, fast release bioink loaded with BMP-2 (2 g/ml; 0.5 g per construct) deposited only in the periphery with the fast release bioink not loaded with BMP-2 in the center; and (ii) Slow release, slow release bioink loaded with BMP-2 (2 g/ml; 0.5 g per construct) deposited only in the periphery with the fast release bioink not loaded with BMP-2 in the center (see Fig. 2A). Postprinting constructs were cross-linked again in a bath of 100 mM CaCl2 for 1 min.

For the rat femoral defect, the vascular bioink, the osteoinductive bioink, and a base bioink (3.5% RGD -irradiated alginate and 1.75% methylcellulose) were prepared, cross-linked with 60 mM CaSO4, and printed within the PCL framework to generate three experimental groups: (i) VEGF Gradient, the vascular bioink loaded with VEGF (500 ng/ml) in the center of the implant and base bioink in the periphery; (ii) BMP-2 gradient, the osteoinductive bioink loaded with BMP-2 (10 g/ml) in the implant periphery (2 g per construct), with the base bioink in the center; and (iii) Composite (VEGF+BMP-2), the osteoinductive bioink in the periphery with the vascular bioink in the center (see Fig. 3A). Postprinting constructs were cross-linked again in a bath of 100 mM CaCl2 for 1 min.

Subcutaneous surgeries were performed on 20 8-week-old female BALB/c OlaHsd-Foxn 1nu nude mice (12 mice for the VEGF gradient study and 8 for the BMP-2 gradient study) (Envigo, Oxon, UK) as previously described (47). Scaffolds were 3D printed the morning of surgeries and implanted that day. Constructs were implanted in a balanced manner, such that each group contained an implant placed at each of the two subcutaneous locations and samples were randomly distributed across the operated animals.

For the rat segmental surgery, 72 12-week-old F344 Fischer male rats (Envigo, Oxon, UK) were anesthetized in an induction box using a mix of isoflurane and oxygen, initially at a flow rate of isoflurane of 5 liters/min to induce, followed by ~3 liters/min to maintain anesthesia. Once anesthetized, the animal was transferred to a heating plate that was preheated to 37C and preoperative analgesia was provided by buprenorphine (0.03 mg/ml). Surgical access to the femur was achieved via an anterolateral longitudinal skin incision and separation of the hindlimb muscles, the vastus lateralis, and biceps femoris. The femoral diaphysis was exposed by circumferential elevation of attached muscles, and the periosteum was removed. Before the creation of the defect, a PEEK plate was fixed to the anterolateral femur and was held in position using a clamp. Holes were created in the femur with a surgical drill using the plate as a template. Screws were then inserted into the drill holes in the femur to maintain the fixation plate in position. A 5-mm segmental defect was created using an oscillating surgical saw under constant irrigation with sterile saline solution. In the test groups, a scaffold was placed in the defect after a thorough washout of the surgical site. In the case of the empty defect group, the gap between bone ends was left empty. Soft tissue was accurately readapted with absorbable suture material. Closure of the skin wound was achieved using suture material and tissue glue.

Eight weeks after surgery, the BMP-2 gradient scaffolds were extracted and incubated in paraformaldehyde for 24 hours before being imaged via CT scans on a MicroCT42 (Scanco Medical, Brttisellen, Switzerland) as previously described (47).

Two weeks after surgery, 24 rats underwent a vascular perfusion protocol developed by Daly et al. (28). Briefly, the rat was sacrificed using CO2 asphyxiation, and the thoracic cavity was opened to insert a 20-gauge needle through the left ventricle of the heart. The inferior cava was cut and solutions of heparin (25 U/ml), and then, phosphate-buffered saline (PBS) was perfused through the vasculature using a peristaltic pump (Masterflex, Cole-Parmer, Vernon Hills, IL, USA) until the vasculature system was completely flushed clear. A solution of 10% formalin was then perfused for 5 min. Animals received a final perfusion of 20- to 25-ml radiopaque contrast agent MICROFIL (Flow Tech, Carver, MA, USA) and were left at 4C overnight. Explants were extracted and incubated in PBS for 24 hours before being imaged via CT scans on a MicroCT42 (Scanco Medical, Brttisellen, Switzerland) at 70 kVp, 113 A, and a 10-m voxel size. The volume of interest (VOI) was determined by positioning a 5-mm circle around the cross section of the femur with an overall length of 6.26 mm. MICROFIL has the same threshold as bone mineral, and therefore, to segment perfused vasculature from mineralized tissue within each construct, two scans were analyzed: calcified construct versus decalcified construct. The calcified constructs were scanned and postprocessed using a threshold value that accurately depicted both the mineral content and the vessel volume by visual inspection of the 2D grayscale tomograms (Scanco Medical MicroCT42). Noise was removed using a low-pass Gaussian filter (sigma = 1.2, support = 2), and a global threshold of 210 was applied. Next, samples were decalcified in EDTA (15 weight %, pH 7.4) for 2 weeks with the decalcification solution replaced daily (decalcified constructs). After 2 weeks, these decalcified constructs were scanned using the same settings and postprocessed at the same threshold as the calcified constructs to determine mineral content. Mineralized tissue content was determined by subtracting the bone volume of the decalcified scans from the calcified scans. Next, the decalcified scans were postprocessed at a threshold of 99 that accurately depicted just the vessel volume upon visual inspection of the 2D grayscale tomograms.

CT scans were performed on the rats using a Scanco Medical vivaCT 80 system (Scanco Medical, Bassersdorf, Switzerland). Rats (n = 9) were scanned at 4, 8, 10, and 12 weeks after surgery to assess defect bridging and bone formation within the defect. First, anesthesia was induced in an induction box using a mix of isoflurane and oxygen, initially at a flow rate of isoflurane of 5 liters/min to induce, followed by ~3 liters/min to maintain anesthesia. Next, the rats were placed inside the vivaCT scanner, and anesthesia was maintained by isoflurane-oxygen throughout the scan. Next, a radiographic scan of the whole animal was used to isolate the rat femur. The animals femur was aligned parallel to the scanning field of view to simplify the bone volume assessments. Scans were performed using a voltage of 70 kVp and a current of 113 A. A Gaussian filter (sigma = 0.8, support = 1) was used to suppress noise, and a global threshold of 210 was applied. A voxel resolution of 35 m was used throughout. 3D evaluation was carried out on the segmented images to determine bone volume and density and to reconstruct a 3D image. Bone volume and bone density in the defects were quantified by measuring the total quantity of mineral in the central 130 slices of the defect. To differentiate regional differences in bone formation, three VOIs were created. Concentric 2 mm, 4 mm, and 10 mm were aligned with the defect and used to encompass bone formation. The VOIs were aligned using untreated native bone along the femur. The core bone volume was quantified from the inner 2-mm VOI. The annular bone volume was quantified by subtracting the 2-mm VOI from the 4-mm VOI. Ectopic bone volume was quantified by subtracting the 4-mm VOI from the 10-mm VOI. The bone volume percentages for each region were then calculated by dividing the corresponding bone volume (i.e., bone volume in the annulus) by the total bone volume in the defect. The bone volume and densities were then quantified using scripts provided by Scanco.

For segmental defect samples, all constructs that were not being processed for vascular-CT imaging, were decalcified in Decalcifying Solution-Lite (Sigma-Aldrich) for 1 week before tissue processing. Once decalcified, all samples were dehydrated and embedded in paraffin using an automatic tissue processor (Leica ASP300, Leica). All samples were sectioned with a thickness of 8 m using a rotary microtome (Leica Microtome RM2235, Leica). Sections were stained with H&E for vessel infiltration, Safranin O to assess sulphated glycosaminoglycans (sGAG) content, and Goldners trichrome for bone formation. Quantitative analysis was performed on multiple H&E-stained slices, whereby vessels (positive staining for endothelium and erythrocytes present within the lumen), were counted on separate sections taken throughout each construct and averaged for each construct. Safranin O sections were evaluated for new developing bone (positive sGAG content). Massons trichromestained sections were evaluated for new bone formation. The percentage of developing bone, new bone, and marrow per total area of construct was measured in separate sections with the Deconvolution ImageJ plugin.

Immunofluorescence analysis was used to detect -SMA and vWF as previously described (47). Briefly, following blocking step, sections were then incubated overnight at +4C with goat polyclonal -SMA (1:250; ab21027, Abcam) in PBS with 3% of donkey serum (w/v) and 1% bovine serum albumin (BSA). After three washing steps with PBS containing 1% w/v BSA, the sections were incubated with Alexa Fluor 488 donkey anti-goat secondary antibody (1:200; ab150129, Abcam) for 1 hour at room temperature in the dark. The samples were washed three times in PBS with 1% w/v BSA, and the slides were then incubated overnight at +4C with rabbit polyclonal vWF antibody (1:200; ab6994, Abcam) in PBS with 3% of donkey serum (w/v) and 1% BSA (all from Sigma-Aldrich). After three washing steps with PBS and 1% w/v BSA, the sections were incubated with Alexa Fluor 647 donkey anti-rabbit secondary antibody (1:200; ab150075, Abcam) for 1 hour at room temperature in the dark. Last, samples were washed three times with PBS and 1% w/v BSA, and the sections were mounted using 4,6-diamidino-2-phenylindole mounting media (Sigma-Aldrich). Fluorescence emission was detected using a confocal laser scanning microscopy (Olympus FluoView 1000).

Results were expressed as means SD. Statistics was performed using the following variables: (i) When there were two groups and one time point, a standard two-tailed t test was performed. (ii) When there were more than two groups and one time point, a one-way analysis of variance (ANOVA) was performed. (iii) When there were more than two groups and multiple time points, a two-way ANOVA was performed. All analyses were performed using GraphPad (GraphPad Software, La Jolla, CA, USA; http://www.graphpad.com). For all comparisons, the level of significance was P 0.05.

Acknowledgments: We thank the staff at the Bioresources Unit in Trinity College Dublin for veterinary assistance and technical support. Funding: This publication has emanated from research supported by a research grant from the European Research Council (ERC) under grant no. 647004, the Irish Research Council (GOIPD/2016/324), and NIHs NIAMS grant R01AR063194. Author contributions: F.E.F. was responsible for technical design, development of bioinks, performing all animal surgeries, performing vessel perfusion, all CT scans, data interpretation, histological analysis, and drafting the paper. P.P. assisted with the rat surgeries and assisted with the vessel perfusions. L.H.A.v.D. assisted with CT analyses and CT scans. J.N. and D.C.B. assisted with all animal surgeries. J.-Y.S. and E.A. developed the RGD -irradiated alginate. D.J.K. conceived and helped design the experiments, oversaw the collection of results and data interpretation, and finalized the paper. Competing interests: Research undertaken in the laboratory of D.J.K. at Trinity College Dublin is part-funded by Johnson & Johnson. The authors declare no other competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

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NIH names Dr. Rena D’Souza as director of the National Institute of Dental and Craniofacial Research – National Institutes of Health

Thursday, August 13th, 2020

News Release

Thursday, August 13, 2020

National Institutes of Health Director Francis S. Collins, M.D., Ph.D., has selected Rena N. DSouza, D.D.S., M.S., Ph.D., as director of NIHs National Institute of Dental and Craniofacial Research (NIDCR). A licensed dentist, Dr. DSouza is currently the assistant vice president for academic affairs and education for health sciences at the University of Utah, Salt Lake City. There she also serves as a professor of dentistry, the Ole and Marty Jensen Chair of the School of Dentistry and professor of neurobiology and anatomy, pathology and surgery in the School of Medicine and the Department of Biomedical Engineering. She is expected to begin her new role as the NIDCR director later this year.

Dr. DSouza is renowned for her research in craniofacial development, genetics, tooth development and regenerative dental medicine. She has worked as a proponent for NIH for decades, serving on critical advisory committees and as an expert consultant on multiple projects, said Dr. Collins. I look forward to having her join the NIH leadership team later thisyear. I also want to thank NIH Principal Deputy Director Lawrence A. Tabak, D.D.S., Ph.D., for his valuable leadership as the acting director of NIDCR since January 1, 2020.

As NIDCR director, Dr. DSouza will oversee the institutes annual budget of over $475 million, which supports basic, translational and clinical research in areas of oral cancer, orofacial pain, tooth decay, periodontal disease, salivary gland dysfunction, craniofacial development and disorders and the oral complications of systemic diseases. The institute funds approximately 770 grants, 6,500 researchers and 200 organizations. Additionally, NIDCR supports research training and career development programs for approximately 350 people at various stages of their careers, from high school students to independent scientists.

Dr. DSouza has been a principal investigator on multiple NIH and other federal grants since 1987 and has published 140 peer-reviewed journal papers and book chapters. Her research focuses on developmental biology and genetics; matrix biology; biomaterials, tissue engineering and stem cells; and clinical research. Her groups discovery that a novel mutation in PAX9 was responsible for a severe form of human tooth agenesis opened a new field of research to discover genes and mutations as well as therapies for common human inherited disorders of the craniofacial complex.

Dr. DSouzas career honors are significant. She was selected to be the inaugural dean of the University of Utahs School of Dentistry, which was established in 2012. She is currently the elected chair in Dentistry and Oral Health Sciences Section and elected as a fellow of the American Association for the Advancement of Science. She also is a former president of the American Association for Dental Research and the International Association for Dental Research,a fellow of the American College of Dentistsand the recipient of the 2017 American Association for Dental Research Irwin D. Mandel Distinguished Mentoring Award. Dr. DSouza served on the NIH Advisory Committee to the Director in 2013-14, and on NIH study sections. She is a devoted mentor and champion of diversity in the biomedical research workforce. Since 1985, she has served as a volunteer dentist for women in need and people struggling with homelessness in Salt Lake City, Dallas and Houston.

Dr. DSouza received her bachelors degree in dental surgery from the University of Bombay, India, after which she completed her general practice residency. She earned her D.D.S., Ph.D. and masters degree in pathology/biomedical sciences from the University of Texas Health Science Center in Houston.

NIDCR is the nations leading funder of research on oral, dental, and craniofacial health. To learn more about NIDCR, visit https://www.nidcr.nih.gov/.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

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NIH names Dr. Rena D'Souza as director of the National Institute of Dental and Craniofacial Research - National Institutes of Health

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Global Cell Theraputics Market Value Estimated To Grow With A Healthy CAGR Rate During 2020-2025: Cell Theraputics Bristol-Myers Squibb Company…

Friday, July 10th, 2020

This market research study determines the increase in changes and the aspects which are likely to have an impact on the growth of the Global Cell Theraputics Market. Increased demand for the technologies is also one of the factors, which are likely to boost the growth of the market research industry. The market research study uses several tools and techniques which are used for the determination of the growth of the Global Cell Theraputics Market.

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The report is also used in the analysis of the growth rates and the threats of new entrants, which are used for the determination of the growth of the market for the estimated forecast period. Moreover, increased demand for the factors influencing the growth of the market is also one of the major aspects which is likely covered in depth in the report. One of the methods for the determination of the growth of the market is the increased use of the statistical tools, which is used for the estimation of the growth of the market for the estimated forecast period. SWOT and PESTEL analysis is one of the methods for the determination of the growth of the global Cell Theraputics market. These tools are also used for the determination of the major players for the growth of the market for the estimated forecast period.

Key vendors/manufacturers in the market:

Cell TheraputicsBristol-Myers Squibb Company (Celgene)Brainstorm Cell Therapeutics Inc.Roche (Spark Therapeutics)Bluebird BioQuanterixCrispr TherapeuticsCti BiopharmaModerna TherapeuticsPTC TherapeuticsLineage Cell TherapeuticsAtara Biotherapeutics, IncAdaptimmune

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This report focuses and highlights the strategies and the trends, in which the manufacturer and the company is likely to move. The research study is also known to provide in depth analysis of the reports which is one of the key aspects for the growth of the global Cell Theraputics market. The study covers the production, sales, and revenue of various top players in the global Cell Theraputics market, therefore enabling customers to achieve thorough information of the competition and henceforth plan accordingly to challenge them head on and grasp the maximum market share. This report is filled with significant statistics and information for the consumers to attain in-depth data of the Cell Theraputics and further Cell Theraputics growth.

Global Market By Type:

Cell TheraputicsStem CellsImmunocyte

Global Market By Application:

Cell TheraputicsAllogeneic Cell TherapyAutologous Cell TherapyXenogeneic Cell Therapy

Segment type is also an important aspect of any market research study. Reports are product based, they also includes information on sales channel, distributors, traders and dealers. This helps in efficient planning and execution of supply chain management as it drastically affects the overall operations of any business. The up-to-date, complete product knowledge, end users, industry growth will drive the profitability and revenue. Cell Theraputics report studies the current state of the market to analyze the future opportunities and risks.

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Global Cell Theraputics Market Value Estimated To Grow With A Healthy CAGR Rate During 2020-2025: Cell Theraputics Bristol-Myers Squibb Company...

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Global Tissue-Replacement Products Market to Witness Rapid Development During the Period 2017 2025 – Lake Shore Gazette

Friday, July 10th, 2020

Tissue replacement that involves repair or replacement of structural tissues, is one of the most important application covered under tissue engineering. Structural tissues such as blood vessels, bone, cartilage, and bladder are repaired or replaced using tissue engineering that drives the demand for tissue-replacement products, thereby fueling the growth of tissue-replacement products market. In tissue engineering, living cells are utilized as engineering materials to repair the cells performing specific biochemical functions. Thus, tissue engineering on a broad level refers to the procedure of combining biologically active molecules, cells and scaffolds into functional molecules. The major goal of tissue engineering involves assembly of functional constructs to restore, maintain or regenerate damaged tissues. The most common engineered tissues used to restore damaged tissues or organs include artificial skin and cartilages approved by FDA. Regenerative medicine is also one of the broad field that is responsible for recreation of cells and rebuild tissues and whole organs. It involves tissue engineering along with incorporation of self-healing properties wherein body utilizes foreign biological material or its own system to regenerate or repair cells. These two fields tissue engineering and regenerative medicine are largely interchangeable and focus on finding cures for complex chronic disorders. Some of the most common tissue replacement products include cartilage replacement products, meniscus replacement products, tendon replacement products, suture anchors, interference screws, and laparoscopic instruments. Tissue patch/mesh is again one of the most important tissue replacement product used in tissue-replacement products market that is further categorized as biological mesh including xenografts and allografts, and synthetic mesh. However, other cellular regeneration products in the global tissue-replacement products market include chondrocyte transplant, stem cells, growth factors, gene therapy and scaffolds. Presence of extensive tissue replacement products in the medical industry coupled with their increasing demand from end user segments is anticipated to drive the growth of tissue-replacement products market. Also, some of the major end users for tissue-replacement products market include hospitals, specialized clinics, ambulatory surgical centers, research & academic institutions. Regeneration or replacement of damaged tissues is majorly done by using an existing scaffold. This technique of using scaffolds to create a new tissue is used to bioengineer lung, liver, heart and kidney tissue and proves to be a promising approach in tissue engineering.

Tissue replacement is of extreme importance as it find applications in clinically repairing or replacing the damaged or destroyed natural tissue. Tissue replacement is now-a-days extensively used in orthopedic surgery, gastrointestinal surgery and abdominal surgery. It also has wide clinical applications in craniomaxillofacial surgery, spine fusion surgery, dental implant, bone growth factor delivery and others.

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Rising incidence of tissue injuries coupled with increasing geriatric population is anticipated to be the primary factor driving the tissue-replacement products market. Increasing obesity rate, growing disposable income along with increasing healthcare expenditure and lack of tissue substitutes to be used in surgery are some other factors fueling the growth of tissue-replacement products market.Additionally, advancements in tissue engineering coupled with increasing shift of people towards craniomaxillofacial surgery, increasing medical procedures and rising sports injuries is further anticipated to fuel the growth of tissue-replacement products market during the forecast period.However, high costs associated with tissue replacement surgery and lack of reimbursement is restraining the growth of tissue-replacement products market.

The global tissue-replacement products market is segmented on basis of product type, application type, end user and geographic region:

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On the basis of type of product, biological mesh are extensively used over conventional synthetic mesh and other tissue replacement products as biological mesh have advantages over synthetic mesh in case of contaminated wounds and offers effective results. Also, rising awareness among individuals is anticipated to propel the tissue-replacement products market over the forecast period.

Based on application, tissue-replacement products find major applications in orthopedic surgery and spinal fusion surgery on the account of rising demand for tissue-replacement products in hernia repair, skin repair, dural repair and sports injuries.

However, on the basis of geography, global tissue-replacement products market is segmented into five key regions viz. North America, Latin America, Europe, Asia Pacific, and Middle East & Africa. North America captured the largest shares in global tissue-replacement products market and is projected to continue same trend over the forecast period due to the growing geriatric population and rising incidence of sports injuries and increase in medical procedures. North America is followed by Europe which captures the second largest revenue shares in global tissue-replacement products market. However, Asia Pacific is expected to register a fast growth during forecast period and is anticipated to be a profitable market for new market players in global Tissue-Replacement Products market. Countries in Asia Pacific such as China and India are expected to be the fastest growing regions owing to the growing demand for tissue replacement products.

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Some of the key players present in global tissue-replacement products market are StrataGraft, Edwards Lifesciences, Medtronic PLC, Arthrex Inc., Johnson & Johnson Private Limited, C. R. Bard, Inc., Smith & Nephew, Integra LifeSciences Corporation, and others.

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Job interviews zoom without leaving the house | What’s Working – The Union Leader

Monday, July 6th, 2020

Welcome to the new world of hiring, pandemic-style.

A North Carolina woman interviewed for a job as a certified nurse midwife at Dartmouth-Hitchcock, toured the hospital campus, landed the position and bought a house without setting foot in New Hampshire.

A New York doctor sat for eight hours decked out in a suit at home doing virtual interviews after the pandemic scuttled in-person meetings for a job at a clinic in Lyme.

I would stay in the same spot and join a different video conference link. There was a lot of time devoted to sorting out the tech issues, Dr. David Levine said by phone from Albany, N.Y. It was weird and surreal but not super difficult.

D-H reported 28 medical doctors and associate providers who accepted job offers since the pandemic hit never set foot on the D-H campus or met in-person during the virtual interview process, according to Sarah Currier, its workforce development director.

As many Granite State companies continue to hire new workers amid record unemployment, the COVID-19 pandemic has shifted most face-to-face job interviewing to video chats.

Even for supermarket baggers and cashiers?

Yes, all positions, said Hannaford spokesman Eric Blom.

Employers and staffing agency officials interviewed said that video interviews offer sufficient insight into whether job seekers will be good fits in their organizations.

Its amazing to see how much you can learn about someones personality just based on their video screen, said Shannon Herrmann, senior recruiting manager at Alexander Technology Group in Bedford, a technology staffing agency. We have seen many New Hampshire companies embrace the remote workforce and on-board new hires with no expectation to come into the office.

People willing to interview remotely show they are flexible and adaptable, said D-Hs Currier.

Were building a workforce that is comfortable with change: change-comfortable, change-ready or change-willing because health care is changing so much, Currier said by phone. Theyre saying, Im open-minded to new processes, and thats certainly a value we appreciate and look for.

Levine D-Hs first 100% virtual interviewee who accepted a job offer prefers in-person interviews. Its nicer to be able to see people and see the physical space youre going to be occupying, he said.

Levine, 28, whose wife, Linda Gao, starts a fellowship at Dartmouth-Hitchcock next month, admitted to staging his computer room for a better look, opening the blinds and putting a family photo and a vase with flowers within camera-range.

At one funny point, they couldnt tell whether the video was screwed up or I had long hair, said Levine, who still hadnt cut his locks more than two months later.

Fidelitys growth

At Fidelity Investments in Merrimack, video interviews already were a best practice started before COVID-19, and they will continue. The financial services company has hired more than 400 people in New Hampshire since March.

Once hired, its likely the new employee will not need to go to the workplace at this time. In fact, we currently have well over 90% of our employees working remotely, said Jamie Hallinan, regional center head of stock plan services and New Hampshire regional leader.

Fidelitys remote on-boarding process includes shipping of laptops and equipment, an introduction of company benefits and remote access to its technology services for setup and questions. Employees, however, are expected to return eventually to their offices.

Alexis Dunphy found herself among those hired this month.

The pandemic had caused the Raymond thirty-something to think more about a new career after she was idled from her job as a hair stylist.

Its a sign: Its time to start looking and go for it, Dunphy said by phone.

She joined Fidelity Investments as a customer relationship advocate answering customer service calls. She works remotely now, but she expects to shift later to an office setting in Merrimack.

The interview process included filming herself answering questions, followed by phone and Zoom interviews. She was offered the job three days later.

Ive already made friends, so its kind of weird but speaks to our time and our world, Dunphy said.

Through video and email communications with co-workers, we feel very connected to everybody, Dunphy said.

Hannaford estimates it has hired more than 800 people for its 36 New Hampshire stores since mid-March. It is using more phone, Skype and Microsoft Teams meetings, which has chat and video options. Any in-person interviews require face masks, hand sanitizer and social distancing.

We also have been reaching out to businesses affected by COVID-19 restrictions to see if any of their employees would like to work for us temporarily until their businesses reopen, Blom said.

Both furloughed and laid-off workers from elsewhere have been applying for jobs, he said.

Virtual job-hunting

Virtual group events also have grown more popular among job seekers stuck at home.

The New Hampshire Tech Alliance plans to host the first in a series of virtual job fairs in late July, but not everybody is looking to hire.

Some of our members have expressed concern about prospect and client pipelines in a year and some have put temporary holds on hiring to see how this plays out, said Julie Demers, the alliances executive director.

Dartmouth-Hitchcocks physician recruitment team attended seven virtual career fairs and conferences between April 1 and May 20. D-H recruiters talked to between 40 and 80 attendees over the course of a fair, or far more than we could talk to if we sent one recruiter to a career fair in real life, Currier said in an email.

About 10% of these job fair conversations were immediately shared with departments for next-round interviews, and many others were identified as having potential for future openings, Currier said. We found this method of outreach to be very productive and engaging for the candidates.

D-H has used virtual interviews in recent months to hire workers from 17 states, including California and Texas, as well as Canada and Sweden, Currier said.

At Hypertherm in Hanover, hiring officials went from a hybrid format of virtual and on-site interviewing to 100% virtual. The company created help guides for both its hiring teams and candidates.

These guides shared suggestions on how to interview and connect virtually to create a positive experience, said Carolyn Stone, who leads the talent acquisition and experience team.

If done right, a virtual interview experience is very close to an in-person interview, she said.

Hypertherm, which manufactures plasma-cutting and water-jet cutting equipment, employs nearly 1,100 in New Hampshire and has hired 14 workers since mid-March.

In mid-June, it resumed on-site interviews in New Hampshire but plans to use a mixture of both formats going forward.

On-site interviews, especially as you get to the final stages of the hiring process, are important as they allow the candidate to experience our culture first-hand and meet the people they would potentially work with, Stone said.

Virtual interviews presented plenty of memorable moments, but nothing that made anyone more hireable, she said.

There were many unplanned cameo appearances (my household members included) bringing more levity to what you would usually experience during an interview, Stone said by email. As everyone was navigating through this unprecedented experience together, it seemed to increase empathy and create a greater human connection and appreciation from both the interviewer and candidate.

Whats Working, a series exploring solutions for New Hampshires workforce needs, is sponsored by the New Hampshire Solutions Journalism Lab at the Nackey S. Loeb School of Communications and is funded by Eversource, the New Hampshire Charitable Foundation, Dartmouth-Hitchcock Medical Center, the New Hampshire College & University Council, Northeast Delta Dental and the New Hampshire Coalition for Business and Education.

Contact reporter Michael Cousineau at mcousineau@unionleader.com. To read stories in the series, visit unionleader.com/whatsworking.

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Citius Receives FDA Response on Pre-Investigational New Drug (PIND) Application for its Induced Mesenchymal Stem Cells (iMSCs) to Treat Acute…

Tuesday, June 30th, 2020

CRANFORD, N.J., June 26, 2020 /PRNewswire/ --Citius Pharmaceuticals, Inc. ("Citius" or the "Company") (Nasdaq: CTXR), a specialty pharmaceutical company focused on developing and commercializing critical care drug products, announced today that the Company has received a written response from the U.S. Food and Drug Administration (FDA) in regards to its pre-investigational new drug (PIND) application for its induced mesenchymal stem cells (iMSCs) to treat and reduce the severity of acute respiratory distress syndrome (ARDS) in patients with COVID-19.

The FDA acknowledged that the Company could apply for fast track designation and also provided Citius with the chemistry, manufacturing, and control (CMC) requirements for the proposed trials. The Company plans to initiate actions on the FDA's recommendations and follow up with the FDA with an Investigational New Drug (IND) application under the Coronavirus Treatment Acceleration Program (CTAP).

Myron Holubiak, Chief Executive Officer of Citius, commented, "We appreciate the FDA's thoughtful guidance on our unique, allogenic mesenchymal stem cells derived from induced pluripotent stem cells (iPSCs). We understand that iPSC-derived stem cells are not the same as adult-donor derived cells and, therefore, would require different proof of concept studies. Since we believe in the advantages of iPSC MSCs over donor-derived cells, we intend to develop assays recommended by the FDA and demonstrate the safety of these MSCs in our preclinical studies. We are committed to the successful completion of the required clinical trials to provide an effective and safe therapy for ARDS due to COVID-19."

About Citius Pharmaceuticals, Inc.Citius is a late-stage specialty pharmaceutical company dedicated to the development and commercialization of critical care products, with a focus on anti-infectives and cancer care. For more information, please visitwww.citiuspharma.com.

About Citius iMSCCitius's mesenchymal stem cell therapy product is derived from a human induced pluripotent stem cell (iPSC) line generated using a proprietary mRNA-based (non-viral) reprogramming process. The iMSCs produced from this clonal technique are differentiated from adult donor-derived MSCs (bone marrow, placenta, umbilical cord, adipose tissue, or dental pulp) by providing genetic homogeneity. In in-vitro studies, iMSCs exhibit superior potency and high cell viability. The iMSCs secrete immunomodulatory proteins that may reduce or prevent pulmonary symptoms associated with acute respiratory distress syndrome (ARDS) in patients with COVID-19. The Citius iMSC is an allogeneic (unrelated donor) mesenchymal stem-cell product manufactured by expanding material from a master cell bank.

About Acute Respiratory Distress Syndrome (ARDS)ARDS is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. ARDS is a rapidly progressive disease that occurs in critically ill patients most notably now in those diagnosed with COVID-19. ARDS affects approximately 200,000 patients per year in the U.S., exclusive of the current COVID-19 pandemic, and has a 30% to 50% mortality rate. ARDS is sometimes initially diagnosed as pneumonia or pulmonary edema (fluid in the lungs from heart disease). Symptoms of ARDS include shortness of breath, rapid breathing and heart rate, chest pain (particularly while inhaling), and bluish skin coloration. Among those who survive ARDS, a decreased quality of life is relatively common.

About Coronavirus Treatment Acceleration Program (CTAP)In response to the pandemic, the FDA has created an emergency program called the Coronavirus Treatment Acceleration Program (CTAP) to accelerate the development of treatments for COVID-19. By redeploying staff, the FDA is responding to COVID-19-related requests and reviewing protocols within 24 hours of receipt. The FDA said CTAP "uses every available method to move new treatments to patients as quickly as possible, while at the same time finding out whether they are helpful or harmful." In practice, that means developers of potential treatments for COVID-19 would benefit from an unusually faster track at the FDA to shorten wait times at multiple steps of the process.

Safe Harbor

This press release may contain "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such statements are made based on our expectations and beliefs concerning future events impacting Citius. You can identify these statements by the fact that they use words such as "will," "anticipate," "estimate," "expect," "should," and "may" and other words and terms of similar meaning or use of future dates. Forward-looking statements are based on management's current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock price. Factors that could cause actual results to differ materially from those currently anticipated are: the risk of successfully negotiating a license agreement for a potential ARDS therapy with Novellus, Inc. within the option period; the ability to access the FDA's CTAP program for our planned ARDS therapy; risks associated with developing our product candidates, including any licensed from Novellus, Inc., including that preclinical results may not be predictive of clinical results and our ability to file an IND for such candidates; our need for substantial additional funds; risks associated with conducting our Phase 3 trial for Mino-Lok, including completing patient enrollment, opening study sites and achieving the required number of catheter failure events; the estimated markets for our product candidates, including those for ARDS, and the acceptance thereof by any market; risks related to our growth strategy; our ability to identify, acquire, close and integrate product candidates and companies successfully and on a timely basis; risks relating to the results of research and development activities; uncertainties relating to preclinical and clinical testing; the early stage of products under development; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; our ability to attract, integrate, and retain key personnel; government regulation; patent and intellectual property matters; competition; as well as other risks described in our SEC filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law.

Contact:

Andrew Scott Vice President, Corporate Development (O) 908-967-6677 x105[emailprotected]

SOURCE Citius Pharmaceuticals, Inc.

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Medical Professionals in the Ozarks – 417mag

Tuesday, June 30th, 2020

Eustasis Psychiatric & Addiction Health

417-322-6622| 3600 S. National Ave., Springfield

Eustasis Psychiatric & Addiction Health is pleased to announce construction of their brand new site in the heart of Medical Mile, opening in July! There is expanded access to medication management, psychotherapy, testing and advanced treatment options.

Dr. Alok Jain and his wife Breanna Jain started the clinic in 2018 with the mission of providing the highest quality psychiatric care to all patients. Since then they have put together an amazing team of board-certified providers and support staff who have tirelessly served the Springfield community.

We wanted to build something really vital for our patients. A place that everyone could come, regardless of age or diagnosis, says Dr. Jain.

Dr. Alok Jain has been honored as a 417 Top Doctor every year since 2007 and is 2020's top psychiatrist. He is a board-certified psychiatrist, member of the American Psychiatric Association and has an extensive background in consultation-liaison psychiatry and psychopharmacology.

Eustasiss immediate-access site has provided patients with an unprecedented way to receive psychiatric care without delay. Their walk-in and be seen model is changing the face of psychiatry. The new location has eight providers and room for growth! They are providing the most state of the art modalities, including ADHD testing and esketamine.

It is super exciting, says Breanna Jain, CEO, PMHNP-BC. We have patients who come in all hours of the day, pediatric or adult, all payor sources. They will ask, You mean I can really be seen right now? We can proudly tell them of course! This is just the way we believe mental health should be done.

Both Dr. Jain and Breanna know that people need options in this community. Patients struggles are numerous, ranging from addiction, bipolar, ADHD, trauma, anxiety and more. The Jains like to think of Eustasis as a one-stop-shop.

There shouldnt be high levels of bureaucracy. This is what overwhelms patients. Barriers have no place when it comes to mental health, the Jains explain.

Eustasis is committed to helping patients find the optimal balance of emotions during these difficult times. They have expanded their hours and have both in person and telemedicine options available. They are always accepting new patients!

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Dental Fitting Market 2019 Break Down by Top Companies, Countries, Applications, Challenges, Opportunities and Forecast 2026 – Cole of Duty

Wednesday, June 10th, 2020

A new market report by Market Research Intellect on the Dental Fitting Market has been released with reliable information and accurate forecasts for a better understanding of the current and future market scenarios. The report offers an in-depth analysis of the global market, including qualitative and quantitative insights, historical data, and estimated projections about the market size and share in the forecast period. The forecasts mentioned in the report have been acquired by using proven research assumptions and methodologies. Hence, this research study serves as an important depository of the information for every market landscape. The report is segmented on the basis of types, end-users, applications, and regional markets.

The research study includes the latest updates about the COVID-19 impact on the Dental Fitting sector. The outbreak has broadly influenced the global economic landscape. The report contains a complete breakdown of the current situation in the ever-evolving business sector and estimates the aftereffects of the outbreak on the overall economy.

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The report also emphasizes the initiatives undertaken by the companies operating in the market including product innovation, product launches, and technological development to help their organization offer more effective products in the market. It also studies notable business events, including corporate deals, mergers and acquisitions, joint ventures, partnerships, product launches, and brand promotions.

Leading Dental Fitting manufacturers/companies operating at both regional and global levels:

Sales and sales broken down by Product:

Sales and sales divided by Applications:

The report also inspects the financial standing of the leading companies, which includes gross profit, revenue generation, sales volume, sales revenue, manufacturing cost, individual growth rate, and other financial ratios.

The report also focuses on the global industry trends, development patterns of industries, governing factors, growth rate, and competitive analysis of the market, growth opportunities, challenges, investment strategies, and forecasts till 2026. The Dental Fitting Market was estimated at USD XX Million/Billion in 2016 and is estimated to reach USD XX Million/Billion by 2026, expanding at a rate of XX% over the forecast period. To calculate the market size, the report provides a thorough analysis of the market by accumulating, studying, and synthesizing primary and secondary data from multiple sources.

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The market is predicted to witness significant growth over the forecast period, owing to the growing consumer awareness about the benefits of Dental Fitting. The increase in disposable income across the key geographies has also impacted the market positively. Moreover, factors like urbanization, high population growth, and a growing middle-class population with higher disposable income are also forecasted to drive market growth.

According to the research report, one of the key challenges that might hinder the market growth is the presence of counter fit products. The market is witnessing the entry of a surging number of alternative products that use inferior ingredients.

Key factors influencing market growth:

Reasons for purchasing this Report from Market Research Intellect

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Customization of the Report:

Market Research Intellect also provides customization options to tailor the reports as per client requirements. This report can be personalized to cater to your research needs. Feel free to get in touch with our sales team, who will ensure that you get a report as per your needs.

Thank you for reading this article. You can also get chapter-wise sections or region-wise report coverage for North America, Europe, Asia Pacific, Latin America, and Middle East & Africa.

To summarize, the Dental Fitting market report studies the contemporary market to forecast the growth prospects, challenges, opportunities, risks, threats, and the trends observed in the market that can either propel or curtail the growth rate of the industry. The market factors impacting the global sector also include provincial trade policies, international trade disputes, entry barriers, and other regulatory restrictions.

About Us:

Market Research Intellect provides syndicated and customized research reports to clients from various industries and organizations with the aim of delivering functional expertise. We provide reports for all industries including Energy, Technology, Manufacturing and Construction, Chemicals and Materials, Food and Beverage and more. These reports deliver an in-depth study of the market with industry analysis, market value for regions and countries and trends that are pertinent to the industry.

Contact Us:

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Market Research Intellect

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Tel: +1-650-781-4080

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Coronavirus daily news updates, June 9: What to know today about COVID-19 in the Seattle area, Washington state and the world – Seattle Times

Wednesday, June 10th, 2020

Editors note:This is a live account of COVID-19 updates fromTuesday,June 9,as the day unfolded. Click here to see updates from Wednesday, June 10.Tofind resources and the latest extended coverage of the pandemic,click here.

Across the country and around the world, more people are forgoing physical distancing. Its not just the George Floyd protests, which have drawn floods of demonstrators economies are starting to reopen and people are inching back toward their normal routines.

Meanwhile, the protests continue, and medical experts reiterate their warnings that tear gas and pepper spray can increase the spread of respiratory viruses.Local businesses in Washington face unprecedented financial challenges as theystruggle to recover from both the effects of the pandemic and recent looting, although many owners of the hardest-hit businesses have been quick to voice support for the protests.

Throughout Tuesday, on this page, well post updates from Seattle Times journalists and others on the pandemic and its effects on the Seattle area, the Pacific Northwest and the world. Updates from Monday can be foundhere, and all our coronavirus coveragecan be found here.

The following graphic includes the most recent numbers from the Washington State Department of Health, released Tuesday.

The agonizing tale of the coronavirus outbreak on the carrier USS Theodore Roosevelt starting in March led to the infection of hundreds of crew members, an emergency stop in Guam, the removal of the ships captain and the resignation of the acting Navy secretary.

But while the Navy and civic leaders in Guam struggled to quell the spread of the virus, naval officials and researchers at the Centers for Disease Control and Prevention began a medical investigation into the outbreak, the results of which were released Tuesday.

The study found that, among a few hundred service members who volunteered to be tested and questioned about their experiences onboard and while in Guam, more than a third had enough functioning antibodies to the coronavirus to indicate they could have some protection against the virus, at least for a limited time.

Some were still showing the presence of neutralizing antibodies, which block the virus from binding to cells, three months after the onset of symptoms.

The New York Times

The coronavirus pandemic has caused most rents in the Seattle area to stagnate,though theyre falling for the least-expensive apartments, according to data from analytics firm RealPage.One neighborhood West Seattle is seeing especially sharp cuts, according to landlords and property managers, thoughnotjust from the pandemic.

Overall, in the Seattle-Bellevue-Everett area, May asking rentswere nearly the same as they were a year ago, averagingjust under $1,900, whereas before the pandemic, rents were up nearly 5% year-over-year in the area.RealPage looks at effective asking rents, which include advertised discounts offered by landlords and property managers to entice new tenants to ink a deal, like one month of free rent.

The bigslide has beenamong the least-expensive properties, where May asking rents were off 0.8% compared with a year earlier, to an average of $1,518. Rents for apartments near Boeing offices and factories in Renton and Everett were also down, by as much as 3.1%. The company recently announcedcuts of almost 10,000 jobs in Washington state.

Still, even national landlords with huge luxury portfolios are sweeteningdeals to close contracts. Astatewide eviction moratorium and ban on rent increases have keptarea renters in their apartments and slowed demand.

Read the full story here.

Katherine K. Long

King County and other local organizations announced Tuesday they're planning to partner with free coronavirus-testing campaigns led by Beyonc and her mother, Tina Knowles Lawson.

The partnership a part of Knowles Lawson's#IDIDMYPART campaign and Beyoncs BeyGood initiative will provide two days of free drive-thru COVID-19 testing in South King County cities, "where Black and brown communities are suffering disproportionately from coronavirus," said a statement from the county.

Attendees will also receive community care packages, diapers and toiletries for free.

I could not be prouder and elated that organizations in King County, Washington, stepped up in such a responsible way, Knowles Lawson said in the statement. It is imperative that we remember during these difficult times, when we are fighting for social justice, that we are also in a pandemic that is killing people at an alarming rate. We are dealing with two diseases that are disproportionately ravaging the Black community; COVID-19 and racism. We have to do all we can to combat both.

The first day of free testing will take place on June 13 from 11 a.m. to 5 p.m. atHealthPoint Administration at 955 Powell Ave. Southwest in Renton. The second day will take place June 14 from 11 a.m. to 5 p.m. at Sea Mar Community Health Medical Centerat 31405 18th Ave. South in Federal Way.

Weve always known that Black and brown communities face barriers to quality healthcare compared to white communities, said Hamdi Mohamed, King County policy advisor for the Executive Office of Equity and Social Justice, in the statement. We see it in high maternal mortality rates for Black women, we see it in disproportionately high populations of uninsured people in communities of color, and we see it now in the COVID-19 crisis, as people of color are being affected at a rate nearly two-and-a-half times higher than that of whites."

More information about the testing is available here.

Elise Takahama

In negotiations with players to resume a season shut down by the coronavirus pandemic, Major League Baseball is administering self-inflicted wounds from which it might never fully recover, no matter how tight the pennant races or majestic the play, Seattle Times sports columnist Larry Stone writes.

Stone, a lifelong baseball fanatic, has reflexively fought back against criticism of the sport over the years. "But," he writes, "youre on your own this time, fellas."

Read Stone's full column here.

U.S. Rep. Pramila Jayapal, D-Seattle, and at least 14 other Democratic members of Congress planned to ask a court to require greater COVID-19 safety measures at an Amazon warehouse in New York, in a legal brief supporting workers who sued the company last week.

Employees at Amazons Staten Island distribution center known as JFK8 alleged in the suit that the company did not adequately inform them of disease outbreaks in the facility and maintained oppressive productivity requirements, among other conditions that contributed to the spread of COVID-19 and the death of one of the plaintiffs family members.

The lawmakers urged the judge to issue an emergency injunction under New York state labor law and common law, citing inaction by federal workplace safety regulators and noting their own legislative efforts will take time to enact and implement.

Read the full story here.

Benjamin Romano

Around the world, in varying stages, people are cautiouslyventuring out to shop, eat, vote, protest and more.

See more images from today of a world coping with a new version of daily life.

Courtney Riffkin

Herd immunity is when a virus can no longer spread easily because enough people are immune to it. That lowers the chances of the virus jumping from person to person and reaching those who havent been infected yet.

People can become immune to certain viruses after surviving infection or being vaccinated. Typically, at least 70% of a population must be immune to achieve herd immunity. But how long immunity lasts varies depending on the virus, and its not yet known how long COVID-19 survivors might have that protection.

Here's what to know about herd immunity and whether it could work with COVID-19.

The Associated Press

The Vienna Philharmonic returned home, and its famous strings purred for the first time since March 10.

Its 2,854-seat Musikverein, considered by many the worlds most beautiful concert hall, was filled with only 100 people Friday for the first of three days of programs with Daniel Barenboim. Because of the negligible number, tickets were distributed to family, friends and donors for among the first performances by a major orchestra since the pandemic paused the season.

The three-month gap was difficult for members of the orchestra, which is considered in the music world to rank among the best.

Even if we are not allowed to play a concert, we want to do some recordings or just to play for ourselves, because we are quite convinced that we need to play as an orchestra, said DanielFroschauer, a first violinist and the orchestra chairman. The best soccer teams like Real Madrid, they have to play together.

Read the full story here.

The Associated Press

OLYMPIA Gov. Jay Inslee has extended through Aug. 1 an emergency proclamation intended to protect workers at high risk of COVID-19 from losing their jobs or income.

The order applies to workers 65 or older, as well as people of any age with underlying conditions that could put them at risk if they got infected with the virus.

Among other things, the order bars employers from permanently replacing high-risk workers.

It mandates that high-risk workers be given a choice of alternative work settings, such as working remotely.

High-risk workers can also use leave they've accrued or unemployment benefits if an alternate work assignment isnt feasible and the employee cant safely work.

Joseph O'Sullivan

State health officials confirmed 313 new COVID-19 cases in Washington on Tuesday, as well as 15 additional deaths.

The update brings the states totals to 24,354 cases and 1,176 deaths, according tothe state Department of Healths (DOH) data dashboard. The dashboard reports 3,747 people hospitalized in Washington.

So far, 415,054 tests for the novel coronavirus have been conducted in the state, per DOH. Of those, 5.9% have come back positive.

King County, the state's most populous, has reported 8,529 positive test results and 580 deaths, accounting for a little less than half of the state's death toll.

Scott Greenstone

The coronavirus pandemic continues to rage in Yakima County, with the total number of cases closing in on 5,000.

The Yakima Health District reported 215 more infections Monday, bringing the total of confirmed cases to 4,929.

The Yakima Herald-Republic reported deaths from COVID-19 remained at 96.

We are a hot spot for COVID-19, health district spokeswoman Lilian Bravo said.

Read the story here.

The Associated Press

The World Health Organization walked back its comments that asymptomatic people rarely spread the new coronavirus.

Less than 24 hours after Dr. Maria Van Kerkhove, the head of the WHO's emerging disease and zoonosis unit, said that asymptomatic transmission was "very rare" in response to a journalist's question the organization held a press conference Tuesday morning to clarify its position.

But the comment from Monday had already spread widely and been seized upon by conservatives and others to bolster arguments that people do not need to wear masks or maintain social distancing precautions.

The episode sparked criticism of WHOs public health messaging and highlighted just how fraught and easily politicized such work remains months into the pandemic.

I wasnt stating a policy of WHO or anything like that, Kerkhove said. We do know that some people who are asymptomatic, or some people who do not have symptoms, can transmit the virus on.

It was not the intent of WHO to say there is a new or different policy, added Mike Ryan, head of emergency programs for WHO. There is still too much unknown about this virus and still too much unknown about its transmission dynamics.

While asymptomatic transmission does occur, no one knows for sure how frequently that happens. Studies and models have suggested many of those infected never show symptoms. And it remains an open question whether they are a large force driving transmission. At the same time, however, some countries using contact tracing to work backward from confirmed cases have not found many instances of asymptomatic spread, WHO officials noted.

Full story here.

The Washington Post

Moscow emerged from a strict lockdown Tuesday with the city government citing a slowdown in the coronavirus outbreak and critics expressing concerns over the potential for a new wave of infections in the Russian capital.

As of Tuesday, Moscow residents are no longer required to stay at home or obtain electronic passes for traveling around the city, Mayor Sergei Sobyanin said Monday. All restrictions on taking walks, using public transportation or driving have been lifted as well.

The sudden ending of restrictions imposed in late March comes weeks before a nationwide vote on a constitutional change that would allow President Vladimir Putin to stay in power until 2036 and was condemned by Kremlin critics as premature and politically motivated.

The lifted lockdown measures not only permitted Moscow residents to move about, but allowed beauty parlors to reopen Tuesday. Outdoor terraces of cafes and restaurants, as well as museums and dental clinics, are set to open on June 16. Kindergartens, gyms and indoor spaces of cafes and restaurants will be allowed to operate starting June 23.

The fight isnt over yet, Sobyanin said in a video address Monday. Nevertheless, I would like to congratulate you on our common victory and a big step towards returning to a full-fledged life.

Read the story here.

The Associated Press

The British government on Tuesday backed away from plans to have all primary school children return to school in England before the summer holidays, following concerns by principals that they could not meet coronavirus social distancing requirements if everyone returned.

Education Secretary Gavin Williamson admitted that the goal for Englands approximately 5 million primary schoolchildren from age 4 to 11 was not possible, given constraints related to classroom sizes, the need for social distancing and inadequate numbers of teachers.

While we are not able to welcome all primary children back for a full month before the summer, we continue to work with the sector on the next steps, Williamson told lawmakers.

Although many of Englands primary schools have been open this entire spring for the children of key workers including health care professionals, delivery drivers and journalists the Conservative government had planned to get all younger children back in stages. Britains school year normally runs until late July.

Read the story here.

The Associated Press

An indicator of new business starts is running ahead of last years pace at the national level, though in Washington state it still trails.

According to the Census Bureau, applications for new tax IDs, which it considers a sign of new business formation, have turned upward in recent weeks.

When calculated as a rolling average over four weeks, the U.S. figure now surpasses the level at this time last year. Washington state has been slower to relax restrictions imposed because of the coronavirus pandemic, and new business formation has been slower to recover.

For more charts on the coronavirus economy and other economic news, click here.

Rami Grunbaum

For the past few weeks, the United States has been wrestling through two tough conversations with itself about two pandemics though the volume got turned way up on the one about racism and health care workers, particularly those of color, are living in the middle of both.

Racism is the biggest public health crisis of our time, one Black surgeon at UW explained during a recent march.

Read the full story here.

Brendan Kiley

Washington state health officials confirmed 312 new COVID-19 cases yesterday. Globally, the pandemic is worsening, with countries on Sunday reporting the biggest-ever one-day total of cases. Track the spread of the virus here.

"We need to get open, because were hemorrhaging cash." Seattle-area small businesses are facing unprecedented challenges, staggered first by coronavirus closures, then by looting.

Here come the masks, Washington hopes. A federal agency's approval of a coveted N95 mask from China paves the way for the state to complete its huge order.

The shutdowns prevented about 60 million coronavirus infections in the U.S, researchers say, and easing them brings new risks. As Washington state creaks back open again, here's our county-by-county guide to what you can do, from haircuts to horse races.

You can go to Canada ... if you're family. The country is easing border restrictions a bit, but requiring a quarantine period.

Kris Higginson

View post:
Coronavirus daily news updates, June 9: What to know today about COVID-19 in the Seattle area, Washington state and the world - Seattle Times

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Metal Fiducial Marks Market Emerging Trends, Strong Application Scope, Size, Status, Analysis and Forecast to 2025 – Cole of Duty

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Metal Fiducial Marks Market Emerging Trends, Strong Application Scope, Size, Status, Analysis and Forecast to 2025 - Cole of Duty

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