StemCell Therapy

As the rumblings of a pandemic began to be felt at the beginning of the year, scientists at Penn started work to develop a vaccine and assess possible treatments. But the scope of COVID-19 studies at the University goes much broader. Scientists whose typical work finds them investigating autoimmune disease, influenza, HIV/AIDS, Ebola, cancer, hemophilia, and more, are now applying their deep understanding of biology to confront a novel threat.

The more scientists and clinicians observe about the virus, the more avenues of investigation emerge, aiming to shed light on questions such as what happens once the virus enters the body, what treatments might be of benefit, and how society should take action to keep transmission low.

To dig into what scientists around campus are asking and learning, Penn Today spoke with several who have pivoted their research to focus on COVID-19. Their work, while in its early days, is in many cases already finding applications in the fight against this ferocious virus, and may well shape the next steps to defeat it.

Another respiratory infection, influenza, has been a focus of research led by Andrew Vaughan of the School of Veterinary Medicine. But Vaughan didnt hesitate to begin studies of the novel coronavirus once its eventual impact became apparent.

Its not a stretch for our lab, he says. All the projects in our lab focus on repair and regeneration of the lungs after injury. The majority of my studies are to some degree agnostic about what is causing the injury.

Earlier work by his group, for example, showed that a lung cell transplant could boost healing in mice affected by a severe bout with flu. Now, graduate students and research specialists in his labworking no more than two together at a time to maximize social distancingare conducting new experiments focused more specifically on the biology of SARS-CoV-2, alongside parallel efforts by Edward Morrissey from the Perelman School of Medicine (PSOM). Knowing that the Ace2 receptor on lung cells is the gateway for the virus into the human body, theyre genetically manipulating alveolar type-two lung cells, those that are particularly essential for continuing oxygen exchange deep in the lungs, to alter or block ACE2 gene expression to try to prevent viral entry.

These alveolar type-two cells seem to be particularly susceptible to injury in both influenza and perhaps even more so in COVID-19, says Vaughan. In a perfect world, you might be able to take these genetically edited type-two cells and use them as a cellular therapy. I dont know that this is going to happen in time to impact this pandemic, but even if the pathogen the next time around is slightly different, we may still be able to employ these types of regenerative responses to help the lung recover better from injury.

In a separate project, Vaughan is partnering with Penn Vets Montserrat Anguera to explore a curious feature of COVID-19 disease: the fact that more men than women become severely ill and die. A number of hypotheses have been put forward to explain the disparity, but the two labs are investigating one particular possibility.

Dr. Anguera had posted something on Twitter saying that the ACE2 gene happens to be on the X chromosome, meaning that women have two copies of it, says Vaughan. I immediately texted her and said, I think theres something to that.

Normally women inactivate one of their X chromosomes, but some genes can escape this inactivation. This means its possible women may have higher ACE2 expression than men. Somewhat counterintuitively, scientists have actually found that higher ACE2 levels actually reduce lung injury, even though ACE2 is also what the virus depends on to enter cells.

Hormone expression levels are, of course, another factor that may influence sex differences in disease. Together, Anguera and Vaughans groups are both studying ACE2 expression and exposing alveolar type-two cells to various hormones to see how expression of viral receptors, Ace2 and others, changes. Ultimately wed like to see if this changes susceptibility to infection, working with Susan Weiss and others, says Vaughan.

Individual differences in how people respond to infection may be influenced by their unique genomic sequences. Penn Integrates Knowledge Professor Sarah Tishkoff of PSOM and the School of Arts & Sciences, is probing the rich sources of genomic data her group already had in hand to look for patterns that could explain differences in disease susceptibility. As in Vaughan and Angueras work, ACE2 is a focus.

This gene is very important for general health, Tishkoff says. Women have two copies, men have one; it plays a role in regulating blood pressure; its in the kidneys; its in the gut. We want to understand the role that variation at this gene may play in risk for COVID-19, severity of disease in people with underlying health conditions, and differences in the prevalence of disease in men and women.

Using genomic data from 2,500 Africans collected for another project, Tishkoffs team is looking for patterns of genetic diversity. Early findings suggest that natural selection may have acted upon on version of the ACE2 gene, making it more common in some African populations with with high exposure to animal viruses.

Shes also collaborating with Anurag Vermaand Giorgio Sirugo of Penn Medicine to analyze genetic variation in samples from the Penn Medicine Biobank, looking in particular at people of African descent. Were seeing disturbing health disparities with COVID, with African Americans at higher risk for serious illness, says Tishkoff. This disparity mostlikelyhas to do with inequities in access to health care and socioeconomic factors, but were also looking to see if genomic variation may be playing a role.

Looking ahead, Tishkoff hopes to partner with Daniel Rader and others through the Center for Global Genomics and Health Equity to work with the West Philadelphia community. Wed like to do testing to understand the prevalence of infection and identify environmental and genetic risk factors for disease, she says.

The immune reaction to SARS-CoV-2 is a double-edged sword. The immune system is what eliminates the virus, says E. John Wherry of PSOM. The immune system is what we need to activate with a good vaccine. But also, especially in many respiratory infections, the immune system is what also causes damage. A healthy outcome means your immune system is striking a balance between killing off the virus and not doing so much damage that it kills you.

Wherry and PSOMs Michael Betts have embarked on a study to discern both the magnitude of patients immune responses as well as their flavor, that is, what components in the immune system are being activated by the coronavirus. Theyre doing so by working with clinicians at the Hospital of the University of Pennsylvania (HUP) and, soon, at Penn Presbyterian Medical Center, to collect blood samples from patients with severe and more mild infections, as well as patients who have recovered from illness, to profile their immune reactions.

Its one of the beautiful things about Penn. Everyone is working as a team, being selfless, being present, and bringing all their expertise to bear on this crisis. E. John Wherry, Perelman School of Medicine

We are observing a huge amount of heterogeneity across these patient samples, says Betts. But were also identifying some relatively unifying characteristics, indicating there are mechanisms that everyone uniformly uses to fight off this infection.

This variety across patients strongly suggests that the treatments that work for one patient may not for another, Wherry and Betts note. For that reason, they are speaking daily with their colleagues on the front lines of COVID-19 care, relaying what theyre finding out in the lab to adjust and personalize care in the clinic.

Its one of the beautiful things about Penn, says Wherry. Everyone is working as a team, being selfless, being present, and bringing all their expertise to bear on this crisis.

Plenty of recent scientific attention has been paid to the role of the gut microbiome in health. But the medical schools Ronald Collman and Frederic Bushman have been devoting attention to how the community of bacteria, viruses, fungi, and parasites that dwell in the respiratory tract affect health and disease risk. They are now addressing that question in the context of COVID-19.

There are two reasons were interested in studying this, Collman says. First is that the microbiome can help set the tone for the immune response to infections, influencing whether a patient ends up with mild or severe disease. And second, the microbiome is where infectious agents that can cause infection can arise from. So if a patient dies of an eventual pneumonia, the pathogen that caused that pneumonia may have been part of that individuals respiratory tract microbiome.

Working with nurses at HUP to collect samples, Collman and Bushman are analyzing the microbiome of both the upper (nose and throat) and lower (lung) portions of the respiratory tract of COVID-19 patients. These samples are being used by other groups, such as those developing diagnostic tests, while Collman and Bushmans labs work to identify the types and quantities of organisms that compose the microbiome to find patterns in how they correlate with disease.

Were hoping that if we can find that the response to the virus is different in people with different upper respiratory tract microbiomes, then we could manipulate the microbiome, using particular antibiotics, for example, to make it more likely that patients would have a mild form of the disease.

Absent a vaccine, researchers are looking to existing drugssome already approved by the U.S. Food and Drug Administration for other maladiesto help patients recover once infected. Throughout his career, Ronald Harty of Penn Vet has worked to develop antivirals for other infections, such as Ebola, Marburg, and Lassa Fever.

Our antivirals are sometime referred to as host-oriented inhibitors because theyre designed to target the interaction between host and viral proteins, says Harty. Though many of the biological details of how SARS-CoV-2 interacts with the human body are distinct from the other diseases Harty has studied, his group noticed a similarity: A sequence hes targeted in other virusesa motif called PPxYis also present in the spike protein of SARS-CoV-2, which the coronavirus uses to enter cells.

This caught our eye, says Harty, and piqued our interest in the very intriguing possibility that this PPxY motif could play a role in the severity of this particular virus.

Harty is testing antivirals he has helped identify that block the replication of Ebola, Marburg, and other viruses to see if they make a dent on the activity of SARS-CoV-2. Those experiments will be done in collaboration with colleagues whose labs can work in BSL-III or -IV laboratories, such as Penns Weiss.

Also of interest is the speculation that the coronavirus might disrupt cell-cell junctions in the human body, making them more permeable for virus spread. Hartys lab will be examining the potential interactions between the viral structural proteins and human proteins responsible for maintaining these cellular barriers.

Another faculty member is assessing whether a drug developed for a very different conditionin this case, pulmonary arterial hypertension (PAH)could serve coronavirus patients. Henry Daniell of the School of Dental Medicine recently shared news that a drug grown in a plant-based platform to boost levels of ACE2 and its protein product, angiotensin (1-7), was progressing to the clinic to treat PAH. Daniell is now working with Kenneth Margulies from Penn Medicine to explore whether this novel oral therapy can improve the clinical course of patients with symptomatic COVID-19 infection.

Reduced ACE2 expression has been linked to acute respiratory distress, severe lung injury, multi-organ failure and death, especially in older patients. The earlier preclinical studies in PAH animal models showed that orally delivered ACE2 made in plant cells accumulated ten times higher in the lungs than in the blood and safely treated PAH. Now, new clinical studies have been developed to explore whether oral supplementation of ACE2 and angiotensin-1-7 can help mitigate complications of COVID-19 disease. The fact that freeze-dried plant cells can be stored at room temperature for as long as a year and can be taken at home by COVID-19 patients make this novel approach an attractive potential option.

This trial has been given a high priority by the Penn Clinical Trial Working Group, says Daniell. Im pleased that this looks to be on the cusp of moving forward to help the growing number of COVID-19 patients.

As the coronavirus began to spread in the United States, biologist Joshua Plotkin of the School of Arts & Sciences began to raise alarms about Philadelphias St. Patricks Day parade, which had been scheduled to be held March 15, potentially drawing thousands to downtown streets. He had good reason to be concerned: His studies of the 1918 flu pandemic had explored disease incidence and spread, and it was hard to avoid noticing the role of the Liberty Loan parade down Broad Street in triggering a rampant spread of flu a century ago.

Now, with work conducted with two graduate students from Princeton University, Dylan Morris and Fernando Rossine, along with Princeton faculty member Simon Levin, Plotkin has mathematically sound advice for policymakers hoping to effectively stem the spread of a pandemic. In a preprint on arXiv.org, they share optimal, near-optimal, and robust strategies for how to time interventions such as social distancing.

This boils down to knowing what is the best way, of all the infinite possibilities, to intervene using public health measures, says Plotkin. Thats a problem we can solve with math, my colleagues Dylan and Fernando realized.

Their analysis makes the realistic assumption that policymakers can only enforce social distancing for a limited amount of time, and aims to minimize the peak incidence of disease. The optimal strategy, they found, is to start by introducing moderate social distancing measures to keep the incidence rate the same for a period of time. This would mean that every person with COVID-19 would infect one additional person. Then the intervention should switch over to a full suppressionthe strongest possible quarantinefor the rest of the period. At the end of that period, all restrictions would be lifted.

This works because you dont want to fully suppress disease spread right off the bat, says Plotkin, because then at the end, after you remove restrictions, there will be a second peak that is just as large as the first. By employing a moderate suppression at the beginning, youre building up a population of people who are going to recover and become immune, without letting the epidemic get out of control.

Unsurprisingly, timing is key. Attempting the optimal intervention would be disastrous, in practice, because of inevitable errors in timing. Intervening too early is pretty bad, because you get a bigger second peak, he says. But intervening too late is even worse. The key lesson is that a robust intervention is more important than an optimal one.

Plotkin and his colleagues are hoping to share the findings widely, including with local decision makers, to help them navigate a likely second wave of COVID-19.

Montserrat Anguera is an associate professor of biomedical sciences at the University of Pennsylvania School of Veterinary Medicine.

Michael Betts is a professor of microbiology at the University of Pennsylvania Perelman School of Medicine.

Frederic Bushman is the William Maul Measey Professor in Microbiology at the University of Pennsylvania Perelman School of Medicine.

Ronald Collman is a professor of Medicine at the University of Pennsylvania Perelman School of Medicine.

Henry Daniell is vice-chair and W.D. Miller Professor in the Department of Basic and Translational Sciences in the University of Pennsylvania School of Dental Medicine.

Ronald Harty is a professor of pathobiology and microbiology at the University of Pennsylvania School of Veterinary Medicine.

Kenneth Margulies is a professor of medicine and physiology and research and fellowship director of the Heart Failure and Transplant Program at the University of Pennsylvania Perelman School of Medicine.

Joshua Plotkin is the Walter H. and Leonore C. Annenberg Professor of the Natural Sciences in the Department of Biology at the University of Pennsylvania School of Arts & Sciences. He has secondary appointments in the Department of Mathematics and in the School of Engineering and Applied Sciences Department of Computer and Information Science.

Sarah Tishkoff is the David and Lyn Silfen University Professor with appointments in the Perelman School of Medicines Department of Genetics and the School of Arts and Sciences Department of Biology. A Penn Integrates Knowledge Professor, she is also director of the Penn Center for Global Genomics and Health Equity.

Andrew Vaughan is an assistant professor of biomedical sciences at the University of Pennsylvania School of Veterinary Medicine.

E. John Wherry is chair of the Department of Systems Pharmacology and Translational Therapeutics, director of the Institute for Immunology, and the Richard and Barbara Schiffrin Presidents Distinguished Professor at the University of Pennsylvania Perelman School of Medicine.

Homepage image: Researchers around the University are taking a variety of approaches to study the novel coronavirus (particles of which are shown in purple), informed by past expertise and newly formed collaborations. (Image: National Institutes of Health)

Excerpt from:
Coming together to solve the many scientific mysteries of COVID-19 - Penn: Office of University Communications

Gosselies, Belgium, 29April 2020 BONE THERAPEUTICS(Euronext Brussels and Paris: BOTHE), the bone cell therapy company addressing high unmet medical needs in orthopaedics and bone diseases, today announces that it secured EUR 11.0 million financing. The financing will be used to advance both of its key assets, ALLOB and JTA-004, through late stage clinical development. The financing operation consists of EUR4.75million bridge loans, EUR 1,26 million in equity private placement (immediate conversion of CBs) by existing shareholders and, on an as-needed basis, a EUR4.99million in private placement of convertible bonds (CBs). The bridge loans are still subject to obtaining a credit assurance, which is pending regulatory approvals expected in May 2020.

This current financing will allow us to continue the strong progress of the late stage development of our innovative treatment solutions. It will additionally provide support for our wider activity during the measures taken by international governments to combat the global COVID-19 pandemic, said Miguel Forte, MD, PhD, Chief Executive Officer of Bone Therapeutics. This support results from the potential of our allogeneic cell therapy platform and enriched protein solution to transform the lives of patients with debilitating bone conditions. We will continue our preparations for when the sites selected for the approved clinical studies with ALLOB and JTA-004 can resume their normal operations on a country per country basis.

We are delighted by the continued support we have received from our current and reference shareholders, including SFPI and S.R.I.W. Their commitment is instrumental for the development of our innovative products, said Jean-Luc Vandebroek, Chief Financial Officer of Bone Therapeutics. The present fundraise allows us to retrieve funds on an as-needed basis rather than an immediate important dilution of a traditional share issuance. Conforming to our financing strategy, we will continue to explore funding options to further strengthen our cash position and to ensure a successful completion of the upcoming clinical trials.

Subject to the completion of the current financing operation, supporting the companys further development and strengthen its balance sheet, Bone Therapeutics expects to have a runway into Q1 2021. The secured 11.0 million financing combines:

Bone Therapeutics intends to pursue a capital raise when favorable market conditions are met. Existing shareholders have already taken a pre-commitment to participate.

The specific terms of the CBs can be found in theInvestor sectionof Bone Therapeutics website.

[1] The Company may at any time stop the program without penalty.

About Bone Therapeutics

Bone Therapeutics is a leading biotech company focused on the development of innovative products to address high unmet needs in orthopedics and bone diseases. The Company has a broad, diversified portfolio of bone cell therapies and an innovative biological product in later-stage clinical development, which target markets with large unmet medical needs and limited innovation.

Bone Therapeutics is developing an off-the-shelf protein solution, JTA-004, which is entering Phase III development for the treatment of pain in knee osteoarthritis. Positive Phase IIb efficacy results in patients with knee osteoarthritis showed a statistically significant improvement in pain relief compared to a leading viscosupplement. The clinical trial application (CTA) for the pivotal Phase III program has been approved by the relevant authorities allowing the start of the study.

Bone Therapeutics other core technology is based on its cutting-edge allogeneic cell therapy platform (ALLOB) which can be stored at the point of use in the hospital, and uses a unique, proprietary approach to bone regeneration, which turns undifferentiated stem cells from healthy donors into bone-forming cells. These cells can be administered via a minimally invasive procedure, avoiding the need for invasive surgery, and are produced via a proprietary, scalable cutting-edge manufacturing process. Following the CTA approval by the Belgian regulatory authority, the Company is ready to start the Phase IIb clinical trial with ALLOB in patients with difficult tibial fractures, using its optimized production process.

The ALLOB platform technology has multiple applications and will continue to be evaluated in other indications including spinal fusion, osteotomy and maxillofacial and dental applications.

Bone Therapeutics cell therapy products are manufactured to the highest GMP (Good Manufacturing Practices) standards and are protected by a broad IP (Intellectual Property) portfolio covering ten patent families as well as knowhow. The Company is based in the BioPark in Gosselies, Belgium. Further information is available at http://www.bonetherapeutics.com.

Read more:
Bone Therapeutics secures EUR 11.0 million financing - PharmiWeb.com

Global Tooth Regeneration Marketwas 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.

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Global Tooth Regeneration Market

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 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.

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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.

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)

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GLOBAL TOOTH REGENERATION MARKET: INDUSTRY ANALYSIS AND FORECAST (2020-2027) - MR Invasion

Stromal vascular fraction is gaining significant importance in various fields, including internal medicine, orthopaedics, plastic and general surgery,and wound healing.

Ease of harvest, abundant availability, and stable phenotype are some factors increasing the demand for stromal vascular fraction. Also, stromal vascular fraction secretes several soluble factors with anti-inflammatory, immunomodulatory, and analgesic effects, which leads to an alternative treatment option for various diseases, significantly benefitting the growth of thestromal vascular fraction marketduring the forecast period.

Report Highlights:

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Company Profiles

Global Cyber Security Market Poised to Grow Exponentially, Remote Working Culture During COVID-19 Pandemic to Act as Growth Catalyst, Says PMR

Delivery of stromal vascular fraction by intra-articular injection has advantages over surgical implantation, such as less invasiveness, better patient compliance, and lower cost.

The global stromal vascular fraction market was valued atUS$ 76 Mnin 2018, and is expected to witness a CAGR of around4%over the forecast period (2019-2029).

Key Takeaways of Stromal Vascular Fraction Market Study

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Stromal vascular fraction has emerged as an efficient alternative in the field of regenerative medication. However, better-structured and significant clinical investigations need to be carried out to demonstrate and define the therapeutic potential of stromal vascular fraction,says a PMR analyst.

Stromal Vascular Fraction Manufacturers Focusing on Innovative Methods to Optimize Tissue Recovery

Consistent up-gradation and innovation in methods to recover adipose tissue-derived mesenchymal stem cells (ATD-MSCs) for autologous use in regenerative medication applications are expected to offer significant opportunities for the stromal vascular fraction market.

For instance, LipoCell from Tissyou, is furnished with a semipermeable film that separates fat tissues from squander components with the assistance of continuous irrigation. The dialysis of the tissue limits the pressure and trauma to the cell and extracellular matrix, evacuating the blood and oil deposits, which are pro-inflammatory.

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More Valuable Insights on Stromal vascular fraction Market

Persistence Market Research brings a comprehensive research report on the forecasted revenue growth at global, regional, and country levels, and provides an analysis of the latest industry trends in each of the segments from 2014 to 2029.

The global stromal vascular fraction market is segmented in detail to cover every aspect of the market and present a complete market intelligence approach to the reader.

The study provide compelling insights on the stromal vascular fraction market on basis of product (SVF isolation products, SVF aspirate purification products, and SVF transfer products), application (cosmetic applications, orthopedic applications, soft tissue applications, and others), and end user (hospitals, ambulatory surgical centers, stem cell laboratories, and others), across six major regions.

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Stromal Vascular Fraction Market to Register CAGR 4.5% Growth in Revenue During the Forecast Period 2019 to 2029 - Jewish Life News

In test with mice, the sterosome activated bone regeneration was activated without needing additional drugs

Microscopic image showing the interaction between nanoparticles (green) loaded with therapeutic drugs (red), and cells (blue) on a tissue engineering scaffold.

A team of biomaterials scientists and dentists at the UCLA School of Dentistry has developed a nanoparticle that, based on initial experiments in animals, could improve treatment for bone defects.

A paper describing the advance is published today in the journal Science Advances.

Bone defects, which can be caused by traumatic injury, infection, osteoporosis or the removal of tumors, are difficult for orthopedic surgeons to treat. And the need for bone grafts are becoming more common thanks in part to our aging population: Bone injuries are particularly prevalent among the elderly.

Today, the standard treatment for bone defects is a bone graft, which involves transplanting healthy bone from another part of the body to repair the damaged area. However, the procedure can cause complications, including infections where the transplanted bone is taken from, bleeding and nerve damage.

So the researchers turned their attention to liposomes, tiny spherical sacs that are derived from naturally existing lipids. Liposomes have been used since the 1990s to treat cancer and infectious diseases, and more recently they are being explored for their possible use in bone tissue engineering. They can be used to administer nutrients and pharmaceutical drugs in the body and can easily enter cells to administer their valuable cargo, but they do have some drawbacks: They are physically unstable and it can be difficult to control how and when they release drugs.

To help improve their stability and enhance their ability to form bone in the body, the UCLA researchers developed a new type of liposome called a sterosome. (The name is inspired by the fact that they contain a high concentration of steroids.)

To produce the sterosomes, the scientists replaced cholesterol, an important component of liposomes, with oxysterol, a type of cholesterol that has a key role in skeletal development and bone healing. In tests using mice with bone defects, the researchers found that the sterosomes successfully activated bone regeneration on their own, without needing therapeutic drugs.

Liposomes are generally made from pharmacologically inactive substances, said Min Lee, the papers corresponding author and a professor of biomaterials science at the dental school. Including oxysterol into our liposomal formulation not only increased nanoparticle stability but also stimulated cells to develop into bone-forming cells.

In a second phase of the study, the researchers wanted to see how they could make the sterosome even more effective.

They added their sterosome nanoparticle to a tissue engineering scaffold a structure often used to move and grow naturally occurring stem cells, which is matched to the site of the defect and is used during bone graft procedures. They loaded the sterosomes with a bone-building drug called purmorphamine. Next, they immobilized the drug-loaded sterosome onto a scaffold to ensure that the sterosomes stayed concentrated in the defective areas and released the drugs where they were most needed for as long as possible.

In a six-week study using mice with bone defects in their skulls, the researchers saw an average reduction of roughly 50% in the size of the defects after the drug-loaded scaffold was implanted.

By using our nanoparticle, which we found has intrinsic bone-forming capabilities, along with the addition of therapeutic drugs, we were able to speed up the bone regeneration process, Lee said. Our nanoparticle-packaged drugs will be useful in many clinical situations where bone grafting is required to treat non-healing skeletal defects and related bone pathologies.

Dr. Paul H. Krebsbach, professor of periodontics and dean of the dental school, said,The research led by Min Lee and his team demonstrates that UCLA Dentistrys research endeavors go well beyond treating the diseases of the oral cavity, and their findings have wider implications for treating bone defects throughout the entire body.

The studys other authors are Chung-Sung Lee, Soyon Kim, Jiabing Fan, Hee Sook Hwang and Dr. Tara Aghaloo, all of UCLA.

The study was funded by the National Institute of Dental and Craniofacial Research, the U.S. Department of Defense and Musculoskeletal Transplant Foundation Biologics. The authors report no conflicts of interest.

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UCLA scientists invent nanoparticle that could improve treatment for bone defects - UCLA Newsroom

Pune, April 09, 2020 (GLOBE NEWSWIRE) -- The global orthopedic devices market is set to gain traction from the ever-increasing geriatric population across the world. As per a research published in 2015 by the United Health Foundation, every year, more than 300,000 adults belonging to the age group of 65 years and above are estimated to be hospitalized for hip fractures. Besides, around 30% of seniors fall per year. It is further leading to higher number of orthopedic injuries.

Fortune Business Insights published this information in a recent study, titled, "Orthopedic Devices Market Size, Share & Industry Analysis, By Type (Joint Reconstruction Devices, Spinal Devices, Trauma Devices, Dental Implants, Orthobiologic Devices, Arthroscopy Devices, and Others), By End User (Hospitals, Orthopedic Clinic, Ambulatory Surgical Centers, and Others), and Regional Forecast, 2019-2026." The study further mentions that the orthopedic devices market size stood at USD 51.33 billion in 2018 and is projected to reach USD 71.67 billion by 2026, thereby exhibiting a CAGR of 4.3% during the forecast period.

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This Report Answers the Following Questions:

An Overview of the Impact of COVID-19 on this Market:

The emergence of COVID-19 has brought the world to a standstill. We understand that this health crisis has brought an unprecedented impact on businesses across industries. However, this too shall pass. Rising support from governments and several companies can help in the fight against this highly contagious disease. There are some industries that are struggling and some are thriving. Overall, almost every sector is anticipated to be impacted by the pandemic.

We are taking continuous efforts to help your business sustain and grow during COVID-19 pandemics. Based on our experience and expertise, we will offer you an impact analysis of coronavirus outbreak across industries to help you prepare for the future.

To get the short-term and long-term impact of COVID-19 on this Market.

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Drivers & Restraints-

Rising Prevalence of Musculoskeletal Diseases to Drive Growth

The American Academy of Orthopedic Surgeons, a provider of educational programs for allied health professionals and orthopaedic surgeons, published a report that affirms that every year in the Unites States alone, approximately 6.8 million patients suffering from several orthopedic injuries come to medical attention. It proves that the rising prevalence of orthopedic injuries and musculoskeletal diseases is further resulting in agonizing physical pain and limited mobility. It is expected to propel the orthopedic devices market growth during the forthcoming years. However, the surgical procedure is very expensive in nature. It may hamper the growth of the market.

Segment-

Joint Reconstruction Segment to Lead Backed by Increasing Number of Surgical Procedures

Based on type, the market is grouped into joint reconstruction devices, dental implants, trauma devices, spinal devices, orthobiologic devices, arthroscopy devices, trauma devices, and others. Out of these, in 2018, the joint reconstruction segment held 35.8% in terms of orthopedic devices market share and is anticipated to lead the market throughout the forecast period. This growth is attributable to the rising number of procedures, namely, extrementies and shoulder reconstructions, hip and knee replacements, and other similar procedures associated with joints. The arthroscopy devices segment is likely to expand at fast pace owing to the increasing emergence of novel products and upsurging cases of soft tissue injuries related to sports.

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Regional Analysis-

High Purchasing Power of the Masses to Favor Growth in Asia Pacific

Geographically, the market is fragmented into Latin America, Asia Pacific, the Middle East and Africa, North America, and Europe. Amongst these, North America procured USD 23.86 billion orthopedic medical devices market revenue in 2018. This growth is attributable to the presence of adequate reimbursement policies, as well as surging incidence of orthopedic surgeries. Apart from these, availability of state-of-the-art treatment options and rising awareness among the patient pool regarding the presence of these advanced devices would contribute to the market growth.

Europe, on the other hand, is set to generate the second-largest market share in the coming years on account of the rising healthcare expenditure and increasing awareness campaigns about unique products. Asia Pacific would showcase a considerable CAGR because of the growing patient pool and increasing purchasing power of the masses in the developing nations, such as China and India.

Competitive Landscape-

Key Players Are Engaging in the Strategy of Acquisition to Broaden Portfolio

Companies operating in the market are striving persistently to gain high share. To do so, they are focusing majorly on the strategy of mergers and acquisitions. It is aiding them in expanding their product portfolio into a wide range of fields. Below are a couple of the key industry developments:

List of the Key Companies Operating in the Orthopedic Medical Devices Market. They are as follows:

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Orthopedic Devices Market to Reach USD 71.67 Billion by 2026; Increasing Geriatric Population to Boost Growth, says Fortune Business Insights -...

Though many negative repercussions of human immunodeficiency virus infection can be mitigated with the use of antiretroviral therapy (ART), one area where medical advances havent made as much progress is in the reduction of cognitive impacts. Half of HIV patients have HIV-associated neurocognitive disorders (HAND), which can manifest in a variety of ways, from forgetfulness and confusion to behavior changes and motor deficiencies.

To better understand the mechanisms underlying HAND, researchers from Penns School of Dental Medicine and Perelman School of Medicine and from the Childrens Hospital of Philadelphia (CHOP) brought together their complementary expertise to create a laboratory model system using three of the types of brain cells thought to be involved. Led by doctoral student Sean Ryan, who was co-mentored by Kelly Jordan-Sciutto of Penn Dental Medicine and Stewart Anderson of CHOP and Penn Medicine, the model recapitulates important features of how HIV infection and ART affect the brain.

Frankly the models we generally use in the HIV field have a lot of weaknesses, says Jordan-Sciutto, co-corresponding author on the paper, which appears in the journal Stem Cell Reports. The power of this system is it allows us to look at the interaction between different cell types of human origin in a way that is more relevant to patients than other models.

In addition to studying HIV, members of the team plan to use the same model to shed light on the neurological mechanisms that underlie other conditions, such as schizophrenia, Alzheimers, and even normal aging.

Were collaborating with a variety of colleagues to use this system to study Alzheimers disease as well as schizophrenia, says Anderson, co-corresponding author on the paper. We have the components in a dish that we know are interacting in these diseases, and this gives us a new mix-and-match way to understand how certain cells are contributing to neuronal damage.

Indeed, the impetus to create the model grew not out of HIV research but work that Ryan was pursuing in Andersons lab on schizophrenia.

We had been looking at the role of microglia, the resident immune cells of the central nervous system, says Ryan, first author on the work. We wanted to see if we could see the mechanistic changes that occur with microglia in schizophrenia.

To do so, Ryan and Anderson were interested in using human-induced pluripotent stem cellsadult cells that are reprogrammed to resemble embryonic stem cellswhich can be coaxed into differentiating into a variety of different cell types.

But schizophrenia is a complicated disease with a variety of contributing genetic and environmental factors and a broad spectrum of presentations. Rather than looking at something complex, they sought to apply their new system to a disease that likewise causes neurological damage but does so in a more dramatic way and in which microglia are also implicated: HIV/AIDS infection.

They reached out to Jordan-Sciutto, who has deep experience investigating the mechanisms of HAND and was eager for the opportunity to develop a model superior to those currently available. Together, the scientists identified the three cell types they were most interested in studying: neurons, astrocytes, and microglia.

Neurons arent directly infected by HIV but are known to be damaged during infection. Meanwhile astrocytes are believed to interact with neurons, causing damage by sending pro-inflammatory factors into the spaces between cells, called synapses. And microglia, which are responsible for maintaining a healthy environment in the absence of disease, are seen to expand and contribute to inflammation during HIV infection.

After nailing the technical challenge of creating this tractable model in which each cell type is generated independently and then mixed together, the team used it to probe how HIV infection and ART impact the cells, both alone and in combination.

A lot of people are taking PreEP [pre-exposure prophylaxis] if theyre in a situation where their risk of contracting HIV is heightened, says Ryan. Just as we want to understand the cognitive impacts of HIV, we also want to see whether these drugs alone are impacting the brain health of otherwise healthy people.

The researchers looked at RNA expression in their cultures to get a sense of what proteins and signaling pathways were becoming activated in each scenario. During infection, they saw inflammatory pathways that had previously been implicated in HIV in earlier research. When they introduced the antiretroviral drug EFZ, which is not in common use in the United States but remains a frontline therapy in many other areas of the world, with an infection, the activity of most of these pathways was reduced.

But this scenario involved its own unique response, says Ryan. Certain pathways associated with inflammation and damage remained despite the introduction of EFZ.

EFZ treatment of the tricultures that included HIV-infected microglia reduces inflammation by around 70%, Ryan says. Interestingly, EFZ by itself also triggered inflammation, though to a lesser extent than infection.

It seems a combination of infection and ART is creating its own unique response that is different from the sum of its parts, Ryan says. Knowing what pathways are still active due to ART could help us appropriately target additional therapies so patients dont develop HAND.

Many features of infection seen in the three-cell culture mirror what is known from HIV infection and ART treatment in people, giving the researchers confidence in the reliability of their model.

Just looking at the microglia, says Anderson, we see in our system that they are taking on both of their normal roles in keeping key signaling systems balanced during their normal state and activating and causing damage when theyre fighting infection. Were able to model normality and abnormality in a way we havent been able to before.

For Jordan-Sciutto, the new system is really going to change the way my lab operates going into the future. Shes hopeful many other HIV scientists will take it up to further their studies as she also explores more aspects of HIVs impact on the brain, such as how it navigates through the blood-brain barrier that normally protects the central nervous system from inflammation and infection.

The study authors give credit to the collaborative environment at Penn for this cross-disciplinary project. Tentacles of this project extend from CHOP to the dental school to the vet school to the medical school, says Anderson. Penn is a very special place where people seem to be more likely to share their technologies around and let other people work with and develop them. This project is a great example of that.

Kelly L.Jordan-Sciutto is vice chair and professor in the Department of Basic and Translational Sciences in Penns School of Dental Medicine, associate dean of graduate education, and director of biomedical graduate studies at the Perelman School of Medicine.

Stewart A. Anderson is director of research in the Department of Child and Adolescent Psychiatry and Behavioral Services at the Childrens Hospital of Philadelphia and a professor of psychiatry at the Perelman School of Medicine.

Sean K. Ryan was a graduate student in Penns Cell and Molecular Biology Graduate Group in the Genomics and Epigenetics program, co-mentored by Jordan-Sciutto and Anderson. He is now a postdoctoral researcher at the Perelman School of Medicine.

Jordan-Sciutto, Anderson, and Ryans coauthors on the study were CHOPs Michael V. Gonzalez, James P. Garifallou, Nathaniel P. Sotuyo, Kieona Cook, and Hakon Hakonarson; Penn Medicines Frederick C. Bennett and Eugene Mironets; and Spelman Colleges Kimberly S. Williams.

The research was supported by the National Institute of Neurological Disorders and Stroke (Grant NS107594), Penn Center for AIDS Research, and Penn Mental Health AIDS Research Center.

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A new way to study HIV's impact on the brain - Penn: Office of University Communications

Gosselies, Belgium, 26March 2020, 7am CET BONE THERAPEUTICS(Euronext Brussels and Paris: BOTHE), the bone cell therapy company addressing high unmet medical needs in orthopaedics and bone diseases, today announces that it is further strengthening its management team with the appointment of Stefanos Theoharis, PhD, as Chief Business Officer (CBO).

Stefanos will be responsible for the companys corporate development activities and executing its business strategy. His immediate priorities will be concentrating on partnering Bone Therapeutics products and in-licensing innovations. He will also further develop the commercial strategies for the product portfolio and cell therapy platform.

At this stage of the development of Bone Therapeutics, it is very important to appoint a proven executive with a high level of business experience to achieve our next set of commercial goals,said Miguel Forte, MD, PhD, Chief Executive Officer of Bone Therapeutics. Stefanos has gathered considerable achievements in business development at both rapidly growing biotech and global biopharma companies, coupled with an extensive expertise in cell therapy drug development and manufacturing. His diverse skill set, which includes licensing, M&A transactions and R&D partnerships, will be invaluable to bolster our business initiatives as we continue to advance our mid- to late stage product pipeline through clinical development with a potential commercialization in sight.

Stefanos will contribute more than 15 years of business development experience in the pharma and biotech industry to Bone Therapeutics, specifically in the cell and gene therapy space. This includes his achievements as Senior Vice-President at Cell Medica, a clinical-stage biotech company, where he expanded the companys allogeneic T-cell immunotherapy platform through strategic partnerships with leading research institutions and targeted acquisitions. Prior to Cell Medica, Stefanos was Chief Business Officer at apceth GmbH, a company developing genetically-engineered mesenchymal stromal (MSC) cell products and also acting as a contract manufacturer in the ATMP space. He led all apceths business development activities, including in- and out-licensing and service contracts negotiations. He also held positions as Head of Business Development at the antisense RNA drug specialist Antisense Pharma (now Isarna), and Director Business Development at Roche, focused on partnering activities in emerging science and technologies. Stefanos also worked at Lazard, the global investment bank, advising to a variety of life sciences firms on M&As and financing transactions. Stefanos achieved an MSc. in Molecular Medicine and a PhD in Pathology and Immunology from Imperial College London.

I really wanted to join a cell therapy company where I was able to make a significant difference to the company, the wider field and patients outcomes.With an innovative allogeneic, off the shelf, cell therapy platform and a potentially best-in-class knee osteoarthritic pain treatment, Bone Therapeutics is uniquely positioned to make a meaningful difference in the lives of patients with severe orthopaedic conditions,said Stefanos Theoharis, PhD, Chief Business Officer of Bone Therapeutics. As both products are entering advanced stage clinical trials, Im delighted to join the company at such a critical time and I look forward to working with its talented leadership and scientific teams to take these promising treatments to market.

About Bone Therapeutics

Bone Therapeutics is a leading biotech company focused on the development of innovative products to address high unmet needs in orthopedics and bone diseases. The Company has a broad, diversified portfolio of bone cell therapies and an innovative biological product in later-stage clinical development, which target markets with large unmet medical needs and limited innovation.

Bone Therapeutics is developing an off-the-shelf protein solution, JTA-004, which is entering PhaseIII development for the treatment of pain in knee osteoarthritis. Positive PhaseIIb efficacy results in patients with knee osteoarthritis showed a statistically significant improvement in pain relief compared to a leading viscosupplement. The clinical trial application (CTA) for the pivotal PhaseIII program has been approved by the Danish relevant authorities allowing the start of the study.

Bone Therapeutics other core technology is based on its cutting-edge allogeneic cell therapy platform (ALLOB) which can be stored at the point of use in the hospital, and uses a unique, proprietary approach to bone regeneration, which turns undifferentiated stem cells from healthy donors into bone-forming cells. These cells can be administered via a minimally invasive procedure, avoiding the need for invasive surgery, and are produced via a proprietary, scalable cutting-edge manufacturing process. Following the CTA approval by the Belgian regulatory authority, the Company is ready to start the PhaseIIb clinical trial with ALLOB in patients with difficult tibial fractures, using its optimized production process.

The ALLOB platform technology has multiple applications and will continue to be evaluated in other indications including spinal fusion, osteotomy and maxillofacial and dental applications.

Bone Therapeutics cell therapy products are manufactured to the highest GMP (Good Manufacturing Practices) standards and are protected by a broad IP (Intellectual Property) portfolio covering ten patent families as well as knowhow. The Company is based in the BioPark in Gosselies, Belgium. Further information is available at http://www.bonetherapeutics.com.

Contacts

Bone Therapeutics SAMiguel Forte, MD, PhD, Chief Executive OfficerJean-Luc Vandebroek, Chief Financial OfficerTel: +32 (0) 71 12 10 00investorrelations@bonetherapeutics.com

International Media Enquiries:Image Box CommunicationsNeil Hunter / Michelle BoxallTel: 44 (0)20 8943 4685neil@ibcomms.agency / michelle@ibcomms.agency

For French Media and Investor Enquiries:NewCap Investor Relations & Financial CommunicationsPierre Laurent, Louis-Victor Delouvrier and Arthur RouillTel: + 33 (0)1 44 71 94 94bone@newcap.eu

Certain statements, beliefs and opinions in this press release are forward-looking, which reflect the Company or, as appropriate, the Company directors` current expectations and projections about future events. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, the Company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither the Company nor its advisers or representatives nor any of its subsidiary undertakings or any such person`s officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release.

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Bone Therapeutics appoints Stefanos Theoharis as Chief Business Officer - OrthoSpineNews

Fortunately, the unusual insects, who live on every continent except Antarctica, are readily available as subjects.

"It's a very prevalent invasive species that can be found all throughout California, including right here on campus, Ramirez said. "All of our specimens we study were collected when they're out and about at night around the nearby creek, since they're nocturnal."

Colors are an important part of a stick insects camouflage defense. When these stick insects first hatch, theyre brown. As they mature and go through successive molts, they may change to an array of vibrant colors from light green to a much darker brown.

"Having adults in a variety of colors allows them to occupy and better survive in different parts of a plant, Ramirez said. "Having a darker stick insect may allow it to blend in more with the trunk of a tree or the darker stems of ivy and blackberry. On the other hand, lighter green stick insects have an advantage on greener surfaces such as the bottom of leaves or greener stems of plants."

These differences in color also affect how well they can escape predators. A darker stick insect can use another means of defense behavioral mimicry if it feels threatened. Once it tucks in its limbs, itll fall down to the ground and "look like a dead twig," Ramirez said.

One puzzle Ramirez is trying to solve is why theres such a colorful palette of Indian walking sticks. Theyre parthenogenic, which means the females dont need males to reproduce. They can actually clone themselves.

"So to see a wide variety of different colors in the stick insects is very interesting because if they're clones of the mother they should all be the same exact thing, but they're not," he said.

"That's something that's really interesting to explore and would definitely require more genetic analysis, which we haven't gotten to quite yet. But hopefully someday that'll be possible in the future," he added.

One reason could be due to genetic mutations.

"There are plenty of other species that undergo parthenogenesis such as aphids, species of bees, ants, wasps, flies, and others which all go through similar asexual cloning mechanisms and can have mutations," Ramirez said. "However, these insects contain very little or do not have any noticeable color variation compared to the Indian stick insects."

Ramirez said he hopes to use the CRISPR/Cas9 gene editing tool to try and unlock the mysteries behind the Indian walking stick.

Hes also planning to apply to dental school after he graduates later this year, with the goal of using what hes learned studying walking sticks. His background in genetics and gene editing will help him in emerging fields of research, such as bioengineering human teeth using stem cells.

"This would be revolutionary for dentistry as patients who have lost their permanent teeth could have them replaced," Ramirez said.

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Walking Sticks Stop, Drop and Clone to Survive - KQED

A team of UCLA School of Dentistry researchers has developed the first adhesive hydrogel specifically to regenerate bone and tissue defects following head and neck surgeries. Their invention was inspired in part by the way that marine mussels can stick to wet surfaces.

Their research is publishedonline in the journal Science Translational Medicine.

Over the past few years, surgeons and clinicians have begun using hydrogels to administer therapeutic drugs and stem cells to help regenerate lost tissues and bone defects. This approach has advantages over the previous standard treatment, bone grafts, which can lead to inflammation and infection, and which can be costly.

Hydrogels, which are made of networks of polymers, have been found to be effective for carrying drugs and stem cells to targeted spots in the body. But when theyre used during surgeries in the mouth, hydrogels tend to become less effective, because blood and saliva prevent them from properly adhering to a surgical site. As a result, the drugs or stem cells they contain dont stay in place long enough to deliver their regenerating and therapeutic properties.

We knew that we needed a product that had optimal adhesion within the confines of the mouth or else our goal to effectively regenerate bone and tissue in the oral cavity would fail, said Dr. Alireza Moshaverinia, an assistant professor of prosthodontics at the UCLA School of Dentistry and the studys corresponding author.

Taking inspiration from mussels natural ability to adhere to surfaces underwater, the researchers modified their hydrogel by applying an alginate-based solution. Alginates are found in the cells of algae and, when hydrated, form a sticky, gum-like substance.

The researchers tested their new hydrogel loaded with stem cells taken from gum tissue and bone-building bioactive ceramics in an 18-week study on rats with a version of peri-implantitis, an infectious disease that causes inflammation of the gum and the bone structure around a dental implant.

By the end of the study, the bone around the implants in all of the rats had completely regenerated.

The scientists injected the hydrogel in the mouth and, to seal it in place, applied a light treatment, similar to the method dentists use in humans to solidify dental fillings.

The light treatment helped harden the hydrogel, providing a more stable vehicle for delivery of the stem cells, Moshaverinia said. We believe that our new tissue engineering application could be an optimal option for patients who have lost their hard and soft craniofacial tissues due to trauma, infection or tumors.

The studys other authors are Mohammad Mahdi Hasani-Sadrabadi, Patricia Sarrion, Sevda Pouraghaei, Yee Chau, Sahar Ansari, Song Li and Dr. Tara Aghaloo, all of UCLA.

The research was supported by the National Institute of Dental and Craniofacial Research and the California Institute for Regenerative Medicine.

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Hydrogel could be step forward in therapies to generate bones in head and neck - UCLA Newsroom

A cell bank refers to a facility that store cells derived from various body fluids and organ tissue for future needs. The bank store the cells with detailed characterization of the cell line hence decrease the chances of cross contamination. Cell banking outsourcing industry involves collection, storage, characterization, and testing of cells, cell lines, and tissues. Cell banks provide cells, cell lines, and tissues for R&D, production of biopharmaceuticals with maximum effectiveness and minimal adverse events. The process for storage of cells includes first proliferation of cells that multiplied in large number of identical cells and then stored into cryovials for future use. Cells mainly used in the regenerative medicine production. Increasing demand of stem cell therapies and number of cell banks expected to boost the global market.

Global cell banking outsourcing market segmented based on bank type, cell type, phase, and geography. Based on bank type market is further segmented into master cell banking, working cell banking, and viral cell banking. Cell type segment further divided based on stem cell banking and non-stem cell banking. Stem cell banking includes dental, adult, cord, embryonic, and IPS stem cell banking.

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Based on phase, the global cell banking outsourcing market segmented into preparation, storage, testing, and characterization. Geographically, market divided into North America, Europe, Asia Pacific, Latin America, and Middle East Africa. By considering bank type master cell banking accounted largest share owing to longer duration of preservation that would attract the researcher. Stem cell banking accounted larger share than non-stem cell banking due to lower risk of contamination. In stem cell banking cord stem cell banking accounted larger share by revenue in 2014 due to increasing number of cord blood banks, and services globally.

Additionally, donor convenience, immediate availability, lower risk of viral contamination is major driving factors for cord stem cell banking. In bank phase, segment storage phase accounted largest share and expected to maintain its share due to development of sophisticated preservation technologies such as cryopreservation technique. Geographically, North America accounted largest share due to high number of ongoing research projects. However, Asia Pacific expected to show significant growth during forecast period owing to supportive government initiatives coupled with increasing awareness about cell therapies.

The global cell banking outsourcing market is witnessing lucrative growth during forecast period due to increased research in cell line development owing to rise in incidence of infectious chronic disorder, and cancer. Additionally, development of advanced preservation techniques, increasing adoption to the stem cell therapies, rise in cell bank facilities across globe, and moving focus of researcher towards stem cell therapies would drive the market.

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However, high cost of therapies, availability of right donors, and legal and changing ethical issues during collection across the globe are major restraint of the market. Risk associated with cell line banking is contamination of cell lines by manual errors or environmental conditions hence care should be taken during storing and handling of cells.

Major player in cell banking outsourcing market include;

BioOutsource (Sartorious)

BioReliance

BSL Bioservice

Charles River Laboratories

Cleancells

CordLife

Covance

Cryobanks International India

Cryo-Cell International Inc.

GlobalStem Inc.

Goodwin Biotechnology Inc.

LifeCell International Pvt. Ltd.

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Cell Banking Outsourcing Market to Witness Surge in Demand Owing to Increasing End-use Adoption - Lake Shore Gazette

Pretty much anyone can do a disturbingly accurate imitation of the sound of a dentists's drill at varying speeds as it prepares a tooth cavity for filling. It's not an experience most people savor, and we won't even get into what kind of person chooses to spend eight hours a day except Wednesdays inside other people's mouths.

A few years ago, researchers suggested that low doses of a small molecule glycogen synthase kinase (GSK-3) antagonist in the form of anti-Alzheimer's drug Tideglusib applied to a decayed area could stimulate the coronal pulp in a tooth to repair itself. Now scientists at King's College in London have expanded upon that earlier research and found further evidence that Tideglusib may indeed provide a pathway toward self-healing teeth. The new research is published as a paper in the Journal of Dental Research.

Drilling may still be necessary, unfortunately, to clean decay from the affected area before treatment.

Image source: BruceBlaus Wikimedia

The are three elements to the structure of a tooth:

When you get a cavity, the outer enamel has a hole in it. With that outer protection breached, infecting bacteria nestle in, causing decay that burrows ever-deeper into the tooth, causing damage to its inner layers. To repair it using traditional methods, a dentist cleans bacteria from out the inside of cavity before filling it with a cement composite that replaces the lost natural dentin.

Image source: Quang Tri Nguyen/Unsplash

"In the last few years we showed that we can stimulate natural tooth repair by activating resident tooth stem cells. This approach is simple and cost effective. The latest results show further evidence of clinical viability and brings us another step closer to natural tooth repair." paper lead author Paul Sharpe

Share and his colleagues were interested in understanding how large a damaged area could be repaired with Tideglusib, and where, and they hoped to analyze the composition of repaired dentin in comparison to naturally occurring dentin and/or bone.

The researchers confirmed that Tideglusib can cause the generation of sufficient replacement dentin to be of use. The paper asserts that the drug can "fully repair an area of dentin damage up to 10 times larger." More than enough to be of value.

Second, Sharpe and his team learned that Tideglusib works only on a particular kind of tooth material: the coronal pulp, that region of pulp extending to the crown of the tooth. They also learned that the drug must be applied only to the affected area to be effective, finding that untreated areas of pulp, notably the root pulp, are not adversely affected by treatment, a good thing.

Finally, analyzing repaired dentin using Raman microspectroscopy, the researchers determined that the generated dentin is chemically quite similar to natural dentin, being comprised of a similar ratios of carbonate and phosphate and mineral-to-matrix as natural dentin.

One limiting factor in the use of Tideglusib, therefore, is that the coronal pulp must be exposed in a cavity in oder to be treated. Nonetheless, the research stands as confirmation not only of this specific drug's talent to for triggering dentin regeneration, but of something even bigger and more intriguing: That teeth have the ability to repair themselves.

There's a great deal of investigation these days into the possibilities of humans regenerating body parts much as other animals such as salamanders and axolotls do. How far all of this research will get remains an open question for now, but undoubtedly remains one of the most exciting areas of current medical research.

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New evidence teeth can fill their own cavities - Big Think

Bone remodeling and regeneration are dependent on resident stem/progenitor cells with the capability to replenish mature osteoblasts and repair the skeleton.

Until now, it has been thought that stem cells for bone lie within the bone marrow and the outer surface of the bone. Many studies have described the existence of a network of vascular channels that helped distribute blood cells out of the bone marrow. However, none of the studies had proved the existence of cells within these channels.

A new study by the scientists from the UConn School of Dental Medicine has discovered the population of stem cells that reside along the vascular channels within the cortical bone and have the ability to generate new bone. These stem cells stretch across the bone and connect the inner and outer parts of the bone.

Lead investigator Dr. Ivo Kalajzic, professor of reconstructive sciences, said, This is a discovery of perivascular cells residing within the bone itself that can generate new bone-forming cells. These cells likely regulate bone formation or participate in bone mass maintenance and repair.

This is the first study that reports the existence of these progenitor cells within the cortical bone that can generate new bone-forming cellsosteoblaststhat can be used to help remodel a bone.

To reach this conclusion, the scientists observed the stem cells within an ex vivo bone transplantation model. These cells migrated out of the transplant and started to reconstruct the bone marrow cavity and form new bone.

However, further study is required to determine the cells potential to regulate bone formation and resorption.

The study is presented in the journal Stem Cells.

Excerpt from:
These new stem cells have the ability to generate new bone - Tech Explorist

Gosselies, Belgium, 11 March 2020, 7am CET BONE THERAPEUTICS(Euronext Brussels and Paris: BOTHE), the bone cell therapy company addressing high unmet medical needs in orthopaedics and bone diseases, today announces its business update and full year financial results for the year ending 31 December 2019, prepared in accordance with IFRS as adopted by the European Union.

During the past year, Bone Therapeutics has laid a strong foundation for advancing our key assets, the allogeneic cell therapy platform ALLOB and the enriched protein solution JTA-004, into the next phase of clinical development and beyond, saidMiguel Forte, MD, PhD, CEO of Bone Therapeutics.We have obtained additional clinical evidence supporting the safety and efficacy for ALLOB in patients undergoing spinal fusion procedures. We have also successfully implemented the optimised allogeneic cell therapy manufacturing process and additionally submitted the clinical trial applications for the crucial Phase III JTA-004 and Phase IIb ALLOB studies. With the preparation of both clinical trials complete, we are fully focussed on timely execution of our clinical programmes and delivering our business and partnering strategy in 2020. This will enable us to move toward our goal of creating innovation solutions that will make a true difference in the lives of patients suffering from debilitating orthopaedic conditions.

Clinical and operational highlights during 2019

Corporate highlights 2019

Financial highlights 2019

Outlook for the remainder of 2020

Bone Therapeutics anticipates starting patient recruitment for the Phase III study with JTA-004, for the treatment of pain in patients with knee osteoarthritis in Q1 2020, subject to the approval of the CTA by the regulatory authorities.

The company has started the CTA submission process in Europe for a Phase IIb clinical trial with its allogeneic bone cell therapy product, ALLOB, in patients with tibial fractures at risk for delayed healing, using its optimized production process. The company expects to enroll the first patient in Q2 2020.

In the second half of 2020, the company expects to report results from the 2-year follow-up period of thePhaseIIa study with ALLOB in patients undergoing a spinal fusion procedure.

Good cost and cash management will remain a key priority. The net cash burn for the full year 2020 is expected to be in the range of 15-17 million assuming normal operation as the effect of the ongoing COVID-19 epidemy cannot be excluded. The situation will be actively and closely monitored. The company anticipates having sufficient cash to carry out its business objectives into Q3 2020.

In this context, strengthening the cash position is a key priority. The company is currently evaluating and working on different financing options and plans to raise new funds from the capital markets and/or through alternative funding strategies.

Conference call

Miguel Forte, MD, PhD, CEO, and Jean-Luc Vandebroek, CFO, will host a conference call today at 5pm CET / 11am EST / 8am PST. To participate in the conference call, please select your dial-in number from the list below quoting the conference ID 7547944#:

Belgium: +32 (0)800 48 740 / +32 (0)2 400 98 74France: +33 (0)805 103 028 / +33 (0)1 76 70 07 94United Kingdom: +44 (0)800 376 7922 / +44 (0)844 571 8892United States: +1 (866) 966 1396 / +1 (631) 510 7495

Shortly prior to the call, the presentation will be made available on the Investors section of the Companys website. A replay will be available by dialling the following number +44 (0)333 300 9785 / +33 (0)1 70 95 03 48 and by using the conference ID: 7547944#

About Bone Therapeutics

Bone Therapeutics is a leading biotech company focused on the development of innovative products to address high unmet needs in orthopedics and bone diseases. The Company has a broad, diversified portfolio of bone cell therapies and an innovative biological product in later-stage clinical development, which target markets with large unmet medical needs and limited innovation.

Bone Therapeutics is developing an off-the-shelf protein solution, JTA-004, which is entering Phase III development for the treatment of pain in knee osteoarthritis. Positive Phase IIb efficacy results in patients with knee osteoarthritis showed a statistically significant improvement in pain relief compared to a leading viscosupplement. The clinical trial application (CTA) to start the pivotal Phase III program has been submitted to the regulatory authorities in Europe and Hong Kong SAR. The trial is expected to start in Q1 2020.

Bone Therapeutics other core technology is based on its cutting-edge allogeneic cell therapy platform (ALLOB) which can be stored at the point of use in the hospital, and uses a unique, proprietary approach to bone regeneration, which turns undifferentiated stem cells from healthy donors into bone-forming cells. These cells can be administered via a minimally invasive procedure, avoiding the need for invasive surgery, and are produced via a proprietary, scalable cutting-edge manufacturing process. Following the promising Phase IIa efficacy and safety results for ALLOB, the Company has started the CTA submission procedure with the regulatory authorities in Europe to start the Phase IIb clinical trial with ALLOB in patients with difficult-to-heal fractures, using its optimized production process.

The ALLOB platform technology has multiple applications and will continue to be evaluated in other indications including spinal fusion, osteotomy and maxillofacial and dental applications.

Bone Therapeutics cell therapy products are manufactured to the highest GMP (Good Manufacturing Practices) standards and are protected by a broad IP (Intellectual Property) portfolio covering ten patent families as well as knowhow. The Company is based in the BioPark in Gosselies, Belgium. Further information is available at http://www.bonetherapeutics.com.

Contacts

Bone Therapeutics SAMiguel Forte, MD, PhD, Chief Executive OfficerJean-Luc Vandebroek, Chief Financial OfficerTel: +32 (0) 71 12 10 00investorrelations@bonetherapeutics.com

International Media Enquiries:Image Box CommunicationsNeil Hunter / Michelle BoxallTel: 44 (0)20 8943 4685neil@ibcomms.agency / michelle@ibcomms.agency

For French Media and Investor Enquiries:NewCap Investor Relations & Financial CommunicationsPierre Laurent, Louis-Victor Delouvrier and Arthur RouillTel: + 33 (0)1 44 71 94 94bone@newcap.eu

Certain statements, beliefs and opinions in this press release are forward-looking, which reflect the Company or, as appropriate, the Company directors` current expectations and projections about future events. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, the Company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither the Company nor its advisers or representatives nor any of its subsidiary undertakings or any such person`s officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release.

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Bone Therapeutics announces 2019 full year results - OrthoSpineNews

A new population of stem cells that can generate bone has been revealed by researchers, which they say could have implications in regenerative medicine.

A population of stem cells with the ability to generate new bone has been newly discovered by a group of researchers at the University of Connecticut (UConn) School of Dental Medicine, US.

The researchers present a new population of cells that reside along the vascular channels that stretch across the bone and connect the inner and outer parts of the bone.

This is a new discovery of perivascular cells residing within the bone itself that can generate new bone forming cells, said lead investigator Dr Ivo Kalajzic. These cells likely regulate bone formation or participate in bone mass maintenance and repair.

Stem cells for bone have long been thought to be present within bone marrow and the outer surface of bone, serving as reserve cells that constantly generate new bone or participate in bone repair. Recent studies have described the existence of a network of vascular channels that helped distribute blood cells out of the bone marrow, but no research has proved the existence of cells within these channels that have the ability to form new bones.

In this study, Kalajzic and his team are the first to report the existence of these progenitor cells within cortical bone that can generate new bone-forming cells osteoblasts that can be used to help remodel a bone.

To reach this conclusion, the researchers observed the stem cells within an ex vivo bone transplantation model. These cells migrated out of the transplant and began to reconstruct the marrow cavity and form new bone.

While this study shows there is a population of cells that can help aid formation, more research needs to be done to determine the cells potential to regulate bone formation and resorption, say the scientists.

According to the authors of the study: we have identified and characterised a novel stromal lineagerestricted osteoprogenitor that is associated with transcortical vessels of long bones. Functionally, we have demonstrated that this population can migrate out of cortical bone channels, expand and differentiate into osteoblasts, therefore serving as a source of progenitors contributing to new bone formation.

The results are published inSTEM CELLS.

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Stem cells that can grow new bone discovered by researchers - Drug Target Review

Researchers from UConn School of Dental Medicine have recently discovered a group of stem cells that help in generating a new bone. In regards with this, Dr Ivo Kalajzic, professor of reconstructive sciences, stated that, this newly discovered perivascular stem cells that reside in the bone itself have capability of generating the bone and these cells are highly instrumental in repair & mass maintenance of the bone along with its formation.

Since ages, it has been thought that stem cells only reside in bone marrow and exterior surface of the bone stores the cells that continuously generate new bone or repair the bone. Postdoctoral individuals Dr Sierra Root and Dr Natalie Wee, and collaborators at Harvard, Maine Medical Research Center, and the University of Auckland also were part of this study along with Dr Ivo Kalajzic and confirmed that these new cluster of cells residing in the vascular channels that range across the bone and serve as connection between inner and outer part of the bone is capable of generating a new bone.

This team is also pioneer in bringing forward a study that says existence of these progenitor cells inside cortical bone not only generates a new bone but also help remodeling of the bone. The conclusion was made after these researchers observed that these stem cells within an ex vivo bone transportation model migrated out of the transplant and started manufacturing a new bone marrow cavity along with completely new bone.

In order to establish this, more research needs to done as it will definitely turn out wonderful to the field of medical science and mankind.

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Stem Cells that will aid new bone generation discovered as per latest research - Medical Herald

A population of stem cells with the ability to generate new bone has been newly discovered by a group of researchers at the UConn School of Dental Medicine.

In the journal STEM CELLS, lead investigator Dr. Ivo Kalajzic, professor of reconstructive sciences, postdoctoral fellows Dr. Sierra Root and Dr. Natalie Wee, and collaborators at Harvard, Maine Medical Research Center, and the University of Auckland present a new population of cells that reside along the vascular channels that stretch across the bone and connect the inner and outer parts of the bone.

This is a new discovery of perivascular cells residing within the bone itself that can generate new bone forming cells, said Kalajzic. These cells likely regulate bone formation or participate in bone mass maintenance and repair.

Stem cells for bone have long been thought to be present within bone marrow and the outer surface of bone, serving as reserve cells that constantly generate new bone or participate in bone repair. Recent studies have described the existence of a network of vascular channels that helped distribute blood cells out of the bone marrow, but no research has proved the existence of cells within these channels that have the ability to form new bones.

In this study, Kalajzic and his team are the first to report the existence of these progenitor cells within cortical bone that can generate new bone-forming cells osteoblasts that can be used to help remodel a bone.

To reach this conclusion, the researchers observed the stem cells within an ex vivo bone transplantation model. These cells migrated out of the transplant, and began to reconstruct the bone marrow cavity and form new bone.

While this study shows there is a population of cells that can help aid bone formation, more research needs to be done to determine the cells potential to regulate bone formation and resorption.

This study was funded by the Regenerative Medicine Research Fund (RMRF; 16-RMB-UCHC-10) by CT Innovations and by National Institute of Arthritis and Musculoskeletal and Skin.

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UConn Researchers Discover New Stem Cells That Can Generate New Bone - UConn Today

Maryp | Dreamstime.com

A plethora of dental research is underway in the US as well as globally. Some of these advancements will come to fruition and be commercially available, and some will die on the vine. There are innovations in essentially every dental discipline, with breakthroughs that have the potential to enhance oral health in ways we couldnt imagine in the past.

The impact of artificial intelligence (AI) will increase in the future. AI is already at work in hospitals to diagnose cancer and anticipate trends in health care. AI will have a significant effect in the dental profession on a daily basis, from evaluating images for pathology, to prosthetics and systemic care, among many others. AI promises to increase efficiency in dental practice by facilitating faster diagnosis, predictive analytics, and autocharting.

Other areas of research and development include gene therapy and stem cells. Research is underway using gene therapy to restore salivary function in patients who have undergone radiation treatment, which could be a tremendous improvement in health for these individuals. The negative impact of dry mouth extends far beyond the discomfort associated with inadequate or complete lack of saliva. It has a significant effect on the quality of life of the individual and the health of the oral cavity. The ability to restore salivary function could be life-changing for many people.

Other initiatives involve transformative research in periodontics, specifically agents operating on the host response and others applied to the diseased periodontal pockets. Some of the research on host-response therapies involves agents that repair the immune system dysfunction responsible for tissue degeneration. This is accomplished by using minute quantities of an agent that creates a gradient, resulting in the mobilization of regulatory cells that dampen down the inflammatory response, which is responsible for the tissue destruction that accompanies periodontal disease.

Some of the research focused on the clinical application of agents into periodontal pockets does not involve antimicrobial therapies, but rather are regenerative in nature. Preparation of the affected area is simple and quick, followed by application of the regenerative agent. Clinical trials have demonstrated significant pocket depth reduction and bone regeneration. If these results are consistent and reproducible, a complete paradigm shift in the treatment of periodontitis could occurone that is essentially noninvasive, quick, and inexpensive.

There are a number of disruptive technologies in various stages of development that will dramatically change the manner in which we practice dentistry. Some of these changes will mirror developments in the medical profession, such as gene therapy and influencing the immunoinflammatory system to reduce tissue damage, which ultimately benefits the individuals oral and overall health.

Editor's note: Would you like to learn more about the latest in oral-systemic research?Write to Dr. Richard Nagelbergabout topics youve read about in this blog or submit items youd like to see covered here.

Previous blog: Updates on periodontal disease pathogens and the heart

Editor's note: This article originally appeared in Breakthrough Clinical, aclinical specialties newsletter from Dental Economics and DentistryIQ. Read more articles at this link.

Richard H. Nagelberg, DDS, has practiced general dentistry in suburban Philadelphia for more than 30 years. He is a speaker, advisory board member, consultant, and key opinion leader for several dental companies and organizations. He lectures on a variety of topics centered on understanding the impact dental professionals have beyond the oral cavity. Contact Dr. Nagelberg atrnagelberg@orapharma.com.

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What's coming down the pike in the dental profession? - Dentistry IQ

For years, scientists have predicted that 3-D printingwhich has been used it to make toys, homes, scientific tools and even a plastic bunny that contained a DNA code for its own replicationcould one day be harnessed to print live, human body parts to mitigate a shortage of donor organs. So far, researchers also used 3-D printing in medicine and dentistry to create dental implants, prosthetics, and models for surgeons to practice on before they make cuts on a patient. But many researchers have moved beyond printing with plastics and metalsprinting with cells that then form living human tissues.

No one has printed fully functional, transplantable human organs just yet, but scientists are getting closer, making pieces of tissue that can be used to test drugs and designing methods to overcome the challenges of recreating the bodys complex biology.

A confocal microscopy image showing 3-Dprinted stem cells differentiating into bone cells

The first 3-D printer was developed in the late 1980s. It could print small objects designed using computer-aided design (CAD) software. A design would be virtually sliced into layers only three-thousandths of a millimeter thick. Then, the printer would piece that design into the complete product.

There were two main strategies a printer might use to lay down the pattern: it could extrude a paste through a very fine tip, printing the design starting with the bottom layer and working upward with each layer being supported by the previous layers. Alternatively, it could start with a container filled with resin and use a pointed laser to solidify portions of that resin to create a solid object from the top down, which would be lifted and removed from the surrounding resin.

When it comes to printing cells and biomaterials to make replicas of body parts and organs, these same two strategies apply, but the ability to work with biological materials in this way has required input from cell biologists, engineers, developmental biologists, materials scientists, and others.

So far, scientists have printed mini organoids and microfluidics models of tissues, also known as organs on chips. Both have yielded practical and theoretical insights into the function of the human body. Some of these models are used by pharmaceutical companies to test drugs before moving on to animal studies and eventually clinical trials. One group, for example, printed cardiac cells on a chip and connected it to a bioreactor before using it to test the cardiac toxicity of a well-known cancer drug, doxorubicin. The team showed that the cells beating rate decreased dramatically after exposure to the drug.

However, scientists have yet to construct organs that truly replicate the myriad structural characteristics and functions of human tissues. There are a number of companies who are attempting to do things like 3-D print ears, and researchers have already reported transplanting 3-D printed ears onto children who had birth defects that left their ears underdeveloped, notes Robby Bowles, a bioengineer at the University of Utah. The ear transplants are, he says, kind of the first proof of concept of 3-D printing for medicine.

THE SCIENTIST STAFF

Bowles adds that researchers are still a ways away from printing more-complex tissues and organs that can be transplanted into living organisms. But, for many scientists, thats precisely the goal. As of February 2020, more than 112,000 people in the US are waiting for an organ transplant, according to the United Network for Organ Sharing. About 20 of them die each day.

For many years, biological engineers have tried to build 3-D scaffolds that they could seed with stem cells that would eventually differentiate and grow into the shapes of organs, but to a large extent those techniques dont allow you to introduce kind of the organization of gradients and the patterning that is in the tissue, says Bowles. There is no control over where the cells go in that tissue. By contrast, 3-D printing enables researchers with to very precisely direct the placement of cellsa feat that could lead to better control over organ development.

Ideally, 3-D printed organs would be built from cells that a patients immune system could recognize as its own, to avoid immune rejection and the need for patients to take immunosuppressive drugs. Such organs could potentially be built from patient-specific induced pluripotent stem cells, but one challenge is getting the cells to differentiate into the subtype of mature cell thats needed to build a particular organ. The difficulty is kind of coming together and producing complex patternings of cells and biomaterials together to produce different functions of the different tissues and organs, says Bowles.

To imitate the patterns seen in vivo, scientists print cells into hydrogels or other environments with molecular signals and gradients designed to coax the cells into organizing themselves into lifelike organs. Scientists can use 3-D printing to build these hydrogels as well. With other techniques, the patterns achieved have typically been two-dimensional, Eben Alsberg, a bioengineer at the University of Illinois, tells The Scientist in an email. Three-dimensional bioprinting permits much more control over signal presentation in 3D.

So far, researchers have created patches of tissue that mimic portions of certain organs but havent managed to replicate the complexity or cell density of a full organ. But its possible that in some patients, even a patch would be an effective treatment. At the end of 2016, a company called Organovo announced the start of a program to develop 3-D printed liver tissue for human transplants after a study showed that transplanted patches of 3-D printed liver cells successfully engrafted in a mouse model of a genetic liver disease and boosted several biomarkers that suggested an improvement in liver function.

Only in the past few years have researchers started to make headway with one of the biggest challenges in printing 3-D organs: creating vasculature. After the patches were engrafted into the mouses liver in the Organovo study, blood was delivered to it by the surrounding liver tissue, but an entire organ would need to come prepared for blood flow.

For any cells to stay alive, [the organ] needs that blood supply, so it cant just be this huge chunk of tissue, says Courtney Gegg, a senior director of tissue engineering at Prellis Biologics, which makes and sells scaffolds to support 3-D printed tissue. Thats been recognized as one of the key issues.

Mark Skylar-Scott, a bioengineer at the Wyss Institute, says that the problem has held back tissue engineering for decades. But in 2018, Sbastian Uzel, Skylar-Scott, and a team at the Wyss Institute managed to 3-D print a tiny, beating heart ventricle complete with blood vessels. A few days after printing the tissue, Uzel says he came into the lab to find a piece of twitching tissue, which was both very terrifying and exciting.

For any cells to stay alive, [the organ] needs that blood supply, so it cant just be this huge chunk of tissue.

Courtney Gegg, Prellis Biologics

Instead of printing the veins in layers, the team used embedded printinga technique in which, instead of building from the bottom of a slide upwards, material is extruded directly into a bath, or matrix. This strategy, which allows the researchers to print free form in 3-D, says Skylar-Scott, rather having to print each layer one on top of the other to support the structure, is a more efficient way to print a vascular tree. The matrix in this case was the cellular material that made up the heart ventricle. A gelatin-like ink pushed these cells gently out of the way to create a network of channels. Once printing was finished, the combination was warmed up. This heat caused the cellular matrix to solidify, but the gelatin to liquify so it could then be rinsed out, leaving space for blood to flow through.

But that doesnt mean the problem is completely solved. The Wyss Institute teams ventricle had blood vessels, but not nearly as many as a full-sized heart. Gegg points out that to truly imitate human biology, an individual cell will have to be within 200 microns of your nearest blood supply. . . . Everything has to be very, very close. Thats far more intricate than what researchers have printed so far.

Due to hurdles with adding vasculature and many other challenges that still face 3-Dprinted tissues, laboratory-built organs wont be available for transplant anytime soon. In the meantime, 3-D printing portions of tissue is helping accelerate both basic and clinical research about the human body.

Emma Yasinski is a Florida-based freelance reporter. Follow her on Twitter@EmmaYas24.

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On the Road to 3-D Printed Organs - The Scientist

I wonder what the pedalo does as I slip into a waffle robe Im at Bellecell, a central London molecular-wellness clinic that offers hyper-personalised science-based solutions to health this place could be a Bond villains laboratory on the moon.

I am standing in a hushed, blue-lit underground brick tunnel with Kubrick-white furnishings and so many fascinating toys: EMS suits, laser IVs, and what looks like an exercise bike built into a love boat, with a vacuum for your legs.

As distracting as these things are, I am here to try something specific: a hyperbaric oxygen chamber. I am fascinated by these things. Culturally, they have long been signifiers of megalomania, detachment and anxiety. Michael Jackson had one in his house, which isnt a great recommendation. The Olympian swimmer Michael Phelps is another fan. But what do these chambers actually do? Do you have to be called Michael to use one?

I climb into a plastic body bag in my hospital booties. Hyperbaric oxygen therapy involves breathing pure oxygen in a pressurised environment. The structure is a semi-circular cage with comfortable bedding, surrounded by thick plastic walls. Once I am inside, a technician inflates the bag. I am basically inside a balloon, which will be maintained at constant pressure, as I breathe 100% oxygen through a mask.

Hyperbaric chambers are mostly used to treat gas gangrene, carbon monoxide poisoning and the bends, while the medical uses of oxygen include wound-healing and reducing the risk of infection. Many people report feeling energised afterwards. I have some oral swelling following dental work, and am interested to see if that goes down.

For some, the close confinement and constant sound of pressurisation will be a recipe for a panic attack. For me, it is heaven. I am what you might call a claustrophile. I have always loved climbing into cupboards and corners, making dens and closing a door on the world. I fantasise about Japanese capsule hotels. Now, I lie and watch a zip close above me. There is a hissing noise. I adjust my oxygen mask and observe star-headed thumb screws being turned to calibrate the pressure. The gauge crawls upwards, my ears are getting stuffy. I swallow as it hits 4psi, equivalent to a depth of nine feet under water. Gazing at ambient blue through a hatch to the outside world, I imagine Im much deeper, packed into a nuclear missile on the undercarriage of a submarine. I am in my happy place.

The use of oxygen for performance-enhancement is mostly misunderstood. The effects of inhaling it are extremely short-lived. Athletes are often seen huffing cans of oxygen at the touchline, but science indicates that this is a mostly meaningless activity. Pressure makes all the difference. Under pressure, oxygen is dissolved in larger quantities in the blood plasma itself, not just the red blood cells. That means a much higher amount of the gas is transported into tissues that need it for healing, in theory mobilising stem cell release to repair the body quickly. It is definitely promising; the catch is, you would probably need a few treatments to see the benefit. At 160 an hour, post-workout muscle soreness probably isnt reason enough.

I thoroughly enjoy the experience for its own sake. Lulled by the pressure and soft lighting outside, I fall into a deep, restorative nap. After an hour, I emerge as wobbly as a newborn. I dont feel supercharged, admittedly. I feel drowsy, and absolutely starving. Im assured this is normal. I do feel astonishingly relaxed, though. The swelling inside my mouth reduces significantly over the next day, too, for which I can probably thank the chamber.

I would totally have one of these in my house. I miss the missile, but cant afford to go back. Instead, Im cursed to walk these normobaric streets, breathing 21% oxygen like everyone else, dreaming of when I had less freedom to move.

Walter White, eat your heart out Could I recreate the effect with hydrogen peroxide, bakers yeast and a tarp over the bath?

Wellness or hellness? Airs and graces. 5/5

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Hyperbaric chamber therapy: Im under a lot of pressure and I love it! - The Guardian