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Archive for the ‘Nano medicine’ Category

Single-particle imaging of nanomedicine entering the brain | Proceedings of the National Academy of Sciences – pnas.org

Thursday, January 25th, 2024

Single-particle imaging of nanomedicine entering the brain | Proceedings of the National Academy of Sciences  pnas.org

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Single-particle imaging of nanomedicine entering the brain | Proceedings of the National Academy of Sciences - pnas.org

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Controlling the biodistribution and clearance of nanomedicines – Nature.com

Friday, December 22nd, 2023

Controlling the biodistribution and clearance of nanomedicines  Nature.com

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HKUMed achieves breakthrough in photoactivatable nanomedicine for the treatment of age-related macular … – Ophthalmology Times

Friday, December 22nd, 2023

HKUMed achieves breakthrough in photoactivatable nanomedicine for the treatment of age-related macular ...  Ophthalmology Times

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HKUMed achieves breakthrough in photoactivatable nanomedicine for the treatment of age-related macular ... - Ophthalmology Times

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Oro Rx Healthcare LLP Unveils Oroceuticals: The Next-Gen Nutrition Delivery Tech – Hindustan Times

Friday, October 27th, 2023

Oro Rx Healthcare LLP Unveils Oroceuticals: The Next-Gen Nutrition Delivery Tech  Hindustan Times

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Oro Rx Healthcare LLP Unveils Oroceuticals: The Next-Gen Nutrition Delivery Tech - Hindustan Times

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Leapfrogging as pharma leader of the worldNational Policy on Research and Development and Innovation in Pharma-MedTech Sector in India – The Sangai…

Friday, October 27th, 2023

Leapfrogging as pharma leader of the worldNational Policy on Research and Development and Innovation in Pharma-MedTech Sector in India  The Sangai Express

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Leapfrogging as pharma leader of the worldNational Policy on Research and Development and Innovation in Pharma-MedTech Sector in India - The Sangai...

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What will Indian healthcare look like in 2047? Robotics, AI, biotech will shape the future – The Economic Times

Thursday, February 16th, 2023

What will Indian healthcare look like in 2047? Robotics, AI, biotech will shape the future  The Economic Times

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What will Indian healthcare look like in 2047? Robotics, AI, biotech will shape the future - The Economic Times

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Going Beyond Target Or Mechanism Of Disease: Disruptive Innovation In Drug Delivery Systems – Forbes

Monday, September 12th, 2022

AI-generated image using Midjourney depicting scientists inventing new medicines

In 1998 I was exposed to the term disruptive innovation for the first time. I read a wonderful book, The Innovators Dilemma by Clayton Christensen, where I learned the difference between incremental innovation and disruptive innovation. He analyzed the hard drive industry and showed that while many companies were trying to increase the capacity of the drives, other companies changed the form factor and made the drives smaller. This resulted in disruptive progress in the industry. We also recently witnessed dramatic advances in artificial intelligence (AI), where in 2013/2014 AI systems started outperforming humans in image recognition. This was made possible by taking several existing technologies, deep neural networks (DNNs) and GPU computing, and training DNN on really big data sets. In fact, disruptive innovation often results from the combination of already existing technologies to make them work to address a massive unmet need.

Over past decades, the field of nanomedicine, mostly characterized by the targeted delivery of drugs for numerous types of diseases, has gained a special attention in oncology research. While some anti-cancer drugs work well when administered to the right patient and in the right dose, no drug is perfect, and no dose fits all. One of the most frequently used classes of anti-cancer drugs is platinum-based compounds, such as carboplatin, oxaliplatin, and cisplatin (one of the most effective anti-cancer drugs for the treatment of solid malignancies). Chemotherapeutic agents are necessarily toxic, as from a therapeutic stance, we need to kill the rapidly dividing cancer cells. However, as these drugs are nonselective (targeting both healthy and malignant tissues), patients often suffer the unfortunate combination of substantial side effects and low efficacy at the target site when these compounds are administered systemically via traditional routes (orally or intravenously).

Enhancing the accumulation of these drugs locally at the tumor site may significantly reduce the systemic toxicities and adverse side effects, while simultaneously improving treatment efficacy substantially. The major limitation is that these drugs do not penetrate very well, and so enhancing penetration has become a necessary goal in the optimization of delivering these agents. One technology that can help with this task is encapsulating the chemotherapeutic agents in nanoparticles (NPs). During the last decade, a wide range of nano-based drug delivery systems has been explored as alternative cisplatin delivery methods that may promote its accumulation and retention in cancer cells. While some of these NP formulations have demonstrated promising preclinical results and a few have entered clinical trials, none have been approved for the treatment of human cancers. Targeted accumulation of the drug can be further optimized through topical delivery of NPs in the form of gels and film composites, which may also increase the local and precise administration of chemotherapeutic drugs to accessible tumors (such as cancers arising in the oral cavity). Therefore, disruptive innovation has originated from merging these approaches and generating topical NP-based drug delivery platforms that primarily intend to ameliorate the adverse effects of systemically administered treatment and maximize the total dose and retention of the carried therapeutic agent at the local site, improving treatment efficacy.

Manijeh Goldberg, PhD, MBA, CEO of Privo Technologies

A multidisciplinary group led by Dr. Manijeh Goldberg, founder and CEO of Privo Technologies, together with Dr. Nishant Agrawal and Dr. Evgeny Izumchenko, Chief of Head and Neck Surgery and Professor of Hematology and Oncology at the University of Chicago, respectively, recently published the results of Privos preclinical and clinical studies using PRV111 treatment. This treatment is a topical mucoadhesive cisplatin delivery system that has the potential to revolutionize the field.

A screen capture of the header of the Nature Communications paper titled "A nanoengineered topical ... [+] transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer" https://doi.org/10.1038/s41467-022-31859-3

In the recent Nature Communications paper titled A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer, the scientists describe a nanotechnology-based patch system for non-invasive, local delivery of cisplatin-loaded chitosan particles that penetrate tumor tissue and lymphatic channels while avoiding systemic circulation and toxicity. The system was used in both animal models (mice and hamsters) and patients with oral cancer and demonstrated promising, potentially disruptive, results.

Professor Nishant Agrawal, MD, Director, Head and Neck Surgical Oncology Chief, Section of ... [+] Otolaryngology-Head and Neck Surgery, University of Chicago

The hamster cheek model is a well-characterized system for studying oral cancer because of the similarities between the tissue in the pouch and the tissue in the human mouth. In the clinical trial, patients were treated with PRV111 as long as a week before undergoing surgery (surgery is standard for all patients with oral cancer). 87% of patients responded to treatment and showed decreased tumor volume, with an average decrease of 70% of tumor volume across all patients. As further confirmation of PRV111s efficacy, examination of the tumor tissue after surgery demonstrated that treatment also stimulated the patients innate immune system. Thus, the results from PRV111 use in humans suggest that PRV111 has shown a one-two punch therapeutic effect, simultaneously killing tumor cells and recruiting immune cells to attack the tumor site.

Briefly, in the PRV111 platform, chitosan (a non-toxic, biocompatible, and biodegradable polysaccharide derived from natural chitin), is used as a polymer for both the NPs and the porous matrix. As such, matrix-based water-soluble chitosan acts as a bioadhesive since the positively-charged chitosan can bind to negatively-charged mucoproteins, allowing the electrostatic interaction with mucin proteins in the oral cavity. Each cisplatin-loaded chitosan NPs containing patch covers a tumor region of 4 cm2, and incorporates a permeation enhancer that allows optimal penetration and absorption of the NPs released from the patch. When exposed to moisture, the NPs swell, allowing them to diffuse across the porous matrix and into the tumor tissue. However, these particles are too large to penetrate into the vasculature, and therefore prevent systemic cisplatin exposure.

Professor Evgeny Izumchenko, PhD

Since I made a tiny and insignificant contribution to the paper, and I am familiar with the leading authors. I got a chance to ask them a few questions about this possibly groundbreaking work.

Alex: I consider cisplatin to be one of the ancient uber-toxic cancer drugs that are responsible for the many misconceptions about modern cancer treatments. Why did you choose cisplatin for this study?

Cisplatin is one of the most potent anti-cancer agents. It has been studied and used in the field of oncology for decades. However, its dose-limiting systemic toxicities such as nephrotoxicity, ototoxicity and neurotoxicity can be severe and many times irreversible. In its early days, Privo discussed the best choice for its active ingredient with its advisor at the time, Dr. Jos Baselga at Bostons Mass General Hospital (MGH). Dr. Baselga, a renowned cancer researcher and the chief of hematology/oncology at MGH, recommended using cisplatin. He noted that cisplatin is a beast of a cancer drug and if tamed, it can be extremely effective in destroying cancer cells. Privo optimized the use of cisplatin to reduce its nasty systemic side effects while significantly improving its efficacy by its ability to directly deliver high concentrations of cisplatin to the tumor. This is like an atomic bomb applied specifically to the tumor, sparing the patients healthy tissues.

Alex: Nanomedicine is a frequently overused word, and it defines a very broad field. How do your group and your consortium of collaborators fit into this field?

We use both nano- and micro-particles in our matrix as part of our two-stage release platform technology. We design the particles with specific properties such as surface chemistry and size. The nano- and micro-particles can be programmed to control the release of the active ingredient based on the treatment requirements. In addition, the particle-containing polymeric matrix further protects the particles, allowing for longer lasting drugs following administration. For example, cisplatin is a very volatile drug which rapidly binds to proteins in the body, causing its deactivation before it can even reach the tumor site and have the chance to destroy cancer cells. Privos PRV111 is designed to protect and effectively insulate the drug for much longer, serving to decrease side effects and increase cellular uptake of the drug. The surface chemistry of the particles can also be optimized to increase cellular uptake further.

Alex: Can you tell me the story behind this paper - how did it come together?

Privo has been collaborating with Dr. Nishant Agrawal from Chicago Medicine since its early development days. I was introduced to Dr. Agrawal via a mutual friend, who was an oncologist that had lost a friend to oral cancer. He saw the potential of our research helping patients suffering from head and neck cancers. Dr. Agrawal is the chief of head and neck surgical oncology team at UChicago Medicine and has been a great mentor to our Privo team in addition to being a champion of our platform technology. Once Privo had successful preclinical data followed by phase 1 / 2 clinical study, the team agreed to publish the results. During the several years of research, Dr. Agrawal has made several introductions to other key opinion leaders such as Dr. Evgeny Izumchenko, an expert head and neck researcher at the University of Chicago who has been instrumental in compiling and publishing the data.

Alex: How much impact will this study have on patient lives once the technology reaches the market?

I think Privos technology has the potential to disrupt the treatment paradigm for several cancers starting with mucosal cancers such as oral, lung, cervical, and even brain tumors.

In todays world, social media has provided an unbiased, uncomfortable, and often raw insight into what a cancer patients journey is like. Over the past several years, we have followed a few oral cancer patients on their journey from initial diagnosis, treatment, surgery, physical therapy in addition to their mental health journey at each step of the road. Oral cancer has one of the highest suicide rates among cancers, and is second only to pancreatic cancer in terms of quality of life. Considering the accessibility of oral cancer, we aim to provide patients with a better alternative that offers them a better quality of life. Our data collected to date has shown that PRV111 has significantly reduced tumor volume for patients with T1/T2 stage tumors. In our Phase 3 design, we aim to target an early form of oral cancer, carcinoma in situ, where our goal is to eliminate the need for surgery indefinitely.

Alex: Are you planning to commercialize the technology and what are your plans to take it to market?

We are planning to commercialize the technology, especially after the successful first-in-human trial, which showed that PRV111 treatment performed better than expected, leading to early completion of the study. On average, PRV111 treatment decreased tumor volume by about 70% in just one week. Privo has successfully received support and collaboration from the FDA-OOPD, the NIH-NCI, the NIH-NIDCR, and the NSF. Their guidance and support is helping us be well on our way toward market approval.

In principle, this novel mucoadhesive system can be engineered to deliver virtually any chemotherapy and non-chemotherapy agent with a particular drug release profile, making it customizable for specific clinical applications. The unique properties of this carefully designed nanomedicine provide a promising framework and holds potential for the improved treatment of not only oral accessible cancers but also other solid malignancies.

Professor Alexander T Pearson, MD, PhD, Professor Evgeny Izumchenko, PhD, Alex Zhavoronkov, PhD at ... [+] the University of Chicago

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Going Beyond Target Or Mechanism Of Disease: Disruptive Innovation In Drug Delivery Systems - Forbes

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Nanomedicine Market Size, Share, Types, Products, Trends, Growth, Applications and Forecast 2022 to 2028 – Digital Journal

Monday, September 12th, 2022

The Global Nanomedicine Market 2022 research report presents an in-depth analysis of the Nanomedicine Market size, growth, share, segments, manufacturers, and forecast, competition landscape and growth opportunity. The researchs goal is to provide market data and strategic insights to help decision-makers to make educated investment decisions while also identifying potential gaps and development possibilities.We also analysed the impact of COVID-19 (Corona Virus) on the product industry chain based on the upstream and downstream markets, on various regions and major countries and on the future development of the industry are pointed out.

The market size was determined by estimating the market through a top-down and bottom-up approach, which was further validated with industry interviews. Considering the nature of the market we derived it by segment aggregation, the contribution of the materials and vendor share.

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Companies involved in theNanomedicine Market research report are:

What exactly is included in the Report?

Industry Trends and Developments:In this section, the authors of the research discuss the significant trends and developments that are occurring in the Nanomedicine Market place, as well as their expected impact on the overall growth.

Analysis of the industrys size and forecast:The industry analysts have provided information on the size of the industry from both a value and volume standpoint, including historical, present and projected figures.

Future Prospects:In this portion of the study, Nanomedicine Market participants are presented with information about the prospects that the Nanomedicine Market industry is likely to supply them with.

The Competitive Landscape:This section of the study sheds light on the competitive landscape of the Nanomedicine Market by examining the important strategies implemented by vendors to strengthen their position in the Nanomedicine Market.

Study on Industry Segmentation:This section of the study contains a detailed overview of the important Nanomedicine Market segments, which include product type, application, and vertical, among others.

In-Depth Regional Analysis:Vendors are provided with in-depth information about high-growth regions and their particular countries, allowing them to place their money in more profitable areas.

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Nano-preterm infants may not benefit from noninvasive versus invasive ventilation at birth – University of Alabama at Birmingham

Monday, September 12th, 2022

Noninvasive ventilation is possible in infants at limits of viability. But unlike in slightly older preterm infants, noninvasive ventilation did not show an advantage in infants of 22 weeks-0 days to 23 weeks-6 days gestational age.

Vivek Shukla, right, and Brian Sims, left, help hold Guinness World Records Certificate for Most Premature Baby to Survive, awarded in honor of mother Michelle Butler and child Curtis Means, born at 21 weeks gestation (center). Adults are masked for COVID precautions in 2021. Photography: Andrea MabryExtremely premature infants still face daunting risks of sickness or death, even though advances in neonatal-perinatal care have improved infant survival at progressively lower gestational ages. Bronchopulmonary dysplasia a serious condition of undeveloped lungs is a leading morbidity in these tiny infants.

Studies have shown that noninvasive respiratory support at birth rather than immediate intubation and delivery of lung surfactant improves short-term respiratory outcomes in premature infants born at gestational age 24 weeks-0 days to 27 weeks-6 days.

So, clinicians at the University of Alabama at Birmingham led by Charitharth Vivek Lal, M.D., and Vivek Shukla, M.D., asked whether the same was true for the tiny newborns at the limits of viability, whom they categorize as nano-preterm infants those born at gestational age 22 weeks-0 days to 23 weeks-6 days. These nano-preterms compose a highly specialized niche subgroup that is considerably more immature and has much higher risks of mortality and morbidity than the 24- through 27-week gestational age preterms, Lal says.

A full-term pregnancy is 39 to 40 weeks.

In one of the largest studies of this population, UAB researchers did a retrospective analysis of 230 consecutively born, eligible nano-preterm infants born from January 2014 through June 2021 at the UAB level IV neonatal intensive care unit. Eighty-eight infants in the noninvasive group were those whose first intubation attempt was more than 10 minutes after birth, and 142 infants in the invasive respiratory support at birth were those intubated within 10 minutes after birth. Unlike in several previous studies of slightly older pre-term infants, Lal and colleagues found no benefits for the noninvasive respiratory support of those nano-preterm infants, as measured by the composite outcome of bronchopulmonary dysplasia or death by 36 weeks postmenstrual age.

Vivek Lal, M.D.Some 94.3 percent of the noninvasive group and 90.9 percent of the invasive group had bronchopulmonary dysplasia or death by 36 weeks, which was not a significant difference. The clinicians did see that severe intraventricular hemorrhage or death by 36 weeks was lower in the invasive respiratory support group, a trend that will require a larger number of infants to confirm.

This cohort studys findings suggest that noninvasive respiratory support in the first 10 minutes after birth is feasible but may not be associated with a decrease in the risk of bronchopulmonary dysplasia or death compared with intubation and early surfactant delivery in nano-preterm infants, said Lal, an associate professor in the UAB Department of Pediatrics, Division of Neonatology. Shukla is an assistant professor in the Division of Neonatology.

The average weight of the noninvasive nano-preterm infants was 1 pound 4.4 ounces, and the average weight of the invasive preterm infants was 1 pound 2.4 ounces.

The study, Hospital and neurodevelopmental outcomes in nano-preterm infants receiving invasive vs noninvasive ventilation at birth, is published in the journal JAMA Network Open.

Co-authors with Lal and Shukla are Grant Imbrock, Colm P. Travers, Namasivayam Ambalavanan and Waldemar A. Carlo, UAB Department of Pediatrics, Division of Neonatology; and J. Paige Souder, Muhan Hu and A.K.M. Fazlur Rahman, Department of Biostatistics, UAB School of Public Health.

Support came from National Institutes of Health grant HL141652, UAB and Childrens of Alabama.

Pediatrics is a department in the Marnix E. Heersink School of Medicine at UAB.

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Nano-preterm infants may not benefit from noninvasive versus invasive ventilation at birth - University of Alabama at Birmingham

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Juan De Borbon – Introducing Cutting-Edge Techniques To The Healthcare Industry – CEOWORLD magazine

Monday, September 12th, 2022

Spanish-American clinical research executive Juan de Borbn resides in the United States. He has vast experience running nearly 2000 clinical trials in various therapeutic fields. These include cancer, nephrology, hepatology, infectious illness (Covid-19, Ebola, Marburg, Influenza, HIV, Hepatitis), and neurology. Juan de Borbn has been inspiring and motivating the clinical drug development sector for more than 20 years by utilizing his extensive industry knowledge.

Alfonso XIII of Spains senior great-grandson Juan de Borbn is his matrilineal direct descendant. King Alfonso XIII of Spain and his wife, Princess Victoria Eugenie of Battenberg, had a son, Alfonso, the oldest of five siblings. Alfonso, Prince of Asturias, who lived from 10 May 1907 to 6 September 1938, was the presumptive heir to the Spanish crown and grandfather to Juan. At the time, Alfonsos renunciation and untimely death as the heir to Spains monarchy sparked debate. King Felipe VI of Spain, his cousin, now sits the Spanish throne.

At the age of two months, Juan de Borbn immigrated to the US and spent his formative years in Los Angeles. Growing up, he practiced martial arts, surfed, skateboarded, and shared a deep passion for baseball with his father. His parents wished for him to have a wider variety of experiences and a deeper appreciation of his roots. Today, he is a top-ranking CEO honored for his accomplishments and model leadership by the business, his employers, and coworkers; Juan now holds the positions of Principal and President of Global Strategy at Global Earth USA, Executive Chairman of Borbon dAnjou Holdings, and Principal of the Borbon Family Office.

He is a compassionate leader who upholds the principles of integrity, honesty, and creativity, collaborating directly with Nano Cures Pharma in 2021 to provide Covid-19 vaccinations to underserved countriesworking now with Thailand and the Central African Republic to obtain Emergency Use Authorization for the vaccination in those nations.

Juan de Borbn established the first American Heart Training Center in a Clinical pharmacology facility in 2017, guaranteeing the best level of staff training in acute care for research participants. He combined WCCT with Medelis, an institution that conducts oncology clinical research, in 2016. The deal focused on the complex and quickly expanding oncology drug development industry in the United States, Europe, and Asia. This requires a unique answer with knowledge, insight, and a focus on the future.

With a focus on oncology, ophthalmology, gastroenterology, gastrointestinal, renal, hepatic, and virology, Juan de Borbn created a multisite management service offering CRO Services for WCCT in 2014. This service provided data processing, statistics, medical monitoring, drug safety, tracking, site selection, and site management. He established the early clinical research facilities for cosmetology and ophthalmology in 2013 and combined OC Clinical Trials & Consulting with WCCT Global.

Juan believes that the era of doing regular activities in healthcare is finished. Despite the tireless efforts of well-meaning, well-trained professionals, every health care system in the world is battling escalating prices and unequal quality. Health care leaders and policymakers have attempted to combat fraud, reduce errors, enforcing practice guidelines, improve patient consumers, and deploy electronic medical records. Still, none of them have had much of an impact. It is time for a whole different approach.

He is focused on shifting from a supply-driven, physician-centered healthcare system to one that is patient-centered, patient-centered, and organized around patient needs. A system where services for specific medical diseases are focused in health-delivery organizations and in the appropriate places to deliver high-value care must be put in place to replace the fragmented system of today, in which every local provider offers a broad range of services. The volume and financial success of the services providedphysician visits, hospital stays, operations, and testsmust be shifted to the success of the patient outcomes.

Juan aims to launch the worlds first medical metropolis to promote lifespan and good health while utilizing information and communications technology for the exchange of reliable data for the assessment, care, and prevention of illness and injuries, research, and evaluation, as well as for the continuing education of health care professionals, all to improve the health of people and their communities. Additionally, it is intended to assist the patient in maintaining their performance level throughout their entire lifespan. The main risk factor for most diseases is advancing age, particularly of cellular structures, and life expectancy in the population is still rising.

Juan emphasizes that the cutting-edge longevity center offers tailored preventative medicine by implementing methods to promote healthy aging, delay diseases primarily related to aging, and lengthen a persons active time of life. Providers who continue to use the outdated methods of today will go extinct. Reputations that are built on perception rather than actual results will deteriorate. In the face of increased openness and declining reimbursement levels, maintaining present cost structures and prices will be impossible. The only reputation that should matter in health care is assisting people in leading the healthiest and longest-lasting lives possible.

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Juan De Borbon - Introducing Cutting-Edge Techniques To The Healthcare Industry - CEOWORLD magazine

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Organic thin-film sensors for light-source analysis and anti-counterfeiting applications – Nanowerk

Monday, September 12th, 2022

Sep 05, 2022(Nanowerk News) In a recent publication in the scientific journal Advanced Materials ("Accurate Wavelength Tracking by Exciton Spin Mixing"), a team of physicists and chemists from TU Dresden presents an organic thin-film sensor that describes a completely new way of identifying the wavelength of light and achieves a spectral resolution below one nanometer.As integrated components, the thin-film sensors could eliminate the need for external spectrometers in the future. A patent application has already been filed for the novel technology.The active film for the novel sensor concept is only as thick as a human hair, here processed on thin glass substrates, and exhibits a wavelength-dependent luminescence. (Image: Anton Kirch)Spectroscopy comprises a group of experimental methods that decompose radiation according to a specific property, e.g. wavelength or mass. It is considered one of the most important analytical methods in research and industry.Spectrometers can determine colors (wavelengths) of light sources and are used as sensors in various applications, such as medicine, engineering, food industry and many more. Commercially available instruments are usually relatively large and very expensive. They are mostly based on the principle of the prism or grating: light is refracted and the wavelength is assigned according to the angle of refraction.At the Institute for Applied Physics (IAP) and the Dresden Integrated Center for Applied Physics and Photonic Materials (IAPP) of the TU Dresden, such sensor components based on organic semiconductors have been researched for years. With the spin-offs Senorics and PRUUVE, two technologies have already been developed towards market maturity.Now, researchers at the IAP and IAPP, in cooperation with the Institute of Physical Chemistry, have developed a thin-film sensor that describes a completely new way of identifying the wavelength of light and, due to its small size and cost, has clear advantages over commercially available spectrometers.The principle of operation of the novel sensors is as follows: Light of unknown wavelength excites luminescent materials in a hair-thin film. The film consists of a mixture of long-glowing (phosphorescent) and short-glowing (fluorescent) entities, which absorb the light under investigation in different ways. The intensity of the afterglow, can be used to infer the wavelength of the unknown input light."We exploit the fundamental physics of excited states in luminescent materials," explains Anton Kirch, doctoral student at the IAP. "Light of different wavelengths excites in such a system, when properly composed, certain proportions of long-lived triplet and short-lived singlet spin states. And we reverse that dependence. By identifying the spin fractions using a photodetector, we can identify light wavelengths.""The great strength of our research alliance here in Dresden is our partners," says Prof. Sebastian Reineke, who coordinated the project. "Together with the groups of Prof. Alexander Eychmller from Physical Chemistry and Karl Leo, professor of Optoelectronics, we can carry out all the fabrication and analysis steps ourselves, starting with material synthesis and film processing and ending with the fabrication of the organic detector."Dr. Johannes Benduhn is group leader for Organic Sensors and Solar Cells at the IAP: "I was honestly very impressed that a simple photoactive film combined with a photodetector can form such a high-resolution device."Using this strategy, the scientists have achieved sub-nanometer spectral resolution and have successfully tracked minor wavelength changes of light sources. In addition to characterizing light sources, the novel sensors can also be used in counterfeit protection: "The small and inexpensive sensors could be used, for example, to quickly and reliably check banknotes or documents for certain security features and thus determine their authenticity, without any need for expensive laboratory technology," explains Anton Kirch.

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Organic thin-film sensors for light-source analysis and anti-counterfeiting applications - Nanowerk

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Whole Exome Sequencing Market Projected to Reach CAGR of 19.0% Forecast by 2029, Global Trends, Size, Share, Growth, Future Scope and Key Player…

Monday, September 12th, 2022

CHICAGO, Sept. 07, 2022 (GLOBE NEWSWIRE) -- A Qualitative Research Study accomplished by Data Bridge Market research's database of 350 pages, titled as "Global Whole Exome Sequencing Market" with 100+ market data Tables, Pie Charts, Graphs & Figures spread through Pages and easy to understand detailed analysis. This Whole Exome Sequencing report contains a comprehensive data of market definition, classifications, applications, engagements, market drivers and market restraints of this industry all of which is derived from Porte's Five Forces analysis. Market definition covered in this Whole Exome Sequencing report gives the scope of particular product with respect to the driving factors and restraints in the market. The sources of data and information mentioned in the Whole Exome Sequencing report are very reliable and include websites, annual reports of the companies, journals, and mergers which are checked and validated by the market experts.

Global whole exome sequencing market is expected to gain market growth in the forecast period of 2022 to 2029. Data Bridge Market Research analyses that the market is growing with a CAGR of 19.0% in the forecast period of 2022 to 2029. The increase in healthcare expenditure and funding are the major drivers which propelled the demand of the market in the forecast period.

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MarketSynopsis:-

Whole exome is a genomic technique for sequencing the entire protein-coding region of genes in a genome. Whole exome sequencing is available to patients who are searching for a unifying diagnosis for multiple medical conditions. A laboratory process that is used to determine the nucleotide sequence primarily of the exonic (or protein-coding) regions of an individuals genome and related sequences, representing approximately 1% of the complete DNA sequence, also called WES. Whole-exome sequencing is a widely used whole exome sequencing method that involves sequencing the protein-coding regions of the genome. The human exome represents less than 2% of the genome, but contains ~85% of known disease-related variants, making this method a cost-effective alternative to whole-genome sequencing.

Exome sequencing using exome enrichment can efficiently detect coding variants across a wide range of applications, including population genetics, genetic disease and cancer studies. The growth of the global whole exome sequencing market is attributed to the reduction in time and cost for sequencing. With the development of new technologies and cancer cure treatment, the whole exome sequencing market in clinical oncology has huge potential in the coming years.

The major companies which are dealing in the whole exome sequencing market are

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Recent Development

Opportunity

The demand for whole exome sequencing is increasing in the market owing to the increased incidence of geneticdisease along with increased geriatric population across the region. Thus, the top market players have implemented the strategy of collaboration with other market players aimed at improving business operations and profitability.

Global Whole Exome Sequencing Market Segmentation

Global Whole Exome Sequencing Market is segmented on the basis of component, product and service, application, end user and distribution channel. The growth among segments helps you analyze niche pockets of growth and strategies to approach the market and determine your core application areas and the difference in your target markets.

Component

Product and Services

Application

End User

Distribution Channel

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Regional Analysis/insights

The whole exome sequencing market is analyzed and market size information is provided by component, product and service, application, end user and distribution channel.

The countries covered in the whole exome sequencing market report are U.S., Canada, Mexico, Germany, France, Italy, U.K., Spain, Netherlands, Russia, Switzerland, Turkey, Belgium, Rest of Europe, Japan, China, India, South Korea, Australia, Singapore, Malaysia, Thailand, Indonesia, Philippines, Vietnam, Rest of Asia-Pacific, Brazil, Argentina, Rest of South America, Saudi Arabia, South Africa, UAE, Israel, Egypt and Rest of Middle East & Africa.

North America is dominating due to the presence of key market players along the largest consumer market with high GDP. U.S. is expected to grow due to rise in technological advancement.

Key Industry Drivers:-

Drivers

As genomics-focused pharmacology continues to play a greater role in the treatment of various chronic diseases especially cancer,next-generation sequencing(NGS) is evolving as a powerful tool for providing a deeper and more precise insight at molecular underpinnings of individual tumours and specific receptors.

NGS offers advantages in accuracy, sensitivity and speed compared to traditional methods that have the potential to make a significant impact on the field of oncology. Because NGS can assess multiple genes in a single assay, the need to order multiple tests to identify the causative mutation is eliminated.

As genomics-focused pharmacology continues to play a greater role in the treatment of various chronic diseases especially cancer, next-generation sequencing (NGS) is evolving as a powerful tool for providing a deeper and more precise insight at molecular underpinnings of individual tumours and specific receptors.

NGS offers advantages in accuracy, sensitivity and speed compared to traditional methods that have the potential to make a significant impact on the field of oncology. Because NGS can assess multiple genes in a single assay, the need to order multiple tests to identify the causative mutation is eliminated.

Points Covered in Table of Content of Global Whole Exome Sequencing Market:

Chapter 1: Report Overview

Chapter 2: Global Market Growth Trends

Chapter 3: Value Chain of Whole Exome Sequencing Market

Chapter 4: Players Profiles

Chapter 5: Global Whole Exome Sequencing Market Analysis by Regions

Chapter 6: North America Whole Exome Sequencing Market Analysis by Countries

Chapter 7: Europe Whole Exome Sequencing Market Analysis by Countries

Chapter 8: Asia-Pacific Whole Exome Sequencing Market Analysis by Countries

Chapter 9: Middle East and Africa Whole Exome Sequencing Market Analysis by Countries

Chapter 10: South America Whole Exome Sequencing Market Analysis by Countries

Chapter 11: Global Whole Exome Sequencing Market Segment by Types

Chapter 12: Global Whole Exome Sequencing Market Segment by Applications

Check Complete Table of Contents @ https://www.databridgemarketresearch.com/toc/?dbmr=global-whole-exome-sequencing-market

Key Coverage in the Whole Exome Sequencing Market Report

Detailed analysis of Global Whole Exome Sequencing Market by a thorough assessment of the technology, product type, application, and other key segments of the report

Qualitative and quantitative analysis of the market along with CAGR calculation for the forecast period

Investigative study of the market dynamics including drivers, opportunities, restraints, and limitations that can influence the market growth

Comprehensive analysis of the regions of the Whole Exome Sequencing industry and their futuristic growth outlook

Competitive landscape benchmarking with key coverage of company profiles, product portfolio, and business expansion strategies

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Whole Exome Sequencing Market Projected to Reach CAGR of 19.0% Forecast by 2029, Global Trends, Size, Share, Growth, Future Scope and Key Player...

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Another ‘Dr. Copper’ – MINING.COM – MINING.com

Monday, September 12th, 2022

Clifford has a background in materials engineering, worked for Teck as an undergrad student on a co-op doing corrosion studies on base metals, and became an expert on functional coatings for biomaterials.

Copper alloy surfaces are naturally antimicrobial with self-sanitizing properties, and research showed these surfaces eliminate up to 99.9% of harmful bacteria and viruses but there was a lag time in killing gram positive bacteria and that was the challenge to overcome.

My idea was for copper it has one limitation that it kills gram positive more slowly, if we could change the surface chemistry, the topography or roughness, we can kill bacteria more quickly, Clifford told MINING.com.

One way we can do this, is copper is antimicrobial because its actually corroding very slowly, so its not copper in a zero state oxidation thats antimicrobial, its positively charged copper ions that kill bacteria.

The Coptek covid killing copper coating that has been deployed at most of the Applied Science buildings on the UBC campus and at the British Columbia Institute of Technology was funded by Tecks Copper & Health program. The formula came from the surface engineering Dr. Clifford and her research team Dr. Edouard Asselin, Dr. Elizabeth Bryce, and Dr. Marthe Charles developed a collaboration between the Department of Materials Engineering and the Faculty of Medicine at the University of British Columbia.

The study was published inJuly in Advanced Materials Interfaces.

What the team did to mitigate the lag time in killing bacteria with pure copper while its corrodes or oxidizes, was couple two dissimilar metals, in this case zinc, which due to the different reduction potential corrodes first.

That gets things going its spontaneous, the zinc will just start corroding and then the copper will corrode. It got everything going and we got a lot better results. Another thing we did was add nano-scale roughness, Clifford said.

That idea came from knowing that certain insects and reptiles skins have nanoscale roughness, which are naturally anti-bacterial.

For our coating we took copper and zinc and added this nanoscale roughness, and now all of a sudden its overcoming the issue of killing gram positive bacteria slowly and now its killing 99.7% within an hour, so half the time, Clifford said.

The coating could significantly reduce the incidence of contracting bacterial infections from high-touch surfaces in healthcare facilities and other public spaces.

The next phase is to do a trial in hospitals where the germ killing copper could have the most impact. Clifford said the strategy is to combat antibiotic resistance which can lead to superbugs afflicting patients who are already sick.

Part of that is decreasing the overall amount of pathogens and antibiotic resistant bugs that are already in public spaces, so this coating has that.

The team is still studying how the coating works on other viruses in the hopes of making a bigger impact.

Almost all the principles that were used to make this medical innovation were just pure metallurgical engineering applied to a medical application, Clifford pointed out.People who think that metallurgical mining engineering has a very niche application the tools that you learn you can also apply to other applications such as medicine.

Clifford didnt realize the idea she had walking home from the subway that winter day would be developed to the point where it would be deployed on university campuses and next in hospitals.

As an academic you can make educated guesses, she said.

I thought it would work, and it did.

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Another 'Dr. Copper' - MINING.COM - MINING.com

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Artemisinin Combination Therapy Market Insights and Emerging Trends by 2027 – BioSpace

Friday, August 19th, 2022

Wilmington, Delaware, United States, Transparency Market Research Inc. The conventional low-priced mainstay drugs for the treatment of malaria, sulphadoxine-pyrimethamine (SP) and chloroquine (CQ), are witnessing a decline in sales, as they are becoming comparatively ineffective. During the last two decades in Asia, the issue has become a major concern. This has resulted in the adoption of artemisinin (derived from the Chinese herb Artemisia annua) in Africa as a standard treatment.

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It helped in setting a milestone for the artemisinin combination therapy market. The herb has been used to treat fevers and malaria for more than 2000 years. The World Health Organization (WHO) has adopted artemisinin-based combination therapy (ACTs) as the first-line treatment for plasmodium falciparum malaria.

As a combination therapy, it has demonstrated superiority to other drugs because of its ability to wipe out parasites and its life cycle stages faster. Its use with cancer transferrin to cure cancer is also adding value to the artemisinin combination therapy market.

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Triple ACTs (TACTs) combine with artemisinin and two other existing partner drugs to work effectively as stop-gap therapy for the treatment of multidrug-resistant malaria. It will be used till the arrival of new antimalarial drugs. TACTs are secure, competent, well-accepted, and economical. This artemisinin combination therapy is likely to gain wider acceptance among the target consumers. The barriers in the deployment should be identified and stakeholders should make efforts to overcome them, which will new growth avenues in artemisinin combination therapy market.

Artemisinin Combination Therapy Market Introduction

Artemisinin is a plant derivative isolated from Artemisia annua, or sweet wormwood, which is known to effectively and swiftly reduce the number of plasmodium parasites in the blood of malaria patients. The WHO recommends artemisinin combination therapies (ACTs) as the first line of treatment for uncomplicated plasmodium falciparum malaria and as the second line of treatment for chloroquine-resistant P. vivax malaria.

This therapy combines an artemisinin derivative along with a partner drug, wherein artemisinin aids in reducing the number of parasites and the partner drug eliminates the remaining parasites. Efficacy of the treatment is determined by the drug combined with artemisinin, such as artesunate-mefloquine, dihydroartemisininpiperaquine, and artemether-lumefantrine.

Falciparum malaria was one of the most common lethal infections which was treated with chloroquine and sulfadoxine-pyrimethamine. However, these drugs are not effective as treatment primarily in the tropical regions owing to the resistance developed against these drugs. According to the Medicines Malaria Venture (MMV), over 445,000 deaths were reported in 2016 due to malaria. The globally rising malaria endemic and the changing climatic conditions would contribute to the trend aiding in the artemisinin combination therapy market growth.

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Artemisinin Combination Therapy Market- Competitive Landscape

The strategies adopted by the market players to enhance their market position include indication extension, focus on geographic expansion, and research & development. The national funding allocations, as announced by the Global Fund for 2018-2020, report that the funding available for the promotion of malaria programs is around US$1 billion.

Novartis AG

Novartis AG, established in 1895, is engaged in research, development, manufacturing and marketing of healthcare products across a range of areas, including neuroscience, ophthalmology, immunology, hepatology, respiratory, cardiology, dermatology, and cardio metabolic.

Sanofi

Sanofi, a leading pharmaceutical company is engaged in the manufacturing of prescription pharmaceuticals and vaccines. It is engaged in the development of cardiovascular, metabolic disorder, central nervous system (CNS), oncology, and thrombosis drugs and medicines.

Ipca Laboratories Ltd.

Ipca Laboratories is an Indian pharmaceutical company engaged in the manufacturing of over 350 formulations and 80 APIs for a range of therapeutic indications. According to the company, it is the market leader in India for anti-malarials with a market share of over 34% in 2018.

Artemisinin Combination Therapy Market - Dynamics

Growing malaria endemic

Malaria is a major health concern in endemic countries such as Sudan, wherein over 75% of the population is at the risk of acquiring the disease. Moreover, the widespread presence of chloroquine-resistant strains of P. falciparum in the malaria endemic countries makes artemisinin combination therapy the preferred choice of treatment. This is projected to fuel the growth of the artemisinin combination therapy market.

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Increase in the procurement of ACT treatment courses

Increase in access to ACTs in the malaria-endemic countries contributes to the rising success in reducing the global malaria burden. According to the WHO, over 2.7 billion ACT treatment courses were procured by global countries between 2010 and 2017. Moreover, over 62% of these procurements were made by the public sector. Strong pipeline for the development of new anti-malarial drugs and launch of newer artemisinin combinations for the treatment of malaria boost to the growth of the global artemisinin combination therapy market.

Challenges related to the availability of raw materials

Challenges pertaining to the availability of intermediate products and raw materials in the production of artemisinin-based combination therapies from agricultural sources are expected to restrain the global artemisinin combination therapy market. Furthermore, volatility in the artemisinin market leading to concerns over supply tightening could create significant risks to patients and market participants.

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NASEM Recommends That EPA Conduct Ecological Risk Assessment of UV Filters Found in Sunscreen, Including Titanium Oxide and Zinc Oxide – JD Supra

Friday, August 19th, 2022

The National Academies of Sciences, Engineering, and Medicine (NASEM) released on August 9, 2022, a report entitled Review of Fate, Exposure, and Effects of Sunscreens in Aquatic Environments and Implications for Sunscreen Usage and Human Health. NASEM was tasked by Congress and funded by the U.S. Environmental Protection Agency (EPA) to undertake a consensus study of the potential risk of ultraviolet (UV) filters on already threatened aquatic environments and the potential consequence to human health should sunscreen usage or composition be modified. NASEMs report reviews the state of science on the sources and inputs, fate, exposure, and effects of UV filters in aquatic environments, and the availability and applicability of data for conducting ecological risk assessments (ERA). It also reviews the epidemiological and clinical literature on the efficacy of sunscreen in preventing UV damage to human skin, the state of knowledge on potential human behavior changes, and the resulting health impacts related to skin cancer prevention from changes in sunscreen usage (e.g., reducing sunscreen use or switching to sunscreens with different active ingredients).

NASEM notes that the scope of the study is limited to the United States. According to the report, there are currently 16 UV filters allowed by the U.S. Food and Drug Administration (FDA) for use in any sunscreen sold in the United States, plus an additional proprietary UV filter, ecamsule, approved for use in limited products. While UV filters are used in a broad range of products, NASEMs scope was to focus on their use in sunscreens. The 16 UV filters include two inorganic UV filters, titanium dioxide and zinc oxide. The summary of the attributes of UV filters relevant for assessment of environmental risk includes the following information for titanium oxide and zinc oxide:

[View source.]

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NASEM Recommends That EPA Conduct Ecological Risk Assessment of UV Filters Found in Sunscreen, Including Titanium Oxide and Zinc Oxide - JD Supra

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Fast and noninvasive electronic nose for sniffing out COVID-19 based on exhaled breath-print recognition | npj Digital Medicine – Nature.com

Friday, August 19th, 2022

For the GeNose C19 sensor array, the sensitivity of each sensor during exposure to varying VOC concentrations depends on the used active material. Moreover, the sensor behaviors might be slightly altered when they were tested to the breath samples from different patients, although they were from the same group (either positive or negative COVID-19). This occurrence could be understood because the content and complexity of the exhaled VOCs are diverse, as discovered in another breath analysis study using GCIMS24. Several VOC biomarkers could be identified as the discriminants for distinguishing between positive and negative COVID-19 patients (e.g., ethanal, acetone, acetone/2-butanone cluster, 2-butanone, methanol monomer and dimer, octanal, feature 144, isoprene, heptanal, propanol, and propanal)24. Nonetheless, the compounds observed from two different hospitals (i.e., Edinburgh, the United Kingdom (UK), and Dortmund, Germany) in their study were dissimilar for the same case of COVID-19 patients, which then added more complexity in analyzing the obtained breath data. These limitations were due to uncertainties in the instrument setup, operating conditions, and background contamination levels.

Thus far, a detailed study in those matters has not been performed. Meanwhile, another clinical GCIMS study conducted by researchers in Beijing, China, suggested several other potential breath-borne VOC biomarkers for COVID-19 (i.e., acetone (C3H6O), ethyl butanoate, butyraldehyde, and isopropanol)72. They found that the decrease and increase in acetone (C3H6O) and ethyl butanoate levels, respectively, due to the changes in metabolites resulting from SARS-CoV-2 infections, are distinctive for COVID-19 patients72,73. Moreover, the average measured isopropanol and butyraldehyde for the COVID-19 patients were lower than those for the healthy control and lung cancer and non-COVID-19 respiratory infection patients. The metabolomics of exhaled breaths in critically ill COVID-19 patients were also investigated from a research consortium in France using a proton transfer reaction quadrupole time-of-flight mass spectrometer74. They observed four prominent VOCs (i.e., methylpent-2-enal, 2,4-octadiene, 1-chloroheptane, and nonanal) that could discriminate between COVID-19 and non-COVID-19 acute respiratory distress syndrome patients74. Overall, the reported MS studies in several different countries (i.e., UK, Germany, France, and China) indicate that the distinctive VOC biomarkers for COVID-19 may vary across the world and should be further investigated based on the community, race, and cases with large cohorts75.

In contrast to the MS method that attempts to quantitatively find and identify the exact VOC biomarkers from exhaled breaths, our technique used in GeNose C19 focuses more on the AI-based pattern analysis of integrated sensor responses to complex VOCs, qualitatively resulting from the combined extra-pulmonary metabolic and gastrointestinal manifestations of COVID-1976. Thus, the breath data analysis and decision-making procedure can be performed in a simple way and short time, respectively, with a high detection accuracy. To enable this, besides having a high sensitivity, chemoresistive sensors should ideally be designed to possess a high selectivity to a specific analyte in a gas mixture and zero cross-sensitivity to other compounds in the operating background. Such sensors were normally constructed in hybrid organic/inorganic structures with 3D nano-architectures (e.g., nanofibers, nanowires, and nanofins), enhancing the active surface-area-to-volume ratios77,78. Here, the surfaces of semiconductor nanostructures were often functionalized with certain self-assembled monolayers or polymers to specifically detect the target gas molecules32,34,79. Nevertheless, these organic materials suffer from low robustness. They are all well-known to degrade within a short duration of use (i.e., their chemical compositions will alter downgrading the sensor performance). As a result, pure inorganic materials (metal oxide semiconductors) are still preferably manufactured by sensor companies and widely used in gas sensing applications, including in the GeNose 19 system. Here, a single sensor alone is not sufficient for performing a specific breath pattern recognition because exhaled VOCs might have similar characteristics. This selectivity drawback could be alleviated by employing an array of 10 sensors with different sensitivities and integrating the machine learning-based breath pattern recognition algorithms.

Furthermore, to demonstrate the proof of concept ability of GeNose C19 for detecting VOCs in human breaths, we performed additional sensing assessments for acetone vapors in a modified test setup (see Supplementary Fig. 2). However, COVID-19 itself cannot be detected by simply sensing or measuring the acetone alone. This testing was mainly dedicated to demonstrate that the GeNose C19 sensor array can detect one of the VOCs normally contained in human breaths and exhibits different sensitivity levels when exposed to various gas concentration levels, which also mimics the real case of exhaled breaths from different persons or patients. The gas sensing configuration for the acetone testing, which utilizes a microsyringe for vapor injection, has already been used in our former experiments for other VOC sensor types (e.g., nanofiber-functionalized QCMs for sensing trimethylamine and butanol gases)35,80,81. Acetone was chosen as a VOC model in this additional study because it is not only produced in the rebreathed breath (0.8 to 2.0 ppm)82, along with other VOCs (alcohol) and CO, but is also one of the significant breath-borne COVID-19 biomarkers based on the study by Chen et al.72. Moreover, in clinical practices, breath-containing acetone has been extensively examined to diagnose other diseases (i.e., lung cancer, diabetes mellitus, starvation, and ketogenic diet)83.

As shown in Supplementary Fig. 2b, c, the S3 and S7 sensors (or their extracted features of F3 and F7) demonstrated the poorest responses toward acetone vapors. Conversely, the S2, S8, and S9 sensors exhibited higher sensitivities than the others. The sensor output signals given by the GeNose C19 data acquisition system agree well with those measured by a calibrated digital voltmeter. Increasing the acetone vapor concentrations from 0.04 to 0.1L with 0.02 intervals resulted in higher responses of the three sensors (S2, S8, and S9), whereas the S3 and S7 sensors were irresponsive (see Supplementary Fig. 2d). In particular, each vapor concentration was measured 10 times to acquire quantitative results. Lastly, as depicted in Supplementary Fig. 2e, LDA discriminated the output voltages produced by the sensors during their exposures to four different acetone concentrations (i.e., 0.040.1L).

In terms of ambient conditions, temperature and humidity might influence the performances of metal oxide semiconductor sensors84. Thus, to investigate their effect, we also performed cross-sensitivity assessments in respect to the two parameters for all the employed GeNose C19 sensors (see Supplementary Figs. 3 and 4). This testing is important because depending on the sensitivities of the sensors toward temperature and humidity, the obtained sensor results during the breath analysis can be disturbed, leading to a difficult interpretation of the data. Moreover, if the sensors are too reactive to the two ambient parameters, the measured data can then be unreliable to analyze the effect of VOCs in the human breath because changes in the signals were mainly affected by the temperature and humidity, not the target gases. Such a cross-sensitivity is a common reliability test for gas sensors. For GeNose C19, the environmental effect can be minimalized and controlled by performing two main procedures. First, environmental checking needs to be conducted while placing GeNose C19 in the measurement room/area. Here, the selection of the machine placement (analysis on air circulation, humidity, and temperature) plays a key role in maintaining good-quality results. GeNose C19 could sense the environmental humidity and temperature levels by utilizing humidity and temperature sensors integrated inside the system. The measurement was displayed in the program interface. Hence, the user or operator could notice the condition. In a real situation during breath sampling, the machine could only be operated if the humidity and temperature inside the chamber were in the ranges of 3050% and 2642C, as defined by the AI-based program in the system. Such a setting is adjustable to meet future demand and placement environments. Second, after checking the environmental condition, the baseline normalization protocol during the sample analysis can be done (see Methods on the GeNose preconditioning). During the AI interpretation of the VOC patterns, several protocols were employed, including signal baseline normalization. By performing baseline normalization, all the sensors that behaved and started from different baselines in different environments can always be calibrated to the standard normalization. Hence, the adaptability of the machine can be improved in new foreign environments.

In the case of acetone testing, the sensors yielded similar responses from three repeated measurements, indicating their reliable sensing results. The sensor resistance decreased (i.e., a higher output voltage was obtained) when the temperature was ramped up from 40C to 46C, and the humidity was kept stable at (30%1%) RH (see Supplementary Fig. 3). Different from silicon micromechanical resonant sensors that have frequency shift interferences caused by the temperature-induced Youngs modulus change (material softening)37,85, the resistance decrease in the employed metal oxide semiconductor sensors (e.g., n-type SnO2 with a bandgap of 3.6eV) at high temperatures was caused by the increasing number of electrons that have sufficient energy crossing to the conduction band and thus contributing to the conductivity86. Because this is a natural characteristic of semiconductor materials, we could overcome this effect in GeNose C19 by controlling the temperature inside the test chamber at relatively stable values (i.e., (42C2C)) during the sensing phase of the exhaled breath.

Similar to the trend shown in the cross-temperature test, the sensor resistance also dropped to a lower value, resulting in a higher output voltage when the relative humidity was raised from 30% to 35% and the temperature was set constant at (40C1C) (see Supplementary Fig. 4). The electrical characteristics of metal oxide semiconductors changed due to the water adsorption on their surface while being exposed to humid air. Two different mechanisms of chemisorption and physisorption processes took place to create the first layer (i.e., chemisorbed layer) and its subsequent films of water molecules (i.e., physisorbed water layers), respectively87. If the first chemisorbed layer has been formed, then the successive layers of water molecules will be physically adsorbed on the first hydroxyl layer. Because of the high electrostatic fields in the chemisorbed layer, the dissociation of physisorbed water can easily occur, producing hydronium ion (H3O+) groups. Here, the conduction mechanism relies on the coverage of adsorbed water on the metal oxide semiconductor. First, in the event only hydroxyl ions exist on the metal oxide surface, the charge carriers of protons (H+) resulting from hydroxyl dissociation will hop between adjacent hydroxyl groups. Second, after the water molecules have been adsorbed but not fully covered the oxide surfaces, the charge transfer will be dominated by H3O+ diffusion on hydroxyl groups, despite the occurring proton transfer between adjacent water molecules in clusters. Finally, once the continuous film of the first physisorbed water has been formed (i.e., full coverage of metal oxide by the physisorbed water layer), proton hopping between neighboring water molecules in the continuous film will be responsible for the charge transport88. More detailed explanations of the sensing mechanism and adsorption of water molecules on metal oxide semiconductor surfaces are described elsewhere84,87,88. Again, in the conducted cross-sensitivity measurements (Supplementary Fig. 4), the signal changes of the GeNose C19 sensors affected by humidity are relatively lower (i.e., <100mV) compared to those exposed to exhaled breaths (i.e., ~1V, as shown in Fig. 3a, b). Thus, temperature and humidity will insignificantly influence the system performance during breath measurements, when GeNose C19 has been well preconditioned.

To confirm the performance of our GeNose C19, RT-qPCR was used as the reference standard on the basis of the health service standard protocol underlined by the Indonesian Ministry of Health. Based on the analysis of the RT-qPCR protocol using Bayes theorem, RT-PCR tests cannot be solely relied upon as the gold standard for SARS-CoV-2 diagnosis at scale. Instead, a clinical assessment supported by a range of expert diagnostic tests should be used. Here, although our study mentioned that RT-qPCR was used as the reference standard, clinical data from each patient were also collected and analyzed.

According to a recently published systematic review study, the need for repeated testing in patients with suspicion of SARS-Cov-2 infection was reinforced because up to 54% of COVID-19 patients might have an initial false-negative RT-qPCR89. Meanwhile, in the case of false-positive rates of RT-qPCR, much lower values (i.e., 016.7% with an interquartile range of 0.84.0%)90,91 were exhibited in several studies, which were affected by the quality assurance testing in laboratories. Public Health England also reported that RT-qPCR assays showed a specificity of over 95%, so up to 5% of cases were false positives91. Moreover, the overall false-positive rate of high throughput, automated, sample-to-answer nucleic acid amplification testing on different commercial assays was only 0.04% (3/7,242, 95% CI, 0.01% to 0.12%)92. False-positive SARS-CoV-2 RT-qPCR results could originate from different sources (e.g., contamination during sampling, extraction, PCR amplification, production of lab reagents, cross-reaction with other viruses, sample mix-ups, software problems, data entry errors, and result miscommunication)93. In our case, all the bought and used reagents were checked and calibrated daily to avoid false positives (i.e., no false positive of RT-qPCR result was found in this study). Meanwhile, the false-negative of the RT-qPCR result was found in three patients in their first examination, but positive results were revealed on the second examination the next day. Again, the detailed test procedure can be found in the Methods.

Currently, diagnostic methods used to screen COVID-19 are antigen test, rapid molecular test, and chest CT scan. Antigen tests have an average sensitivity of 56.2% (95% CI: 29.579.8%) and average specificity of 99.5% (95% CI: 98.199.9%)94. The average sensitivity and specificity for the rapid molecular tests are 95.2% (95% CI: 86.798.3%) and 98.9% (95% CI: 97.399.5%), respectively94. Meanwhile, chest CT scan possesses an average sensitivity and specificity of 87.9% (95% CI: 84.690.6%) and 80.0% (95% CI: 74.984.3%), respectively95. Nonetheless, these diagnostic methods have their drawbacks. The average sensitivity of antigen tests is not high, as shown by the study above, and it declines when the viral load decreases, which often happens to COVID-19 patients. Moreover, the sample collection is invasive (by a nasopharyngeal or oropharyngeal swab). Rapid molecular testing also employs an invasive sample collection method (by a nasopharyngeal or oropharyngeal swab), and the turnaround time of point-of-care rapid molecular tests still takes at least 20 min96. Moreover, chest CT scan exposes patients to radiation and is not specific.

Compared to these diagnostic methods, GeNose C19 has the potential to be a screening test. A breath test with the portable GeNose C19 is noninvasive and easy to use because it only requires patients to breathe into a sampling bag with minimal preparation, has a fast analysis time, and does not have radiation concerns. Similar to other biological samplings in several laboratory examinations (e.g., blood glucose sampling and chemical blood analysis), GeNose C19 also requires preparation of subjects before breath sampling, such as fasting (i.e., refraining from eating, smoking, or drinking anything other than water at minimum 1h before sampling). However, the duration of the analysis starting from the breath sampling to the test result decision only takes ~3min. The sensitivity and specificity results of GeNose C19 from the profiling tests show that combining GeNose C19 with an optimum machine learning algorithm can accurately distinguish between positive and negative COVID-19 patients. Hence, it opens an opportunity for using this developed breathalyzer as a rapid, noninvasive COVID-19 screening device based on exhaled breath-print identification.

Several factors may influence breath-prints, i.e., pathological and disease-related conditions (smoking, comorbidities, and medication), physiological factors (age, sex, food, and beverages), and sampling-related issues (bias with VOCs in the environment)97. A previous study revealed that older age altered breath-prints in patients with lung cancer98. There were concerns that several other respiratory diseases may present similar VOC patterns to those from the COVID-19. Several studies reported that several comorbid and confounding factors (e.g., chronic obstructive pulmonary disease, asthma, tuberculosis, and lung cancer) might affect the composition of VOCs99,100. Thus, patients with other respiratory diseases can have different patterns of VOCs that result in different sensor signals, suggesting that the electronic nose may still determine the COVID-19 infection to a certain degree by continuing to train its AI database in reading VOCs from confirmed positive COVID-19 patients. Our studies showed no significant difference in the detected sensor signal patterns of patients with comorbidities compared to those without comorbidities. Nonetheless, due to the few comorbid cases obtained in our subjects, which could be considered the limitation in our current study, the influence of existing comorbidities on the VOC pattern cannot be concluded and will be further evaluated in the next research.

Food and beverages (e.g., poultry meat and plant oil) can influence breath-prints, whereas smoking may increase the levels of benzene, 2-butanone, and pentane and simultaneously decrease the level of butyl acetate in exhaled breaths101,102,103. In our study, none of the patients was smoker. The comorbidities were also comparable between the case and control groups. There was no significant difference in the consumption of food and beverages between the two groups. The measurements were conducted in the same environment for all the participants. Thus, there was no bias with other interfering VOCs.

However, the possible presence of physiological variations resulting from physiological and biochemical changes in the body due to alterations in the respiratory rhythm affected by the manipulated breathing technique should also be considered61. Therefore, in our work, breath sampling was performed in such a defined protocol to collect only the third exhaled end-tidal breath. Accordingly, the natural breathing pattern and rhythm can be preserved, resulting in minimal changes in VOCs. We avoided excessive effort or repeated sampling in each breath collection as previous studies reported that it might alter the quality of collected VOCs104. The disturbance from other factors to breath test results is minimal. However, such confounding factors are most likely present in the real implementation and can affect at least breath-prints to a certain degree. Further study is now being conducted to reveal the effects of various confounders.

Our study using GeNose C19 did not evaluate the distinctive concentration of each VOC found in breath samples of patients with positive or negative COVID-19. However, to investigate the types of VOCs produced in exhaled breaths of the positive and negative COVID-19 patients, we conducted another characterization based on GCMS for several exhaled breaths of patients (see Supplementary Table 3). In the extracted results, there was no significant difference in the composition of VOCs between patients with positive and negative COVID-19, suggesting that the difference in the breath-print pattern may be contributed by the variation in the concentration or proportion of several VOCs rather than the presence of one or two signature VOCs. For example, acetone was reported to be one of the VOCs with the highest concentration emitted by healthy humans104. However, in COVID-19-positive patients, acetone was reported to be in a lower proportion, compared to the healthcare worker or healthy control group72. Meanwhile, another VOC (i.e., ethyl butanoate) has been reported as one of the signature VOCs in COVID-19 patients, whose concentration is slightly higher compared to the healthy control72.

Anosmia (i.e., the olfactory system cannot accurately detect or correctly identify odors) is one of the most frequently identified COVID-19 symptoms45,105. CO has been linked with this issue because it is an olfactory transduction byproduct related to the reduction of cyclic nucleotide-gated channel activity that causes a loss of olfactory receptor neurons45,106. In our GCMS results (Supplementary Table 3), six sensors in GeNose C19 (i.e., S1, S3, S4, S5, S6, and S8) could detect CO. Aside from CO, the GCIMS studies in Dortmund, Germany, and Edinburgh, UK indicated that aldehydes (ethanol and octanal), ketones (acetone and butanone), and methanol are biomarkers for COVID-19 discrimination24. This result is however different from the finding from another research group in Garches, France, using the proton transfer reaction quadrupole time-of-flight MS, where four types of VOCs (i.e., 2,4-octadiene, methylpent-2-enal, 1-chloroheptane, and nonanal) could discriminate between COVID-19 and non-COVID-19 acute respiratory distress syndrome74. Studies conducted in two cities in the USA (Detroit, Michigan and Janesville, Wisconsin) by Liangou et al. reported another set of eight compounds (i.e., nitrogen oxide, acetaldehyde, butene, methanethiol, heptanal, ethanol, methanol-water cluster, and propionic acid) as key biomarkers for the COVID-19 identification in human breath. Moreover, in Leicester, UK, seven exhaled breath features (i.e., benzaldehyde, 1-propanol, 3,6-methylundecane, camphene, beta-cubebene, iodobenzene, and an unidentified compound) measured by the desorption coupled GCMS were employed to separate RT-qPCR-positive COVID-19 patients from healthy ones107. In our measurement, camphene was detected only in the negative COVID-19 breath sample by S10.

Furthermore, Chen et al. reported two sequential GCMS studies in Beijing, China, that resulted in totally different breath-borne biomarkers for COVID-19 screening, despite using the same measurement approach72,108. Their first measurement reported in 2020 indicated that COVID-19 and non-COVID-19 patients could be differentiated by solely monitoring three types of VOCs (i.e., ethyl butanoate, butyraldehyde, and isopropanol)72. Nonetheless, in their second report in 2021, acetone was detected as the biomarker among many VOC species because its levels were substantially lower for COVID-19-positive patients than those of other conditions73. In our GeNose C19 sensor array, acetone can be detected in S8109. Recently, ammonia has also been proposed as another biomarker for COVID-19, whose relation to complications stemming from the liver and kidneys was affected by the SARS-CoV-2 infection110.

In all the already described examples of MS studies worldwide, the identification and determination of specific COVID-19 biomarkers in breath clearly remain challenging. Here, different discriminant compounds can be yielded depending on several parameters (e.g., measurement technique, filtering approach, location, and breath sample type). Nonetheless, we can still extract some information from our GCMS results (Supplementary Table 3). A hydrocarbon of ethylene was sensed by S10 in the positive COVID-19 breath sample. Meanwhile, for the negative COVID-19 breath samples, other hydrocarbons (i.e., butyl aldoxime, decane, and benzene) were detected by S10. Furthermore, S2 and S9 could measure a few specific esters (i.e., benzoic acid, 3-hydroxymandelic acid, and acetic acid) in the negative COVID-19 samples. Generally, the appearances of the three sensors (S2, S9, and S10) were dominant as compared to those of the others. For instance, S2 and S9 were highly sensitive toward aldehydes and esters, whereas S10 was likely to be reactive toward hydrocarbons.

Regardless of the successful compound extraction and its association with GeNose C19 sensor array, our GCMS characterization was only performed in a low number of samples. Therefore, a further investigation with a larger number of breath samples still requires to be carried out in the near future to correlate the measurement results of GeNose C19 and GCMS methods in a more thorough way, especially in Indonesia. This method also includes more investigations on the possible influence from other respiratory-related viruses (e.g., influenza, respiratory syncytial virus, and rhinovirus). The presence of viruses other than SARS-CoV2 will affect the VOC profile in breaths to a certain degree. However, in our current setup, it will be mostly recognized by the AI algorithm in GeNose C19 as non-reactive, which means that it contains VOC-based breath-prints not typical to a SARS-CoV2 infection. Influenza and rhinovirus infections manifest a high amount of heptane, nitric oxide, and isoprene111. Consistently, our preliminary study on breath samples from a few patients confirmed to have rhinovirus based on RT-qPCR and showed a high response on S8, suggesting a high amount of isoprene or isopropanol. However, further comparison analysis with more numbers of validated breath samples data will be definitely necessary to obtain a solid conclusion on this matter.

In terms of the enhanced sensing technology, once the VOC biomarkers can be clearly determined, a molecular imprinting method could be applied to generate highly selective sensors that target these specific VOC markers. Hence, the sensitivity and specificity of GeNose C19 and its overall accuracy can be further improved. Another critical step for the system development is to conduct a diagnostic test with a large cohort to strongly elucidate its potential as a diagnostic tool in the near future.

Other limitations of our study are that a direct correlation between the level of the virus gained from the swab and the amount of VOC concentration could not be drawn. These conditions are partly caused by the fact that VOCs were not directly produced by the virus, but rather by host cells infected by the virus as a part of their metabolic response to the infection. GeNose C19 could only predict the presence of the virus based on the resulting VOCs in the breath produced by respiratory tract epithelial cells and immune cells that were infected by the SARS-CoV2 virus. Nevertheless, a study on the correlation between the positivity rate of breath results and level of the cycle threshold value (Ct value) gained from RT-qPCR examination has been of interest for the next research. Here, more insights into the performance of GeNose C19 will be gained in terms of sensitivity, specificity, and accuracy levels correlated with the level of Ct value of RT-qPCR. The Ct value itself is currently accepted as an alternative parameter to determine the level of the viral load in each individual on the basis of the minimum cycle threshold necessary to duplicate the viral component to be read. Nonetheless, GeNose C19 combined with RT-qPCR using the Ct value has a limitation for estimating the exact number of the viral load. It was also a question of whether a person with a positive PCR test result for SARS-CoV-2 is automatically infectious or infectious only if the Ct value is below a certain limit (e.g., Ct value of <35)112,113. In another study, knowing the typical viral load of SARS-CoV-2 in bodily fluids and host tissues, the total number and mass of SARS-CoV-2 virions in an infected person could be estimated114. Each infected person carries the total number and mass of SARS-CoV-2 virions of 1091011 virions and 1100g, respectively, during the peak infection114.

Again, this study was meant to demonstrate a proof of concept that breath sampling and detection can be used to predict COVID-19 infection. Essentially, the calculated performance values in our study show the reliability of the DNN algorithm in predicting the training and testing data of breath samples, suggesting the great potential of the GeNose technology, fortified by the DNN algorithm to be used as a COVID-19 screening tool. Here, we performed the study using a so-called open-label design, where we already knew the COVID-19 status of the subjects before conducting sampling and classifying the sampled data into case and control groups. Using this method, we read, found, and compared the breath sample pattern profiles in each respected group and employed them as training data to build our first AI database, in which all data were validated by the test results of RT-qPCR supported with clinical data. A combined measurement of GeNose C19 with GCMS will be conducted in the near future to answer questions related to distinctive VOCs for COVID-19.

Lastly, another critical step for the system development is to confirm the usability and performance in the clinical setting, where a study on the clinical diagnosis of COVID-19 with a larger number of exhaled breath samples is currently performed to prove the potential of GeNose C19 as a rapid COVID-19 screening tool using a cross-sectional design and double-blind randomized sampling. Here, breath samples and nasopharyngeal swab specimens are taken in the situation where the operator or sampler does not know the true condition of patients. A double-blind fashion means that neither the sampler nor subjects know their true condition during the sampling process. The breath samples were analyzed by GeNose C19 without knowing the result of RT-qPCR, and swab samples were examined by RT-qPCR without prior knowledge of the GeNose C19 result. Both results were then compared to each other to draw a conclusion. In this approach, RT-qPCR will still be used as the reference standard.

Read more from the original source:
Fast and noninvasive electronic nose for sniffing out COVID-19 based on exhaled breath-print recognition | npj Digital Medicine - Nature.com

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Applications in Chronic Wound Healing | IJN – Dove Medical Press

Monday, July 25th, 2022

Introduction

The skin is the largest organ in the body, accounting for 15% of the total body weight. It is the first line of defense against physical, chemical, and biological factors.1,2 In some cases, the anatomical structure and biological function of the skin are impaired due to internal (local blood obstruction, inflammation, or underlying diseases) or external factors (mechanical injury, chemical corrosion, electric injury, or thermal injury).1,3

After damage, skin can self-heal, and this process involves four phases: hemostasis, inflammation, proliferation, and remodeling (Figure 1).4,5 In the first few minutes after skin damage, the platelets accumulate around the wound and get activated, forming a scab to preventing bleeding.6 After 23 days, the inflammatory phase starts around the wound, and the immune cells remove the dead and devitalized tissues and prevent microbial infections.4 The proliferation phase occurs after the inflammation phase, and it is characterized by the activation of keratinocytes, fibroblasts, endothelial cells, and macrophages, which contribute to wound closure, matrix formation and angiogenesis.7 In the 12 or more months after the primary repair is completed, the regenerated skin tissue is remodeled. During this phase, the processes activated after injury slow down, and the healed wound reaches it maximum mechanical strength.4,5

Figure 1 Phases of wound healing, including the hemostasis, inflammatory, proliferation, and remodeling phase.

Notes: Reprinted from: Tavakoli S, Klar AS. Advanced Hydrogels as Wound Dressings. Biomolecules. 2020;10(8):1169. doi:10.3390/biom10081169.5 2020 by the authors. Licensee MDPI, Basel, Switzerland. Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

However, in some cases, the skins self-healing property is inadequate, leading to the formation of chronic wounds. Chronic wounds are defined as wounds that remain unhealed even after 12 weeks.8 The main factors delaying wound repair include diabetes, infections, and long-term inflammation. Diabetic mellitus damages the microenvironment of skin tissue, which is involved in wound regeneration. It causes increases in reactive oxygen species (ROS) levels and poor collagen deposition.911 The hyperglycemia weakens the functions of fibroblasts, keratinocytes, endothelial cells, and stem cells or progenitor cells involved in wound healing.12 Microbial infections deplete the energy and cells required for tissue regeneration, and the bacteria can form biofilms that display antibiotic resistance, immune evasion, and wound adherence.13,14 In unhealed skin, excess inflammation also contributes to wound chronicity owing to its cytotoxic effects and the induced tissue damage, both of which delay wound healing.1517 Traditionally, the chronic wounds are treated with wound dressing made of gauze, skin grafting, or even flap transplantation. Moreover, targeted antibiotics are administered in case of infection. However, Surgery for chronic wounds can be challenging due to limited donor sites, donor damage, scar formation, and even severe functional and psycho-social disorders.1820 Moreover, antibiotic overuse can lead to drug resistance, creating new problems for infectious chronic wounds.21,22 Moreover, chronic wounds become refractory due to infections, diabetes, ischemia, over-degradation of collagen, and other factors, leading to the failure of traditional treatment methods. Thus, novel methods for treating chronic wounds need to be explored.

Skin wounds are the most common type of tissue injury, and they can be caused by trauma, surgery, burns, chronic diseases, or cancers.4,23 Under adverse conditions, wounds often turn chronic. The acceleration of wound repair and improvement of the healing process are the primary objectives of chronic wound treatment. Nanobiotechnology, which involves the use of nano-sized particles in biological systems, represents the convergence of several scientific fields, including chemistry, biology, physics, optics, mechanics, and nanoscale Science and technology. Nanobiotechnology can provide tools and technologies for examining and modulating biological systems.24,25 By applying nanotechnology in the field of bioMedicine, several novel biomaterials, biosensors, and bio-therapies have been designed and studied. It is believed that the combination of nanotechnology and biology can aid in wound management, monitoring, and repair.26,27 Initially, the application of nanobiotechnology in chronic wound treatment was focused on the provision of scaffolds for cell migration and the replacement of traditional gauze dressing.2830 However, with the development of nanotechnology and our understanding of wound healing mechanisms, various nanobiotechnology-based wound-treatments systems including drug and gene delivery platforms, antimicrobial systems, and cell-carrying systems have been developed and found to have prospective applications.3136 Nevertheless, despite these advances, wound dressings remain largely primitive and lack functions that allow wound monitoring and dynamic wound responses. Therefore, smart hydrogels or bandage systems developed using nano-sized biomaterials, which can respond to stimuli or monitor the status of chronic wounds, have been examined.37,38

This review article provides a summary of nanobiotechnology-based scaffold, delivery, antimicrobial, cell-carrying, collagen modulating, stimuli-responsive, and wound monitoring systems for chronic wound healing. Further, the prospects of nanobiotechnology to achieve better treatment outcomes for chronic wounds are discussed.

Physiologically, the wound healing process is affected by several factors, including gene expression; cell functions such as migration, proliferation, and differentiation; the skin microenvironment; infection; ischemiahypoxia; inflammation; and collagen formation and arrangement.1,3,17,3942 These factors are used as references for the design of nanobiotechnology systems that promote chronic wound repair (Figure 2) and need to be carefully considered before designing such systems.

Figure 2 Nanoplatform for chronic wound healing.

To repair tissue defects in the wound area, a platform for cell adhesion, migration, and proliferation ie, a scaffold for cells needs to be established. Such a scaffold can also serve as a platform for multi-functional modification. Given their good biocompatibility, angiogenic capacity, and biomimetic behavior to natural human skin, nano-scaffold systems are widely used in tissue engineering.4346

Tradition treatment methods for chronic wounds that show delayed Union involve local or systemic drug administration. However, the performance of these drugs is suboptimal owing to limitations such as low solubility and low bioactivity. Nanobiotechnology has thus been leveraged for the development of drug, gene, and exosome delivery systems that can help in overcoming these limitations.34,47,48

Infections, which impede tissue repair, should receive careful attention in chronic wound treatment. Silver nano-particles, a product of nanobiotechnology, have been used clinically in the treatment of microbial infection for decades. Moreover, several more recent studies have explored new nanoplatform-based anti-infection therapies, including potential anti-infection nanoparticles (NPs).4952

Cell therapy, especially stem cell therapy, is currently a focus in regenerative medicine and diabetic wound repair. In some basic medical and preclinical studies, chronic wound treatment with stem cells has shown excellent outcomes.5355 However, despite its great potential, the clinical translation of stem cell therapy for chronic wound healing is hindered by the lack of appropriate methods for cell encapsulation and transplantation. Thus, the development of nanobiotechnology-based cell-carrying systems can provide improved therapeutic effects.56,57

With the development of precision medicine, therapeutic systems that monitor wounds and respond to individual stimuli are expected to become popular. One such system is based on ferrihydrite NPs, which can respond to blue light and are effective for antimicrobial and wound healing treatments.58 More stimuli-responsive materials and monitoring systems for chronic wound healing can be generated through nanobiotechnology.

The term scaffold system generally refers to materials that can integrate with living tissues and cells and can be implanted into different tissues where they supplement natural tissue function based on specific conditions. In order to enable seed cells to proliferate and differentiate, a scaffold composed of biological materials that acts as an artificial extracellular matrix (ECM) is required. Scaffolds are critical for tissue engineering systems, including those for bone, cartilage, blood vessels, nerves, skin, and artificial organs (eg, liver, spleen, kidney, and bladder).

Nano-scaffold systems aimed at chronic wound healing need to possess certain important features.

1. Safety and good biocompatibility: Scaffolds should be safe. Furthermore, their chemical components and degradation products should cause minimal immune or inflammatory responses in the body during a predetermined period.59

2. Appropriate size, dimensions, and mechanical strength: The chemical features of the scaffold should provide suitable microenvironments and maintain the biological activity of loaded cells or tissues for a long time.

3. Appropriate pore size and distribution: Scaffolds should have a highly and well-connected porous structure with an ideal pore size to allow cells, drugs, and bioactive molecules to get evenly distributed throughout the scaffold.60

4. Excellent biological behaviors: Scaffolds and the substances present in the scaffold should promote the proliferation and migration of fibroblasts, keratinocytes, and endothelial cells, thus promoting wound healing.61,62

5. Appropriate wound healing environment: The scaffold system should be able to absorb the wound exudate and prevent wound dehydration, reducing surface necrosis on the wound.63,64

Scaffold systems can be classified as follows based on the source and function of the materials.

When designing scaffold systems for chronic wound, an appropriate matrix source needs to be selected. Table 1 lists a few sources of nanocomposites used in wound dressing. Natural nanomaterials and their derivates have good biocompatibility and can be degraded by enzymes or water. However, their characters and quality differ from batch to batch and cannot be standardized. In contrast, synthetic biomaterials, such as polyethylene glycol (PEG) nano-scaffolds, show more stable structural properties and can be chemically modified. However, the biosafety of synthetic materials needs to be strictly examined.

Table 1 Sources of Nanocomposites

According to their functions, tissue engineering materials can be used for bones, nerves, blood vessels, skin, and other tissues (eg, tendon, ligament, cornea, liver, and kidneys).

Tissue engineering scaffolds for the skin can be of several types. These include natural polymers (chitosan, hyaluronic acid, and collagen), nanocomposite scaffolds (eg, nanobioactive glass and metal NPs), and conducting polymers (eg, polyaniline, polypyrrole, and polythiophene).7375 Taghiabadi et al synthesized an intact amniotic membrane-based scaffold for cultivating adipose-derived stromal cells (ASCs). By ASCs on an acellular human amniotic membrane (HAM), they created a neoteric skin substitute.76 Zhang et al designed a conductive and antibacterial hydrogel based on polypyrrole and functionalized Znchitosan molecules for the management of infected chronic wounds. They demonstrated the promising potential of the hydrogel in promoting the healing of the infected chronic wound after electrical stimulation. Currently, other tissue engineering scaffolds such as calcium phosphates and composite materials (eg, hydroxyapatite, -tricalcium phosphate, and whitlockite) for bone tissue engineering and amniotic membranes for corneal tissue engineering are under research.69,77

Skin tissue engineering scaffolds can be categorized as porous, fibrous, microsphere, hydrogel, composite, and acellular materials.73 Typically, natural biomaterials and their derivatives are biodegradable, absorbable, and harmless to the body, but their strength and processing performance are poor and their degradation speed cannot be controlled. Hence, in order to improve the mechanical and biological properties of scaffolds (eg, adhesion, strength, processing performance, and degradation speed) and accelerate wound healing, composite scaffolds have been developed by combining the characteristics and advantages of different materials. Depending on their constituents, these composite scaffolds can achieve specific functions. Currently, most novel scaffolds being developed use composite materials to obtain multifunctional characteristics.

Delivery systems are used to deliver drugs, cells, genes, and other neoteric bioactive molecules to the body or target area via transplantation or injection.78 Traditionally, delivery systems are broadly divided into two categories, drug delivery and cell delivery. With continuous Innovation in scientific research, new approaches, including gene delivery and the delivery of bioactive molecules such as growth factors, proteins, and peptides, are being developed.

Recently, there has been a significant increase in new biotechnology-based treatments, among which cell and gene therapies are quite sophisticated. Exosomes have shown superior therapeutic potential against various conditions, and delivery methods are being devised to maximize their therapeutic effectiveness. Moreover, exosomes are also emerging as a delivery system for other substances (eg, small molecules and miRNAs).79 NPs are essential for the delivery of these refined substances. In addition to serving as delivery vehicles, NPs can also act as diagnostic and therapeutic agents for some diseases.80 Research on nanoparticle-based drug delivery has mainly been focused on targeted drug delivery, and especially tumor-targeted drug delivery.81

A drug delivery system serves as a vehicle for therapeutic molecules. It allows drug delivery in the body, improves drug efficacy, and allows safe and controlled drug release.

The conventional routes for drug delivery80 are gastrointestinal drug delivery (eg, oral and rectal), parenteral administration (eg, subcutaneous, intramuscular, and intravenous injection) and topical administration (eg, percutaneous injection and wound dressings). Novel drug delivery systems for wound healing can be classified into the following categories: NPs, microcarriers, and tissue-engineered scaffolds.82 Skin tissue engineering scaffolds have been introduced earlier in this review, and NPs and microcarriers will be introduced in detail here (Table 2).

Table 2 Drug Delivery Systems Developed Using Nanotechnology

Drug-loaded nano-scaffolds that promote wound healing after topical administration have been developed. However, due to their poor solubility, short half-life, and other drawbacks, some drugs do not accumulate at an optimal concentration at the wound site for a long duration.83 Nano-scaffolds with varying porous structures can be used to load drugs or bioactive molecules, and the porous structure can provide a breathable environment for the wound.84 NPs carrying poorly soluble drugs are widely used to prepare controlled drug delivery systems. Nano-scaffolds typically show slow degradation, allowing long-term drug release and thereby maintaining an ideal concentration of the drug in the plasma.85 Shamloo et al developed polyvinyl alcohol (PVA)/chitosan/gelatin hydrogels to overcome the short half-life of basic fibroblast growth factor (bFGF). The biocompatibility of the hydrogel supported the continuous delivery of bFGF and significantly accelerated wound healing.86

During the treatment of chronic wounds, the drug is usually applied directly on affected region. Nanotechnology-based drug delivery systems could enable controlled drug release. Meanwhile, the degradability and stability of the drug could also be modified using nanosystems. Hence, these drug delivery systems could improve treatment compliance among patients with chronic wounds by reducing the application frequency and the cost of treatment.

It is widely acknowledged that metal ion-based biomaterials exhibit promising antimicrobial activity when applied to wounds, making them very suitable for the management of diabetic wounds, which are prone to infection. Given their reducing properties, under oxidative stress, cuprous ions provide a promising therapeutic option for diabetic wounds. Copper ions have also been reported to promote angiogenesis.115117 Equipped with infrared absorption and efficient heat generation abilities, semiconductor cuprous sulfide (Cu2S) NPs are widely employed as photothermal agents. Wang et al utilized the photothermal effect of Cu2S and the angiogenic effect of Cu ions to prepare electrospun fibers containing Cu2S NPs, achieving a combination of advantages based on the components and successfully promoting diabetic wound healing. Moreover, their biomaterial could also effectively inhibit the growth of skin tumors both in vivo and in vitro.70 This system demonstrated the effectiveness of bifunctional tissue engineering biomaterials, providing a novel method for drug delivery for the treatment of biological conditions.

Classic gene therapy generally involves the expression of exogenous genes or the silencing of target genes via viral or non-viral delivery.118,119 In general, gene delivery via viral transfection may be carcinogenic.119 Most gene therapies for diabetic wounds are based on siRNAs. Gene therapy has become a promising strategy for the treatment of various diseases, and its effects are mediated via the regulation of RNA and protein expression.120 Many unmodified gene therapy agents, such as proteins, peptides, and nucleic acids, are rapidly degraded or eliminated from systemic circulation before they can accumulate at effective concentrations at the target site. Owing to poor pharmacokinetics, repeated administration is warranted. This, in addition to the narrow range of safe doses, often leads to adverse effects during treatment.121

Several studies on wound management and especially chronic diabetic wound management have focused on gene- or RNA-based (eg, mRNA, microRNA, circRNA, and lncRNA) therapies.122 Subcutaneous local injections can be used to directly deliver RNAs or proteins to the wound site.123 However, due to the short half-life of the therapeutic agent, repeated administration is required, often leading to pain and poor treatment compliance. Drug delivery systems not only solve these problems but also protect gene-related small molecules from degradation and eliminated from the body. The greatest challenge in gene therapy is ensuring the successful transduction or transfection of target genes into host cells by crossing extracellular and intracellular barriers. Therefore, the engineering of gene delivery vehicles is complex.118 Moreover, the materials used to encapsulate gene-related small molecules are required to have low toxicity and promote a high transfection efficiency.124 Currently, the NPs that deliver siRNAs to promote wound management are composed of lipids, polymers (eg, chitosan, PEG), hyperbranched cationic polysaccharides (HCP), and silicon.125130

Shaabani et al developed layer-by-layer self-assembled siRNA-loaded gold NPs with two different outer layers Chitosan ([emailprotected]) and Poly L-arginine ([emailprotected]).126 They compared the two types of NPs, which had a similar core structure. They found that the two polymers had different escape mechanisms: the buffering capacity of chitosan resulted in endosome disruption,131 while PLA bound to the endosome lipid bilayer and promoted escaped through pore formation. Their results indicated that an outer layer of PLA allows the endosomal escape of siRNA, thus improving transfection efficiency and delivering target molecules to promote diabetic wound healing. Given that naked siRNAs are easily eliminated from the body, Li et al and Lan et al designed four HCP derivative-based vehicles128,129 for the delivery of siRNA against MMP9. This treatment led to the knockdown of MMP9, which prevents the healing of diabetic wounds, and thus promoted diabetic wound healing. Currently, nanocomposite-based gene delivery applications are focused on siRNA. However, efforts to deliver other products such as miRNA, lncRNA, or even DNA will be required in the future.

Exosomes are endosome-derived vesicles (30 to 150 nm in size) secreted by a variety of cells, including adipose stem cells (ADSCs), bone marrow stem cells (BMSCs), and mesenchymal stem cells (MSCs).132,133 Different types of cells secrete exosomes with different specific markers, which account for their specific functions. Despite their different origins, exosomes have a similar appearance and size and often have a common composition. Once they are isolated from an extracellular medium or from biological fluids, the source of exosomes cannot be ascertained of.134 Exosomes can be employed as small molecules for wound treatment. The combination of exosomes with porous NPs can increase therapeutic effects while maintaining the advantages of a scaffold. Importantly, exosomes can also be used as nanocarriers for drug delivery and targeted therapy, and these are called engineered exosomes.133,135

Exosomes can effectively promote diabetic wound healing.136,137 Shiekh et al embedded ADSC-derived exosomes (ADSC-exo) into antioxidant polyurethane scaffolds to achieve sustained exosome release. Their nanosystem leveraged the advantages of the scaffold, including antioxidant and antibacterial effects, to accelerate diabetic wounds healing both in vivo and in vitro.71 To prolong the half-life and lower the clearance rate of exosomes, Lei et al designed an ultraviolet-shielding nano-dressing based on polysaccharides that allowed exosome delivery and had self-healing, anti-infection and thermo-sensitive properties.61 These findings indicate that exosomes can be stabilized and well-delivered to target cells by combining them with porous NPs or nanocarriers and can be applied for treating chronic wounds.

It is widely accepted that infection is an important factor to monitor during the wound healing process as it can lead to progression of the chronic wound or even sepsis.138140 Conventional prevention and treatment approaches for wound infection involve local or systemic antibiotic administration, which can lead to failed anti-infection treatment or even antibiotic resistance.141,142 Several nano-formulations that have antimicrobial ability have been developed and used in anti-infectious wound therapy, playing a critical role in infection management. Table 3 lists some antimicrobial nanobiotechnology-based systems used in wound healing.

Table 3 Nanomaterials Used in Anti-Microbial Wound Dressing

Metals have been used as inorganic antimicrobial agents for thousands of years and were even used as anti-infection agents in ancient Persia.162 Metal NPs, such as AgNPs, AuNPs, and CuNPs, have attracted great attention due to their anti-infection properties and low toxicity.163 Given that metal NPs do not cause antimicrobial resistance and release metal ions or produce ROS which can kill microorganisms they appear to be suitable alternatives to antibiotics as.164,165

AgNPs, which are the more well-known metal NPs, have been used widely in clinical practice and basic medical research. Wound treatment products containing AgNPs have been commercially available for decades.166 AgNPs can continuously generate Ag+, which reacts with proteins and nucleic acids, causing molecular defects and killing bacteria and viruses.167170 Several studies have shown that AgNPs have good potential as antiseptics. Luna-Hernndez et al found that a combination of functional chitosan and silver nanocomposites showed antibacterial effects against S. aureus and P. aeruginosa in burn wounds.152 Moreover, in mice treated with the composite dressing, silver accumulation was found to be far lower than that in mice treated with the clinically used AcasinTM nanosilver dressing. Zlatko et al demonstrated that the AgNPs hydrogel serves as a versatile platform, with features such as antibacterial efficacy, exudate absorbance, low cost, biocompatibility, hemocompatibility, and improved healing for chronic wounds.171 Huang et al constructed an organic framework-based microneedle patch containing AgNPs. The product showed transdermal delivery and could prevent S. aureus, E. coli, and P. aeruginosa infections in diabetic wounds.172 In addition, several commercialized products containing AgNPs have been developed for clinical treatment. These include Acticoat, Allevyn Ag, Aquacel Ag Surgical, Atrauman Ag, Biatain Silicone Ag, Flaminal, Mepilex Transfer Ag, SILVERCEL, and Urgo Clean Ag.

Nano-sized gold is also useful as an anti-infection agent. It has been confirmed that AuNPs bind to bacterial DNA and show bactericidal and bacteriostatic properties.173,174 Some studies show that Au nanocomposites can kill MRSA and P. aeruginosa through photothermal effects and could promote wound closure.150,175

Compared with gold and silver, copper is less expensive and more easily available. CuNPs are considered the best candidates for developing future technologies for the management of infectious and communicable diseases.49 Cai et al developed a CuNP-embedded hydrogel that accelerated wound healing and showed effective antibacterial capacity against both gram-positive and gram-negative bacteria as well as great photothermal properties.176

Inorganic non-metal nano-materials have been also considered potential antimicrobial agents owing to their intrinsic anti-infection effects.177 Based on the unique structural and physio-chemical properties of carbon nanomaterials, a research team prepared a carbon nanofiber platform that inhibits the growth of E. coli and MRSA.178 In this study, CuNPs and ZnNPs were asymmetrically distributed in carbon NFs grown on an activated carbon fiber substrate using chemical vapor deposition (CVD). The carbon NFs platform inhibited the growth of gram-positive and gram-negative bacterial strains with superior efficiency than simple metal NPs. Another study showed that carbon nanotubes can be used to prepare wound-repairing bandages with infection-preventing properties.179

The natural organic biomaterial chitosan and its derivatives are popular in biomedicine. Chitosan possesses good biocompatibility, antimicrobial properties, and low immunogenicity.180 Using nanobiotechnology, Ganji et al fabricated a nanofiber with chitosan-encapsulated nanoparticles loaded with curcumin for wound dressing. The electrospun chitosan-based nanofiber inhibited the growth of E. coli and MRSA by 98.9% and 99.3% in infected wounds in mice.50 Another type of chitosan nanofiber also showed potential in wound care owing to its antibacterial and re-epithelialization-promoting effects.181 Antibiotic-loaded chitosan nanofibers have also been used for local drug delivery and wound treatment.182 Other metalorganic framework nanorods have also shown bacterial inhibition in infectious wounds.183 Dias et al developed a series of soluble potato starch nanofibers sized 70264 nm. They incorporated carvacrol during the synthesis of the potato starch nanofibers, and the obtained nanocomposites showed great anti-pathogenic activity against S. aureus, E. coli, L. monocytogenes, and S. typhimurium, highlighting their potential as agents for wound dressing.184

With respect to organic nano-materials, anti-infection approaches focus on natural antibacterial compounds such as chitosan and its derivatives. Further, owing to the bactericidal effects of metals, metal-organic frameworks are also used. Given that metal NPs are associated with the potential risks of metal deposition, organic nano-antimicrobial materials, especially natural macromolecules with antibacterial properties, may become useful for wound dressing.

Biofilm, which are made up of surface-attached groups of microbes, are considered to be the primary cause of chronic wounds owing to their role in antibiotic resistance.141,185187 Most biofilms are formed on the surface of wounds. However, some special biofilms can get implanted into the deep layers of skin tissue, making traditional diagnose and treatment challenging.188 The clinical treatment of biofilms in wounds involves wound cleansing with polyvinylpyrrolidone or hydrogen peroxide, debridement, refashioning of wound edges, dressing, and the topical or general administration of antibiotics.189 With further insights into the mechanisms of biofilm formation and developments in nanobiotechnology, nanomaterials effective for biofilm therapy have been developed.

Nanomaterials based on metals or metal oxides are widely used against wound biofilms, including silver, copper, gold, titanium, zinc oxide, magnesium oxide, copper oxide, and iron oxide.190,191 Owing to the small size of these particles, metal or metal oxide NPs can move across bacterial membranes and rupture them. They can destroy enzyme activity and the respiratory chain in bacteria. It has been demonstrated that Ag NPs and silver oxide NPs are the most effective against microbial biofilms.192,193 Abdalla et al functionalized nano-silver with lactoferrin and incorporated them in a gelatin hydrogel, generating a dual-antimicrobial action dressing for infectious wounds and maximizing the anti-biofilm property of silver.194

Chitosan, bacterial cellulose (BC) and other natural antimicrobials have been modified using nanotechnology to treat wound biofilms. Owing to the positive charge on the polymeric chain of chitosan, chitosan NPs easily adhere to the negatively charged microbial membrane, triggering changes in permeability and preventing biofilm formation.195 Zemjkoski et al obtained chitosan NPs through gamma irradiation and encapsuled them into BC to form BC-nChiD hydrogels with excellent anti-biofilm potential. These hydrogels could provide a 90% reduction in viable biofilms and a 65% reduction in biofilm height.196 Mahtab reduced the amount of bacteria in a planktonic condition by treating bacterial biofilms with photodynamic therapy using curcumin encapsulated into silica NPs. After exposure to blue light, ROS was produced owing to the photodynamic properties of silica NPs. The ROS damaged biofilms, and the curcumin released prevented bacterial growth.197

The size of nanoparticles can be controlled, and they have a large specific area, can penetrate bacterial membranes, and show bactericidal properties. Hence, nanotechnology has great potential in destroying biofilms and treating infectious chronic wounds. In addition to providing nanoparticles with anti-infection properties, nanotechnology could also be used to provide a platform for antibiotics, enhance their solubility, prolong their half-life, and reduce the required treatment dose.

Due to its superiority with respect to tissue engineering, cell-based therapy is extensively used for chronic wound treatment.198201 Stem cells derived from bone marrow, the umbilical cord, and adipose and cutaneous tissue can differentiate into various tissue types and modulate cell migration, collagen deposition, re-epithelialization, and tissue remodeling.198,202205 Nanofibers prepared using electrostatic spinning are widely used for scaffolding. Mao et al prepared polycaprolactone nanofibrous scaffolds and combined collagen with bioactive glass NPs (CPB nanofibrous scaffold). The CPB nanofibrous scaffold exerted positive effects as a cell-carrying system containing epithelial progenitor cells (EPCs). The EPC-carrying CPB bioactive complex promoted wound healing by enhancing cell proliferation, granulation tissue formation, re-epithelialization, and cell adhesion (Figure 3).206 Khojasteh et al found that curcumin-carrying chitosan/poly(vinyl alcohol) nanofibers can carry pad-derived mesenchymal stem cells and show excellent curcumin release and improve cell adhesion and proliferation, indicating that they could be useful in wound dressings.207 Kaplan et al produced an injectable silk nanofiber hydrogel embedded with BMSCs. The nanofiber hydrogel maintained the stemness of the BMSCs, successfully carrying them to the target site and promoting wound healing through increased angiogenesis and collagen deposition.57

Figure 3 Schematic of a CPB/EPC construct that promotes wound healing. CPB enhances cell proliferation, collagen deposition, and EPC differentiation via the Hif-1/VEGF/SDF-1 pathway. This results in the rapid vascularization and healing of full-thickness wounds.

Notes: Reprinted from: Wang C, Wang Q, Gao W et al. Highly efficient local delivery of endothelial progenitor cells significantly potentiates angiogenesis and full-thickness wound healing. Acta Biomaterialia. 2018;69:156169. doi:10.1016/j.actbio.2018.01.019.206 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. With permission from Elsevier. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1742706118300308#f0060.

Usually, cell therapy in wound care is performed using micrometer-scale carriers as cell sizes fall in the range of microns. With the development of nanotechnology, an increasing number of nanofibers and NPs are being developed for cell therapy aimed at treating chronic wound given the excellent pro-differentiation, stemness-holding, and immunoregulation properties of the nanocomposites.

As an important component of the extracellular matrix, collagen mediates communication between cells, provides a scaffold for cell migration and adhesion, and plays a role in chronic wound healing.4 Some nanobiotechnology-based platforms have been used for collagen modulation. Sun et al loaded N-acetyl cysteine onto graphene oxide (GO) NPs to enable scarless wound healing (Figure 4).208 In their study, GO NPs decreased collagen metabolism and improved the balance between collagen formation and degradation, thus allowing the wound to heal without scarring. In another study by the same group, a polyamide nanofiber-based multi-layered scaffold was found to promote wound healing by encouraging the uniform arrangement of collagen.209 Krian et al synthesized a 3-D biomatrix with nanotized praseodymium that promotes collagen function via the stabilization of native collagen. Their rare-earth metal nanoparticles thus showed potential applications in wound care.210

Figure 4 Wound healing effect of a scaffold based on GO NPs.

Notes: Adapted from: Li J, Zhou C, Luo C et al. N-acetyl cysteine-loaded graphene oxide-collagen hybrid membrane for scarless wound healing. Theranostics. 2019;9(20):58395853. doi:10.7150/thno.34480.208 The author(s). Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

In chronic wound treatment, deposited collagen acts as a natural scaffold for cells, and therefore, modulating collagens is synonymous with re-establishing tissue structure in the wound area. As a result, collagen-modulating nano-systems have mainly been used for accelerating tissue repair. However, the studies by Suns group are inspirational and demonstrate that this approach should also be utilized for developing chronic wound treatments that decrease scarring.

Despite the availability of dozens of commercial wound-care products, bionic systems have not yet been adopted for wound healing. There is an urgent need for smart wound-healing systems that can respond to the stimuli (temperature, pH, glucose, enzyme, etc.) at the site of the chronic wound area.211,212 Through developments in nanobiotechnology, NPs with stimuli-response characteristics have received great attention. Gong et al synthesized a nanozyme consisting of poly(acrylic acid)-coated Fe3O4 NPs (pFe3O4) and then combined them with GO to produce pFe3O4@GO NCs. The pFe3O4@GO NCs could react with glucose and function as a self-supplying H2O2 nanogenerator at the wound site, allowing the chemodynamic treatment of wound infections.157 Some researchers developed photoactive electrospun nanofibers using cellulose acetate, polyethylene oxide, methylene blue, and three-layered cellulose acetate/polyethylene oxide/silk fibroin/ciprofloxacin. The nanofibers could produce ROS after light irradiation at 635 nm, accelerating the healing of infectious wounds by inhibiting S. aureus, K. pneumoniae, and P. aeruginosa biofilms.213 Zhang et al developed a hybrid hydrogel with MnO2 nanosheets. The injectable MnO2 nanosheet hydrogel could perform thermogenesis under 808-nm laser irradiation, eliminating ROS and inflammation and promoting wound repair.214 Overall, nano-structures functionalized using stimuli-response properties could simulate the biological, chemical, and physical characteristics of natural skin, enabling tissue regeneration in refractory wounds.

Given the elucidation of mechanisms and physiological changes associated with wound healing, sensors that allow real-time monitoring of wound repair have been developed.215217 A complex smart wound-monitoring wound dressing has also been invented.218 This dressing contains a nanofiber membrane made of chitosan/collagen, and promotes proliferation and regeneration by upregulating extracellular matrix secretion and promoting integrin/FAK signaling. Olivo et al added AgNPs to a fiber-based membrane monitor to increase the active surface area in the sensor, improving the detection sensitivity for biomarkers in the wound area.219 In order to avoid secondary wound damage caused by dressing changes, Jiang et al created bacterial cellulose-based membranes with aminobenzeneboronic acid-modified gold nanoclusters (A-GNCs), which could be used for treating wounds infected with multidrug-resistant bacteria.220 A-GNCs emit bright orange fluorescence under UV light, and the intensity of this fluorescence decreases with the release of A-GNCs. This allows healthcare professionals to determine when the dressing needs to be replaced. In the past few years, dressings that can monitor the status of chronic wounds in real-time have been tested. However, this field is relatively new, and current research on nanotech-based systems for monitoring chronic wounds is scarce.

Along with advances in nanobiotechnology research, several new nanosystems have advanced from the laboratory investigation stage to the clinical trial stage. Table 4 lists some clinical trials that have tested nano-therapies for wound healing. As early as 2014, Lopes et al investigated the cost-effectiveness of using nanocrystalline silver for treating burns. Their study showed that AgNPs provided faster wound healing than traditional silver sulfadiazine, requiring fewer dressing changes and reducing the human resource burden.221 Meanwhile, some clinical trials tested the use of nano-products for treating chronic wounds (Table 4). Although metal NPs were typically used for antimicrobial therapy, one clinical trial studied the efficacy and safety of autologous nano-fat combined with platelet-rich fibrin for treating refractory diabetic foot wounds. However, overall, there were few clinical trials examining the applications of nanoplatforms in chronic wound care, likely owing to inadequate previous research on biocompatibility. Moreover, few doctors participated in research on nanotechnology-based chronic-wound treatment, and hence, several clinical requirements were ignored or misunderstood.

Table 4 List of Clinical Trials for Nanobiotechnology-Based Wound Treatment

As nanobiotechnology has developed, nano-sized biomaterials have been widely applied for treating chronic wounds. This review article highlights that the application of nanotechnology in chronic wound treatment has, so far, largely focused on scaffold construction, anti-infection treatment, and substance delivery.34,45,47,130,147

In scaffold systems, nanobiotechnology provides both materials and techniques for managing chronic wounds. Electrospinning, a nanotechnique, allows the production of biomimetic structures that mimic the natural skin and help in healing refractory wounds.50 Furthermore, some nano-scaffolds promote cell adhesion and migration by mimicking the construction of natural tissues, thus promoting chronic wound healing. Nevertheless, there is further scope to improve the quality of natural nano-biomaterials and the biocompatibility of synthetic nano-biomaterials to increase their application.

Dozens of metal NPs, and especially AgNPs, have been used in antimicrobial therapy for chronic wounds.163 However, metal deposition can cause DNA and cell damage. Hence, nanomaterials that prevent infection without causing toxicity are required. Further effort should be made to decrease the accumulation of heavy metals. Alternatively, nanocomposites without metal elements should be adopted more often in the future.

To overcome the ever-changing environment of the skin during chronic wound healing, several wound-monitoring and stimuli-responsive biomaterials have been developed.58,157,218 By leveraging specific characteristics, such as the photothermal effect, chemo-dynamic effect, fluorescence, and thermo-sensitivity, more nano-biomaterials that can be used in stimuli-responsive and dynamic monitoring systems for wound care should be developed. Most studies on wound healing have focused on migration-promoting effects, antimicrobial activity, and substance delivery. However, few nanotech-based multifunctional smart systems, such as smart dressings that show specific responses to stimuli, have been developed. Researchers in this field should work towards developing smart systems based on the mechanisms of disunion in chronic wounds, which could effectively demonstrate the potential of nanobiotechnology in promoting chronic wound repair.

Despite the decades-long history of nanotechnology research, few products and therapies based on nanobiotechnology have become available commercially or entered the clinical trial phase. One reason for this is that most basic nanotech research on chronic wound healing is performed in rodent models, such as C57BL/6 mice or SpragueDawley rats, even though the skin structure and chronic wound healing processes differ between rodents and humans.222 The wound healing effects observed in primates, such as humans, may not be as good as those in rats and mice. Meanwhile, the cost of nano-materials and processing platforms required for large-scale preparation also hinder the clinical translation of nanotechnologies.

During the past few years, numerous nano-materials and techniques have been used to repair chronic wounds. This review summarizes some nanobiotechnology-based systems and nanoplatform designs that can be used for treating chronic wounds. It highlights that a smart dressing for chronic wounds that allows real-time monitoring and has stimuli-responsive abilities is one possible direction for the future of nano-wound-repairing systems. We hope this review motivates the development of more sophisticated wound management systems based on nanobiotechnology in the future.

The authors acknowledge the support from the National Natural Science Foundation of China (81974289, 81772094), the Key Research and Development Program of Hubei Province (grant number 2020BCB031), the Guangdong Basic and Applied Basic Research Foundation (2019B1515120043), the international cooperation research project of Shenzhen, the international cooperation research project of Shenzhen (GJHZ20190822091601691), and the Key Project of Basic Research of Shenzhen (JCYJ20200109113603854).

The authors report no conflicts of interest in relation to this work.

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2. Vig K, Chaudhari A, Tripathi S, et al. Advances in skin regeneration using tissue engineering. Int J Mol Sci. 2017;18(4):789.

3. Stojadinovic A, Carlson JW, Schultz GS, Davis TA, Elster EA. Topical advances in wound care. Gynecol Oncol. 2008;111(2):S70S80.

4. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008;453(7193):314321.

5. Tavakoli S, Klar AS. Advanced hydrogels as wound dressings. Biomolecules. 2020;10(8):1169.

6. Versteeg HH, Heemskerk JW, Levi M, Reitsma PH. New fundamentals in hemostasis. Physiol Rev. 2013;93(1):327358.

7. Wilkinson HN, Hardman MJ. Wound healing: cellular mechanisms and pathological outcomes. Open Biol. 2020;10(9):200223.

8. Olsson M, Jarbrink K, Divakar U, et al. The humanistic and economic burden of chronic wounds: a systematic review. Wound Repair Regen. 2019;27(1):114125.

9. Stadelmann WK, Digenis AG, Tobin GR. Physiology and healing dynamics of chronic cutaneous wounds. Am J Surg. 1998;176(2ASuppl):26S38S.

10. Lerman OZ, Galiano RD, Armour M, Levine JP, Gurtner GC. Cellular dysfunction in the diabetic fibroblast: impairment in migration, vascular endothelial growth factor production, and response to hypoxia. Am J Pathol. 2003;162(1):303312. doi:10.1016/S0002-9440(10)63821-7

11. Duscher D, Januszyk M, Maan ZN, et al. Comparison of the hydroxylase inhibitor dimethyloxalylglycine and the iron chelator deferoxamine in diabetic and aged wound healing. Plast Reconstr Surg. 2017;139(3):695e706e. doi:10.1097/PRS.0000000000003072

12. Rodrigues M, Wong VW, Rennert RC, Davis CR, Longaker MT, Gurtner GC. Progenitor cell dysfunctions underlie some diabetic complications. Am J Pathol. 2015;185(10):26072618. doi:10.1016/j.ajpath.2015.05.003

13. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science. 1999;284(5418):13181322. doi:10.1126/science.284.5418.1318

14. Versey Z, da Cruz Nizer WS, Russell E, et al. Biofilm-innate immune interface: contribution to chronic wound formation. Front Immunol. 2021;12:648554.

15. Wang X, Coradin T, Helary C. Modulating inflammation in a cutaneous chronic wound model by IL-10 released from collagen-silica nanocomposites via gene delivery. Biomater Sci. 2018;6(2):398406.

16. Xu Z, Liang B, Tian J, Wu J. Anti-inflammation biomaterial platforms for chronic wound healing. Biomater Sci. 2021;9(12):43884409.

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19. Schiestl C, Stiefel D, Meuli M. Giant naevus, giant excision, eleg(i)ant closure? Reconstructive surgery with Integra Artificial Skin to treat giant congenital melanocytic naevi in children. J Plast Reconstr Aesthet Surg. 2010;63(4):610615.

20. Schiestl C, Neuhaus K, Biedermann T, Bottcher-Haberzeth S, Reichmann E, Meuli M. Novel treatment for massive lower extremity avulsion injuries in children: slow, but effective with good cosmesis. Eur J Pediatr Surg. 2011;21(2):106110.

21. Eming SA, Wynn TA, Martin P. Inflammation and metabolism in tissue repair and regeneration. Science. 2017;356(6342):10261030.

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23. Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med. 2014;6(265):265sr6.

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How different cancer cells respond to drug-delivering nanoparticles – MIT News

Monday, July 25th, 2022

Using nanoparticles to deliver cancer drugs offers a way to hit tumors with large doses of drugs while avoiding the harmful side effects that often come with chemotherapy. However, so far, only a handful of nanoparticle-based cancer drugs have been FDA-approved.

A new study from MIT and Broad Institute of MIT and Harvard researchers may help to overcome some of the obstacles to the development of nanoparticle-based drugs. The teams analysis of the interactions between 35 different types of nanoparticles and nearly 500 types of cancer cells revealed thousands of biological traits that influence whether those cells take up different types of nanoparticles.

The findings could help researchers better tailor their drug-delivery particles to specific types of cancer, or design new particles that take advantage of the biological features of particular types of cancer cells.

We are excited by our findings because it is really just the beginning we can use this approach to map out what types of nanoparticles are best to target certain cell types, from cancer to immune cells and other kinds of healthy and diseased organ cells. We are learning how surface chemistry and other material properties play a role in targeting, says Paula Hammond, an MIT Institute Professor, head of the Department of Chemical Engineering, and a member of MITs Koch Institute for Integrative Cancer Research.

Hammond is the senior author of the new study, which appears today in Science. The papers lead authors are Natalie Boehnke, an MIT postdoc who will soon join the faculty at the University of Minnesota, and Joelle Straehla, the Charles W. and Jennifer C. Johnson Clinical Investigator at the Koch Institute, an instructor at Harvard Medical School, and a pediatric oncologist at Dana-Farber Cancer Institute.

Cell-particle interactions

Hammonds lab has previously developed many types of nanoparticles that can be used to deliver drugs to cells. Studies in her lab and others have shown that different types of cancer cells often respond differently to the same nanoparticles. Boehnke, who was studying ovarian cancer when she joined Hammonds lab, and Straehla, who was studying brain cancer, also noticed this phenomenon in their studies.

The researchers hypothesized that biological differences between cells could be driving the variation in their responses. To figure out what those differences might be, they decided to pursue a large-scale study in which they could look at a huge number of different cells interacting with many types of nanoparticles.

Straehla had recently learned about the Broad Institutes PRISM platform, which was designed to allow researchers to rapidly screen thousands of drugs on hundreds of different cancer types at the same time. With instrumental collaboration from Angela Koehler, an MIT associate professor of biological engineering, the team decided to try to adapt that platform to screen cell-nanoparticle interactions instead of cell-drug interactions.

Using this approach, we can start thinking about whether there is something about a cells genotypic signature that predicts how many nanoparticles it will take up, Boehnke says.

For their screen, the researchers used 488 cancer cell lines from 22 different tissues of origin. Each cell type is barcoded with a unique DNA sequence that allows researchers to identify the cells later on. For each cell type, extensive datasets are also available on their gene expression profiles and other biological characteristics.

On the nanoparticle side, the researchers created 35 particles, each of which had a core consisting of either liposomes (particles made from many fatty molecules called lipids), a polymer known as PLGA, or another polymer called polystyrene. The researchers also coated the particles with different types of protective or targeting molecules, including polymers such as polyethylene glycol, antibodies, and polysaccharides. This allowed them to study the influence of both the core composition and the surface chemistry of the particles.

Working with Broad Institute scientists, including Jennifer Roth, director of the PRISM lab, the researchers exposed pools of hundreds of different cells to one of 35 different nanoparticles. Each nanoparticle had a fluorescent tag, so the researchers could use a cell-sorting technique to separate the cells based on how much fluorescence they gave off after an exposure of either four or 24 hours.

Based on these measurements, each cell line was assigned a score representing its affinity for each nanoparticle. The researchers then used machine learning algorithms to analyze those scores along with all of the other biological data available for each cell line.

This analysis yielded thousands of features, or biomarkers, associated with affinity for different types of nanoparticles. Many of these markers were genes that code for the cellular machinery needed to bind particles, bring them into a cell, or process them. Some of these genes were already known to be involved in nanoparticle trafficking, but many others were new.

We found some markers that we expected, and we also found much more that has really been unexplored. We're hoping that other people can use this dataset to help expand their view of how nanoparticles and cells interact, Straehla says.

Particle uptake

The researchers picked out one of the biomarkers they identified, a protein called SLC46A3, for further study. The PRISM screen had shown that high levels of this protein correlated with very low uptake of lipid-based nanoparticles. When the researchers tested these particles in mouse models of melanoma, they found the same correlation. The findings suggest that this biomarker could be used to help doctors identify patients whose tumors are more likely to respond to nanoparticle-based therapies.

Now, the researchers are trying to uncover the mechanism of how SLC46A3 regulates nanoparticle uptake. If they could discover new ways to decrease cellular levels of this protein, that could help make tumors more susceptible to drugs carried by lipid nanoparticles. The researchers are also working on further exploring some of the other biomarkers they found.

This screening approach could also be used to investigate many other types of nanoparticles that the researchers didnt look at in this study.

The sky is the limit in terms of what other undiscovered biomarkers are out there that we just haven't captured because we haven't screened them, Boehnke says. Hopefully its an inspiration for others to start looking at their nanoparticle systems in a similar manner.

The research was funded, in part, by SPARC funding to the Broad Institute, the Marble Center for Cancer Nanomedicine at the Koch Institute, and the Koch Institute Support (core) Grant from the National Cancer Institute.

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Fundamental Knowledge on Nanobots – Bio-IT World

Monday, July 25th, 2022

Nanorobots are electromechanical devices comprised of components that are within the nanometer size range. Within medicine, nanorobotic applications have been successfully used for a variety of microbiological, hematological, surgical and dental applications, to name a few.

The nanobots market global size accounted for USD 5.3 billion in 2021 and is expected to reach around USD 21.45 billion by 2030, expected to register growth at a CAGR of 16.8% from 2022 to 2030.

What is Biomedical Nanorobots?

As compared to industrial robots that were originally developed to automate routine and dangerous tasks, biomedical robots are highly specialized and miniature devices that must be capable of performing precise tasks within the human body. Recent advancements in nanotechnology and materials science have therefore promoted the development of both micro- and nanorobots for a wide range of biomedical applications.

Whereas the traditional power sources for industrial robots that require large power supplies and/or battery storage capabilities, both micro- and nanorobots will typically depend on chemically powered motors for their energy needs. To this end, these motors acquire energy by converting locally supplied fuels, such as oxygen or glucose within the body, to propel themselves towards different cellular structures. Nanorobots can also rely on externally powered motors based on either magnetic or ultrasound technology to drive their motion.

One of the most challenges that biomedical researchers have faced during the miniaturization of robotic systems has been the optimization of nanolocomotion. Recent developments in this field have demonstrated the ability of both micro- and nanorobots to efficiently propel themselves through complex biological media or narrow blood vessels. Furthermore, once these microscopic robots have penetrated through these areas, researchers have successfully developed ways in which these devices can collect and remove tissue biopsy samples, obtain detailed images, release active agents at predetermined locations and perform localized diagnoses.

Key market players

Report Scope of theNanobots Market

USD 21.45 Billion

Segments covered in the report

By Type

By Application

By Type of Manufacturing

By End User

Regional Segment

Nanomedicine segment is expected to dominate the application segment of the nanobots market

Based on application, the nanobots market is segmented into nanomedicine, biomedical and other applications. The Nanomedicine segment is expected to dominate the global nanobots market by holding more than 36% of the overall market. Nanobots are widely used in nanomedicine due to the increasing healthcare applications of nanobots. The large market share of this segment is attributed to the large level of commercialization in the healthcare sector for drug delivery, in vivo imaging, active implants, in vitro diagnostic, biomaterial, and drug therapy.

Additionally, increasing innovations in the field of cancer treatment related to the specific target are also contributing to the growth of nanobots market. The biomedical applications segment accounted for the second-largest market share of the overall nanobots marketplace.

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Nanorobots Market to close to USD 19576.43 million with CAGR of 12.23% during the forecast period to 2029 – Digital Journal

Monday, July 25th, 2022

Nanorobots Marketare also utilised in the maintenance and assembly of complex systems. Nanorobotics widespread use in the medical field is also propelling market revenue growth. In individuals with sickness or weakened immunity, nanorobots can act as antiviral or antibody agents. In addition to cancer detection and treatment, the technique is also being employed in gene therapy.

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A nano robot is a new technology for designing, programming, and controlling nanoscale robots. Nanorobots are capable of doing specified jobs with components that are on the nanometer size (10-9 meters). Nanorobots are capable of diagnosing certain types of cancer and serve a critical role in human pathogen protection and treatment.Biomedicalinstrumentation, pharmacokinetics, surgical procedures, diabetes monitoring, and other healthcare services can all benefit from nano robots. Data Bridge Market Research analyses that the nanorobots market was valued at USD 7739.19 in 2021 and is further estimated to reach USD 19576.43 million by 2029, and is expected to grow at a CAGR of 12.23% during the forecast period of 2022 to 2029.

Some of the major players operating in the nanorobots market are

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NanorobotsMarket Dynamics

Drivers

In the healthcare industry, advances in molecular robot technology are increasingly being used to execute complex tasks and eliminate human error.

Recent research in DNA nanotechnology supports the use of nanorobots inregenerative medicineon a big scale which is further anticipated to contribute to the market growth.

Nanotechnology will be used in the medical field to aid in the detection and treatment of diseases such as diabetes.

Opportunities

In addition, the growing application areas of microscopes and incorporation of microscopy with spectroscopy are further estimated to provide potential opportunities for the growth of the nanorobots market in the coming years.

GlobalNanorobotsMarket Scope and Market Size

The nanorobots market is segmented on the basis of type and application. The growth amongst these segments will help you analyze meager growth segments in the industries and provide the users with a valuable market overview and market insights to help them make strategic decisions for identifying core market applications.

Type

On the basis of type, the nanorobots market is segmented into microbivore nano robots, respirocyte Nano robots, clottocyte Nano robots, cellular repair Nanorobots and others. The others segment is further sub segmented into Nano swimmers and bacteria powered robots.

Application

On the basis application, the nanorobots market is segmented into nano medicine, biomedical, mechanical and other applications.

NanorobotsMarket Regional Analysis/Insights

The nanorobots market is analysed and market size insights and trends are provided by country, type and application as referenced above. The countries covered in the nanorobots market report are U.S., Canada and Mexico in North America, Germany, France, U.K., Netherlands, Switzerland, Belgium, Russia, Italy, Spain, Turkey, Rest of Europe in Europe, China, Japan, India, South Korea, Singapore, Malaysia, Australia, Thailand, Indonesia, Philippines, Rest of Asia-Pacific (APAC) in the Asia-Pacific (APAC), Saudi Arabia, U.A.E, South Africa, Egypt, Israel, Rest of Middle East and Africa (MEA) as a part of Middle East and Africa (MEA), Brazil, Argentina and Rest of South America as part of South America.

North America dominates the nanorobots market due to the rise in the adoption of nano robotics technology. Furthermore, the presence of sophisticated healthcare infrastructure will further boost the growth of the nanorobots market in the region during the forecast period. Asia-Pacific is projected to observe significant amount of growth in the nanorobots market due to the rise in the attention of the manufacturers.

Browse the complete table of contents at- https://www.databridgemarketresearch.com/toc/?dbmr=global-nanorobots-market

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Nanorobots Market to close to USD 19576.43 million with CAGR of 12.23% during the forecast period to 2029 - Digital Journal

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