About This ProjectEight million Americans, mostly older diabetic
individuals, have skin wounds that don’t heal. Open sores are painful and often lead to serious infections and amputations, thus severely affecting quality of life. Current treatments are marginally effective and fail to address the underlying causes of impaired healing. Our goal is to develop smart bandages containing living stem cells that will restore healing to be just like in healthy individuals.
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What is the context of this research?
Skin heals by a series of events including an
inflammatory phase that recruits immune cells that kill bacteria and remove dead cells, followed by a proliferation phase where the cell types that reform the damaged skin components grow and migrate. Chronic wounds are “stuck” in the inflammatory phase.
Bone marrow-derived mesenchymal stem cells (MSCs) produce factors that decrease inflammation and promote cell migration and growth. Pilot studies have shown that MSCs applied onto diabetic wounds promote healing; however, it is hard to keep the MSCs at the wound site during treatment, typically several weeks. We have developed a strategy to embed MSCs in a biocompatible matrix that can be applied onto the wound that immobilize the cells while maintaining their viability and function.
What is the significance of this project?
Chronic wounds cost the US healthcare $25 billion per year and account for 5% of Medicare expenditures. With an aging population and an ongoing obesity and type II diabetes epidemic, these numbers will increase sharply in the future. Chronic wounds are a major cause of amputation in diabetes, with age-adjusted amputation rates for diabetics at 5.5 per 1,000 vs. 0.2 per 1,000 for nondiabetic individuals.
Current therapies generally focus on basic wound care with the hope that the wound will eventually heal on its own. The most advanced options, namely bioartificial skin substitutes, only work 50% of the time. Alternative methods that directly address the overt and chronic inflammatory conditions of the wound and overcome the poor oxygen and nutrient supply are needed.
What are the goals of the project?
Our goal is to show that MSCs embedded in a
bandage-like hydrogel speed up the healing of diabetic wounds. We have developed in vitro wound models that mimic some aspects of diabetic wounds (for example, low oxygen supply, elevated glucose levels) where we have showed that embedded MSCs can decrease the production of inflammatory mediators while increasing wound closure rate by enhancing the contractile activity of skin fibroblasts.
Because only few aspects of wound healing can be reproduced “in a dish,” what we must do next is to show that these benefits can be observed in a pre-clinical in vivo diabetic wound model. In vivo data will provide proof-of-principle for this new therapeutic approach, which will in turn help us attract additional major sources of funding.
The bulk of our prior studies have been done
using in vitro models because of the high cost of in vivo studies. Yet, in vivo data are much more clinically relevant and we are specifically requesting funding to cover the cost to perform pre-clinical animal studies. This includes the genetically diabetic mice, the stem cells, and reagents for protein and histological analyses. This funding will enable us to evaluate the effect of MSCs in a relevant in vivo context, which will allow us to target a high impact journal for publication and increase visibility of our research. This seed money will in turn, increase our chances to receive funding from major agencies (e.g. NIH and the American Diabetes Association) that are interested in our research but require extensive and convincing preliminary data to be considered for funding. Furthermore, if the in vivo data look promising, the research team will seek investors that would be interested to develop the product for clinical use.
Meet the Team
Team BioDr. Francois Berthiaume obtained a Bachelor of Science and Ph.D. degrees in Chemical Engineering from Laval University in Québec City, Canada, and Penn State University, respectively. He then did post-doctoral work in Biomedical Engineering at the Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School, and served there as a faculty member for over 15 years before joining Rutgers University in the spring of 2009. He is currently Associate Professor in the Department of Biomedical Engineering at Rutgers University, and a Research Fellow in Rutgers’ Center for Innovative Ventures of Emerging Technology, where he works to strengthen ties between university and industry.
Renea Faulknor is a Ph.D. candidate in the Department of Biomedical Engineering at Rutgers University. Renea earned her B.S. in Biomedical Engineering from the University of Rochester. This project is part of her Ph.D. dissertation and she will be designing and performing experiments.
Dr. Francois Berthiaume obtained a PhD in Chemical Engineering from Penn State University, after which he had a post-doctoral fellowship at Harvard Medical School before becoming an instructor and then assistant professor of surgery at Harvard Medical School. In 2009, he moved to the Department of Biomedical Engineering at Rutgers as an Associate Professor. Here at Rutgers, his research in Tissue Engineering focuses on developing methods that attract stem cells to a site of injury in order to promote faster wound healing and reduced scarring. It is known that adult stem cells, some of which coming from the bone marrow, naturally have the capacity to home into injured areas of the body where they grow and differentiate to form new tissue. Our goal is to elucidate this mechanism and to develop methods that enhance it using a combination of implantable polymeric scaffolds and stem cell attracting agents. We are specifically interested to use this strategy for improving the healing of skin wounds, in particular deep skin wounds that are susceptible to infection and scarring, as well as non-healing and chronic wounds, such as diabetic ulcers, venous ulcers, and bed sores.
Nothing posted yet.
Additional InformationThis is an example of a diabetic foot ulcer. This individual already lost some of the toes and is at risk of losing more due to the open wound.
One way to mimic a wound in a dish is to embed fibroblasts in a collagen gel. The fibroblasts cause the gel to shrink, which emulates the in vivo process of wound closure by contraction. The graph below shows the effect of immobilized mesenchymal stromal cells (MSCs) on this in vitro wound contraction model. Low oxygen tension, as is typical in chronic wounds, decreases gel contraction. However, the contraction is largely restored in the presence of products secreted by the immobilized MSCs.
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