Non-Technical Abstract This CAREER Award by the Biomaterials program in the Division of Materials Research to Vanderbilt University is to develop injectable hydrogels that contain stem/stromal cells to promote wound healing. Diabetic patients are more susceptible to formation of non-healing skin wounds. These wounds create a huge burden (and cost) on our health care system and lead to tremendous loss in quality of life. In the worst cases, nonhealing skin wounds lead to infection, cause debilitating pain, and necessitate limb amputation. In this project, the PI will develop a biomaterial that has the potential to help hold the stem cells in place at the wound, while simultaneously delivering a drug to the cells that will promote their survival, growth, and wound regenerative function. This biomaterial can be injected directly into the wound as a liquid that rapidly "gels" and then is slowly resorbed over time as the wound heals. Education and outreach activities carried out as part of this project will leverage the human health relevance of this research to motivate high school students to pursue education/research in STEM areas. The primary target group will be underrepresented students from the STEM Summer Institute (SSI) for Girls at Harpeth Hall, a local girls' high school. The PI will work with Harpeth Hall to develop and implement summer programs at the school. Also, a new component of the SSI will be established that will promote longer-term contacts with girls who participate in the program in order to provide them opportunities for additional STEM exposure and career-related mentoring on campus at Vanderbilt University.
Adult mesenchymal stem/stromal cells (MSCs) are in plentiful supply, relatively easy to harvest, and promising for local delivery to enhance tissue repair. However, an unsolved challenge is achieving efficient engraftment of viable cells that proliferate and robustly promote tissue regeneration following delivery to challenging environments characterized by hypoxia, inflammation, and high oxidative stress. Small interfering RNA (siRNA) provides a tool for specific and potent gene silencing and has strong potential to be used to manipulate cell phenotypes in regenerative therapies. For this project, a new, cell-degradable polyethylene glycol (PEG) based hydrogel is proposed that will promote local retention, viability/self-renewal, and regenerative performance of stem cell therapies through substrate mediated delivery of siRNA. This hydrogel will be synthesized using novel polymeric crosslinkers that degrade through oxidative mechanisms relevant to sites of wounded and inflamed tissues (e.g., diabetic skin wounds). Optimized hydrogel formulations will be applied for substrate-mediated siRNA delivery to encapsulated MSCs in situ. Knockdown of gene targets will be explored with the goal of enhancing proliferation and regenerative capacity of MSCs transplanted into diabetic skin wounds. Education and outreach activities initiated through this project will capitalize on the exciting, translational nature of this research in order to catalyze student enthusiasm and creativity in STEM areas. The primary target group will be underrepresented students from the STEM Summer Institute (SSI) for Girls at Harpeth Hall, a local girls' high school. The PI will continue ongoing work with Harpeth Hall to implement challenge-based, "legacy cycle" curricula. In addition, a new component of the SSI will be initiated that will establish longer-term contacts with girls who participate in the program to provide them with opportunities for additional STEM exposure and career-related mentoring at Vanderbilt University.
