PFI:AIR - TT: DNA-LINKED ECM GELS FOR ENHANCED HEALING IN CHRONIC WOUNDS

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This PFI: AIR Technology Translation project focuses on translating new, DNA-modified collagen dressings to fill the need for improved wound products that heal chronic wounds. DNA-modified collagen dressings are an important development because they will address two key shortcomings inhibiting success of existing treatments for chronic wound management - insufficient bioactivity/stability and high growth factor dosing - that lead to incomplete healing and serious side effects. This project will result in a proof-of-concept DNA-modified collagen dressing with the potential to fill a significant market need in advanced wound care, a growing segment in which the global market is projected to approach $15B by the year 2020. Specifically, the project uses a unique approach to create gel-based dressings employing collagen-mimetic "peptide" (CMP) molecules to integrate growth factor-encoding DNA into collagen gel "scaffolds" (CMPGs). This method for incorporating gene constructs into collagen scaffolds allows the gene constructs to remain localized and protected within the wound bed over extended time frames, yet as healing initiates, the gene constructs are released readily to stimulate further healing activity. Competing advanced wound dressings, which are largely based on collagen matrices or topical growth factor (PDGF-BB), have continued to show wound closure rates of ca. 50%, with concerns over growth factor toxicity. In contrast, the CMPG-based technology has shown (i) complete healing of 3D model wounds, requiring only 1/10 the growth factor necessary as compared with commercial approaches and (ii) sustained activity in a mouse wound model over periods of multiple weeks. These features indicating its definitive potential to offer patients improved wound healing with significantly fewer administrations, lower growth factor dosing, and fewer side effects.The CMPG design strategy addresses several important technology gaps as it translates from research discovery toward commercial application. Specifically, multiple reports delineate the clear synergies in wound repair between insoluble (matrix) and soluble signaling factors, suggesting that dual optimization of CMPG gene delivery and matrix composition is needed to maximize healing potential. At the same time, the matrix composition also has clear implications for clinical usage, as it will impact the ease with which CMPG gel solutions can be deployed, and the stability of the resulting gels after application. Hence, new intellectual merit will be generated by evaluating how nanostructure incorporation affects gel properties, and in turn, by elucidating how gel properties and cellular gene regulation can synergistically enhance tissue repair, leading to new materials and therapeutic strategies for a clinically difficult problem in chronic wound repair. The postdoctoral fellow involved in this project will receive training in intellectual property, regulatory issues, and market need through participation in formal University of Delaware courses (e.g. "High Technology Entrepreneurship") as well as short-courses (e.g. via SBE2 IGERT), which will afford a team well positioned to transition this technology into the commercial environment. The project engages the University of Delaware's Office of Economic Innovation and Partnerships (OEIP), as well as partnerships with specific healthcare companies to enable further intellectual property development and large-scale market analysis, while also positioning the CMPG technology to fill specific needs in wound care technologies.