(491b) DNA Modification of Collagen Scaffolds for Applications in Regenerative Medicine

The use of collagen-based biomaterials in regenerative medicine has rapidly increased over the past decade due to the biocompatibility, approved clinical usage, and broad importance of collagens in mammalian tissues.  During this period, a variety of collagen modification techniques have been developed for the purpose of retaining and delivering therapeutics.  Many techniques rely on chemical treatments, but a biomimetic strategy to modify collagen scaffolds offers compelling advantages.  We have designed a collagen mimetic peptide (CMP)-based approach to create DNA-linked collagens for applications in therapeutic gene transfer.  CMPs offer an enormously versatile (and reversible) method for modification of collagen with a range of materials.  We created CMPs with a range of hybridization temperatures (T_m) on collagen I, and demonstrated the functionalization of DNA polyplexes with addressable CMPs at a range of densities.  The retention of DNA polyplexes on collagen could be directly manipulated through variation of the CMP density on the polyplexes, and the CMP-based retention strategy also increased polyplex stability and sustained gene transfer over a period of several weeks in cultured murine fibroblasts.  This novel collagen modification approach offers new opportunities to address key issues in therapeutic gene transfer for applications in regenerative medicine.