We have developed new strategies to employ extracellular matrix (ECM)-inspired peptides as drivers of gene and drug delivery during bone and skin repair. This talk will specifically highlight the use of collagen mimetic peptides (CMPs) as tethers that enable integration of DNA polyplexes and antimicrobial agent-loaded liposomes within collagen/fibrin hydrogels (“co-gels”) for applications in wound healing. Chronic wounds are a growing unsolved health problem with a prevalence rate of 1-2% of the general population in developed countries. Two key issues hindering repair include limitations in growth factor activity and accessibility, and the prevalence of infection and biofilm formation in the chronic wound environment. However, while a variety of ECM, growth factor, and antimicrobial treatments have received wide attention, clinical efficacy has been limited. Matrix-mediated delivery offers a lower cost pathway for growth factor delivery that addresses the confounding issues with recombinant protein therapies through its capacity to induce sustained, localized production of bioactive growth factor by endogenous cells; moreover, matrix represents an ideal depot to enable sustained delivery of antimicrobials. In our study, we demonstrate spatio-temporally-controlled PDGF gene transfer by conjugating CMPs to PDGF-encoding polyplexes, such that the polyplexes were stably tethered into the co-gel via CMP strand invasion into the collagen triple helix. In vitro results confirmed that the polyplexes were highly efficient in transfecting fibroblasts to induce PDGF expression and subsequent cell proliferation and migration. Simultaneously, we demonstrate that CMPs also provide useful tethers for incorporation of sustained liposomal depots for antimicrobials that enable improved resistance to infection over prolonged time periods. In vivo excisional wound healing studies in mice established faster wound closure using both CMP deliveyr approaches: CMP polyplex-loaded co-gels induced faster wound closure with minimal scar formation as well as improved collagen production, myofibroblast activity, and collagen orientation. Meanwhile, CMP-tethered antimicrobial liposomes offered increased resistance to bacterial infection at the surface of the wounds, resulting in improved healing. These results are indicative of the potential of matrix-modified biomaterial scaffolds in effective treatment of chronic non-healing wounds.<br/>

Enhancing tissue repair via peptide-mediated gene and drug delivery

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.