Nanofabricated Devices and Nanomedicine Approaches for Wound Healing

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Project Summary/Abstract This mentored research proposal seeks to aims establish a laboratory of an engineer and nanoscientist in biomedical research. The scientific focus of this proposal is on tissue nanotransfection (TNT), an electromotive gene transfer technology that delivers plasmids, RNA and oligonucleotides to the live tissue in vivo. This technology was the first to achieve non-viral in vivo reprograming of the skin to functional blood vessels (iV, induced vasculogenesis) or to electrophysiologically active neural cells (iN, induced neuritogenesis) under immune survillence using a nanoelectroporation approach that does not pose the risk of genomic integration or transformation. TNT facilitates packaging of reprogramming cargo into biological nano carrier called exosome. Although the feasibility of this approach has been tested in murine skin, its application in pre-clinical setting is yet to be tested. The proposed work focuses on a new design of TNT chip that can be leveraged for release of endogenous engineered exosomes in vivo for therapeutic purposes in both diabetic mice and humans. Such approach was adopted to ensure high clinical significance. The project includes the following three aims. ?Aim 1: Nanoelectroporation induces release of exosome from cells. ?1.1: Nanoelectroporation increases cellular cytoskeletal reorganization and recruitment of Rab-GTPase at the microtubules for transfer of multivesicular bodies to the actin-rich cortex for release of exosome. ?1.2: Nanoelectroporation can be used as a method to package endogenous mRNA and miRNA for release via exosome. ?Aim 2: Test the efficacy of tissue nanotransfection induced engineered exosome in accelerating diabetic wound closure. ?2.1: Design of plasmids for cell-specific packaging of mRNA in vivo. ?2.2: In vivo cell specific mRNA packaging within exosome via TNT accelerates diabetic wound healing. ?Aim 3: Develop human scale TNT2.1 chip for preliminary preclinical testing.