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A Novel Method for Induction of Tissue Reprogramming: Tissue Nano-Transfection (TNT)
Casey T. Kraft, MD, Subhadip Ghatak, PhD, Chandan K. Sen, PhD, Ian Valerio, MD
Ohio State University
2018-01-27
Presenter: Casey Kraft
Affidavit:
I certify that the material proposed for presentation in this abstract has not been published in any scientific journal or previously presented at a major meeting. The work was shared equally among all authors for this presentation.
Director Name: Gregory Pearson, MD
Author Category: Resident Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Background: Tissue engineering continues to be a promising area of plastic surgery research. Current available methods for tissue engineering are limited, however, due to lack of precision or the requirement of viral vectors. We present a novel method of localized, non-viral, delivery of reprogramming factors to skin cells and report our experience with induced neuron and induced endothelial cell formation.
Methods: Using a silicone wafer with etched nanochannels and micro-reservoirs to hold genetic cargo, electrical stimulation can induce transduction of reprogramming factors into epidermal cells. ABM (Ascl1/Brn2/Myt1l) overexpression, a well-validated method of neuronal induction, was used for this study in a murine model to demonstrate TNT efficacy. EFF (Etv2/Foxc2/Fli1) was used for endothelial cell induction
Results: Skin treated with TNT reprogramming using ABM demonstrated increased Tuj1 expression and neurofilament formation, markers of induced neuron formation. Extracellular vesicles taken from TNT-treated skin were shown to induce neuron formation in untreated skin as well, implying continued effects of transfection. Skin treated with TNT using EFF showed increased expression of PECAM-1 and vWF, indicative of endothelial cell formation. Treated tissue also demonstrated enhanced, pulsatile blood flow in the treated area, and increased perfusion after treatment in ischemic skin.
Conclusions: Tissue Nano-Transfection is a novel method for focused, localized tissue engineering. Preliminary data demonstrate successful induction of neuron and endothelial cell formation. This technology can have wide-ranging applications in plastic surgery, particularly in areas such as nerve injury and tissue perfusion.
