Grants Funded

Abstract
In the ever-changing field of peripheral nerve reconstruction, the most recent advancement involves the introduction of acellular nerve allografts (ANAs). Preclinical and early clinical results on these acellular nerve allografts have shown consistent and reproducible recovery at gap lengths of up to 30 mm. Nerve regeneration through ANAs in distances greater than 30 mm is noticeably diminished. This limitation is due to a lack of key supporting elements such as Schwann cells (SCs), which have been shown to support nerve regeneration. Supplementation of ANAs with primary Schwann cells has been shown to enhance nerve regeneration through these grafts. It is known that the recipient's SCs migrate down the graft from both the proximal and distal ends. However, as the distance from the anastamotic site increases, the concentration of SCs in the graft decreases. Recent work involving the study of cellular senescence (loss of proliferative capabilities) has implicated this process in the overall mechanism of aging and regenerative dysfunction. Senescent SCs have diminished proliferative abilities, contributing to the lack of population in the longer ANAs. This study will quantify the incidence of SC senescence in the face of chronic denervation. The absence of axons in the ANA may create a stressful environment for the SCs, thus enhancing the induction of senescence, compounding the already stunted regeneration. Another factor contributing to this enhanced senescence is the lack of blood flow in the ANAs. Due to the processing of ANAs, all intrinsic vasculature is destroyed. Because of this, greater time may be needed to establish adequate blood flow. In the time it takes to do this, the ischemic insult may increase the incidence of SC senescence. We aim to determine the relationship of blood flow in a nerve graft to that of SC senescence. Enhancing angiogenesis and ultimately decreasing the ischemic insult on SC may in fact have a positive impact on nerve regeneration by reducing SC senescence.

Biography
Scott J. Farber, MD is a resident the division of Plastic and Reconstructive Surgery at Washington University School of Medicine in St. Louis, Missouri. He earned his medical degree at SUNY Downstate College of Medicine in Brooklyn, New York. As a plastic surgery resident, Dr. Farber is dedicating two full years to studying peripheral nerve injury and regeneration as a research fellow in the Mackinnon Peripheral Nerve Laboratory. He is excited about the opportunity to pursue independent research in the field as a surgeon-scientist. He hopes to answer clinical questions by studying the mechanisms of nerve regeneration at the basic science level in an effort to advance the understanding of nerve injury and to improve functional recovery in the clinic.