Grants We Funded

Abstract

Project Summary: Peripheral nerve injuries are life-altering events that can often carry significant physical and psychosocial consequences for patients. When a direct end-to-end repair is not possible, reconstruction may require the use of autografts, synthetic conduits or acellular nerve allografts (ANAs) to repair the nerve gap. ANAs are a promising alternative as they are readily available and retain native nerve tissue extracellular matrix proteins and structure, which are conducive to nerve regeneration. Tissue regeneration requires seeding these biomaterials with exogenous cells, which is constrained by their infiltration into the acellular tissue and the promotion of angiogenesis to ensure their survival. Despite the broad availability of ANAs, studies have found mixed results with regards to the ability of these to promote a regenerative phenotype in peripheral nerve injuries, which results in clinical limitations on the recovery of patients suffering from these. We propose that an injectable composite modified with stromal cell-derived factor 1 (SDF-1), a chemokine vital for stem cell recruitment, can increase angiogenesis and Schwann cell migration within ANAs in nerve injuries. By determining the effect of SDF-1 containing composite within ANAs in nerve injury models, we can develop novel therapies that support and accelerate nerve regeneration in live models. Through applied translational work, our study could have a tremendous impact on the management of complex peripheral nerve injuries and on plastic surgery at large via the development of novel therapies. In addition, this research will result in greater understanding of the optimal microenvironment for the promotion of peripheral nerve regeneration, which has profound ramifications for further development of research models and targeted therapies. Our proposed project explores a specific therapeutic alternative for managing nerve injuries while providing the context to study the fundamental processes that underlie similar approaches. In summary, this study will provide a critical evaluation of biomaterials that promote nerve regeneration in a clinical context as well as open key opportunities for development of alternative approaches.

Impact Statement: Breast cancer-related lymphedema (BCRL) is a serious risk facing a large proportion of women undergoing axillary lymph node removal for the treatment of breast cancer. Chronic BCRL is irreversible, debilitating, and requires lifelong and labor-intensive treatment. High-quality data on the efficacy of a new comprehensive lymphedema prevention program that combines preoperative (education/risk reduction), intraoperative (immediate lymphatic reconstruction), and postoperative (self-directed lymphedema physiotherapy, compression garments, physical therapy) interventions to reduce or prevent BCRL would be a paradigm shift in current practice and could be used routinely in patients at high risk for BCR

Biography
Daniel Colchado is a general surgery resident at Washington University in St. Louis whose career goal is to become a plastic surgeon with academic focus in developing novel regenerative therapies for nerve and soft tissue injuries. His research experience includes diverse basic sciences approaches to understand neuro-regeneration, wound healing, and the micro-environmental factors that govern their clinical outcomes. Among these, his work on the role of stem cell-derived exosomes as a mediator of wound healing as regulated by mechanical tension has been recognized with awards. Daniel is the first physician in his family, all of whom originally moved from living in Mexico in 2008. Since then and with the help of his mentors, he obtained a dual B.A. in Biochemistry and Cell Biology and in Cognitive Sciences with a full scholarship from the Bill and Melinda Gates Foundation at Rice University, followed by his M.D. from Baylor College of Medicine as part of their early-admissions program. He continues serve as a mentor to students at different levels of training via outreach events, fostering personal connections to bolster their academic course, and offering support with applications.