BME PhD Prospectus Defense - Laboni Hassan

Title: “Trehalose-Based Coacervates for Biomolecular and Cellular Delivery to Improve Wound Healing in Spinal Cord Injury”

Advisory Committee: Tim O’Shea, PhD – BME, MSE (Advisor) Joyce Wong, PhD – BME, MSE (Chair) Liangliang Hao, PhD – BME Chen Yang, PhD – ECE, CHEM, MSE

Abstract: Traumatic spinal cord injury (SCI) leads to lifelong paralysis and complications affecting cardiovascular, respiratory, bladder, bowel, and sexual function. Because damaged neural tissue does not spontaneously regenerate, hundreds of thousands of individuals live with SCI and current treatments are limited to supportive measures. Therapeutic strategies involving bioactive molecular delivery and cell grafting hold promise for improving functional recovery outcomes after SCI by directing regeneration-supportive glia repair at lesion cores. However, there are challenges that still need to be addressed for clinical translation of these therapeutic approaches, with mitigating the deleterious effects of lesion environments on the bioactivity of delivered molecules and the survival, localization and function of grafted cells being central among them. Coacervates are an emerging biomaterial class that have a unique set of properties suitable to address these challenges. I have developed an innovative method to prepare tunable coacervates composed of trehalose, a non-reducing disaccharide excipient that can stabilize proteins and cell membranes under stress conditions, to confer coacervates with bioactive support functions. I hypothesize that coacervate-based molecular delivery and cell grafting using coacervate carriers will augment wound repair processes in lesion environments, leading to improved outcomes after SCI in mice. To investigate this hypothesis, I will (1) develop a trehalose-based coacervate system and optimize specific formulations for intra- and extracellular bioactive protein delivery to neural cells; (2) augment astrocyte wound response after SCI using coacervate-mediated molecular delivery of pro-proliferative cues; and (3) test coacervate-based strategies to address both mechanical and molecular barriers for successful cell grafting in acute and chronic SCI. This work will contribute important technical innovations necessary for developing effective biomaterial-based therapeutic strategies for SCI and further our understanding of key biological mechanisms that determine and modulate wound responses after SCI.