BME PhD Prospectus Defense - Emily Davis

Title: "Investigating the Role of Cellular Mechanics and Provisional Matrix Assembly in Wound Healing"

Advisory Committee: Michael Smith, PhD – BU BME (Chair) Jeroen Eyckmans, PhD – BU BME (Co-Advisor) Christopher Chen, PhD – BU BME, MSE (Co-Advisor) Daniel Roh, MD, PhD - BUMC Surgery, Division of Plastic & Reconstructive Surgery

Abstract: Wound healing is a prevalent biological process that affects the global population in every form of injury, from small scrapes to burns to spinal cord injuries. The wound care market was estimated at $22.5 billion in the US alone in 2023 and millions of people worldwide suffer from impaired wound healing. Studying the mechanisms behind impaired wound healing is crucial for developing new therapeutics. At a cellular level, fibroblasts are pivotal in proper wound healing, depositing a provisional matrix and aiding wound closure. However, dysfunctional fibroblast activity can lead to failed wound healing through many avenues, one example being overproduction of matrix proteins by a highly contractile fibroblast phenotype, which can lead to scarring. The interplay between mechanotransduction cues in fibroblasts during wound closure is not fully understood. We propose that a balance between cellular contractility and adhesion is necessary to coordinate provisional matrix assembly for proper stromal closure and further, proper wound re-epithelialization. Using a 3D microtissue model, we aim to test this hypothesis and identify imbalances that cause microtissue failure, offering insights for future wound care therapeutics. I first plan to investigate the role of cell adhesion and contractility on wound closure in a fibroblast microtissue. Then, I plan to examine the effects of modulating these two processes on provisional matrix assembly and production during stromal healing. Lastly, I plan to extend the insight gained about provisional matrix assembly to establish the role of provisional matrix assembly on wound re-epithelialization.