Title: Distortion Energy as a Mechanobiological Driver for Fibroblast Activity and Soft Tissue Remodeling

Program: Biomedical Engineering PhD

Committee Chair: Trevor Lujan

Committee: Trevor Lujan, Gunes Uzer, Zhangxian Deng, Julia Thom Oxford

Abstract: Ligaments and tendons undergo structural remodeling and repair when exposed to mechanical loads. While multiple studies have investigated this phenomenon by applying stress or strain to cell-seeded scaffolds, the physical mechanisms that regulate cell responses to any loading configuration and drive structural and functional improvements of the tissue remain unclear. This gap hinders the development of effective therapeutic strategies for ligament and tendon injuries, which affect about 12 million U.S. citizens. This work introduces a novel approach to stimulating 3D cell-seeded constructs based on strain energy, a scalar quantity that combines stress and strain. Using this approach, we applied cyclic loads to 3D fibroblast-seeded collagen scaffolds in different loading configurations and evaluated changes in functional and structural properties across loading types. We also examined the ability of different mechanical measures (stress, strain, energy) to predict remodeling behaviors in the constructs. Findings revealed that distortion energy, a measure of shape change, was the best predictor of changes in cell density, tissue stiffness, and some protein expression and synthesis across various loading modes. This suggests that distortion energy may be a key physical driver of soft tissue remodeling during healthy activity and during healing.