Modelling of fracture in soft biological tissues

ended

Blood vessel rupture in brain aneurysm is fatal in 40% of cases; vision loss initiated by Retina Pigment Epithelium rupture affected 60 million people in 2020. This proposal establishes new approaches to simulate these systems and the fellowship develops a unique skillset to solve problems involving tissue fracture, having major impact on future medical intervention. Soft tissues are essential in our body and their failure to maintain mechanical integrity leads to diseases. Despite its importance, present understanding of fracture in tissues is limited. Fracture significantly alters the mechanics of tissues and experiments alone are unable to disentangle the interacting processes occurring concurrently at the crack tip and in the bulk material. Hence, a mathematical approach is needed to understand how fracture propagates at cell level up to failure. Models that account for all the complex processes that occur during fracture are still missing. BIOFRAC aims to develop an accurate numerical model of tissue fracture by adopting an innovative micromechanical approach—supported by laboratory and clinical experiments—to account for the multi-physical complexities by means of a novel constitutive relationship. This approach will allow us to predict crack evolution up to catastrophic failure. BIOFRAC focuses on the study of a single layer of epithelial cells—a simple yet clinically relevant tissue that lines many organs. Using this system, BIOFRAC seeks to uncover the biophysical and mechanical processes that control fracture initiation and propagation. The approach will then be used to address ophthalmological problems by development of a novel computational model for Retinal Pigment Epithelium able to quantify the risks of fracture during Age-related Macular Degeneration treatment. BIOFRAC will stimulate more studies of disease evolution and novel therapy. The new skills will boost my career by placing me at the forefront of tissue failure research.