Soft biological tissues such as epithelia are essential for maintaining organ integrity, yet their rupture under physiological or therapeutic loading can have devastating consequences. Blood vessel rupture in brain aneurysms is fatal in approximately 40% of cases, while rupture of the retinal pigment epithelium (RPE) contributes to vision loss affecting millions of people worldwide. Despite this major clinical relevance, the fundamental mechanisms governing fracture in soft living tissues remain poorly understood. Their complex microstructure, ability to undergo large deformations, time-dependent behaviour, and active biological processes make fracture prediction extremely challenging. Current experimental approaches cannot fully disentangle the interacting mechanical and biological phenomena occurring simultaneously at the crack tip and in the surrounding tissue, and existing models typically address only isolated aspects of this complexity. As a result, a quantitative link between tissue-scale loading and cellular-scale failure mechanisms is still missing.
The BIOFRAC project was conceived to address this gap by developing a new modelling and experimental framework to understand fracture initiation and propagation in soft biological tissues. The overarching objective was to establish a quantitative link between macroscopic loading conditions and microscale stress and strain patterns that lead to tissue rupture. By doing so, the project aims to improve the mechanistic understanding of tissue failure and to support the development of safer therapeutic strategies and better-informed biomedical interventions.
The project pursued three main objectives. First, it aimed to develop a micromechanical model capable of predicting local stress and strain fields in tissues under large deformations, explicitly accounting for tissue microstructure and time-dependent material behaviour. Second, it sought to identify the spatial and temporal mechanical signatures associated with fracture initiation and early crack propagation. Third, it focused on identifying anatomical and mechanical risk factors for rupture of the retinal pigment epithelium (RPE), a critical tissue whose failure can lead to irreversible vision loss.
The project pathway to impact is based on combining advanced computational modelling with human-relevant experimental systems. By integrating mechanics, applied mathematics, and biological experimentation, BIOFRAC contributes to EU priorities in health, biomedical innovation, and open science. The results are expected to have significant scientific impact by advancing fracture mechanics in soft matter, and societal relevance by improving understanding of tissue failure in disease contexts. Social sciences and humanities perspectives were indirectly integrated through education, outreach, and responsible research practices, supporting accessibility, transparency, and public engagement with EU-funded research.
