HEIndividual fellowship2023–2025

BIOFRAC · Modelling of fracture in soft biological tissues

Horizon Europe — Marie Skłodowska-Curie Actions

Duration
2023-12-16 → 2025-12-15
EU contribution
€172,750
Participants
2
Scheme
HORIZON-TMA-MSCA-PF-EF

Lines connect the coordinator with its partners.

Results in brief

Modelling of fracture in soft biological tissues

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.

Data: CORDIS, © European Union

Project objective

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.

Original text from CORDIS.

Participants

  • POLITECNICO DI MILANO · MilanoCoordinatorItaly
  • UNIVERSITY COLLEGE LONDON · LondonUnited Kingdom

Links

Data: CORDIS, © European Union