A skin substitute optimised using mechanobiological simulation to restore weight-bearing function

ended

Large or chronic wounds affect 4 million people in the EU each year. Tissue engineered skin substitutes offer the potential to enhance the repair and regeneration of these wounds. However, there are currently no skin substitutes that can fully restore the weight-bearing function of foot skin. Therapies to reconstruct the foot sole are urgently needed, with an increasing prevalence of diabetic foot ulcers that cost the EU €4 billion annually and have a five-year survival rate as low as 29%. Native skin’s load-bearing structure is dynamic and adaptable to changes in its mechanical environment. By studying the mechanical forces that lead to robust native skin, we can enhance regenerative therapies. The aim of this project is to enhance skin substitute design by optimising its properties using mechanobiological simulation, providing the basis for site-specific skin regeneration that targets weight-bearing function. The specific objectives of this project are: 1. To quantify cell-level mechano-regulation processes in human skin. A dynamic bioreactor will be designed to control the mechnical environment of human skin explants while the cell-level biological responses to load are quantified. 2. To optimise the mechanobiological properties of a skin substitute. A multi-scale computational model of skin mechano-regulation will be developed and used to predict the optimal mechanical and morphological properties for skin regeneration. 3. To demonstrate that this optimisation leads to enhanced dermal substitutes. The optimised skin substitute will be fabricated using bioprinting and micropatterning methods. This substitute will be tested in vitro for its ability to promote robust epidermis formation. This proposal involves substantial knowledge transfer, with the candidate gaining expertise in biomaterials and regenerative medicine, while providing the host with computational modelling and skin biology expertise. This proposal will enhance and broaden the candidate's career.