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

Project Information

SKIN-REGEN-MECH

Grant agreement ID: 892407

DOI

10.3030/892407

Project terminated on 9 June 2023

EC signature date 16 April 2020

Start date 1 October 2020

End date 30 January 2024

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 196 590,72

EU contribution

€ 196 590,72

Coordinated by

ROYAL COLLEGE OF SURGEONS IN IRELAND
Ireland

Periodic Reporting for period 1 - SKIN-REGEN-MECH (A skin substitute optimised using mechanobiological simulation to restore weight-bearing function)

Reporting period: 2020-10-01 to 2022-09-30

Summary of the context and overall objectives of the project

Tissue-engineered skin is used to treat chronic wounds that affect nearly four million people in Europe alone. However, there is currently no effective solution for the weight-bearing function of foot skin, and with the increasing incidence of diabetic foot ulcers, there is a pressing need for new reconstructive therapies. The EU-funded SKIN-REGEN-MECH project developed computational and experimental models that can be used to enhance design of engineered skin. The project's results will improve the design of engineered skin and generate new substitutes for reconstructing the skin of the foot sole.

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 computational and experimental models, 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 was designed to control the mechnical environment of human skin explants while the cell-level biological responses to load are quantified.
2. To develop a multi-scale computational model of skin mechano-regulation
3. To predict the optimal mechanical and morphological properties for skin regeneration in the foot sole.
This proposal involved 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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The MSCA Fellow delivered a series of work packages across three broad scientific objective areas: (1) a computational model for skin mechanobiology, (2) a bioreactor for ex vivo study of skin mechanobiology, and (3) an ex vivo model suitable for studying effects of skin injuries on native and engineered skin.

In work area (1), the Fellow successfully developed a computational model which could probe the biomechanics of skin at the cell level, and correlated this with cell behaviour. This work led to a manuscript currently in preparation for publication.

In work area (2), the Fellow successfully delivered a working prototype for a dynamic bioreactor capable of maintaining live skin samples at appropriate temperature and nutrient levels while delivering a precise, force-controlled mechanical load. This work has been backed up by technical documentation and validation tests, which will enable long-term exploitation within the Tissue Engineering Research Group. A manuscript detailing the design principles, and validation testing is planned.

In work area (3), the Fellow developed and validated an ex vivo model in which the effects of adverse loading on the skin can be accurately recorded using a commercial, non-invasive scannign device. This work has laid the foundation for evaluating the robustness of tissue engineered skin in animal model testing in the future. This work has also led to a publication currently under second review.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

This research project will have a strong impact on the Fellow's career, and on the host institution. The expertise gained while delivering this research will assist the Fellow in pursuing a career in medical device innovation, testing and design. The experience gained by the Fellow in Tissue Engineering will ensure that their future scientific contributions will enhance the field. The expertise and knowledge transferred to the host institution in the fields of computational modelling and skin biology will enhance the delivery of therapeutics from the lab focused on skin repair and regeneration.

The research delivered in this project will have impact by supporting the development of therapies for skin repair and regeneration. The models developed in this project have the potential to accelerate the development of novel therapeutic devices and approaches.

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