Mechanotherapy: Modulating immune cell function in tissue regeneration and fibrosis

Ward, Niamh A., Prendeville, Hannah, Wallace, Eimear J., Shokrani, Parand, Trask, Lesley, Dillon, Rachael, Beatty, Rache, Roche, Ellen T., Duffy, Garry P., Dolan, Eimear B. (2025). Mechanotherapy: Modulating immune cell function in tissue regeneration and fibrosis. Acta Biomaterialia. https://doi.org/10.1016/j.actbio.2025.08.048

Abstract

Mechanotherapy – therapy which uses mechanical forces to produce a remedial or prophylactic effect – has great potential to improve therapeutic outcomes in the fields of regenerative medicine and drug delivery due to its adaptable and tunable nature. In particular, numerous in vivo studies have demonstrated the ability of mechanotherapies to improve functional muscle regeneration and modulate fibrosis. However, the cellular interactions that underlie these tissue level responses are poorly understood. To further harness the potential of mechanotherapies and inform their design and development, a more comprehensive understanding of immune cell responses to mechanical loading is required. Here, we review findings from preclinical investigations of mechanotherapies as both a treatment for muscular injury and as an immunomodulating component of medical implants. We then discuss the mechanosensitive nature of immune cells, emphasizing how mechanical loading and microenvironmental stresses can influence immune signalling pathways in the context of tissue regeneration and fibrosis. Finally, we offer our perspective on the future of the field, including the challenges facing mechanotherapeutic device development and the potential to further broaden the therapeutic targets of mechanotherapies.

Publisher

Elsevier and Acta Materialia

Rights

CC BY

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