A computational model reveals an early transient decrease in fiber cross-linking that unlocks adult regeneration

• Published in: npj Regenerative medicine Vol. 9; no. 1; pp. 29 - 9
• Main Authors: Pacary, Anastasia, Peurichard, Diane, Vaysse, Laurence, Monsarrat, Paul, Bolut, Clémence, Girel, Adeline, Guissard, Christophe, Lorsignol, Anne, Planat-Benard, Valérie, Paupert, Jenny, Ousset, Marielle, Casteilla, Louis
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.10.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/443; 631/80; Adipocytes; Biomaterials; Biomedical and Life Sciences; Biomedicine; Body fat; Cell Biology; Hypotheses; Immunology; Regenerative medicine; Regenerative Medicine/Tissue Engineering; Scars; Sensitivity analysis; Stem Cells; Tissue engineering
• ISSN: 2057-3995; 2057-3995
• DOI: 10.1038/s41536-024-00373-z

The decline in regeneration efficiency after birth in mammals is a significant roadblock for regenerative medicine in tissue repair. We previously developed a computational agent based-model (ABM) that recapitulates mechanical interactions between cells and the extracellular-matrix (ECM), to investigate key drivers of tissue repair in adults. Time calibration alongside a parameter sensitivity analysis of the model suggested that an early and transient decrease in ECM cross-linking guides tissue repair toward regeneration. Consistent with the computational model, transient inhibition or stimulation of fiber cross-linking for the first six days after subcutaneous adipose tissue (AT) resection in adult mice led to regenerative or scar healing, respectively. Therefore, this work positions the computational model as a predictive tool for tissue regeneration that with further development will behave as a digital twin of our in vivo model. In addition, it opens new therapeutic approaches targeting ECM cross-linking to induce tissue regeneration in adult mammals.