Extracellular matrix particle treatment induces digit regeneration in soft-tissue preserved amputation (SPA) model of adult mice

Abstract

BackgroundIn mouse classic amputation model, second phalanx (P2) is incapable of regeneration. Extracellular matrix (ECM) solution has shown limited ability to induce digit regeneration in classical amputation model of the murine digit. However, the effect of solid ECM particles on bone regeneration is not well understood due to difficulties in treating solid particles in classical amputation model. MethodsWe examined the regenerative effects of ECM particles in mice digit by establishing a soft tissue preserved amputation (SPA) model on P2, through removing the amputated bone whilst preserving soft tissue. ECM particles implanted into the amputation site and wrapped in the preserved soft tissues. Bone regeneration was assessed by morphological examination and micro-CT scans. ResultsWe observed bone regeneration in the SPA model; specifically, new bone formed at the P2 distal end. Implantation of ECM particles exerted a pro-regenerative effect, characterized by increased bone volume and decreased bone density. Moreover, the ECM induced the formation of free-floating bone, further supporting its role in bone regeneration. Combined treatment with ECM particles and bone morphogenetic protein 2 (BMP2) resulted in a significant increase in bone volume. ConclusionsWe demonstrate that soft tissue preservation at the amputation site can overcome the intrinsic regenerative limitationsl. Using SPA model, we found that ECM particles have a proven ability to promote bone regeneration, and that the combination of ECM particles with BMP2 further enhances bone regeneration. These findings underscore the therapeutic promise of ECM-based strategies, for clinical translation in non-regenerative finger injuries. Summary statementSolid-state Extracellular matrix can induce mice digit regeneration and has the potential for clinical application. HighlightsThe SPA model we developed enables ECM particles to adhere to wounds, and our research has found that: O_LIDigit bone regeneration was shown in SPA model . C_LIO_LIECM particles treatment promoted bone regeneration and can generate free-floating bone in SPA model. C_LIO_LICombination of ECM + BMP2 treatment induced strong digit regeneration in SPA model. C_LI