Matrix-bound nanovesicles drive the engineering of immunomodulatory meshes for abdominal hernia repair.

Abstract

Immunomodulatory responses to implanted meshes are critical determinants of abdominal hernia repair, as they orchestrate host cellular activities within distinct immune microenvironments to drive tissue remodeling. Matrix-bound nanovesicles (MBVs) are bioactive components embedded within the extracellular matrix (ECM), which are released during ECM degradation to mediate biological events via cell-matrix interactions. Notably, MBVs encode tissue-specific bioinformation from their parental ECM, making them promising candidates for enhancing mesh immunomodulation. In this study, MBVs were isolated from decellularized human amniotic membrane (dHAM) through sequential enzymatic digestion followed by ultracentrifugation. The isolated vesicles exhibited nanoscale bilayered morphology but lack the expression of typical extracellular vesicle markers. The MBVs demonstrated good biocompatibility and were effectively internalized by various cell types. Under inflammatory stimulation, dHAM-derived MBVs promoted macrophage polarization toward an anti-inflammatory phenotype and exhibited dose-dependent antioxidant effects. To develop an immunoregulatory mesh, MBVs were incorporated into poly(lactic acid-co-ε-caprolactone)/silk fibroin (PLCL/SF) fibers via aqueous coaxial electrospinning, resulting in a biocompatible, degradable and mechanically sufficient mesh (PSM) featuring a core-shell structure for sustained MBV release in vitro. The immunomodulatory effect of the PSM mesh was confirmed by macrophage polarization profiles, pro- and anti-inflammatory cytokine expression, and enhanced antioxidant capacity. This work demonstrates that the integration of tissue-specific MBVs into electrospun meshes represents a promising strategy to modulate immune response in mesh-aided hernia repair and provides new insights into the therapeutic potential of MBVs for regenerative medicine.