Mussel-inspired coaxial electrospun nanofiber membranes promote scarless oral mucosal repair by enhancing macrophage M2 polarization.

Abstract

The repair of oral mucosal defects is often hindered by the failure of traditional materials to maintain adhesion in humid, dynamic environments. Inspired by the wet-adhesion properties of mussels, we developed a biomimetic self-adhesive nanofibrous membrane via coaxial electrospinning. This membrane utilizes a polycaprolactone (PCL) core for mechanical strength and a dopamine (DA)-modified gelatin methacrylate (GelMA) shell for biocompatibility and adhesion. Experimental results demonstrate that the membrane possesses excellent mechanical properties, with a tensile strength of 2.52 MPa and a swelling degree of 554.6%. The incorporation of 2% DA significantly enhanced wet-adhesive strength to 30.53 kPa, allowing for stable adhesion to oral tissues for over 24 h. In vitro experiments demonstrated good cytocompatibility and promoted fibroblast adhesion and proliferation. In vivo studies using murine skin and rat oral mucosal defect models showed accelerated wound closure, reduced scar formation, and improved tissue regeneration. Immunological analyses revealed that the DA-modified nanofiber membrane modulated the local immune microenvironment by promoting macrophage polarization toward the anti-inflammatory M2 phenotype. Transcriptomic analysis and subsequent molecular validation identified activation of the peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathway as a key mechanism underlying this immunoregulatory effect. These results demonstrate that the mussel-inspired coaxial nanofiber membrane provides stable wet adhesion and actively regulates immune responses to promote scarless healing of oral mucosal defects, highlighting its potential as a functional biomaterial for soft tissue repair.