Abstract

Oral mucosal lesions, prevalent and multifactorial disorders characterized by immune dysfunction and infection, pose significant challenges to oral functions due to the lack of effective and safe treatments. We herein introduce a multifunctional microneedle patch (MMP) that uniquely combines bone marrow mesenchymal stem cell-derived exosomes (Exos) and folic acid-magnetic nanoparticles (Fmns) within a methacrylated carboxymethyl chitosan (CMCSMA) microneedle structure. This innovative design synergistically enhances therapeutic outcomes by promoting immune regulation, angiogenesis, and epithelial repair. The MMP also features a gelatin layer for rapid pain relief via local anesthetic release and provides antimicrobial protection against opportunistic pathogens, reducing secondary infection risks. In vitro and in vivo results showed significant improvements in wound closure rates, re-epithelialization, and angiogenesis compared to control treatments. Additionally, the MMP effectively modulated immune responses, reducing inflammatory cytokine levels and promoting macrophage polarization towards a pro-healing phenotype. These findings demonstrate the efficacy and biosafety of the MMP, and highlight its potential to address critical clinical challenges in treating oral mucosal lesions, offering a multifunctional approach that integrates immune modulation, infection control, and regenerative therapy.

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