Hydrogel Encapsulating Platelet Lysate-Derived Microvesicles Promoted Facial Nerve Repair

Facial nerve injury (FNI) is one of the most common oral and maxillofacial injuries. Current surgical treatments for FNI are technically challenging and often yield uncertain prognoses. This study investigates a novel repair strategy for FNI with an adhesive and self-healing hydrogel encapsulating platelet lysate-derived extracellular vesicles (pEVs), and explores its underlying effect mechanisms. pEVs were encapsulated in a phenol-modified chitosan/dual-functionalized polyethylene glycol (PCDP) hydrogel with adhesive and self-healing properties. The release kinetics and material characterization of pEVs-loaded hydrogels were analyzed. In vitro experiments evaluated the anti-inflammatory and pro-angiogenic effects of pEVs and validated the associated signaling pathways. In FNI rats, the hydrogel was applied to the injured site to assess motor function recovery and histological repair. pEVs exerted anti-inflammatory effects by suppressing the p65/NF-κB pathway via PPAR activation and promoted angiogenesis through the c-Met/HGF pathway, respectively. Rats treated with pEVs-loaded hydrogels demonstrated superior function recovery. Immunohistochemical analysis revealed that the hydrogel-mediated delivery of pEVs created a favorable microenvironment for nerve regeneration by mitigating inflammation and enhancing vascularization. Platelet lysate-derived extracellular vesicles (pEVs), leveraging their multi-target neurotrophic, anti-inflammatory, and pro-angiogenic properties, represent a promising therapeutic strategy for facial nerve repair. The integration of pEVs with functionalized hydrogels holds significant potential for clinical translation.