A novel oxygen-releasing bilayer delivery system for cell survival and peripheral nerve regeneration.

Peripheral nerve injuries with long-gap defects pose a major regenerative challenge due to hypoxic microenvironments that impair cell survival and nerve repair. Here, we engineered a bilayer microsphere delivery system that encapsulates Perfluorotributylamine (PFTBA) within a PLGA core and an outer chitosan coating to achieve sustained oxygen release. In vitro, P-PLGA/CS markedly enhanced olfactory ensheathing cell proliferation and survival, reduced apoptosis, and boosted secretion of neurotrophic and angiogenic factors under hypoxic conditions. In vivo, a polycaprolactone conduit loaded with P-PLGA/CS and OECs bridged a 15 mm critical-sized sciatic nerve defect in rats, resulting in augmented axonal regeneration and remyelination, and superior functional recovery compared with controls. Collectively, our oxygen-delivery bilayer system provides a robust microenvironment that supports cell viability and promotes nerve regeneration, offering a translational platform for enhancing peripheral nerve repair under hypoxic conditions.