Schwann Cell Exosomes and Hyperbaric Oxygen Therapy Enhance Sciatic Nerve Regeneration and Functional Recovery After a Crush Injury in Rats

Peripheral nerve injuries, particularly sciatic nerve crush, are associated with limited regeneration and prolonged functional deficits. Recent studies highlight the regenerative potential of Schwann cell-derived exosomes (SCEx) and the neuroprotective effects of hyperbaric oxygen (HBO) therapy. This study aimed to evaluate the combined effects of SCEx and HBO on sciatic nerve regeneration in a rat model. Seventy-five adult male rats were randomly assigned to five groups (n = 15 each): sham, crush injury, crush injury treated with SCEx, crush injury treated with HBO, and crush injury treated with SCEx + HBO. Histological, biochemical, molecular, and functional assessments were conducted. SCEx and HBO, individually and in combination, significantly enhanced nerve fiber count and myelin sheath thickness compared to the crush group (p < 0.05). The combination group exhibited superior outcomes compared to monotherapies (p < 0.05). Molecular analysis showed decreased expression of pro-inflammatory genes IL-1β and TNF-α, and increased expression of the anti-inflammatory gene IL-10, particularly in the SCEx + HBO group. Biochemical assays revealed elevated antioxidant levels (GSH, SOD, CAT) and reduced lipid peroxidation (MDA) in treated groups, with combination therapy yielding the most pronounced effects. Functional recovery, evaluated via the sciatic functional index (SFI), was significantly improved in all treatment groups, especially in the SCEx + HBO group at all-time points. The co-administration of Schwann cell-derived exosomes and hyperbaric oxygen therapy synergistically enhances sciatic nerve regeneration through anti-inflammatory, antioxidative, and neuroregenerative mechanisms.