Construction of a sustainably NO-releasing RGDC grafted chitosan oriented peripheral nerve scaffold

Peripheral nerve injury repair is hindered by an imbalanced regenerative microenvironment involving inflammation, oxidative stress, and inadequate blood supply. Traditional drugs are limited by poor blood-nerve barrier penetration and lack of multifunctionality. Nitric oxide (NO) is crucial for axonal growth, synaptic plasticity, and neuroprotection, offering anti-inflammatory, antioxidant and pro-angiogenic potential. However, uncontrolled NO release causes toxicity. To leverage NO therapeutically, sustained delivery is essential. This study developed a multifunctional nerve graft using a modified chitosan hydrogel grafted with RGDC peptide, featuring an internal orientation microstructure. Glutathione was incorporated as a precursor for the NO donor S-nitrosoglutathione (GSNO). This system promotes cell adhesion/migration and reduces oxidative stress. Results show the hydrogel is non-cytotoxic and synergistically enhances cellular adhesion. GSNO loading significantly reduces cellular reactive oxygen species (ROS) levels in human umbilical vein endothelial cells (HUVECs), facilitating their migration and angiogenesis. The GSNO-incorporated neural scaffold achieved sustained NO release and demonstrated significant antioxidant capacity. This innovative approach presents a promising strategy for clinical application in peripheral nerve injury repair.