Unidirectional and sustainable release of NGF and BDNF from a chitosan gel-mediated multilayer ordered composite membrane in promoting both spinal cord and sciatic nerve injury repair

To develop a scaffold suitable for simultaneous repair of both spinal cord injury (SCI) and sciatic nerve injury (SNI), we designed a multilayer composite membrane capable of unidirectional and sustained release of two factors: nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). The membrane's morphology, mechanical properties, cytocompatibility, drug release kinetics, swelling, and degradation behavior were thoroughly characterized. Additionally, its ability to promote the differentiation of PC-12 cells was assessed. The findings indicated that the composite membrane featured a tri-layered structure and exhibited robust mechanical strength, enabling it to protect and regulate the release of NGF and BDNF. This regulation ensured the appropriate timing and concentration of the factors necessary for cell differentiation and growth. Moreover, the membrane demonstrated excellent cell compatibility and significantly fostered the differentiation of PC-12 cells into axons. In rat models of SCI and SNI, the composite membrane markedly enhanced axon and neuron regeneration, myelination, neural stem cell proliferation, and nerve fiber clustering, while reducing astrocyte formation. It also improved the integrity of spinal cord tissue and motor function recovery, suggesting that this scaffold holds promise for the repair of both SCI and SNI.