Hierarchically functionalized PCL/CS with synergistic PDA-mediated antioxidant therapy and NGF-activated neurogenesis for spinal cord injury regeneration

Spinal cord injury (SCI) is a common disease worldwide. Tissue engineering scaffolds are considered a promising strategy for SCI treatment, but their efficacy is significantly limited by the local abundance of MSC (mesenchymal stem cell) and a highly inflammatory microenvironment. In this study, a multifunctional composite scaffold of polycaprolactone/chitosan (PCL/CS) loading polydopamine (PDA)-coated nerve growth factor (NGF) loaded onto was prepared using a freeze-drying method. The PCL/CS composite scaffold exhibited tunable degradation properties and excellent biocompatibility. The PDA coating demonstrated potent free radical scavenging capabilities, achieving clearance rate of 90.65%, 77.53%, and 60.77% for DPPH, H2O2, and ·OH radicals, respectively. Remarkably, the scaffold effectively reduced intracellular ROS levels within 24 h under oxidative stress conditions. Flow cytometry revealed rapid cellular internalization, with the FITC-labeled PC-5-PDA group exhibiting a 99.87% FITC+ rate within 12 h. NGF release from the scaffold induced robust neuronal differentiation of PC-12 cells, as evidenced by a 58.1% increase in neurite length (from 104.77 μm at day 3 to 165.66 μm at day 4) and upregulated expression of microtubule-associated protein 2 (MAP2). These findings demonstrate the dual functionality of the scaffold, which is effectively modulating the post-SCI inflammatory microenvironment while promoting neural regeneration.