Polydopamine-functionalized 3D-printed scaffold co-loaded with resveratrol and NGF for enhanced neuronal differentiation under inflammatory stress

To address core issues in spinal cord injury repair such as oxidative stress, excessive inflammation and impaired nerve regeneration, this study developed a 3D-printed multifunctional PCP-Res-NGF scaffold. The scaffold achieves stable loading of resveratrol and nerve growth factor by sequentially coating chitosan and polydopamine on the polylactic acid skeleton. Experiments show that the scaffold has pH/ROS dual-responsive drug release characteristics, fitting the S-type Weibull model in simulated injury environments and following a first-order kinetic model under physiological conditions; it exhibits significant scavenging capabilities against DPPH, ·OH, and H 2 O 2 , effectively reducing intracellular ROS levels, an effect attributed to the radical quenching properties of polydopamine and the dual action of resveratrol. By inhibiting the NLRP3 inflammasome, the scaffold shifts lipopolysaccharide-stimulated macrophages from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype, as evidenced by reduced iNOS expression (from 19.62 to 3.43) and increased ARG-1 expression (from 2.06 to 6.04). Furthermore, the scaffold promotes the differentiation of injured PC12 cells into MAP2-positive neurons. In the PCP-Res-NGF (LPS-PR) group, the neurite length reached 119.59 μm, representing a 13.26% increase compared to the LPS-only control group. This scaffold provides a promising therapeutic platform for spinal cord injury repair through synergistic antioxidant, anti-inflammatory and neurodifferentiation-promoting effects.