Spinal Cord Injury (SCI) is a devastating neurological disorder that often leads to permanent neural dysfunction. Current treatments fail to address the core challenges of insufficient intrinsic axonal regeneration, lack of directional guidance, and an inhibitory pathological microenvironment. There is an urgent need for synergistic therapeutic strategies that integrate structural support, molecular regulation, and microenvironment optimization to achieve effective neural function recovery.
Now, a joint research team from Zhejiang University and Fuzhou University has developed a collaborative treatment platform combining a multichannel 3D-printed bioactive scaffold with a small interfering RNA (siRNA) delivery system. This innovative approach simultaneously provides physical guidance, improves the inhibitory microenvironment, and activates the intrinsic regenerative capacity of neurons. In animal experiments, the combined therapy significantly enhanced long-distance parallel axon regeneration, promoted myelination and synaptic formation, and remarkably improved hindlimb motor function in SCI rats, with BBB scores significantly higher than other treatment groups from the 6th week post-surgery.
"The treatment of spinal cord injury has long been limited by the inability of single strategies to tackle multiple pathological barriers," said corresponding author Dr. Wei Wei, a professor at Zhejiang University. "Our integrated platform merges physical cues, biological signaling, and microenvironment regulation, offering a promising solution to overcome the bottlenecks in SCI therapy and advancing the translation from basic research to clinical application."
Jin Zhang, a professor at Fuzhou University and co-corresponding author, added: "The precision 3D-printed scaffold, functional hydrogel, and siRNA delivery system work synergistically to reconstruct neural circuits. This design not only enhances axonal regeneration but also ensures functional integration, laying a solid foundation for future clinical transformation."
Synergistic Triple-Function Design
The research team integrated three core functions into a single therapeutic system through innovative design:
1. A high-precision 3D-printed GM-PEGDA scaffold with parallel channels provides clear "growth paths" for axon regeneration, matching the structural characteristics of spinal cord conduction bundles.
2. GM-RA4IV bioactive hydrogel filled in the channels mimics the natural extracellular matrix, delivers neurotrophic support, and regulates the immune microenvironment by inhibiting the activation of harmful M1 macrophages.
