A novel hydrogel-based combination therapy for effective neuroregeneration after spinal cord injury

Abstract Spinal cord injury (SCI) remains a challenging clinical problem worldwide. Combination therapy is a promising therapeutic strategy for SCI. Recent investigations have reported that docetaxel (DTX) facilitates intrinsic axonal regeneration, and basic fibroblast growth factor (bFGF) regulates neuronal survival, plasticity, and extracellular matrix (ECM) after SCI. We constructed a novel biocompatible liposome (LIP) with a silk fibroin (SF) hydrogel core (SLIP) to simultaneously deliver bFGF and DTX, which have different physiochemical characteristics. Subsequently, SLIP-bFGF/DTX was added to the SF hydrogel to form a three-dimensional scaffold gel (SLIP-bFGF/DTX@SF). We evaluated the pharmacological properties of SLIP@SF and investigated histological and functional outcomes. A SLIP-bFGF/DTX@SF treatment effectively prolonged the drug half-life in the injured spinal cord area, bridged cysts by remodeling the extracellular matrix (ECM), and improved the motor function of rats with SCI. Additionally, this hydrogel demonstrated a strong affinity for the polysaccharides enriched in the lesion area providing a unique therapeutic approach for the treatment of SCI. Furthermore, the mechanisms of inhibition of microtubule dynamics and reshaping of the ECM by the drugs were demonstrated to reflected the pathological features of SCI. This novel multidrug delivery system achieves a significant functional improvement a simultaneously addresses multiple key aspects of SCI pathology indicating favorable clinical translational prospects.