An injectable and self-healing hydrogel with controlled release of curcumin to repair spinal cord injury

The harsh local micro-environment following spinal cord injury (SCI) remains a great challenge for neural regeneration. Local reconstitution of a favorable micro-environment by biocompatible scaffolds with desirable functions has thus been an area of concern. Herein, a hybrid hydrogel was developed using Fmoc-grafted chitosan (FC) and Fmoc peptide (FI). Dynamic reversible pi-pi stacking interactions of the fluorenyl rings enabled the FC/FI hybrid hydrogel to exhibit excellent injectable and self-healing properties, as characterized by visual appearances and rheological tests. Furthermore, the FC/FI hybrid hydrogel showed a slow and persistent release of curcumin (Cur), which was named as FC/FI-Cur hydrogel. In vitro studies confirmed that with the support of FC/FI-Cur hydrogel, neurite outgrowth was promoted, and Schwann cell (SC) migration away from dorsal root ganglia (DRG) spheres with enhanced myelination was substantiated. The FC/FI-Cur hydrogel well reassembled extracellular matrix at the lesion site of rat spinal cord and exerted outstanding effects in modulating local inflammatory reaction by regulating the phenotypes of infiltrated inflammatory cells. In addition, endogenous SCs were recruited in the FC/FI-Cur graft and participated in the remyelination process of the regenerated nerves. These outcomes favored functional recovery, as evidenced by improved hind limbs movement and enhanced electrophysiological properties. Thus, our study not only advanced the development of multifunctional hydrogels but also provided insights into comprehensive approaches for SCI repair.