Peptide Hydrogel Incorporating Hydroxyapatite and Neural Stem Cells to Facilitate Spinal Cord Injury Regeneration

Introduction: Spinal Cord Injury (SCI) results in irreversible neuronal loss and glial scar formation, severely impairing motor function and quality of life. This study aimed to develop a bioactive composite scaffold—comprising Hydroxyapatite nanorods (HAp) and a selfassembling peptide hydrogel (IGL-Gel)—to promote Neural Stem Cell (NSC)-based regeneration in SCI treatment. Methods: HAp nanorods were synthesized via hydrothermal methods and incorporated into an acetylated peptide hydrogel functionalized with the IKVAV motif. The physicochemical properties, rheology, and self-healing behavior of the hydrogel were characterized. In vitro biocompatibility, NSC proliferation, and differentiation were evaluated using CCK-8 and RT-qPCR assays. In vivo therapeutic efficacy was assessed in a rat SCI model via behavioral tests (BBB scoring, inclined plane test), immunofluorescence staining, and biochemical analysis. Results: The Hap-IGL-Gel composite showed favorable mechanical strength, injectability, and rapid self-recovery. In vitro studies confirmed excellent cytocompatibility and enhanced NSC proliferation and neuronal and astrocyte differentiation at an optimal HAp concentration of 200 μg/mL. In vivo, rats treated with Hap-IGL-Gel and NSCs showed significantly improved motor recovery, reduced glial scar formation, enhanced neuronal regeneration, and restored bladder and organ function compared to controls. Discussion: The incorporation of HAp into the peptide hydrogel provided sustained ionic cues to support NSC differentiation and maturation, while the IKVAV motif enhanced cellular adhesion and neurite outgrowth. The composite hydrogel provided a permissive environment for regeneration, addressing both local injury and systemic complications of SCI. Conclusion: Hap-IGL-Gel is a promising biomaterial for SCI repair, effectively promoting NSC survival and differentiation, facilitating axonal regeneration, and restoring motor function. These findings support its potential for clinical translation in neuroregenerative therapies.