<b>Tissue-Engineered Neural Stem Cell Scaffolds in Spinal Cord Injury: Insights into Materials, Molecular Pathways, and Regenerative Applications</b>

Spinal cord injury (SCI) poses significant regenerative challenges because the central nervous system (CNS) has a limited intrinsic ability to repair itself after damage. The complex nature of SCI, including neuronal loss, glial scarring, and disrupted neural pathways, makes effective treatment difficult. In recent years, stem cell–based scaffolds have emerged as a promising therapeutic strategy aimed at facilitating functional recovery. These scaffolds provide a supportive three-dimensional (3D) structure that closely mimics the natural extracellular matrix (ECM) of the spinal cord. This biomimetic environment plays a crucial role in enhancing the differentiation of neural stem cells (NSCs). By guiding NSC behavior and integration into the injured spinal tissue, these scaffolds can help restore some degree of neural function. The synergy between stem cells and engineered scaffolds offers a multifaceted approach to spinal cord regeneration and holds substantial potential for clinical applications. A variety of biomaterials including natural and synthetic polymers, as well as hydrogels, have been developed for this purpose, often enhanced by growth factors, neurotrophic agents, and electrical stimulation to boost axonal regeneration and remyelination. Key signaling pathways like Notch, Wnt/β-catenin, Shh, and BMP play a role in guiding NSC differentiation and are being explored as therapeutic targets. Preclinical studies have shown functional improvements with scaffold-assisted cell delivery, and early clinical trials using collagen scaffolds with umbilical cord–derived MSCs show promising results. However, challenges such as immune response, scaffold degradation, and cost remain, highlighting the need for further research to ensure safe and effective clinical application.