Potential of hyaluronic acid and collagen-based scaffolds in promoting stem cell neuronal differentiation for neuroregenerative therapies: A review

Stem cell therapy has revolutionized neurodegenerative disease treatment by presenting promising medical applications. Despite their potential, stem cell therapy remains constrained by various limitations, including low differentiation efficiency, difficulties in guiding differentiation, proliferation control, shorter half-life of growth factors, experimental reproducibility, etc. The cellular niche environment is pivotal in effective differentiation of stem cells. Neural regeneration ventures require biomaterial-based 3D scaffolds to simulate in-vivo tissue to solve the niche environment problem. Recent breakthroughs in neural regeneration have led to the development of a biomimetic scaffolds made of Hyaluronic acid (HA) and collagen (COL) that imitate the CNS's extracellular matrix (ECM) for better neural regeneration and repair. HA and COL based scaffold creates a favourable microenvironment for cellular migration, proliferation and survival of the embedded stem cells and promotes neural regeneration. HA regulates cellular activities while COL contributes in healing CNS injuries. Therefore, the utilization of HA-COL based scaffolds is appropriate for regulating cellular responses and behaviour for neural regeneration. This review investigates the synergy between HA and COL in the context of neural-specific applications for repair, regeneration, and recovery as well as augmentation of bioactivity through fabrication techniques such as 3D bioprinting, electrospinning, etc. for neural tissue regeneration.