Neuroregulatory Biomaterials for Intervertebral Disc Regeneration via Neuro-Disc Microenvironment Modulation

Intervertebral discs have long been considered to lack neural innervation. However, recent studies have revealed that intervertebral disc degeneration is accompanied by marked pathological nerve invasion. In addition, the transmission mechanism of degeneration and related pain is exacerbated through the neural intervertebral disc microenvironment interaction network. Despite advances in this field, comprehensive reviews remain limited, and systematic analyses are lacking. In this review, we aimed to systematically analyze the potential application of "neural intervertebral disc microenvironment interaction" in the repair of intervertebral disc degeneration. First, in this article, we discussed the neural innervation and functional characteristics of healthy intervertebral discs, elaborated on the mechanism of abnormal nerve growth in the microenvironment of degenerated intervertebral discs, and explained how nerve invasion exacerbates intervertebral disc degeneration and its clinical symptoms by activating pain transmission pathways. Subsequently, we reviewed bioengineering strategies that provided new pathways for the innovative treatment of intervertebral disc degeneration through the synergistic effects of neural regulation and microenvironment interactions. Finally, we explored application prospects of neural-regulated biomaterials in precision medicine, clinical translation, and interdisciplinary fusion, providing a theoretical basis and technical guidance for neural-based intervertebral disc regeneration therapy.