Engineered human nucleus pulposus-derived decellularized matrix hydrogel loaded with hNPMSCs for degenerative disc regeneration.

Intervertebral disc degeneration remains a persistent clinical challenge, necessitating the development of functional biomaterials for repair. This study developed a cell-delivery system utilizing a human-derived decellularized extracellular matrix (hNP-dECM) and human nucleus pulposus-derived mesenchymal stem cells (hNPMSCs) to promote nucleus pulposus regeneration. hNP-dECM scaffolds were fabricated from human NP tissues, demonstrating effective decellularization with substantial preservation of key ECM components. hNPMSCs exhibited characteristic mesenchymal stem cell phenotypes and multilineage differentiation potential. A dual-crosslinked hydrogel was synthesized from hNP-dECM, chitosan, genipin, and tannic acid, which showed suitable mechanical properties, high porosity, thermosensitivity, and excellent support for cell viability. In a rabbit model of disc degeneration, the system proved biosafe and significantly attenuated degenerative progression. This was evidenced by reduced T2 signal loss on MRI, upregulation of anabolic genes, suppression of catabolic MMP-13 expression, and enhanced type II collagen deposition. In conclusion, the hNP-dECM-based dual-crosslinked hydrogel provides a biocompatible and mechanically adaptive microenvironment conducive to the delivery of hNPMSCs and the promotion of disc regeneration in vivo.