Engineered organoid precursor with micro-nano materials for boosting nucleus pulposus reconstruction after discectomy

Nucleus pulposus (NP) discectomy is a clinical procedure used to treat late-stage intervertebral disc degeneration. Although it can relieve pain symptoms, self-repair and regeneration of the NP tissues cannot be realized due to low regenerative capacity and inhibitory microenvironment. Here, we develop an engineered NP organoid precursor (OP) to reconstruct severely defective NP tissues, which is self-assembled and induced from bone marrow mesenchymal stem cells with functional micro-nanomaterials. Decellularized extracellular matrix microparticles from NP provide biomimetic matrix structure and enriched active ingredients to enhance the survival and chondrogenic differentiation of bone marrow mesenchymal stem cells. Commodified with transforming growth factor -β3, titanium carbide nanozyme with high reactive oxygen species scavenging capacity, exhibiting dual pro-differentiation and anti-inflammatory functions. The total integration of these functional components into 3D cell spheroid induces the formation of OP resembling certain structures and functions of the natural NP, as well as microenvironmental regulatory capabilities. In the rat nucleotomy model, the injection of pre-differentiated NP-OP significantly alleviates oxidative stress and inflammation, maintains disc height and water content, and accelerates new extracellular matrix deposition, thus promoting effective NP reconstruction. Overall, this engineered NP-OP provides a promising therapeutic approach for severe intervertebral disc degeneration.