Injectable nanostructured colloidal gels resembling native nucleus pulposus as carriers of mesenchymal stem cells for the repair of degenerated intervertebral discs

Intervertebral disc degeneration is strongly implicated as a cause of low-back pain. Stem cell-based tissue engineering in treating intervertebral disc (IVD) degeneration recently obtained increasing attention. An appropriately engineered scaffold is considered essential to maintain the viability and function of transplanted cells if it can provide a more physical-relevant condition to replicate the extracellular microenvironments and even to reverse the process of IVD degradation. Here we proposed to utilize nanostructured gelatin colloidal hydrogels loaded with mesenchymal stem cells (MSCs) for the treatment of IVD degeneration. The colloidal gel consisting of self-assembled gelatin nanoparticles formed a homogeneous porous network dispersed in a continuous phase of an aqueous solution. These special structural and compositional properties render the colloidal gels with shear-thinning and self-healing behavior, as well as injectability and moldability. More importantly, the mechanical properties of gelatin colloidal gels can be adjusted to resemble native nucleus pulposus (NP) which is also viscoelastic and thixotropic. Results demonstrated that gelatin colloidal gels were cytocompatible, biodegradable, and able to support the NP-like differentiation of MSCs. Also, gelatin colloidal gels had the potential to prevent leakage of MSCs and retain cell viability after injection. Upon transplantation into rabbit degenerated IVDs, mesenchymal stem cell-loaded nanostructured colloidal gels promoted IVD regeneration evidenced by the significant improvement in morphological and histological assessment, cellularity, glycosaminoglycan contents, disc height index, and MRI index. Taken together, these findings demonstrate the potential of stem cell-laden gelatin colloidal gels as a tissue-engineered construct for IVD repair and regeneration.