Photo‐crosslinked gelatin‐hyaluronic acid methacrylate hydrogel‐committed nucleus pulposus‐like differentiation of adipose stromal cells for intervertebral disc repair

: Nucleus pulposus-like differentiation is always the challenge with application of stem cells for intervertebral disc repair. The combination of injectable biomaterials and stem cells may provide a resolution for this problem, as the transmembrane force can affect the intracellular environment through integrin αβ. In this study, we developed a strategy of photo-crosslinked gelatin-hyaluronic acid methacrylate (GelHA) hydrogel to commit the nucleus pulposus-like differentiation of adipose stromal cells (ASCs) for intervertebral disc repair. ASCs were isolated and cultured in GelHA hydrogel to evaluate nucleus pulposus-like differentiation. The function of integrin αvβ6 was investigated with neutralising antibody. The efficacy of ASCs with GelHA hydrogel for intervertebral disc repair was studied in a rat model of intervertebral disc degeneration. The results showed that GelHA hydrogel promoted ASCs nucleus pulposus-like differentiation and that integrin αvβ6 neutralising antibody prevented ASCs from expression of nucleus pulposus matrix in vitro. The combination of GelHA hydrogel and ASCs promoted quality intervertebral disc repair in rats with much more nucleus pulposus matrix and significantly higher disc height index. The findings have demonstrated that the combination of photo-crosslinked GelHA hydrogel and ASCs can commit ASCs to nucleus pulposus-like differentiation and improve the efficacy of ASCs for intervertebral disc repair. These findings suggest a promising stem cell-based strategy for intervertebral disc repair.