Bioactive hydrogel encapsulated dual-gene engineered nucleus pulposus stem cells towards intervertebral disc tissue repair

Abstract

Intervertebral disc (IVD) degeneration is a pathological process that affects the molecular, cellular, and tissue levels, but neither conservative nor surgical treatments currently address its root causes. Recent developments in genetic engineering and tissue engineering technologies indicate that a biomedical treatment for IVD degeneration may be possible. Lentivirus has been utilized in this study as a gene vector to introduce insulin-like growth factor-1 (IGF-1) and transforming growth factor-β3 (TGF-β3) into nucleus pulposus mesenchymal stem cells (NPMSCs) for the first time. This resulted in the construction of dual-gene engineered seed cells that could differentiate into nucleus pulposus cells overexpressing both IGF-1 and TGF-β3 growth factors. A bicomponent polymer network (BCN) hydrogel based on gelatin methacrylate (GelMA) and hyaluronic acid methacrylate (HAMA) was prepared and used as a carrier to deliver genetically engineered NPMSCs to the target tissues. BCN hydrogels effectively upregulated the extracellular matrix expression and nucleus pulposus differentiation after being loaded with NPMSCs overexpressing IGF-1 and TGF-β3. The novel biotherapeutic modality presented could be used to repair degenerated IVD tissues, replenish seed cells with a rich potential, and promote extracellular matrix synthesis and nucleus pulposus differentiation, thereby providing a theoretical basis and experimental rationale for the etiological treatment of IVD degeneration.