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

Intervertebral disc (IVD) degeneration is a pathological process that affects the molecular, cellular , tissue levels, but neither conservative nor surgical treatments currently address its root causes. Recent developments in genetic engineering , tissue engineering technologies indicate that a biomedical treatment for IVD degener-ation 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-beta 3 (TGF-beta 3) 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-beta 3 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-beta 3. 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.

Automated summary

Intervertebral disc degeneration is a common disease and current treatments do not address the root causes. Recent advancements in genetic engineering and tissue engineering suggest that a gene vector and hydrogel carrier could be used for effective treatment.