Bicomponent hydrogel laden with TGF-β3-nucleus pulposus stem cells for disc degeneration repair

Scheme 1. Schematic illustration. (A) Construction of genetically engineered TGF-β3-NPMSCs and bicomponent GH hydrogels. (B) Injection of TGF3-NPMSCs-GH hydrogel in IVD and its potential therapeutic mechanism. (C) “Transgenic Cell-Hydrogel” microenvironments provide multiple functions in IVD regeneration. [Display omitted] •TGF-β3 were introduced to nucleus pulposus mesenchymal stem cells;•Bicomponent polymer network hydrogels upregulated nucleus pulposus differentiation;•Bicomponent polymer network hydrogels upregulated extracellular matrix expression; Degenerative intervertebral disc (IVD) disease, which cannot be completely treated with open or minimally invasive surgery, is primarily caused by nucleus pulposus (NP) degeneration. Meanwhile, NP regeneration requires the intricate coordination of stem cells, growth factors, and biomaterials. The current study sought to develop a regenerative approach for IVD degeneration. To this end, we used a lentiviral vector to introduce the transforming growth factor-β3 (TGF-β3) gene into NP mesenchymal stem cells (NPMSCs) to construct genetically modified seed cells. In addition, bicomponent gelatin methacrylate/hyaluronic acid methacrylate (GH) hydrogels were synthesized based on gelatin methacrylate (GelMA) and hyaluronic acid methacrylate (HAMA) precursors as carriers for TGF-β3-NPMSCs delivery. In vitro differentiation of the loaded stem cells into NP-like structures was improved by the hydrogels' superior mechanical and cytocompatibility features. Moreover, the stem cell-loaded GH hydrogel was delivered to NP tissue via a minimally invasive approach to construct an injectable “transgenic cell-hydrogel” in situ microenvironment, which attenuated IVD degeneration, preserved the integrity of the NP tissue, and sped up extracellular matrix synthesis in a rat model. Collectively, the results of this study demonstrate the potential of this novel therapeutic strategy as an effective regenerative approach for IVD degeneration.