Injectable double-crosslinked hydrogels with kartogenin-conjugated polyurethane nano-particles and transforming growth factor β3 for in-situ cartilage regeneration.

Articular cartilage has a limited ability for self-repair after injury. Implantation of scaffolds functionalized with bioactive molecules that could induce the migration and chondrogenesis of endogenous mesenchymal stem cells (MSCs) provides a convenient alternative for in-situ cartilage regeneration. In this study, we found the synergistic effects of kartogenin (KGN) and transforming growth factor β3 (TGF-β3) on chondrogenesis of MSCs in vitro, indicating that KGN and TGF-β3 are a good match for cartilage regeneration. Furthermore, we confirmed that KGN promoted the chondrogenesis of MSCs through attenuating the degradation of Runx1, which physically interacted with p-Smad3 in nuclei of MSCs. Meanwhile, we designed an injectable double-crosslinked hydrogel with superior mechanical property and longer support for cartilage regeneration by modifying sodium alginate and gelatin. When loaded with KGN conjugated polyurethane nanoparticles (PN-KGN) and TGF-β3, this hydrogel showed biological functions by the release of KGN and TGF-β3, which promoted the MSC migration and cartilage regeneration in one system. In conclusion, the cell-free hydrogel, along with PN-KGN and TGF-β3, provides a promising strategy for cartilage repair by attracting endogenous MSCs and inducing chondrogenesis of recruited cells in a single-step procedure.