Anti-Inflammatory and Prochondrogenic In Situ-Formed Injectable Hydrogel Crosslinked by Strontium-Doped Bioglass for Cartilage Regeneration

Directed differentiation of bone marrow mesenchymal stem cells (BMSCs) toward chondrogenesis plays a predominant role in cartilage repair. However, the uncontrolled inflammatory response to implants is found to impair the stability of scaffolds and the cartilage regeneration outcome. Herein, we fabricated an injectable hydrogel crosslinked by strontium-doped bioglass (SrBG) to modulate both human BMSC (hBMSC) differentiation and the inflammatory response. The results revealed that the introduction of Sr ions could simultaneously enhance the proliferation of hBMSCs, upregulate cartilage-specific gene expression, and improve the secretion of glycosaminoglycan. Moreover, after cultured with SA/SrBG extracts in vitro, a majority of macrophages were polarized toward the M2 phenotype and subsequently facilitated the chondrogenic differentiation of hBMSCs. Furthermore, after the composite hydrogel was injected into a cartilage defect model, neonatal cartilage-like tissues with a smooth surface and tight integration with original tissues could be found. This study suggests that the synergistic strategy based on an enhanced differentiation ability and a regulated inflammatory response is promising and may lead the way to new anti-inflammatory biomaterials.

Automated summary

This study demonstrates successful modulation of human BMSC differentiation and inflammatory response using a hydrogel crosslinked by strontium-doped bioglass. The introduction of Sr ions not only enhanced cell proliferation, upregulated cartilage-specific gene expression, and improved glycosaminoglycan secretion, but also facilitated macrophage polarization and subsequent chondrogenic differentiation. Injection of the composite hydrogel into a cartilage defect model resulted in the formation of neonatal cartilage-like tissues with smooth surface and tight integration with original tissues, showing promise for new anti-inflammatory biomaterials.