Enhancing BMSC chondrogenesis with a dynamic viscoelastic hyaluronan hydrogel loaded with kartogenin for cartilage repair

作者：Guanrong Li, Renhao Ni, Zheyuan Shi, Haijiao Mao, Yang Luo, Xu Cao, Chi Zhang, Yuetian Liu, Zhanping Jin, Jun Chen, Jun Fu, Hua Zhang, Yingchun Zhu · 发表于：International Journal of Biological Macromolecules · 年份：2025 · DOI：10.1016/j.ijbiomac.2025.144042 · 被引用次数：10 · 研究领域：Osteoarthritis Treatment and Mechanisms、Proteoglycans and glycosaminoglycans research、Silk-based biomaterials and applications

Hydrogel-based cartilage tissue engineering (HCTE) offers a promising strategy for the regeneration of articular cartilage. However, the effectiveness of current HCTE is hindered by the low efficiency of stem cell transplantation and insufficient chondrogenic differentiation. Here, we develop a mechanically optimized and biochemically sustained biomaterial system that integrates a dynamic hydrazone/covalent dual-crosslinked hyaluronan (HA) hydrogel with kartogenin (KGN)-loaded poly(lactic-co-glycolic acid) microspheres to facilitate stem cell chondrogenesis and repair articular cartilage. This composite hydrogel features excellent injectability and self-healing behavior, allowing for minimally invasive implantation while protecting cell viability. The tunable viscoelasticity of the hydrogel enhances focal adhesion formation in bone-marrow mesenchymal stem cells (BMSCs), promoting their spreading, proliferation, and aggregation. Furthermore, the combined effects of hydrogel viscoelasticity and sustained KGN release markedly promote the expression of cartilage-specific genes and the secretion of extracellular matrix components through the integrin-mediated Hippo signaling pathway and KGN-mediated TGF-β signaling pathway. This dual-stimuli hydrogel embedded with BMSCs significantly promotes the regeneration of articular cartilage in rabbit models. Overall, the designed KGN composite dynamic HA-based hydrogel enables highly effective transplantation and promotes efficient chondro...