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

May 9, 2025International journal of biological macromolecules

Improving cartilage cell growth in bone marrow stem cells using a flexible gel with kartogenin for cartilage repair

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

The composite hydrogel significantly promotes the regeneration of articular cartilage in rabbit models.

A dual-crosslinked hyaluronan hydrogel integrated with kartogenin-loaded microspheres enhances stem cell chondrogenesis.
The hydrogel exhibits excellent injectability and self-healing properties, which protect cell viability during implantation.
Tunable viscoelasticity of the hydrogel is associated with improved spreading, proliferation, and aggregation of bone-marrow mesenchymal stem cells.
Sustained release of kartogenin enhances the expression of cartilage-specific genes and extracellular matrix secretion.
Chondrogenic effects are mediated through integrin-related Hippo signaling and kartogenin-related TGF-β signaling pathways.

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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 chondrogenesis of stem cells, providing a promising approach for stem cell therapy and cartilage regeneration.

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

Abstract

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