Bionic ECM scaffolds for directional articular hyaline cartilage regeneration and long-term homeostasis maintenance

Cartilage defects play a key role in osteoarthritis, causing functional impairment as the disease progresses. Microfracture surgery is commonly used to treat articular cartilage defects, providing early pain relief and functional improvement. However, the blood clot formed during the procedure differs from the natural cartilage microenvironment, hindering hyaline cartilage formation and promoting fibrocartilage, which limits long-term outcomes. This study proposes combining a bionic flexible extracellular matrix (ECM) scaffold with microfracture surgery as a treatment for cartilage defects. By filling the microfracture site with the scaffold and thermosensitive agarose gel, we can anchor BMSCs leaking from the bone marrow while creating a 3D microenvironment that regulates stem cell differentiation. Our results show that the scaffold's mechanical strength is comparable to that of hyaline cartilage, offering excellent biomimetic properties and biocompatibility. In vitro, BMSCs migrating into the scaffold exhibited a survival rate of nearly 90 % by day 2, significantly higher than the 25 % survival rate in the control agarose gel group, with cells observed anchoring around the scaffold. In vivo, stem cells anchored to the scaffold successfully differentiated into articular hyaline cartilage, driven by the combined effects of the scaffold's physical structure and its contained cytokines. The generated hyaline cartilage maintains homeostasis over time, reducing the risk of fibrocartilage formation. This strategy addresses a key limitation of microfracture surgery, where regenerated cartilage is often fibrocartilage, offering a promising new approach for cartilage repair.