Collagen hydrogel-driven pyroptosis suppression and combined microfracture technique delay osteoarthritis progression

Abstract

The pathogenesis of osteoarthritis (OA), a disease causing severe medical burden and joint deformities, remains unclear. Chondrocyte death and osteochondral injury caused are the main pathological changes in OA. Thus, inhibiting chondrocyte death and repairing defective osteochondral are two important challenges in the treatment of OA. In this study, we found morphological changes consistent with cell pyroptosis in OA cartilage tissues. To inhibit chondrocyte pyroptosis and delay the progression of OA, we proposed to use decellularized extracellular matrix (dECM) and gelatin methacrylate (GelMA) to form a composite hydrogel GelMA/dECM. Regarding osteochondral defect repair, our proposed treatment strategy was hydrogel combined with microfracture (MF) surgery. MF established a biological link between the osteochondral defect and the bone-marrow cavity, prompting the recruitment of bone-marrow mesenchymal stem cells (BMSCs) to the osteochondral defect site, and the retained biopeptides in the hydrogel regulate the polarization of the BMSCs into hyaline cartilage, accelerating the repair of the defect. In vitro/vivo experiments and RNA sequencing analyses demonstrated that GelMA/dECM inhibited the occurrence of chondrocyte pyroptosis and delayed OA disease progression. Hydrogel also recruited numerous of BMSCs and contributed to chondrogenic differentiation, accelerating the in situ repair of defective osteochondral combined with MF. Collectively, GelMA/dECM composite hydrogel inhibited cartilage pyroptosis and reduced the pathway of chondrocyte death. Moreover, the hydrogel combined with microfracture technique could accelerate the repair of osteochondral defects. This is a groundbreaking attempt by tissue engineering, cell biology, and clinical medicine.