Inflammatory responsive hydrogels incorporated with bevacizumab-loaded infinite coordination nanopolymers for accelerating cartilage repair

Cartilage injury repair remains challenging because of its unique physical structure and pathological micro-environment, including vascular invasion and inflammatory environment. In this study, inflammatory responsive hydrogels (TA-Mg@Bev iHGs) reinforced by bevacizumab (Bev)-loaded infinite coordination nanopolymer (TA-Mg@Bev) were fabricated for accelerated cartilage repair via anti-angiogenic and anti-inflammatory effects. The incorporation of TA-Mg@Bev iHGs enhanced the mechanical strength of TA-Mg@Bev via phenolic hydroxyl group-mediated hydrogen bond, enabling a sustained drug release under inflammatory environment. Moreover, the released TA-Mg@Bev greatly accelerated chondrogenic proliferation and differentiation from bone marrow mesenchymal stem cells but inhibited the hypertrophy of chondrocytes. The TA-Mg@Bev iHGs inhibited the proliferation of human umbilical vein endothelial cells and corresponding angiogenesis. In a rabbit model of full-layer cartilage defect, the TA-Mg@Bev iHGs promoted in situ cartilage regeneration through immunohistochemistry (type I collagen, type II collagen, and aggrecan). Overall, our study presents a cooperative induction system for accelerated cartilage regeneration.