An injectable hydrogel loaded with Icariin attenuates cartilage damage in rabbit knee osteoarthritis via Wnt/β-catenin signaling pathway

Knee osteoarthritis (KOA) is a chronic disease characterized by joint wear and cartilage degeneration. Current clinical treatments are based on symptomatic relief and are not effective in regenerating cartilage, and inflammation-induced cartilage damage accelerates the progression of osteoarthritis, making the protection of articular cartilage important for controlling the development of knee osteoarthritis. In this study, a biodegradable hydrogel (HA-Ca-Alg@Ica) loaded with Icariin (Ica) was prepared by in situ cross-linking of hyaluronic acid-calcium complex (HA-Ca) and sodium alginate (Alg-Na) for local sustained delivery of Ica. The hydrogel promoted chondrocyte proliferation and inhibited the degradation of cartilage matrix by regulating key factors (Wnt3a, β-catenin and GSK-3β) in the Wnt/β-catenin signaling pathway. In addition, the hydrogel reduced the expression of inflammatory factors, including IL-1β, IL-6, TNF-α, COX-2, and MMP13, leading to a reduction in inflammation and pain relief. In summary, this hydrogel containing Icariin has shown significant effects in reducing chondrocyte degradation and promoting chondrocyte proliferation, which can play a role in delaying osteoarthritis by protecting chondrocytes. These findings offer innovative prospects for the therapeutic management of knee osteoarthritis.