Injectable Quercetin-Loaded Hydrogel with Cartilage-Protection and Immunomodulatory Properties for Articular Cartilage Repair

Articular cartilage plays an important role in human body. How to repair articular cartilage defects when they appear due to various factors has always been a major clinical challenge. Recently, studies have shown that slowing the degradation of cartilage extracellular matrix (ECM) and modulating the inflammatory response of the host thereby promoting cartilage tissue regeneration are important in the cartilage repair process. In this study, a drug-loaded injectable hydrogel was constructed for repairing articular cartilage. This hydrogel could not only maintain the phenotype of chondrocytes but also regulate the inflammatory response of the host. The injectable sodium alginate (SA)/bioglass (BG) hydrogel was mixed with the injectable thermal-responsive SA/agarose (AG)/quercetin (Que) hydrogel to obtain an injectable hydrogel containing both Que and BG (Que-BG hydrogel) for articular cartilage regeneration. The Que-BG hydrogel has a proper swelling ratio that can promote integration between the formed tissue and host tissue, and it allows Que to release slowly in situ to improve its bioavailability. The Que-BG hydrogel could upregulate SRY-box 9 (SOX9), aggrecan (ACAN), and collagen type II alpha 1 chain (COL2A1) of normal chondrocytes to maintain the normal chondrocyte phenotype. In addition, it could promote macrophage M2 polarization, reduce inflammation, and inhibit ECM degradation by downregulating the expression of inducible nitric oxide synthase (iNOS), matrix metalloproteinase-13 (MMP13), and matrix metalloproteinase-1 (MMP1) in degenerative chondrocytes. After injecting the Que-BG hydrogel into a rat cartilage defect model, the formed tissue was observed to be similar to the normal tissue and was highly integrated with the surrounding tissue. Therefore, the injectable Que-BG hydrogel improves Que bioavailability, maintains chondrocyte phenotype, inhibits ECM degradation, and reduces inflammatory response.