Composite supramolecular hydrogel for osteoarthritis and cartilage repair enables localized and sustained drug delivery

Schematic diagram of the role of CSH in the in-situ treatment of arthritis and promotion of cartilage regeneration. CSH crosslinked through host–guest interactions can be injected into the joint cavity and adhere to the host tissue in vivo . CUR in the hydrogel induces the polarization of M1 macrophages to the M2 phenotype, and KGN in SNPs promotes the production of cartilage extracellular matrix, resulting in significantly enhanced chondrogenesis. • A new composite supramolecular hydrogel (CSH) with localized and sustained drug delivery was prepared. • Double layers drug release system adjusting by host–guest interactions and self-assembly strategy • This strategy aims to demonstrate that the CSH has gradient release of drug to achieve treatment of arthritis and enhance chondrogenesis. Osteoarthritis (OA) is one of the most common degenerative joint diseases, and its treatment is challenging in clinical settings. The main pathological structural characteristics of OA are cartilage defects, subchondral bone damage, and osteophyte formation. Existing treatment methods for OA mainly focus on symptomatic treatment, but cannot prevent disease progression or promote recovery of function. The key objectives of OA treatment are to suppress inflammation, alleviate infection, and promote osteogenesis. New topical therapies based on hydrogel have emerged as effective treatments for OA. In this work, we developed a composite supramolecular hydrogel (CSH) with sustained drug release capability for precise treatment of OA. The CSH was composed of supramolecular self-assembled nanoparticles and supramolecular hydrogel with anti-inflammatory effects. The host–guest interaction based on curcumin (CUR) and hyaluronic acid-cyclodextrin (HA-CD) led to rapid cross-linking of the hydrogel and sustained release of CUR, exerting long-lasting anti-inflammatory effects. Furthermore, the self-assembled nanoparticles enabled the precise controlled release of kartogenin (KGN) at the lesion site. CUR effectively attenuated the inflammatory response in bone joints and inhibited the formation of osteophytes, KGN effectively promoted subarticular cartilage regeneration. Owing to its excellent anti-inflammatory activity, biosafety and cartilage regeneration potential, the CSH represents an effective treatment for OA.