In situ polysaccharide-based double-network hydrogels as a sustained kartogenin delivery system for cartilage tissue engineering

Abstract

In situ forming biodegradable hydrogel scaffolds are crucial in tissue engineering and drug delivery systems, with extensive applications in articular cartilage (AC) repair. Polysaccharide-based hydrogels are ideal materials for cartilage tissue engineering owning to their biochemical and structural resemblance to the native extracellular matrix (ECM). In this study, a double-network (DN) hydrogel was fabricated through Schiff base reaction and photocrosslinking, utilizing glycidyl methacrylate-modified chitosan (GCS) and aldehyde-modified hyaluronic acid methacrylate (AHM) as precursors. To prepare the drug-loaded hydrogel, we grafted the bioactive factor kartogenin (KGN) onto GCS, generating KGN-conjugated GCS (KGCS), which subsequently formed a crosslinked network with AHM. In contrast to conventional hydrogels encapsulating either drug alone or drug-loaded microspheres, the proposed hydrogel demonstrated a more stable and sustained release profile. Furthermore, the physicochemical properties of both hydrogels were systematically characterized, comprising morphology, mechanical properties and swelling rate. The biocompatibility of hydrogels was comprehensively investigated through in vitro cell proliferation assays, hemocompatibility analysis, and in vivo evaluation of subcutaneous implant. Subsequently, a cartilage defect model was utilized to assess their efficacy in cartilage regeneration. In summary, the two DN hydrogels exhibited suitable porous structure, mechanical properties, and swelling rates. Furthermore, they demonstrated excellent biocompatibility and significantly promoted cartilage defect regeneration.