Abstract
<title>Abstract</title> <p>Osteochondral defects pose a significant clinical challenge owing to the avascular nature of articular cartilage, limited intrinsic repair capacity, and the persistent inflammatory and infectious microenvironment post-injury. To address these barriers, we developed an injectable, self-healing hydrogel platform composed of oxidized sodium alginate (OSA) and gelatin (GEL), integrated with in-situ formed amin-functionalized Ag-based metal-organic framework (Ag-MOF) nanoparticles for simultaneous sustained delivery of the non-steroidal anti-inflammatory drug diclofenac (DF). The hydrogel network was formed through dynamic Schiff-base imine crosslinking between aldehyde groups of OSA and amine groups of GEL, conferring shear-thinning injectability, rapid gelation, and autonomous self-healing without external stimuli. Ag-MOF incorporation enhanced mechanical reinforcement, imparted potent broad-spectrum antibacterial activity against Escherichia coli and Staphylococcus aureus, and modulated the release kinetics of DF. Physicochemical characterizations confirmed successful MOF crystallization, porous morphology with nanoscale surface features, tunable swelling/erosion profiles, and biphasic DF release dominated by Fickian diffusion (best fitted to Higuchi model). In vitro evaluations demonstrated excellent cytocompatibility with human foreskin fibroblasts (> 85% viability), negligible hemolysis (< 4%), and robust antibacterial efficacy. The multifunctional design, combining conformal defect filling, prolonged local anti-inflammatory action, mechanical support mimicking native cartilage viscoelasticity, and infection prevention, creates a favorable regenerative niche while minimizing systemic NSAID toxicity. This Ag-MOF-reinforced, DF-loaded injectable hydrogel thus emerges as a promising, minimally invasive therapeutic strategy for modulating inflammation, combating infection, and promoting osteochondral tissue repair.</p>