Composite 3D-Printed Scaffold Based on Glucosamine-Loaded Hyaluronic Acid Methacrylate for Osteochondral Regeneration

Full-thickness osteochondral defects demand the concurrent restoration of cartilage and subchondral bone. Here, hyaluronic acid methacrylate (HAMA) scaffolds were three-dimensional (3D)-printed with <i>in situ</i> photocuring and formulated with glucosamine (GlcN) at different concentrations; 5 mg·mL^-1 was identified as optimal. This formulation preserved print fidelity and curing, while yielding a compliant, continuous network. <i>In vitro</i>, chondrogenic outcomes were strengthened, and early osteogenic activity was enhanced, as evidenced by increased cartilage-associated staining and mineralization with maintained viability and proliferation. Quantitative polymerase chain reaction (PCR) corroborated upregulated chondrogenic transcripts with concomitant osteogenic signaling. In a rabbit full-thickness osteochondral defect, the HAMA scaffold with GlcN achieved more complete defect fill, superior cartilage-like coverage, greater subchondral bone formation, and lower Wakitani and Seller's scores than controls. Collectively, modest GlcN loading of 3D-printed HAMA generated a practical defect-matching scaffold that simultaneously promotes chondrogenesis and early osteogenesis, translating to improved osteochondral repair <i>in vivo</i>.