Fe3O4@PDA Nanoparticle‐Doped Smart Hydrogel Scaffold for Osteochondral Defect Repair by Synergistical Stimulation

Abstract Osteochondral defects are common orthopedic conditions that can lead to osteoarthritis and severe joint pain. Recently, smart biohydrogels have been widely applied in osteochondral repair and regeneration, owing to their 3D structural resemblance to osteochondral tissues and their remarkable responsiveness to external stimuli. Glucosamine hydrochloride (GH) has been proved to stimulate the proliferation and chondrogenic differentiation of bone mesenchymal stem cells (BMSC), thereby accelerating wound healing and tissue regeneration. Herein, double‐crosslinked smart hydrogels SPA5‐Mg/GH/FP are fabricated using sodium alginate, acrylamide and N‐Isopropylacrylamide (NIPAM) as the substrates. Simultaneously, the incorporation of Mg2+ and Polydopamine (PDA)‐coated Fe3O4 NPs into the system further enhanced its properties. The results emphasized the favorable microenvironment created by the 3D architecture of the hydrogel, which effectively facilitated tissue repair and regeneration of the defects. Notably, the controlled release of GH aligned with the repair process is achieved through the responsiveness of Fe3O4@PDA NPs to near‐infrared light. Moreover, in vivo assessments have demonstrated the effectiveness of the smart hydrogel in repairing osteochondral defects, highlighting its structural similarities to native tissue. This promising outcome underscores the potential of SPA5‐Mg/GH/FP as a sophisticated solution for addressing the challenges associated with osteochondral repair.