A novel magnesium alloy-based drug delivery system loaded with marine-derived CHNQD-00603 for synergistic corrosion resistance and autophagy-driven bone regeneration

The reconstruction of critical-sized bone defects, particularly in craniomaxillofacial and orthopedic surgery, remains a formidable clinical challenge. While biodegradable magnesium alloys hold great promise as barrier materials for such applications, their clinical utility is severely limited by a mismatch between their rapid degradation rate and the natural bone healing cycle. To address this challenge, we designed a multifunctional drug delivery system on AZ31 alloy comprising a micro-arc oxidation (MAO) base and a silane-sealed intermediate layer (PAPTMS) loaded with etidronate (ETN) and a novel marine-derived compound named CHNQD-00603. This hierarchical MAO/PAPTMS-ETN-603 coating exhibits a dense structure that significantly mitigates degradation rates while ensuring sustained drug release. In vitro evaluations confirmed that the coating not only supports the adhesion and proliferation of bone marrow mesenchymal stem cells but also enhances osteogenic differentiation by activating autophagy. Furthermore, in vivo assessment in a rabbit calvarial defect model demonstrated that the composite coating significantly accelerates new bone formation. This study establishes a promising strategy for developing novel bioactive barrier membranes that synergistically manage corrosion and drive tissue repair via autophagy-mediated osteogenesis.