Collagen-Coated 3D-Printed Magnesium Alloy Scaffold with Controlled Mg ²⁺ Release for Enhanced Repair of Critical-Sized Bone Defects

Critical-sized bone defects pose a significant clinical challenge due to the limitations of existing repair strategies. An ideal bone scaffold is expected to provide mechanical support while promoting osteogenesis and angiogenesis. However, biodegradable magnesium (Mg) alloys face challenges in controlling rapid degradation, leading to detrimental local Mg²⁺ concentrations and premature mechanical failure. To address this, a collagen-coated 3D-printed magnesium alloy scaffold (COL/Mg) was developed via electrostatic adsorption. The 3D-printed Mg scaffold provides initial structural support matching bone mechanics, while the collagen coating acts as a physical barrier that controls Mg²⁺ release. This strategy successfully maintains the local Mg²⁺ concentration within the optimal "therapeutic window", thereby optimizing biological activity and avoiding toxicity. <i>In vitro</i> results showed that COL/Mg enhanced corrosion resistance, biocompatibility, and cell proliferation and promoted angiogenic and osteogenic potential. Transcriptomic analysis further revealed the osteogenic differentiation mechanism. <i>In vivo</i> studies using a rat calvarial defect model confirmed that the COL/Mg scaffold significantly promoted vascularized bone regeneration and achieved good bone integration compared to uncoated Mg scaffolds, without adverse systemic effects. In conclusion, this collagen-coating strategy provides a simple and effective approach to harness the advantages of Mg alloys for bone repair by dynamically regulating the ionic microenvironment, offering a promising solution for treating critical-sized bone defects.