Cys-Ala-Gly Peptides and Amphiphilic mPEG–PLGA Polymer Modified ZE21B Magnesium Alloy for Enhanced Anticorrosion and Pro-Endothelialization Potential

Magnesium alloy stents (MASs) provide significant therapeutic benefits for the treatment of cardiovascular disease. Unlike conventional permanent stents, MASs gradually degrade after fulfilling their mechanical support function, thereby reducing the risk of long-term complications. However, the clinical application of MAS is hindered by two primary challenges: excessively rapid degradation in physiological environments and inadequate biocompatibility resulting from the alloy’s corrosion behavior. Herein, we developed a multifunctional composite coating on Mg–Zn–Y–Nd (ZE21B) alloy that incorporated a MgF₂ layer, amphiphilic methoxy-terminated poly(ethylene glycol)-b-poly(lactide-co-glycolide) (mPEG–PLGA) polymer, and bioactive CAG peptides to enhance its corrosion resistance, hemocompatibility, and pro-endothelialization potential. The ZE21B with mPEG–PLGA/CAG coating showed a slower degradation rate. In addition, the modified ZE21B alloy exhibited the appropriate lower levels of hemolysis rate, fibrinogen adsorption, and denaturation. Furthermore, the mPEG–PLGA/CAG composite coating promoted the adhesion and proliferation of endothelial cells (ECs), inhibited the same behaviors of smooth muscle cells (SMCs), and enhanced the competitive growth of ECs over SMCs. These findings suggested that the mPEG–PLGA/CAG coating effectively enhanced the corrosion resistance and pro-endothelialization capacity of the ZE21B magnesium alloy, addressing urgent clinical demands for biodegradable vascular stents that balance degradation rate with biological safety, and offering a promising strategy for its advancement. By improving both corrosion resistance and endothelialization, this work contributed to the development of next-generation stents with the potential to reduce long-term complications and healthcare burdens.