Magnesium-based biodegradable metals as cardiovascular stents have shown a lot of excellent performance, which have been used to treat coronary artery diseases. However, the excessive degradation rate, imperfect bioco...Magnesium-based biodegradable metals as cardiovascular stents have shown a lot of excellent performance, which have been used to treat coronary artery diseases. However, the excessive degradation rate, imperfect biocompatibility and delayed re-endothelialization still lead to a considerable challenge for its application. In this work, to overcome these shortcomings, a compound of catalyzing nitric oxide(NO) generation containing copper ions(Cu^(2+)) and hyaluronic acid(HA), an important component of the extracellular matrix, were covalently immobilized on a hydrofluoric acid(HF)-pretreated ZE21B alloy via amination layer for improving its corrosion resistance and endothelialization. Specifically,the Cu^(2+) chelated firmly with a cyclen 1,4,7,10-tetraazacyclododecane-N’, N’’, N’’’, N-tetraacetic acid(DOTA) could form a stability of hybrid coating, avoiding the explosion of Cu^(2+). The chelated Cu^(2+) enabled the catalytic generation of NO and promoted the adhesion and proliferation of endothelial cells(ECs) in vascular micro-environment. In this case, the synergistic effect of NO-generation and endothelial glycocalyx molecules of HA lead to efficient ECs promotion and smooth muscle cells(SMCs) inhibition. Meanwhile, the blood compatibility also had achieved a marked improvement. Moreover, the standard electrochemical measurements indicated that the functionalized ZE21B alloy had better anti-corrosion ability. In a conclusion, the dual-functional coating displays a great potential in the field of biodegradable magnesium-based implantable cardiovascular stents.展开更多
Rare earth elements(REEs)have been long applied in magnesium alloys,among which the mischmetal-containing WE43 alloy has already got the CE mark approval for clinical application.A considerable amount of REEs(7 wt%)is...Rare earth elements(REEs)have been long applied in magnesium alloys,among which the mischmetal-containing WE43 alloy has already got the CE mark approval for clinical application.A considerable amount of REEs(7 wt%)is needed in that multi-phased alloy to achieve a good combination of mechanical strength and corrosion resistance.However,the high complex RE addition accompanied with multiple second phases may bring the concern of biological hazards.Single-phased Mg-RE alloys with simpler compositions were proposed to improve the overall performance,i.e.,“Simpler alloy,better performance”.The single-phased microstructure can be successfully obtained with typical high-solubility REEs(Ho,Er or Lu)through traditional smelting,casting and extrusion in a wide compositional range.A good corrosion resistance with a macroscopically uniform corrosion mode was guaranteed by the homogeneously single-phased microstructure.The bimodal-grained structure with plenty of sub-grain microstructures allow us to minimize the RE addition to<1 wt%,without losing mechanical properties.The single-phased Mg-RE alloys show comparable mechanical properties to the clinically-proven Mg-based implants.They exhibited similar in-vitro and in-vivo performances(without local or systematic toxicity in SD-rats)compared to a high purity magnesium.In addition,metal elements in our single-phased alloys can be gradually excreted through the urinary system and digestive system,showing no consistent accumulation of RE in main organs,i.e.,less burden on organs.The novel concept in this study focuses on the simplification of Mg-RE based alloys for biomedical purpose,and other biodegradable metals with single-phased microstructures are expected to be explored.展开更多
基金supported by the National Key R&D Program of China (grant number 2021YFC2400700)National Natural Science Foundation of China (Nos.51871004 and U1804251)。
文摘Magnesium-based biodegradable metals as cardiovascular stents have shown a lot of excellent performance, which have been used to treat coronary artery diseases. However, the excessive degradation rate, imperfect biocompatibility and delayed re-endothelialization still lead to a considerable challenge for its application. In this work, to overcome these shortcomings, a compound of catalyzing nitric oxide(NO) generation containing copper ions(Cu^(2+)) and hyaluronic acid(HA), an important component of the extracellular matrix, were covalently immobilized on a hydrofluoric acid(HF)-pretreated ZE21B alloy via amination layer for improving its corrosion resistance and endothelialization. Specifically,the Cu^(2+) chelated firmly with a cyclen 1,4,7,10-tetraazacyclododecane-N’, N’’, N’’’, N-tetraacetic acid(DOTA) could form a stability of hybrid coating, avoiding the explosion of Cu^(2+). The chelated Cu^(2+) enabled the catalytic generation of NO and promoted the adhesion and proliferation of endothelial cells(ECs) in vascular micro-environment. In this case, the synergistic effect of NO-generation and endothelial glycocalyx molecules of HA lead to efficient ECs promotion and smooth muscle cells(SMCs) inhibition. Meanwhile, the blood compatibility also had achieved a marked improvement. Moreover, the standard electrochemical measurements indicated that the functionalized ZE21B alloy had better anti-corrosion ability. In a conclusion, the dual-functional coating displays a great potential in the field of biodegradable magnesium-based implantable cardiovascular stents.
基金This work was supported by the National Key R&D Program of China(Grant No.2021YFC2400700),the National Natural Science Foundation of China(Grant No.52101283)the Science and Technology Planning Project of Guangzhou(Grant No.202201011454)+1 种基金the NSFC Incubation Program of GDPH(Grant No.KY012021165)the High-level Hospital Construction Project(Grant No.KJ012019520).
文摘Rare earth elements(REEs)have been long applied in magnesium alloys,among which the mischmetal-containing WE43 alloy has already got the CE mark approval for clinical application.A considerable amount of REEs(7 wt%)is needed in that multi-phased alloy to achieve a good combination of mechanical strength and corrosion resistance.However,the high complex RE addition accompanied with multiple second phases may bring the concern of biological hazards.Single-phased Mg-RE alloys with simpler compositions were proposed to improve the overall performance,i.e.,“Simpler alloy,better performance”.The single-phased microstructure can be successfully obtained with typical high-solubility REEs(Ho,Er or Lu)through traditional smelting,casting and extrusion in a wide compositional range.A good corrosion resistance with a macroscopically uniform corrosion mode was guaranteed by the homogeneously single-phased microstructure.The bimodal-grained structure with plenty of sub-grain microstructures allow us to minimize the RE addition to<1 wt%,without losing mechanical properties.The single-phased Mg-RE alloys show comparable mechanical properties to the clinically-proven Mg-based implants.They exhibited similar in-vitro and in-vivo performances(without local or systematic toxicity in SD-rats)compared to a high purity magnesium.In addition,metal elements in our single-phased alloys can be gradually excreted through the urinary system and digestive system,showing no consistent accumulation of RE in main organs,i.e.,less burden on organs.The novel concept in this study focuses on the simplification of Mg-RE based alloys for biomedical purpose,and other biodegradable metals with single-phased microstructures are expected to be explored.
