Cipriano Aaron F, Sallee Amy, Tayoba Myla, Cortez Alcaraz Mayra C, Lin Alan, Guan Ren-Guo, Zhao Zhan-Yong, Liu Huinan
Department of Bioengineering, University of California, Riverside, CA 92521, USA; Materials Science & Engineering Program, University of California, Riverside, CA 92521, USA.
Department of Bioengineering, University of California, Riverside, CA 92521, USA.
Acta Biomater. 2017 Jan 15;48:499-520. doi: 10.1016/j.actbio.2016.10.020. Epub 2016 Oct 13.
Crystalline Mg-Zinc (Zn)-Strontium (Sr) ternary alloys consist of elements naturally present in the human body and provide attractive mechanical and biodegradable properties for a variety of biomedical applications. The first objective of this study was to investigate the degradation and cytocompatibility of four Mg-4Zn-xSr alloys (x=0.15, 0.5, 1.0, 1.5wt%; designated as ZSr41A, B, C, and D respectively) in the direct culture with human umbilical vein endothelial cells (HUVEC) in vitro. The second objective was to investigate, for the first time, the early-stage inflammatory response in cultured HUVECs as indicated by the induction of vascular cellular adhesion molecule-1 (VCAM-1). The results showed that the 24-h in vitro degradation of the ZSr41 alloys containing a β-phase with a Zn/Sr at% ratio ∼1.5 was significantly faster than the ZSr41 alloys with Zn/Sr at% ∼1. Additionally, the adhesion density of HUVECs in the direct culture but not in direct contact with the ZSr41 alloys for up to 24h was not adversely affected by the degradation of the alloys. Importantly, neither culture media supplemented with up to 27.6mM Mg ions nor media intentionally adjusted up to alkaline pH 9 induced any detectable adverse effects on HUVEC responses. In contrast, the significantly higher, yet non-cytotoxic, Zn ion concentration from the degradation of ZSr41D alloy was likely the cause for the initially higher VCAM-1 expression on cultured HUVECs. Lastly, analysis of the HUVEC-ZSr41 interface showed near-complete absence of cell adhesion directly on the sample surface, most likely caused by either a high local alkalinity, change in surface topography, and/or surface composition. The direct culture method used in this study was proposed as a valuable tool for studying the design aspects of Zn-containing Mg-based biomaterials in vitro, in order to engineer solutions to address current shortcomings of Mg alloys for vascular device applications.
Magnesium (Mg) alloys specifically designed for biodegradable implant applications have been the focus of biomedical research since the early 2000s. Physicochemical properties of Mg alloys make these metallic biomaterials excellent candidates for temporary biodegradable implants in orthopedic and cardiovascular applications. As Mg alloys continue to be investigated for biomedical applications, it is necessary to understand whether Mg-based materials or the alloying elements have the intrinsic ability to direct an immune response to improve implant integration while avoiding cell-biomaterial interactions leading to chronic inflammation and/or foreign body reactions. The present study utilized the direct culture method to investigate for the first time the in vitro transient inflammatory activation of endothelial cells induced by the degradation products of Zn-containing Mg alloys.
结晶态镁锌（Zn）-锶（Sr）三元合金由人体中天然存在的元素组成，为各种生物医学应用提供了具有吸引力的机械性能和生物可降解性能。本研究的首要目标是在体外与人脐静脉内皮细胞（HUVEC）直接培养的条件下，研究四种Mg-4Zn-xSr合金（x = 0.15、0.5、1.0、1.5wt%；分别指定为ZSr41A、B、C和D）的降解情况和细胞相容性。第二个目标是首次研究培养的HUVEC中由血管细胞粘附分子-1（VCAM-1）诱导所指示的早期炎症反应。结果表明，含β相且锌/锶原子百分比比约为1.5的ZSr41合金在体外24小时的降解速度明显快于锌/锶原子百分比约为1的ZSr41合金。此外，在直接培养中但不与ZSr41合金直接接触长达24小时的HUVEC的粘附密度并未受到合金降解的不利影响。重要的是，添加高达27.6mM镁离子的培养基或有意调节至碱性pH 9的培养基均未对HUVEC反应产生任何可检测到的不利影响。相比之下，ZSr41D合金降解产生的显著更高但无细胞毒性的锌离子浓度可能是培养的HUVEC上最初VCAM-1表达较高的原因。最后，对HUVEC-ZSr41界面的分析表明，样品表面几乎完全没有细胞直接粘附，这很可能是由高局部碱度、表面形貌变化和/或表面成分变化引起的。本研究中使用的直接培养方法被认为是一种有价值的工具，可用于体外研究含锌镁基生物材料的设计方面，以便设计解决方案来解决镁合金在血管装置应用中的当前缺点。
自21世纪初以来，专门为生物可降解植入应用设计的镁（Mg）合金一直是生物医学研究的重点。镁合金的物理化学性质使这些金属生物材料成为骨科和心血管应用中临时生物可降解植入物的极佳候选材料。随着镁合金继续被研究用于生物医学应用，有必要了解镁基材料或合金元素是否具有引导免疫反应以改善植入物整合的内在能力，同时避免导致慢性炎症和/或异物反应的细胞-生物材料相互作用。本研究利用直接培养方法首次研究了含锌镁合金降解产物诱导的内皮细胞体外短暂炎症激活。
