In vitro interactions of blood, platelet, and fibroblast with biodegradable magnesium‐zinc‐strontium alloys

Abstract

Magnesium (Mg) alloy is an attractive class of metallic biomaterial for cardiovascular applications due to its biodegradability and mechanical properties. In this study, we investigated the degradation in blood, thrombogenicity, and cytocompatibility of Magnesium-Zinc-Strontium (Mg-Zn-Sr) alloys, specifically four Mg-4 wt % Zn-xSr (x = 0.15, 0.5, 1, and 1.5 wt %) alloys, together with pure Mg control and relevant reference materials for cardiovascular applications. Human whole blood and platelet rich plasma (PRP) were used as the incubation media to investigate the degradation behavior of the Mg-Zn-Sr alloys. The results showed that the PRP had a greater pH increase and greater concentration of Mg(2+) ions when compared with whole blood after 2 h of incubation with the same respective Mg alloys, suggesting that the Mg alloys degraded faster in PRP than in whole blood. The Mg alloy with 4 wt % Zn and 0.15 wt % Sr (named as ZSr41A) was identified as the most promising alloy for cardiovascular stent applications, because it showed slower degradation and less thrombogenicity, as indicated by the lower concentrations of Mg(2+) ions released and less deposition of platelets. Additionally, ZSr41 alloys were cytocompatible with fibroblasts in direct exposure culture in which the cells adhered and proliferated around the samples, with no statistical difference in cell adhesion density compared with the blank reference. Future studies on the ZSr41 alloys are necessary to investigate their direct interactions with other important cells in cardiovascular system, such as vascular endothelial cells and smooth muscle cells.

Cytocompatibility and early inflammatory response of human endothelial cells in direct culture with Mg-Zn-Sr alloys

“…The results of this study suggested that media alkalinity induced more dramatic effects on cellular functions than [Mg 2+ ] from the degradation of Mg-based materials, which were in agreement with previous studies for bone marrow derived mesenchymal stromal cells (BMSCs) [29,76], UMR-106 rat osteosarcoma [77], and hESCs [47]. Overall, the cytocompatibility results of Mg-Zn-Sr alloys with HUVECs reported in this study were in general agreement with previous in vitro studies with hESCs [27] and fibroblasts [28,53,67]. …”

“…Other ternary polycrystalline Mg-Zn-X alloys, including X = Al [40,57–59], Ca [29,60,61], Yttrium [62], Zirconium [63], Mn [64,65], Si [65], and Selenium and Copper (Cu) [66], exhibited solution strengthening and β-phase-mediated corrosion. To highlight the significance and novelty of this study in comparison with the state-of-the-art, a thorough review on the history and current development of as-cast crystalline Mg-Zn-Sr ternary alloys is summarized in Table 2 [26–28,52–56,67]. …”

“…thromboresistant and reducing platelet adhesion), promote endothelialization, reduce neointimal hyperplasia, and have no pro-inflammatory properties [4,107]. The truncated HUVEC viability and increased platelet adhesion [28] at the cell-ZSr41 alloy interface indicated that the ZSr41 alloys (especially ZSr41D) need to be studied further to determine their applicability for cardiovascular stent applications. Previous in vivo and pre-clinical studies of cardiovascular stents showed the potential of Mg-based materials [4]; however, evidence of undesired neointimal hyperplasia and a desire to further reduce the degradation rate was reported in most cases.…”

“…Previously, we reported the development of Mg-Zinc-Strontium (Mg-Zn-Sr) ternary alloys and the evaluation of their biological performance for biomedical applications [26–28]. Furthermore, we reported the in vitro direct culture method to mimic in vivo physiological conditions and evaluate cell responses at the cell-biomaterial interface ( direct contact ) and on the culture plate ( indirect contact ; exposure to solubilized degradation products) surrounding the Mg-based biomaterial [29].…”

Microstructure-modified biodegradable magnesium alloy for promoting cytocompatibility and wound healing in vitro

“…ions) can be gradually reused as required mineral nutrients for body supplement. Several studies have investigated the effects of Mg ions on in vitro cell behavior, and reported the Mg ion-induced promoting effect on the proliferation rate of osteoblasts, endothelial cells and fibroblasts [12][13][14]. Furthermore, Mg and other biocompatible metal ions (e.g.…”