Materials Science and Engineering, University of California, Riverside, Riverside, CA 92521, USA.
Materials Science and Engineering, University of California, Riverside, Riverside, CA 92521, USA; Department of Bioengineering, University of California, Riverside, Riverside, CA 92521, USA.
Acta Biomater. 2018 May;72:407-423. doi: 10.1016/j.actbio.2018.03.049. Epub 2018 Apr 5.
Magnesium (Mg) and its alloys have been widely investigated as the most promising biodegradable metals to replace conventional non-degradable metals for temporary medical implant applications. New Mg alloys have been developed for medical applications in recent years; and the concept of alloying Mg with less-toxic elements have aroused tremendous interests due to the promise to address the problems associated with rapid degradation of Mg without compromising its cytocompatibility and biocompatibility. Of particular interests for orthopedic/spinal implant applications are the additions of calcium (Ca) and strontium (Sr) into Mg matrix because of their beneficial properties for bone regeneration. In this study, degradation and cytocompatibility of four binary MgSr alloys (Mg-xSr, x = 0.2, 0.5, 1 and 2 wt%) and four ternary MgCaSr alloys (Mg-1Ca-xSr, x = 0.2, 0.5, 1 and 2 wt%) were investigated and compared via direct culture with bone marrow-derived mesenchymal stem cells (BMSCs). The influence of the alloy composition on the degradation rates were studied and compared. Moreover, the cellular responses to the binary MgSr alloys and the ternary MgCaSr alloys were comparatively evaluated; and the critical factors influencing BMSC behaviors were discussed. This study screened the degradability and in vitro cytocompatibility of the binary MgSr alloys and the ternary MgCaSr alloys. Mg-1Sr, Mg-1Ca-0.5Sr and Mg-1Ca-1Sr alloys are recommended for further in vivo studies toward clinical translation due to their best overall performances in terms of degradation and cytocompatibility among all the alloys studied in the present work.
Traditional Mg alloys with slower degradation often contain aluminum or rare earth elements as alloying components, which raised safety and regulatory concerns. To circumvent unsafe elements, nutrient elements such as calcium (Ca) and strontium (Sr) were selected to create Mg-Sr binary alloys and Mg-Ca-Sr ternary alloys to improve the safety and biocompatibility of bioresorbable Mg alloys for medical implant applications. In this study, in vitro degradation and cellular responses to four binary Mg-xSr alloys and four ternary Mg-1Ca-xSr alloys with increasing Sr content (up to 2 wt%) were evaluated in direct culture with bone marrow derived mesenchymal stem cells (BMSCs). The roles of Sr and Ca in tuning the alloy microstructure, degradation behaviors, and BMSC responses were collectively compared in the BMSC direct culture system for the first time. The most promising alloys were identified and recommended for further in vivo studies toward clinical translation.
镁（Mg）及其合金作为最有前途的可生物降解金属，已被广泛研究用于替代传统的不可降解金属，用于临时医疗植入物应用。近年来，已经开发出了用于医疗应用的新型镁合金；并且由于承诺解决与镁的快速降解相关的问题，而不影响其细胞相容性和生物相容性，因此将毒性较低的元素与镁合金化的概念引起了极大的兴趣。对于骨科/脊柱植入物应用特别感兴趣的是钙（Ca）和锶（Sr）添加到镁基体中，因为它们对骨再生具有有益的性质。在这项研究中，通过与骨髓间充质干细胞（BMSCs）直接培养，研究和比较了四种二元 MgSr 合金（Mg-xSr，x = 0.2、0.5、1 和 2wt%）和四种三元 MgCaSr 合金（Mg-1Ca-xSr，x = 0.2、0.5、1 和 2wt%）的降解和细胞相容性。研究了合金成分对降解速率的影响并进行了比较。此外，比较评估了二元 MgSr 合金和三元 MgCaSr 合金对细胞的反应；并讨论了影响 BMSC 行为的关键因素。本研究筛选了二元 MgSr 合金和三元 MgCaSr 合金的可降解性和体外细胞相容性。由于在本研究中所有研究的合金中，Mg-1Sr、Mg-1Ca-0.5Sr 和 Mg-1Ca-1Sr 合金在降解和细胞相容性方面具有最佳的整体性能，因此推荐用于进一步的体内研究以实现临床转化。
传统的降解速度较慢的镁合金通常含有铝或稀土元素作为合金元素，这引起了安全性和监管方面的担忧。为了避免不安全的元素，选择营养元素，如钙（Ca）和锶（Sr），以创建 Mg-Sr 二元合金和 Mg-Ca-Sr 三元合金，以提高可生物降解镁合金用于医疗植入物应用的安全性和生物相容性。在这项研究中，在骨髓间充质干细胞（BMSCs）的直接培养中，评估了四种二元 Mg-xSr 合金和四种三元 Mg-1Ca-xSr 合金（Sr 含量逐渐增加，最高可达 2wt%）的体外降解和细胞反应。首次在 BMSC 直接培养系统中综合比较了 Sr 和 Ca 对合金微观结构、降解行为和 BMSC 反应的调节作用。鉴定出最有前途的合金，并推荐用于进一步的体内研究以实现临床转化。
