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A comparative in vitro and in vivo analysis of the impact of copper substitution on the cytocompatibility, osteogenic, and angiogenic properties of a borosilicate bioactive glass
Journal of Biomedical Materials Research Part A ( IF 4.9 ) Pub Date : 2024-04-16 , DOI: 10.1002/jbm.a.37721
Linn Anna Fiehn 1 , Elke Kunisch 1 , Merve Saur 1 , Marcela Arango‐Ospina 2 , Christian Merle 1 , Sébastien Hagmann 1 , Adrian Stiller 3 , Leena Hupa 3 , Hana Kaňková 4 , Dagmar Galusková 4 , Tobias Renkawitz 1 , Aldo. R. Boccaccini 2 , Fabian Westhauser 1
Affiliation  

The 0106‐B1‐bioactive glass (BG) composition (in wt %: 37.5 SiO2, 22.6 CaO, 5.9 Na2O, 4.0 P2O5, 12.0 K2O, 5.5 MgO, and 12.5 B2O3) has demonstrated favorable processing properties and promising bone regeneration potential. The present study aimed to evaluate the biological effects of the incorporation of highly pro‐angiogenic copper (Cu) in 0106‐B1‐BG in vitro using human bone marrow‐derived mesenchymal stromal cells (BMSCs) as well as its in vivo potential for bone regeneration. CuO was added to 0106‐B1‐BG in exchange for CaO, resulting in Cu‐doped BG compositions containing 1.0, 2.5 and 5.0 wt % CuO (composition in wt %: 37.5 SiO2, 21.6/ 20.1/17.6 CaO, 5.9 Na2O, 4.0 P2O5, 12.0 K2O, 5.5 MgO, 12.5 B2O3, and 1.0/ 2.5/ 5.0 CuO). In vitro, the BGs' impact on the viability, proliferation, and growth patterns of BMSCs was evaluated. Analyses of protein secretion, matrix formation, and gene expression were used for the assessment of the BGs' influence on BMSCs regarding osteogenic differentiation and angiogenic stimulation. The presence of Cu improved cytocompatibility, osteogenic differentiation, and angiogenic response when compared with unmodified 0106‐B1‐BG in vitro. In vivo, a critical‐size femoral defect in rats was filled with scaffolds made from BGs. Bone regeneration was evaluated by micro‐computed tomography. Histological analysis was performed to assess bone maturation and angiogenesis. In vivo effects regarding defect closure, presence of osteoclastic cells or vascular structures in the defect were not significantly changed by the addition of Cu compared with undoped 0106‐B1‐BG scaffolds. Hence, while the in vitro properties of the 0106‐B1‐BG were significantly improved by the incorporation of Cu, further evaluation of the BG composition is necessary to transfer these effects to an in vivo setting.

中文翻译:

铜替代对硼硅酸盐生物活性玻璃的细胞相容性、成骨和血管生成特性影响的体外和体内比较分析

0106-B1-生物活性玻璃 (BG) 成分(重量百分比:37.5 SiO2, 22.6 CaO, 5.9 Na2奥,4.0P25, 12.0 K2O、5.5 MgO 和 12.5 B23)已表现出良好的加工性能和有前途的骨再生潜力。本研究旨在利用人骨髓间充质干细胞 (BMSC) 体外评估在 0106-B1-BG 中掺入高度促血管生成的铜 (Cu) 的生物效应及其体内对骨的潜力再生。将 CuO 添加到 0106-B1-BG 中以交换 CaO,得到含有 1.0、2.5 和 5.0 wt% CuO 的 Cu 掺杂 BG 组合物(组合物以 wt% 计:37.5 SiO2)2, 21.6/ 20.1/17.6 氧化钙, 5.9 钠2奥,4.0P25, 12.0 K2O、5.5 MgO、12.5 B23和 1.0/2.5/5.0 CuO)。在体外,评估了 BG 对 BMSC 的活力、增殖和生长模式的影响。蛋白质分泌、基质形成和基因表达的分析用于评估 BG 对 BMSC 在成骨分化和血管生成刺激方面的影响。与体外未修饰的 0106-B1-BG 相比,Cu 的存在改善了细胞相容性、成骨分化和血管生成反应。在体内,大鼠的临界尺寸股骨缺损被由 BG 制成的支架填充。通过微型计算机断层扫描评估骨再生。进行组织学分析以评估骨成熟和血管生成。与未掺杂的 0106-B1-BG 支架相比,添加 Cu 不会显着改变缺损闭合、缺损中破骨细胞或血管结构的存在的体内效果。因此,虽然 0106-B1-BG 的体外特性通过加入 Cu 得到显着改善,但需要进一步评估 BG 成分以将这些效果转移到体内环境中。
更新日期:2024-04-16
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