Shenzhen Key Laboratory of Marine Biomedical Materials, CAS-HK Joint Lab of Biomaterials, The Key Laboratory of Biomedical Imaging Science and System, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, P. R. China.
Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.
ACS Appl Mater Interfaces. 2024 Sep 4;16(35):46016-46034. doi: 10.1021/acsami.4c08487. Epub 2024 Aug 21.
The assessment of biodegradable materials, such as bioactive glass, under the existing ISO 10993 standard test methods poses a significant challenge due to potential cell viability impairment caused by the accumulation of degraded products in a static environment. Therefore, innovative methodologies are urgently needed to tailor the unique biodegradation characteristics of these materials, providing more precise and scientific insights into biosafety and efficacy verification. Motivation by its bidirectional regulation of angiogenesis and immunity, zinc (Zn) was incorporated into sol-gel-derived borosilicate bioactive glasses (SBSGs) to fabricate Zn-incorporated borosilicate bioactive glasses (SBSG-Zn) to complement the tissue repair capabilities of bioactive glasses. Both SBSG and SBSG-Zn glasses consist of nanosized particles, slit mesoporous pores, high specific surface areas, and bioreactivity. In vitro comparative analysis, conducted according to ISO 10993 standards, demonstrates that only at suitable dilution rates─such as the 8-fold dilution employed in this study─do extracts of SBSG and SBSG-Zn glasses exhibit low cytotoxicity when cultured with human umbilical vein endothelial cells (HUVECs). Notably, SBSG-Zn glasses show optimal promotion of angiogenic gene expression in HUVECs. Furthermore, within an appropriate concentration range of released ions, SBSG-Zn glass extracts not only promote cell survival but also modulate the expression of anti-inflammatory genes while simultaneously inhibiting pro-inflammatory genes concurrently. After being implanted in rat subcutaneous defect models, both SBSG and SBSG-Zn glasses demonstrated the local immunoregulation and angiogenic effects. SBSG-Zn stands out by demonstrating superior modulation of M1/M2 polarization in macrophages as validated by altered secretion of key factors in macrophages and expression of relevant growth factors in HUVECs. These findings underscore the potential for convenient manipulation of localized angiogenic and immunoregulation through the incorporation of zinc into bioactive glass, emphasizing the importance of ensuring the appropriate ion doses are applied for achieving optimal therapeutic efficiency.
可生物降解材料（如生物活性玻璃）的评估，根据现有的 ISO 10993 标准测试方法，由于在静态环境中降解产物的积累可能导致细胞活力受损，因此带来了重大挑战。因此，迫切需要创新的方法来调整这些材料独特的生物降解特性，为生物安全性和疗效验证提供更精确和科学的见解。
受其对血管生成和免疫的双向调节作用的启发，锌（Zn）被掺入溶胶-凝胶衍生的硼硅酸盐生物活性玻璃（SBSG）中，以制备掺锌硼硅酸盐生物活性玻璃（SBSG-Zn），从而补充生物活性玻璃的组织修复能力。SBSG 和 SBSG-Zn 玻璃都由纳米级颗粒、狭缝介孔孔、高比表面积和生物活性组成。根据 ISO 10993 标准进行的体外比较分析表明，只有在合适的稀释率下，例如本研究中采用的 8 倍稀释率，SBSG 和 SBSG-Zn 玻璃的浸提液与人脐静脉内皮细胞（HUVECs）共培养时才表现出低细胞毒性。值得注意的是，SBSG-Zn 玻璃在促进 HUVEC 血管生成基因表达方面表现最佳。此外，在释放离子的适当浓度范围内，SBSG-Zn 玻璃浸提液不仅促进细胞存活，还调节抗炎基因的表达，同时抑制促炎基因的表达。
将 SBSG 和 SBSG-Zn 玻璃植入大鼠皮下缺损模型中，两种玻璃均表现出局部免疫调节和血管生成作用。SBSG-Zn 通过改变巨噬细胞中关键因子的分泌和 HUVECs 中相关生长因子的表达，证实了其对巨噬细胞 M1/M2 极化的调节作用，这一点尤为突出。这些发现强调了通过在生物活性玻璃中掺入锌来方便地调节局部血管生成和免疫调节的潜力，同时强调了确保应用适当的离子剂量以达到最佳治疗效果的重要性。
