Ion-supplemented bioactive glass for the stimulation of bone formation in-vitro and in-vivo

目前骨缺损治疗的标准方法是应用自体骨，但自体骨可能引起供区合并症和并发症。合成骨替代材料，如磷酸钙（CaPs）或生物活性玻璃（BGs）是使用自体骨的一个有吸引力的替代品。虽然cap主要具有骨传导特性，但bg通过释放生物活性离子等方式刺激细胞群向成骨分化。45S5-BG （45.0 wt% SiO2, 24.5 wt% CaO, 24.5 wt% Na2O, 6.0 wt% P2O5）和1393-BG （53.0 wt% SiO2, 20.0 wt% CaO, 6.0 wt% Na2O, 4.0 wt% P2O5, 12.0 wt% K2O, 5.0 wt% MgO）属于评价最好和最知名的BGs。与骨组织相比，这两种bg都表现出较低的稳定性，限制了其在骨骼承重部位的潜在应用范围。此外，45S5-BG中的钠部分引起局部pH值的急剧增加，从而形成细胞毒性环境。1393-BG具有较低的细胞毒性，但其生物活性和结合特性较45S5-BG弱。通过改变BG组成，可以克服上述限制。在自己的初步研究中，可以证明将硼掺入1393- bg成分（0106-B1-BG: 37.5% SiO2, 22.6% CaO, 5.9 wt% Na2O, 4.0 wt% P2O5, 12.0 wt% K2O, 5.5 wt% MgO, 12.5 wt% B2O3）可以改善其血管生成特性，并且与45S5-BG相比，它在干细胞群体中的存在也显著增加了成骨分化。生物活性离子锌（Zn）和铜（Cu）具有增殖、促成骨和促血管生成的特性，在BG中添加这些离子可能会进一步提高0106-B1-BG的良好性能。在本项目中，主要实现以下目标：(1)评估45S5-BG、1393-BG和0106-B1-BG的一般生物学（对细胞群活力和增殖的影响）、血管生成和成骨特性的体外直接比较。(2)。不同浓度Zn或Cu在0106-B1-BG中的掺入，新bg的表征，以及对体外生物、血管生成和成骨性能的影响。（3.) 在体内骨缺损模型中，与0106-B1-BG、1393-BG和45S5-BG制备的支架进行直接比较，评价含Zn和cu的0106-B1-BG（使用最佳体外浓度）制备的支架。该项目旨在开发基于各种生物活性离子掺入的新型BG组合物，旨在改善其用于骨缺损的性能。这需要对新组合物的生物学潜力进行精确的表征和分类，并与已建立的45S5-和1393- bg进行直接比较。

The current standard treatment in bone defect therapy is the application of autologous bone which might cause donor-site comorbidities and complications. Synthetic bone substitute materials such as calcium phosphates (CaPs) or bioactive glasses (BGs) are an attractive alternative to the use of autologous bone. While CaPs have mainly osteoconductive properties, BGs stimulate cell populations towards osteogenic differentiation for example by release of bioactive ions. 45S5-BG (45.0 wt% SiO2, 24.5 wt% CaO, 24.5 wt% Na2O, 6.0 wt% P2O5) and 1393-BG (53.0 wt% SiO2, 20.0 wt% CaO, 6.0 wt% Na2O, 4.0 wt% P2O5, 12.0 wt% K2O, 5.0 wt% MgO) belong to the best-evaluated and best-known BGs. Both BGs exhibit reduced stability compared to bone tissue, limiting the potential field of use in the load-bearing parts of the skeleton. Furthermore, the sodium portion in 45S5-BG causes a dramatic increase in local pH leading to the formation of a cytotoxic environment. 1393-BG shows lower cell toxicity, however its bioactivity and thus its bonding properties are weaker compared to 45S5-BG. By altering the BG composition, the mentioned limitations could be overcome. In own preliminary studies it could be demonstrated that the incorporation of boron into the 1393-BG-composition (0106-B1-BG: 37.5 wt% SiO2, 22.6 wt% CaO, 5.9 wt% Na2O, 4.0 wt% P2O5, 12.0 wt% K2O, 5.5 wt% MgO, 12.5 wt% B2O3) leads to an improvement of its angiogenic properties, and its presence in stem cell populations also significantly increases osteogenic differentiation compared to the presence of 45S5-BG. The bioactive ions zinc (Zn) and copper (Cu) have proliferative, pro-osteogenic and pro-angiogenic properties: the promising properties of 0106-B1-BG might be further improved by the addition of these ions to the BG composition. Within this project, the following aims are to be achieved: (1) Evaluation of the general biological (influence on the vitality and proliferation of a cell population), angiogenic and osteogenic properties of 45S5-BG, 1393-BG and 0106-B1-BG in direct comparison in-vitro. (2.) Incorporation of Zn or Cu in 0106-B1-BG in different concentrations, characterization of the new BGs, and evaluation of the effect on biological, angiogenic and osteogenic properties in-vitro. (3.) Evaluation of scaffolds made from Zn- and Cu-supplemented 0106-B1-BG (using the best performing in-vitro concentrations) in direct comparison to scaffolds made from 0106-B1-BG, 1393-BG and 45S5-BG in a bone defect model in-vivo. The project aims to develop new BG compositions based on the incorporation of various bioactive ions with the aim of improving their properties for use in bone defects. This requires a precise characterization as well as a classification of the biological potential of new compositions in direct comparison to the well-established 45S5- and 1393-BGs.