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

目前治疗骨缺损的标准方法是应用自体骨，这可能会导致供骨部位的并发症和并发症。人工骨替代材料如磷酸钙(CAPS)或生物活性玻璃(BGS)是替代自体骨的一种有吸引力的替代材料。虽然CAPS主要具有骨传导特性，但BGS通过释放生物活性离子等方式刺激细胞群体向成骨方向分化。45S5-BG(45.0wt%SiO_2、24.5wt%CaO、24.5wt%Na2O、6.0wt%P2O5)和1393-BG(53.0wt%SiO_2、20.0wt%CaO、6.0wt%Na2O、4.0wt%P2O5、12.0wt%K2O、5.0wt%MgO)属于评价最好、知名度最高的BG。与骨组织相比，这两种骨组织的稳定性都降低了，限制了骨骼承重部分的潜在使用领域。此外，45S5-BG中的钠部分会导致局部pH急剧上升，从而形成细胞毒性环境。与45S5-BG相比，1393-BG具有较低的细胞毒性，但其生物活性较弱，因此其粘合性能较弱。通过改变BG的组成，可以克服上述限制。在自己的初步研究中，可以证明在1393-BG组成(0106-B1-BG：37.5wt%SiO，22.6wt%CaO，5.9wt%Na2O，4.0wt%P2O5，12.0wt%K2O，5.5wt%MgO，12.5wt%B2O)中掺入硼可以改善其血管生成特性，并且与45S5-BG相比，其在干细胞群中的存在也显著促进成骨分化。生物活性离子锌(锌)和铜(铜)具有增殖、促成骨和促血管生成的特性：将这些离子加入到BG的组成中，可能会进一步改善0106-B1-BG的前景。在本项目中，将实现以下目标：(1)在体外直接比较45S5-BG、1393-BG和0106-B1-BG的一般生物学特性(对细胞群体活力和增殖的影响)、血管生成和成骨特性。(2)在0106-B1-BG中以不同浓度掺入锌或铜，对新型BGS进行表征，并在体外评价其对生物学、血管生成和成骨性能的影响。(3)在体内骨缺损模型中，直接与0106-B1-BG、1393-BG和45S5-BG制成的支架进行比较，评价添加锌和铜的0106-B1-BG支架(使用最佳的体外浓度)。该项目旨在开发基于加入各种生物活性离子的新的BG组合物，目的是改善它们的性能，用于骨缺损。这需要对新组合物的生物潜力进行精确的表征和分类，直接与公认的45S5-和1393-BGS进行比较。

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.