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

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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.