Osteogenic and angiogenic potential of mesoporous bioactive glass nanoparticles doped with molybdenum and boron

点击翻译按钮获取中文摘要

Bone defect treatment belongs to the major challenges in orthopedic surgery. Bone tissue engineering (BTE) approaches have been developed to support the regeneration of bone defects, including the application of synthetic biomaterials. Amongst a broad variety of synthetic biomaterials, bioactive glasses (BGs) stand out by their unique properties: BGs bond to surrounding tissues, mediated by the development of carbonated hydroxyapatite on their surfaces after contact with body fluids. Furthermore, by the release of ions from the BGs to the surrounding tissue, bone precursor cells are stimulated towards osteogenic differentiation. BGs were first introduced by Hench et al. in the 1960s with the development of the 45S5-BG (composition in mol%: 46.1 SiO2, 24.5 CaO, 24.5 Na2O, 6.0 P2O5). Since then, the family of BGs grew rapidly also due to developments in the BG synthesis process, resulting in a multiplication of possible chemical compositions by incorporation of further ions with specific therapeutic activity. The success of biomaterials that are intended for the use in BTE is mainly depending on two major properties: (i) biomaterials must stimulate the surrounding cells towards osteogenic differentiation; thus, they must be osteoinductive, and (ii) biomaterials must support vascularization; thus, they must be angiogenic. Furthermore, both properties are directly depending on each other in the in-vivo situation: with a lack of vascularization, bone regeneration will not succeed. The osteogenic and angiogenic properties of BGs can be substantially modified by the addition of therapeutic ions to the BG composition. Our group developed sol-gel derived mesoporous bioactive glass nanoparticles (MBGNs) based on the SiO2–CaO system that can serve as vectors for the local application of ions with osteogenic and/or angiogenic properties. In preparation of this project, our groups have identified Molybdenum (Mo) and Boron (B) as possible candidate biologically active elements: Whilst Mo as a part of MBGNs has proven to be osteogenic in a preliminary experiment, B was identified as an attractive ion with angiogenic potential in a study conducted previously by our groups. Therefore, in this project, MBGNs doped with either Mo or B as well as MBGNs dual-doped with both, Mo and B, will be evaluated in terms of angiogenic and osteogenic properties in-vitro. Eventually, scaffolds containing MBGNs will be subjected to an in-vivo evaluation in the chicken chorioallantoic membrane assay and a rodent femoral defect model in order to analyze their angiogenic and osteogenic in-vivo properties. This will be not only the first time that MBGNs containing scaffolds are being fabricated and investigated in-vivo but also the first time the effects of Mo, B dual-doping of MBGNs will be evaluated – it is expected that ion-doping with both, angiogenic and osteogenic properties, will improve bone defect consolidation more than doping with either one of the ions separately.