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

掺杂钼和硼的介孔生物活性玻璃纳米粒子的成骨和血管生成潜力

• 批准号: 493867610
• 负责人: Professor Dr.-Ing. Aldo Boccaccini
• 金额: --
• 依托单位: Klinik für Orthopädie und Unfallchirurgie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/493867610?language=en
• 关键词: Osteogenic; angiogenic; potential; mesoporous; bioactive

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.

骨缺损的治疗属于骨科手术的主要挑战。骨组织工程（BTE）方法已被开发用于支持骨缺损的再生，包括合成生物材料的应用。在各种各样的合成生物材料中，生物活性玻璃（BG）因其独特的特性而脱颖而出：BG与周围组织结合，通过与体液接触后在其表面上形成碳酸化羟基磷灰石来介导。此外，通过将离子从BG释放到周围组织，骨前体细胞被刺激向成骨分化。BG首先由Hench等人在20世纪60年代随着45 S5-BG的开发而引入（以摩尔%计的组成：46.1 SiO2、24.5 CaO、24.5 Na 2 O、6.0 P2 O 5）。从那时起，BG家族也由于BG合成过程的发展而迅速增长，通过掺入具有特定治疗活性的其他离子导致可能的化学组成倍增。预期用于BTE的生物材料的成功主要取决于两个主要特性：（i）生物材料必须刺激周围细胞向成骨分化;因此，它们必须是骨诱导性的，以及（ii）生物材料必须支持血管形成;因此，它们必须是血管生成性的。此外，这两种性质在体内情况下直接相互依赖：缺乏血管化，骨再生将不会成功。BG的成骨和血管生成特性可以通过向BG组合物中加入治疗离子而基本上改变。我们小组开发了基于SiO2-CaO系统的溶胶-凝胶衍生的介孔生物活性玻璃纳米颗粒（MBGN），其可以作为具有成骨和/或血管生成特性的离子的局部应用的载体。在本项目的准备过程中，我们的团队已经确定钼（Mo）和硼（B）为可能的候选生物活性元素：虽然在初步实验中已证明钼作为MBGN的一部分具有成骨作用，但在我们团队先前进行的一项研究中，B被确定为具有血管生成潜力的有吸引力的离子。因此，在本项目中，将评价掺杂Mo或B的MBGN以及双掺杂Mo和B的MBGN的体外血管生成和成骨特性。最终，含有MBGN的支架将在鸡绒毛尿囊膜测定和啮齿动物股骨缺损模型中进行体内评价，以分析其血管生成和成骨的体内特性。这将不仅是第一次在体内制造和研究含有MBGN的支架，而且也是第一次评估MBGN的Mo、B双掺杂的效果-预期具有血管生成和成骨特性两者的离子掺杂将比单独掺杂任一种离子更多地改善骨缺损固结。