Institute of Materials Science, Technische Universität Dresden, Max Bergmann Center of Biomaterials, 01069 Dresden, Germany.
Department of Trauma, Campus Giessen, Hand and Reconstructive Surgery, University Hospital Giessen-Marburg GmbH, Rudolf-Buchheim-Str. 7, 35385 Giessen, Germany.
Molecules. 2020 Nov 3;25(21):5103. doi: 10.3390/molecules25215103.
The development and characterization of biomaterials for bone replacement in case of large defects in preconditioned bone (e.g., osteoporosis) require close cooperation of various disciplines. Of particular interest are effects observed in vitro at the cellular level and their in vivo representation in animal experiments. In the present case, the material-based alteration of the ratio of osteoblasts to osteoclasts in vitro in the context of their co-cultivation was examined and showed equivalence to the material-based stimulation of bone regeneration in a bone defect of osteoporotic rats. Gelatin-modified calcium/strontium phosphates with a Ca:Sr ratio in their precipitation solutions of 5:5 and 3:7 caused a pro-osteogenic reaction on both levels in vitro and in vivo. Stimulation of osteoblasts and inhibition of osteoclast activity were proven during culture on materials with higher strontium content. The same material caused a decrease in osteoclast activity in vitro. In vivo, a positive effect of the material with increased strontium content was observed by immunohistochemistry, e.g., by significantly increased bone volume to tissue volume ratio, increased bone morphogenetic protein-2 (BMP2) expression, and significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio. In addition, material degradation and bone regeneration were examined after 6 weeks using stage scans with ToF-SIMS and µ-CT imaging. The remaining material in the defects and strontium signals, which originate from areas exceeding the defect area, indicate the incorporation of strontium ions into the surrounding mineralized tissue. Thus, the material inherent properties (release of biologically active ions, solubility and degradability, mechanical strength) directly influenced the cellular reaction in vitro and also bone regeneration in vivo. Based on this, in the future, materials might be synthesized and specifically adapted to patient-specific needs and their bone status.
在预处理骨（例如骨质疏松症）中发生大缺陷的情况下，用于骨替代的生物材料的开发和特性研究需要各个学科的密切合作。特别有趣的是在细胞水平上观察到的体外效应及其在动物实验中的体内表现。在这种情况下，检查了在共培养的情况下材料对体外成骨细胞和成骨细胞比例的影响，并发现其与骨质疏松症大鼠骨缺损中基于材料的骨再生刺激等效。在沉淀溶液中 Ca/Sr 比为 5/5 和 3/7 的明胶改性钙/锶磷酸盐在体外和体内的两个水平上都引起了促成骨反应。在具有较高锶含量的材料上培养时，已证明刺激成骨细胞和抑制破骨细胞活性。相同的材料在体外也会导致破骨细胞活性降低。体内，通过免疫组织化学观察到具有较高锶含量的材料具有积极作用，例如，骨体积与组织体积比显著增加，骨形态发生蛋白-2（BMP2）表达增加，以及核因子κB 配体受体激活剂（RANKL）/骨保护素（OPG）比值显著降低。此外，在第 6 周还通过 ToF-SIMS 和 µ-CT 成像的阶段扫描检查了材料降解和骨再生情况。缺陷中残留的材料和来自超过缺陷区域的锶信号表明锶离子已掺入周围矿化组织中。因此，材料固有的特性（释放具有生物活性的离子、溶解度和降解性、机械强度）直接影响了体外细胞反应，也影响了体内骨再生。基于此，在未来，可能会合成材料并针对特定患者的需求及其骨骼状况进行专门调整。
