Additive manufacturing of personalized bone implants based on calcium magnesium phosphates for applications in human and veterinary medicine

目前可用的合成骨移植物基于磷酸钙（CaP），并且在生理条件下通常显示出不充分的溶解性，并且在骨陶瓷复合物的形成下愈合。特别是，节段性骨缺损的治疗是困难的，因为大多数骨移植物缺乏尺寸稳定性或仅可作为简单成形的整体获得。为了满足这些要求，该项目旨在通过3D粉末打印的方式增材制造快速可降解的镁掺杂CaP水泥，以生产具有优化的骨生成降解曲线的个性化骨植入物。生物陶瓷的高骨再生潜力将通过缺陷特异性宏观结构以及与骨的微观结构和化学组成的相似性来实现。具有一般化学组成CaxMg 3-x（PO 4）2的水泥粉末将用作原材料，而用Mg取代CaP将导致机械稳定性增加。此外，Ca：Mg比率将用于调节降解速率。粉末印刷的CaMgP结构将被烧结，产生体内中等可溶相（Mg3（PO 4）2、Ca 3（PO 4）2、Ca 9 Mg（HPO 4）6）的高度稳定的陶瓷。通过将结构浸入反应性溶液中，陶瓷网络将响应于溶液-沉淀过程而涂覆有高度可溶的相（NH 4 MgHPO 4 * 6 H2O、MgHPO 4 * 3 H2O、CaHPO 4 * 2 H2O）。通过这种定量的可吸收植入物应该被创建，其显示出足够持续时间的体内稳定性，具有与骨再生相反的行为。CaMgP-植入物将分析其机械性能，化学成分，微观结构和尺寸精度，以及有关其生物学行为。将通过使用人成骨细胞和人成骨细胞在体外评价化学和细胞介导的溶解度和成骨潜力。这些结果将在家兔模型中进行体内验证。因此，将结构植入非承重缺损（钻孔，股骨髁）或节段性承重缺损（胫骨近端）中，然后研究缺损区域的降解率和愈合情况。在长达44周的过程中，将通过X射线和体内µCT对骨-植入物网络进行体内分析，以及通过免疫组织学和显微镜分析进行离体分析。最后，将在兽医患者的个体化治疗中验证所开发的骨植入物在人类或兽医学中应用的医疗潜力。

Currently available synthetic bone grafts are based on calcium phosphates (CaP) and show often an insufficiently solubility under physiological conditions and heal under the formation of an osseoceramic composite. In particular, the treatment of segmental bone defects is difficult, since most bone graft are missing a dimensional stability or are only available as simple formed monoliths. In response to these requirements, the project aims at the additive manufacturing of fast degradable magnesiumdoped CaP-cements by means of 3D powder printing, to produce personalized bone implants with an optimized degradation profile regarding osteogenesis. A high osseoregenerative potential of bioceramics will be achieved by a defect-specific macroscopic structure and the similarity of the microstructure and chemical composition to bone. Cement powders with the general chemical composition CaxMg3-x(PO4)2 will be used as raw materials, whereas the substitution of CaP with Mg will result in an increased mechanical stability. Moreover, the Ca:Mg ratio will be used for the adjustment of the degradation rate. The powder-printed CaMgP-structures will be sintered, resulting in a highly stable ceramic of in vivo moderately soluble phases (Mg3(PO4)2, Ca3(PO4)2, Ca9 Mg(HPO4)6). By immersion of the structures in reactive solutions, the ceramic network will be coated with highly soluble phases (NH4MgHPO4*6H2O, MgHPO4*3H2O, CaHPO4*2H2O) in response to a solution-precipitation process. By this quantitatively absorbable implants should be created, which show an in-vivo-stability of adequate duration with an opposite behaviour to bone regeneration. CaMgP-implants will be analyzed regarding their mechanical properties, chemical composition, microstructure and dimensional accuracy, as well as concerning their biological behaviour. The chemical and cellular mediated solubility and the osteogenic potential will be evaluated in vitro by using human osteoblastic and human osteoclastic cells. These results will be validated in vivo in a rabbit model. Therefore, the structures will be implanted either in a non-load-bearing defect (drilled hole, femoral condyle) or in a segmental load-bearing defect (proximal tibia) followed by the investigation of the degradation rate and healing of the defect area. The bone-implant network will be analyzed in vivo by X-ray- and in-vivo-µCT over a course of up to 44 weeks, as well as ex vivo by immunohistological and microscopic analyses. Finally, the medical potential of the developed bone implant for application in human or veterinary medicine will be verified in an individualized treatment of veterinary patients.