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是基于磷酸钙（CaP），在生理条件下通常表现出溶解度不足，在骨陶瓷复合材料的形成下愈合。特别是，治疗节段性骨缺损是困难的，因为大多数骨移植物缺乏尺寸稳定性或仅作为简单形成的整体可用。针对这些需求，该项目旨在通过3D粉末打印的方式增材制造快速降解的掺镁cap -水泥，以生产具有优化的成骨降解特征的个性化骨植入物。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成分的相似性来实现。一般化学成分为caxmm3 -x(PO4)2的水泥粉将被用作原材料，而用Mg代替CaP将会增加机械稳定性。此外，Ca:Mg比值将用于调节降解速率。粉末印刷的camgp结构将被烧结，从而产生高度稳定的体内中溶相(Mg3(PO4)2, Ca3（PO4)2, Ca9 Mg(HPO4)6）陶瓷。通过将结构浸泡在反应溶液中，陶瓷网络将被高溶相（NH4MgHPO4*6H2O, MgHPO4*3H2O, CaHPO4*2H2O）包裹，以响应溶液沉淀过程。通过这种定量吸收的植入物应该被创造出来，它显示出足够持续时间的体内稳定性，与骨再生的行为相反。将分析camgp植入物的机械性能、化学成分、微观结构和尺寸精度，以及它们的生物行为。化学和细胞介导的溶解度和成骨潜能将在体外通过人成骨细胞和人破骨细胞进行评估。这些结果将在兔体内模型中得到验证。因此，这些结构将被植入非承重缺陷（钻孔，股骨髁）或节段性承重缺陷（胫骨近端），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射线和体内微CT对骨植入物网络进行体内分析，并通过免疫组织学和显微镜分析进行体外分析。最后，开发的骨植入物在人类或兽医学上的应用潜力将在兽医学患者的个性化治疗中得到验证。

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.