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

基于磷酸钙镁的个性化骨植入物的增材制造，用于人类和兽医医学应用

• 批准号: 417069397
• 负责人: Professorin Dr. Andrea Meyer-Lindenberg
• 金额: --
• 依托单位: Chirurgische und Gynäkologische Kleintierklinik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/417069397?language=en
• 关键词: Additive; manufacturing; personalized; bone; implants

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.

目前可用的人工骨是以磷酸钙(CaP)为基础的，在生理条件下往往表现出不充分的溶解性，在骨陶瓷复合材料的形成下愈合。尤其是，节段性骨缺损的治疗是困难的，因为大多数骨移植缺乏尺寸稳定性，或者只能作为简单的成型整体。根据这些要求，该项目旨在通过3D粉末打印的方式添加制造快速可降解的镁掺杂盖骨水泥，以生产具有优化的成骨降解曲线的个性化骨植入物。生物陶瓷材料具有高的骨再生潜力，其独特的宏观结构和与骨相似的微观结构和化学成分将使其成为可能。一般化学成分为CaxMg3-x(PO4)2的水泥粉将被用作原料，而用镁取代CaP将导致机械稳定性的提高。此外，还将使用钙镁比来调整降解率。粉末印刷的CaMgP结构将被烧结，得到高度稳定的陶瓷，其在体内具有中等可溶的相(Mg3(PO4)2，Ca3(PO4)2，Ca9(HPO4)6)。通过将结构浸泡在反应溶液中，陶瓷网络将被高度可溶的相(NH4MgHPO4*6H2O，MgHPO4*3H2O，CaHPO4*2H2O)覆盖，以响应溶液-沉淀过程。通过这一点，应该创造出可定量吸收的植入物，这种植入物在体内表现出足够的稳定性，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，以及它们的生物学行为。化学和细胞介导的溶解性和成骨潜能将通过使用人成骨细胞和人破骨细胞在体外进行评估。这些结果将在活体动物模型中得到验证。因此，这些结构将被植入非承重缺损区(钻孔、股骨髁部)或节段性承重缺损区(胫骨近端)，然后观察缺损区的降解率和愈合情况。骨-种植体网络将在长达44周的时间内通过X射线和体内-µCT进行体内分析，并通过免疫组织学和显微分析进行体外分析。最后，开发的骨植入物应用于人类或兽医的医疗潜力将在兽医患者的个体化治疗中得到验证。