Hydrothermal conversion of porous Ca carbonate biominerals into antibiotic and antiosteoporotic Ca phosphate bone implant materials containing Mg, Sr, Zn and Ag ions

多孔碳酸钙生物矿物水热转化为含镁、锶、锌和银离子的抗生素和抗骨质疏松磷酸钙骨植入材料

• 批准号: 261597544
• 负责人: Professor Dr. Hans-Joachim Kleebe
• 金额: --
• 依托单位: Institut für Angewandte Geowissenschaften (IAG)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/261597544?language=en
• 关键词: Hydrothermal; conversion; porous; Ca; carbonate

Millions of bone graft procedures are performed annually to repair bone defects caused by trauma or tumor resection. Synthetic calcium phosphate-based (CaP) materials (mostly ceramics) are commonly used as bone graft substitutes. Their chemical similarity to bone guarantees biocompatibility while macroporosity enables firm integration of CaP materials into the bone by ingrowth of natural bone tissue into the pores. Since the mechanical performance of the synthetic materials is generally inferior to natural bone, gradual resorption of synthetic CaP implants and simultaneous replacement by natural bone is often desirable. In the human body, the thermodynamically most stable mineral phase of CaP, hydroxyapatite, is almost non-resorbable. Therefore, many CaP implants represent biphasic calcium phosphates (BCP) as a composite of hydroxyapatite and the more soluble tricalcium phosphate (similar to the mineral whitlockite). In the presence of Mg ions the formation of whitlockite is favoured over hydroxyapatite. Mg ions incorporated into whitlockite are released during degradation of the synthetic implant and stimulate the formation of natural bone. Similarly, Sr and Zn ions are known to stimulate bone formation and retard bone resorption. Hence, these ions play an important role in the treatment of bone loss and fracture related to osteoporosis. The antibacterial effect of Ag ions can potentially be employed to avoid wound infection during surgical graft procedures.This project aims at the development of novel antimicrobial and antiosteoporotic BCP bone implant materials via a single-step hydrothermal process, avoiding high-temperature sintering. Macroporous calcium carbonate biominerals (coral skeletons and sea urchin spines) will be replaced pseudomorphically by BCP while the natural porosity is preserved. A method suitable for simultaneously incorporating a number of functional ions (Mg, Sr, Zn and Ag) into the BCP scaffolds during the hydrothermal mineral replacement process will be developed. Resulting materials will be analyzed in detail for their dopant concentration and distribution. Additionally, ion concentrations released by the BCP materials upon degradation in simulated body fluid will be analyzed. These concentrations will be optimized for stimulating bone formation (according to published values) by adjusting the ion contents of the materials through modification of the production parameters. Antibacterial properties of the Ag-modified materials will be investigated by bacterial culture experiments (inhibition of bacterial growth and biofilm formation) and optimized as well. This research project is expected to provide an effective new method of producing BCP-based multifunctional bone replacement materials that may represent valuable alternatives to conventional CaP bone grafts substitutes.

每年进行数百万个骨移植手术以修复由创伤或肿瘤切除引起的骨缺损。基于磷酸盐的合成钙（CAP）材料（主要是陶瓷）通常用作骨移植物替代物。它们与骨骼的化学相似性可确保生物相容性，而大量质性可以通过将天然骨骼组织向孔内生长到孔中，从而使帽材料稳固地整合到骨骼中。由于合成材料的机械性能通常不如天然骨头，因此通常需要逐渐吸收合成帽植入物和同时替换自然骨。在人体中，热力学上最稳定的CAP的矿物相，羟基磷灰石几乎是不可吸收的。因此，许多瓶盖植入物代表双相磷酸钙（BCP）作为羟基磷灰石的复合材料和更可溶的磷酸三卡岩（类似于矿物质氯洛克石）。在存在mg离子的情况下，惠特洛锁的形成比羟基磷灰石有利。合成植入物降解并刺激天然骨骼的形成期间，释放了植物中的MG离子。同样，已知SR和Zn离子可以刺激骨形成和延迟骨吸收。因此，这些离子在治疗与骨质疏松症有关的骨质流失和断裂中起着重要作用。可以潜在地采用Ag离子的抗菌作用，以避免手术移植物过程中的伤口感染。该项目旨在通过单步水热过程开发新型抗菌和抗核疏松性BCP BCP骨植入物材料，避免使用高温刺痛。碳酸钙生物矿物质（珊瑚骨架和海胆刺）将被BCP替换，同时保留自然孔隙率。一种适合在水热矿物替换过程中同时纳入BCP支架中的许多功能离子（MG，SR，Zn和Ag）的方法。最终的材料将详细分析其掺杂剂浓度和分布。另外，将分析由BCP材料在模拟体液中降解后释放的离子浓度。这些浓度将通过修改生产参数来调整材料的离子含量，以优化用于刺激骨形成（根据公开值）。 Ag修饰材料的抗菌特性将通过细菌培养实验（抑制细菌生长和生物膜形成）进行研究，并进行了优化。预计该研究项目将提供一种有效的新方法来生产基于BCP的多功能骨替代材料，该材料可能代表了传统的帽骨移植物替代品的宝贵替代品。