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.

每年有数百万例骨移植手术用于修复创伤或肿瘤切除引起的骨缺损。合成磷酸钙基（CaP）材料（主要是陶瓷）通常用作骨移植替代品。它们与骨的化学相似性保证了生物相容性，而大孔隙通过天然骨组织向内生长到孔隙中，使CaP材料牢固地整合到骨中。由于合成材料的机械性能通常不如天然骨，因此合成CaP植入物的逐渐吸收和同时被天然骨替代通常是可取的。在人体内，CaP的热力学最稳定的矿物相羟基磷灰石几乎是不可吸收的。因此，许多CaP植入物采用双相磷酸钙（BCP）作为羟基磷灰石和更易溶解的磷酸三钙（类似于矿物whitlockite）的复合物。在镁离子存在下，whitlockite的形成比羟基磷灰石更有利。镁离子掺入到whitlockite中，在人工种植体降解过程中释放出来，刺激天然骨的形成。同样，已知锶和锌离子刺激骨形成和延缓骨吸收。因此，这些离子在治疗骨质疏松症相关的骨质流失和骨折中起着重要作用。银离子的抗菌作用可以潜在地用于避免手术移植过程中的伤口感染。本项目旨在通过一步水热法，避免高温烧结，开发新型抗菌抗骨质疏松BCP骨植入材料。大孔碳酸钙生物矿物（珊瑚骨骼和海胆刺）将被BCP假形态地取代，同时保留自然孔隙度。在热液矿物替代过程中，将多种功能离子（Mg、Sr、Zn和Ag）同时掺入BCP支架的方法将被开发出来。所得材料将详细分析其掺杂剂浓度和分布。此外，还将分析BCP材料在模拟体液中降解后释放的离子浓度。这些浓度将通过调整生产参数调整材料的离子含量来优化刺激骨形成（根据公布的值）。ag修饰材料的抗菌性能将通过细菌培养实验（抑制细菌生长和生物膜形成）进行研究并进行优化。本研究项目有望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，这可能是传统CaP骨移植替代品的有价值的替代品。