烧结助剂对新型硅磷酸钙生物陶瓷的性能调控与作用机理研究

Si-containing bioceramics are considered as a promising new generation of bioactive materials for bone regeneration, due to their enhanced bone formation ability. A novel bioactive calcium phosphate silicate bioceramic (Ca5(PO4)2SiO4, CPS) has been successfully synthesized in our lab by sol-gel method. However, it is found that the sol-gel derived CPS powder is hard to be well sintered, which results in a poor mechanical strength. Based on the previous work, the biocompatible sintering aids will be used to improve the sintering of sol-gel derived CPS powders in the present work. The effects of sintering aids on the mechanical properties, biodegradation and bioactivity (including the osteogenic activity and vascularization activity) in physiological environment will be investigated systematically. The interfacial characteristics will be emphasized, and the mechanism of interface reactions and the related effects on sintering process and mechanical properties of CPS bioceramics will be revealed by thoroughly analyses on the chemistry and microstructure of interfaces. The mechanism of osteogenic and vascularization behaviors of the CPS bioceramics will also be studied. It will provide strong references for the property tuning and clinical applications of the new bioactive ceramics for bone regeneration.

含硅的生物陶瓷因具有促进成骨的作用，被认为是最具前景的新一代生物活性骨修复材料。项目申请人前期通过溶胶凝胶法成功合成出一种具有良好的体外成骨活性的新型硅磷酸钙生物陶瓷-Ca5(PO4)2SiO4(CPS)，但CPS难以致密化，材料的力学性能不能满足临床要求。本项目将以前期研究结果为基础，以添加生物相容性烧结助剂来改善CPS的烧结性能为出发点，系统研究烧结助剂对CPS生物陶瓷力学性能、生物活性（成骨性能、成血管性能）和降解性的影响规律。以界面特性为着眼点，通过对界面化学及微观结构的系统研究，揭示界面反应机理，探讨烧结助剂影响CPS陶瓷烧结过程及力学性能的机制；深入研究烧结助剂对CPS陶瓷成骨性能和成血管性能的影响，揭示其生物活性机理。本项目的研究将为新型骨修复用生物活性陶瓷的性能调控和临床应用提供理论指导。

本项目通过以氧化锌（ZnO）、氧化铁（Fe2O3）和氧化铜（CuO）三种氧化物为烧结助剂成功改善了硅磷酸钙生物陶瓷（CPS）的烧结性能，并系统深入地研究了几种烧结助剂对CPS材料的烧结特性、力学性能、降解、成骨活性和成血管活性等的影响规律及其机理。研究结果表明，ZnO的加入能够显著地提升CPS陶瓷的力学性能，添加1 wt.% ZnO的Zn-CPS陶瓷在1300℃烧结后抗弯强度可达80.8MPa，大约为纯CPS陶瓷的2倍。Zn-CPS陶瓷可促进rBMSCs细胞的增殖及成骨分化，并展现出一定的抗菌能力。Zn-CPS陶瓷的成骨能力和体内降解速率均显著提升。植入12周后，含5 wt.% ZnO的Zn-CPS陶瓷的成骨率达43.0%，降解率达50.9%。Fe2O3的添加亦能显著提升CPS的烧结性能，添加1.5 wt.%的Fe-CPS陶瓷在1250℃烧结后具有最佳的力学强度，其孔隙率仅为0.8%，抗弯强度可达91.9MPa。此外，Fe-CPS陶瓷还可保持良好的体内外降解能力和成骨活性。ZnO和Fe2O3可协同调控CPS的力学性能和生物学性能，Zn/Fe-CPS陶瓷的磷灰石形成能力、体外降解能力均优于Zn-CPS陶瓷，且其更有利于rBMSCs细胞的增殖和粘附。CuO的加入可显著促进Cu-CPS陶瓷的成骨和血管生成。此外，Si和Cu的互补作用促进了进一步的成骨分化，以及血管生成后期VEGF蛋白的合成和分泌。本项目研究结果表明，合适元素掺杂可有效改善CPS的综合性能，有望开发出治疗骨缺损的理想材料。