用于骨质疏松性骨缺损修复的聚醚醚酮复合材料制备及其作用机理研究

The prevalence of osteoporosis in China is increasing year by year, which seriously threatens the physical and mental health of middle-aged and elderly patients. The pathophysiology is the dysfunction of osteoblasts and osteoclasts, resulting in bone resorption then exceeds bone formation. Therefore, enhancing the functions of the osteoblasts and inhibiting the functions of the osteoclasts are keys for bone regeneration and repair under the osteoporotic conditions. In our previous study, the composite particles containing alendronate sodium and mesoporous calcium magnesium (ALN-CMS) were synthesized, possessing the excellent bioactivity in vitro and drug release property..In this study, bioactive bone implanted materials (ALN-CMS/polyetheretherketone composite scaffolds) will be prepared, and small molecules (Vitamin D) will be loaded into the scaffolds, which are expected to be released in a sustained manner for promoting bone defect repair and osseointegration under osteoporotic conditions. The effects of the bone implanted materials with the capability of sustained release of biologically active metallic elements ions (Ca, Mg) and/or small molecules (ALN, VD3) on the behaviours and functions of osteoblasts/osteoclasts will be investigated and the mechanism will be uncovered. The effects of the composite implants on promoting bone defect repair under osteoporotic conditions will be investigated in vivo and the mechanism will be illuminated. By the synergistic effects of bioactive materials, the metallic elements and small molecules, the combination of bone defect repair and osteoporosis treatment can be achieved. The study will provide the new technology for bone defect repair under osteoporotic conditions, and the guidance for designing bioactive bone implanted materials.

骨质疏松症在我国的患病率逐年攀升，严重威胁着中老年患者的身心健康。其病理基础为成骨细胞和破骨细胞功能失调，导致骨吸收大于骨形成，因此，提高成骨细胞功能、抑制破骨细胞功能是骨质疏松状况下骨缺损修复的关键。课题组前期合成了阿仑膦酸钠-介孔硅酸钙镁（ALN-CMS）复合颗粒，具有优良的体外生物活性及药物缓释性能。本项目研制生物活性骨植入材料（ALN-CMS/聚醚醚酮复合支架），负载/缓释小分子（维生素D），促进骨质疏松状况下骨缺损修复，并治疗植入体周围的骨质疏松；探讨骨植入材料缓释金属元素（钙、镁）或/和小分子（阿仑膦酸钠、维生素D）,对成/破骨细胞行为和功能的影响及机理，及在体内骨质疏松状况下促骨缺损修复的效果及机理。本研究通过发挥生物活性材料、金属元素和小分子的协同作用，实现骨缺损修复和骨质疏松治疗一体化，为骨质疏松性骨缺损修复提供新技术，为骨植入材料的设计提供新思路。

本项目设计合成了硅基生物活性材料掺杂金属元素并搭载小分子药物，与聚醚醚酮（PEEK）结合制备复合材料，研究其理化性能及其细胞相容性，并探讨其在骨质疏松状态下促进成骨的效果。首先制备了一种锶掺杂生物玻璃微球（SrBG），并通过钙离子的螯合作用制备了阿仑膦酸钠-锶掺杂生物玻璃微球（A-SrBG），该生物玻璃微球具有规则均一的球形结构。通过与细胞共培养，该材料具有良好的细胞相容性，且能够缓释锶离子促进骨髓间充质干细胞增殖和成骨分化，通过RT-PCR，该材料能显著促进细胞成骨相关基因的表达。与破骨细胞共培养，结果表明该材料能抑制破骨细胞的活性和增殖。骨植入材料的多孔结构有利于骨组织长入，通过粒子溶出法制备了多孔A-SrBG/PEEK复合种植体。结果表明，该复合种植体具有400μm左右的大孔结构，具有良好的体外生物活性；通过与细胞共培养，该材料具有良好的细胞相容性，能够显著促进骨髓间充质干细胞的黏附、增殖和成骨向分化，并抑制破骨细胞活性。通过动物植入实验，该材料具有良好的促进新骨生成和骨长入的能力。通过本研究，阐明了生物活性玻璃微球及其复合支架对成骨/破骨细胞命运的影响，及其在体内促进新骨生成的能力。该复合支架材料在骨质疏松性骨缺损修复领域具备很好的应用前景。