新型压电陶瓷表面修饰人工椎体的优化构建及其修复骨缺损的机制研究

Three-dimensional (3D) printed artificial vertebral body has been considered as the personalized implants for repairing vertebrae defect and can precisely restore the integrity and stabilization of spine in the early stage. Meanwhile 3D-printed vertebral body possesses good mechanical properties by controlling microstructure and reducing elastic modulus remarkably. However, the 3D printed artificial vertebral body does not have good bone induction ability. To increase its bioactivity through surface modification is currently a research hotspot. The existing surface modification technology has mostly focused on the bone-like component and bioactive simulation of the material itself , but not on the effect of piezoelectric characteristics in promoting the bone ingrowth. Our research group has demonstrated that piezoelectric ceramic materials can generate electrical stimulation which will promote bone ingrowth. Hence, we will prepare nano-piezoelectric ceramic coatings on the surface of artificial vertebral body to promote the bone ingrowth by creating an endogenous electric field. Then, through in vivo and in vitro tests, we will evaluate the effect of nano-piezoelectric ceramic coated artificial vertebral body on bone ingrowth and reveal the mechanism involved by studying osseointegration related proteins and pathway. Finally, this exploratory work will lay foundation for generating new artificial vertebral body with both biomechanics characteristic and bone-healing ability.

3D打印人工椎体作为椎体缺损的个性化修复材料，可以早期精准恢复脊柱的完整性和稳定性；3D打印还可以通过对椎体的内部孔隙进行调控，有效降低其表观弹性模量，获得良好的力学特性。然而3D打印人工椎体骨诱导作用不佳，通过表面修饰改善其生物活性是目前研究的热点。现阶段表面改性技术主要侧重于表面涂层材料的类骨成分和活性仿真特性，但对于力学-电学效应在促进骨长入中所发挥的作用关注不足。课题组在前期的研究发现，压电陶瓷材料通过压电效应产生的电刺激，能够有效促进骨生长。因此，本课题设想在人工椎体表面构建纳米级的压电陶瓷涂层，赋予人工椎体压电特性，提高其诱导骨长入的能力，促进其与周围骨组织发生早期骨整合。通过体内、外实验，研究压电陶瓷表面修饰人工椎体对成骨能力的影响，并通过对成骨细胞相关蛋白及通路的研究，探寻其中可能存在的相关机制，为构建兼具椎体生物力学特性和椎体缺损修复功效的新型人工椎体奠定工作基础。

3D打印钛合金人工椎体通过对椎体的内部孔隙进行调控，能够优化其弹性模量和力学匹配，从而早期精准恢复脊柱的完整性和稳定性，但钛合金材料骨诱导作用不佳，因此通过表面修饰改善其生物活性是目前研究的热点。压电陶瓷材料在外界应力刺激下产生微电流刺激，能够有效重建骨缺区域的力电环境，促进骨整合骨缺损修复，具有良好的生物活性。本课题在上述基础上，课题组首先通过计算机模拟优化和激光熔融打印方法制备出拓扑结构优化，力学性能优异的3D打印钛合金人工椎体。进一步通过微弧氧化法（MAO）在人工椎体表面构建纳米级的钛酸钡压电陶瓷涂层，赋予人工椎体压电特性。体外实验结果表明，极化后的压电陶瓷涂层支架相较于未极化钛合金支架和单纯钛合金支架，促进了成骨细胞的增殖分化及血管内皮细胞的迁移和成血管，同时促进了巨噬细胞的M2型（抑炎型）极化。极化后压电陶瓷涂层多孔钛合金支架通过刺激Ca2+内流引起的P38磷酸化，促进成骨细胞的成骨分化；而且通过PDGF-BB与PDFGR-β作用介导的血管内皮细胞成血管促进了体内的新生血管再生。此外，本课题组进一步自主研发了循环仿生压力装置，为下一步在体外研究力学刺激下压电多孔钛合金支架的生物学效应打下基础。体内羊颈椎修复重建实验结果证实，极化后压电涂层3D打印人工椎体的在更短的时间内形成与周围椎体的骨整合，而且修复晚期的新生骨量显著高于对照组。综上所述，本研究构建了一种新型压电陶瓷涂层3D打印人工椎体，探究了其在促进成骨，成血管和介导免疫应答方面的生物学效应，证明了其在修复椎体缺损中的显著效果。本课题研究为新型压电陶瓷涂层表面修饰人工椎体在椎体切除术后重建的临床应用提供了有效技术手段和充分理论依据。