Ti/COL嵌套式可控诱导复合仿生骨支架的3D打印构建及三维诱导机理研究

3D print titanium (Ti) scaffolds bring new opportunities to bone replacement and repair for osteoporosis patients. However, the pore size of the 3D printed device is way too large and the printed interface is not benefit for cell proliferation and bone tissue growth. To solve this problem, this project proposes to develop Ti/COL nested 2D/ 3D controllable contact induction composite biomimetic bone scaffolds according to bone tissue characteristics of implant sites, combined with 3D printing mechanics optimization, surface patterning and collagen micro-stent mechanics, degradation induced characteristics. Optimizing the 3D printing Ti matrix structure by cross-scale mechanical optimization calculation to match the physiological function of bone tissue; Modulating the electric field, electrolyte ratio, pH value to fabricate surface biomimetic pattern; Modulating the sol ratio, concentration and drying process to fabricate collagen/HA/BMP (CHB) porous scaffold, which is benefit for bone growth, filling into the Ti-based skeleton. Studying the interfacial combining mechanism between the degradation of CHB and bone tissue growth, exploring the induced osteogenesis mechanism of the composite 2D/3D scaffold; Analyzing the matching between CHB degradation and bone tissue growth rate, clarifying the bone growth mechanism affected by cross-scale mechanical properties of composite scaffold and its controllable 3D contact induced osteogenesis mechanism, providing basic research data for the development and application of 3D printing nested biomimic composite bone scaffolds.

3D打印钛支架为解决骨质疏松患者的骨替代与修复带来新的契机，然而，3D打印器件的孔洞尺寸过大、界面不友好，不利于骨细胞增殖及骨组织长入。为此，本项目提出针对植入部位骨组织特征，结合3D打印力学优化、表面图案化及胶原微支架的力学、降解诱导特性等设计开发Ti/COL嵌套式二维/三维可控接触诱导复合仿生骨支架。通过跨尺度计算力学优化3D打印钛基外骨架，使之匹配骨组织生理功能；调节电场特征、电解液配比、pH值，在钛骨架表面制备仿生图案；调控溶胶配比、浓度以及干燥工艺，制备适合骨组织长入的胶原/HA/BMP多孔内支架（CHB）并填充钛基外骨架；研究CHB与钛骨架界面结合机理，探讨二维图案、三维孔结构与BMP复合诱导成骨机制；获得CHB降解与骨组织长入速度的匹配性，明晰复合支架跨尺度力学性能对骨生长的影响机理及其可控三维接触诱导成骨机理，为3D打印仿生嵌套式复合支架的开发与应用提供基础性研究数据。

骨科植入物是治疗众多骨科疾病的重要手段之一。然而金属植入体的力学性能与骨组织的不匹配及其生物惰性对术后植入体的快速骨整合及长期稳定性产生影响。本项目根据骨组织的结构特征及其力学性能，通过力学模拟计算，优化设计多孔结构钛植入体并3D打印成型，使其匹配骨组织力学性能，获得力学仿生整体结构，通过的喷砂酸蚀结合微弧氧化等表面处理技术，去除3D打印植入体表面烧结不完全的颗粒并获得利于成骨细胞黏附、增殖、矿化的表面显微微纳结构，获得二维仿生植入体表面，进一步通过胶原基多孔微支架的填充，调控3D打印植入体的孔隙尺寸，诱导成骨细胞的快速长入并提供更多的黏附位点，获得三维多孔仿生结构，最终实现骨植入体的力学/二维表面/三维结构的复合仿生。研究结果表明，通过力学优化设计，所制备植入体的弹性模量可控制在小于20GPa左右，体外细胞实验结果表明，复合仿生支架较未改性支架具有更好的生物相容性，且片状结构和纤维状结构共存的多孔内支架更有利于成骨细胞的附着和生长。动物体内试验结果表明，复合仿生植入体周围的新生骨量显著高于对照组样品，表明项目所制备的二维/三维仿生改性植入体能够有效诱导骨组织在植入体表面生长并长入植入体的多孔结构中，促进术后骨整合。