3D打印生物活性陶瓷大段人工骨的多尺度结构设计与降解特性调控

The researches on artificial bones with reliable biocompatibility and industrial production ability are in the ascendant. In the early stage, the performance of artificial bones can only be used as osteocytes attaching and supporting scaffolds, which are physically excluded by the body. Now, artificial bones have developed a lot, which can be degradated and osteoinductive by the body, and finally been completely replaced by new bone. However, most of the current artificial bone can only be prepared into a small volume of filling material, a large section of the weight-bearing bone and large structural bone graft material are still facing the lack of ideal bone defect repair materials, and difficulty in materials process controlling problem. The application cooperative institution has investigated the "ideal powders" of high quality nano-hydroxyapatite and tricalcium phosphate and the preparation process technique in the early stage. We have developed a 3D bioceramic printer, which is capable of printing materials which holding complex shapes and pore structures. For further confirmation of this hypothesis, we will optimize the ratio of the HA/TCP materials ratio, the design of multi-scale pore structure in the domain of large-scale load-bearing bone, and reducing the β-TCP degradation rate based on the gradient impregnation and sintering process were studied. Finally, the material will has excellent biological activity and osteoinductivity, meeting the requirements of mechanical carrying capacity, and the material degradation rate will match with the osteogenesis rate. We hope our study can solve the medical problem of repairing a large section of disabled bones with ceramic-based artificial bones in the weight-bearing sites.

为满足巨大临床需求，对生物安全性可靠、能工业化生产的人工骨研究方兴未艾，人工骨已从仅能在早期发挥连接、支撑作用并供骨细胞附着的异物支架，发展为具有骨诱导性、可降解、最终完全由自体新骨替代的仿生骨。但目前大段负重骨及大块结构性植骨材料仍面临缺乏理想骨缺损修复材料和材料成型过程难以加工调控的难题。在前期已探索了高质量纳米羟基磷灰石和磷酸三钙“理想粉体”及制备工艺，开发出能打印复杂形状与孔隙结构的3D生物陶瓷打印机之后，我们提出以3D打印将优化的纳米羟基磷灰石材料制成多尺度结构，并采用梯度温度烧结技术，有望制备出具有良好骨传导与诱导性、降解速率可控的高强度生物活性陶瓷大段人工骨之假说。并将进行大段承重骨设计域内多尺度孔隙结构设计，及基于梯度浸渍烧结工艺调控β-磷酸三钙材料体内降解速率过快的研究。最终使材料具有优良生物活性与骨诱导性、降解速率与成骨速率相匹配的特性，解决承力部位大段人工骨替代的世界难题。

创伤、肿瘤、感染和融合手术引起的骨缺损是临床常见问题，其修复仍具有挑战性。随着骨组织工程（BTE）的发展，越来越多的BTE材料替代自体骨或异体骨用于临床治疗骨缺损。但目前的人工骨绝大多数尚只能制备成小体积的填充用材料，大段负重骨及大块结构性植骨材料的研发尚不成熟。因此，迫切需要研发在材料成分、显微结构和几何外形上具有仿生特征与生物活性的可再生人造骨支架。为此，本项目将通过3D打印技术和浸渍梯度烧结工艺，以纳米HA制备出几何外形复杂、具有一定孔隙率、复杂孔隙结构的大段多孔人工骨支架，并研究不同孔隙率对多孔羟基磷灰石骨坯体力学性能的影响；在经烧结提高了力学强度、保留了一定生物活性的多孔支架孔壁表面，以浸渍工艺附着上多层纳米 HA/β-TCP涂层后，再通过对不同涂层设置温度梯度进行低温烧结以调节β-TCP 降解速度的研究，并对人工骨支架进行系统的生物相容性与体内降解性检测；制备出纳米羟基磷灰石和磷酸三钙双相可降解骨诱导生物活性陶瓷大段人工骨后，进行大段骨缺损修复动物实验。.本研究以改进后的湿化学合成法，通过控制反应温度、压力、时间等条件合成具有特定形貌、高纯度、组分均匀、粒径分布窄、无毒性、重金属含量正常和无团聚的HA和β-TCP粉体。基于医学影像建模和纳米羟基磷灰石原料，采用3D生物陶瓷打印机成型多孔HA骨坯体，利用烧结后的多孔HA支架，进行不同孔隙率对羟基磷灰石骨坯体力学性能影响的研究，得出最优参数为晶须含量10%，烧结温1300°C，保温时间3h。最优方案支架的抗压强度为8.13MPa，孔隙率为64.07%。通过植入动物体内进行骨修复初步研究，复合支架在动物体内有良好的骨修复能力，可作为骨替代材料用于骨缺损的治疗。.本研究就如何促进骨组织快速修复问题所进行的探索，制备出具有良好骨诱导性与传导性、降解速率可控的高强度生物活性陶瓷大段人工骨，为广大骨缺损患者提供一种新的治疗手段，并为临床的进一步应用提供坚实的理论基础。