基于PEKK复合结构植入体的下颌骨缺损重建机理及其实现技术研究

Reconstruction of mandibular defects using autograft harvested from healthy bone segment will make second traumatic hurt for patient, and the size of harvested graft is limited. Reconstructions using metal implant may be defeated caused by the implant loosening since the high mechanical properties of metal material activates the ‘stress shielding’effect. Repair by tissue engineering is far from clinical application because of the low mechanical properties of scaffold. So any of the three reconstruction methods could not supply all of the four functions needed in mandibular repairing including initial stability, soft tissue shaping, mastication force supporting and bone grow guiding, which means the mechanical recover can not be realized by the three present methods. . Based on the three grafting methods, a new artificial mandibular graft with hybrid structures based on nondegradable part (including elements of shaping, fixation and supporting) of PEKK biopolymers and tissue engineering scaffold (growing element) is proposed in this proposal. Constructing the mandibular biomechanical model, and explore the biomechanical mechanisms within mandibular reconstruction, bone healing and scaffold guided bone growing, then based on these mechanisms and models, as well as mechanical properties of PEKK material, the structures of nondegradable elements including shaping, fixation and supporting and the degradable scaffold will be available by digital design and topological optimization. Then the processes of 3D printing based on two materials of PEKK and PCL or PLA simultaneously and surface treatment will be investigated and realized for the new artificial graft with hybrid structures. The feasibility for mandibular defect repairing by the new graft will be evaluated by mechanical experiments, biological tests and animal experiments.

下颌骨缺损通过自体骨移植修复需要取健康骨组织而造成二次伤害，而且供骨量有限；金属植入体则由于力学性能太强，易因“应力遮挡”效应而导致松动；而组织工程修复则支架的力学性能较差，离临床应用较远。三种植入技术目前都不能同时提供修复所需的初期稳定性、软组织塑型、咬合支撑及骨生长引导四种功能，无法实现下颌骨的精确力学重建。. 以三种植入技术为基础，提出一种基于PEKK材料非降解部分(包括塑型、固定、支撑单元)和可降解支架（生长单元）的复合结构人工植入体；构建下颌骨的生物力学模型，探究下颌骨缺损重建的力学机制、骨愈合以及支架引导骨生长的生物力学机理，结合PEKK的力学性能，利用数字化设计和拓扑优化技术得到植入体非降解结构和可降解的支架结构；研究同时基于PEKK和PCL或PLA的复合结构植入体3D打印工艺及表面处理工艺，并通过力学、生物学及动物实验验证复合结构植入体用于下颌骨重建的可行性。

本项目针对当前基于自体骨移植和人工植入体修复下颌骨缺损中存在的供体不足、应力遮蔽等问题，探索构建了基于下颌骨生物力学性能重构的植入体结构拓扑优化设计方法；发明了具有塑型、固定、支撑单元和可降解生长单元的复合结构下颌骨植入体，同时发明了一种具有分层多孔结构的下颌骨多孔植入体新型结构；研究了PEKK材料的3D打印工艺及参数优化技术，实现了基于PEKK材料和钛合金的下颌骨植入体的打印制备，以及植入体表面TiO2纳米活性层的构建工艺；开展了体外细胞培养实验和基于比格犬和兔的新型下颌骨植入体的动物实验验证。项目在以下方面取得了重要进展和成果：（1）构建了基于骨非均匀力学性能和肌肉力的下颌骨生物力学模型，发明了下颌骨生物学力性能测量技术，并搭建了测量系统，验证了模型的准确性；（2）提出了基于生物力学重构的下颌骨植入体的拓扑优化设计方法及技术，并发明了具有塑型、固定、支撑单元和可降解生长单元复合结构植入体，通过基于钛合金的植入体动物实验验证了其有效性；（3）探索了PEKK材料的FDM打印工艺及参数优化，构建了适应于下颌骨植入体生物力学性能最优的打印工艺和表面TiO2纳米活性层的构建工艺，体外细胞培养和兔植入实验验证了植入体良好的生物学和生物力学性能；（4）探讨了下颌骨箱体缺损的病变切除参数对下颌骨生物力学性能的影响，发明了箱状缺损修复植入体的设计方法，生物力学性能测试表明了其良好的生物力学性能。项目成果在国际权威期刊Materials Science and Engineering:C (IF=7.328)、Computers in Biology and Medicine（IF: 4.589）、Journal of the Mechanical Behavior of Biomedical Materials(IF: 3.372)等国际期刊发表论文22篇；申请中国发明专利9项，其中授权专利2项；做大会或特邀报告5次；本项目研究为推动下颌骨缺损修复从外形及功能修复向生物力学性能重构修复提供了技术方法基础。