新型多通道3D打印微环境响应仿生骨在牙周炎环境下种植体周围骨愈合中的作用和机制

修复牙周炎患者的骨缺损是目前口腔种植领域面临的主要挑战。传统通过负载活性药物的骨支架，功能单一，难以达到理想的治疗效果。课题组前期通过3D打印技术制备了具有良好机械性能的活性骨支架，显著促进骨缺损愈合；在牙周炎治疗方面，也制备出具有抗炎抗菌作用的ZIF-8:Ce纳米粒子。本课题拟在前期基础上，利用多通道生物3D打印技术制备多梯度“仿生骨”；制备含干细胞和自体富血小板纤维蛋白的细胞墨水。设计pH响应释放ZIF-8:Ce抗菌抑炎层；优化多通道3D打印策略。从结构、机械强度和生物活性三方面进行“仿生骨”的制备，体外研究“仿生骨”对干细胞、巨噬细胞的影响；建立急性牙周炎伴种植体周围骨缺损的动物模型，体内验证“仿生骨”促进骨愈合的规律和机制。本课题从梯度结构，细胞治疗，智能释药的角度设计“仿生骨”为牙周炎患者的骨缺损治疗提供新方案，从免疫调控机制的角度为牙周炎状态下的骨再生提供理论依据。

Repairing bone defects in patients with periodontitis is still a major challenge in the field of oral implantation. Traditional bone scaffolds with active drugs have limited functions and it is difficult to achieve the desired therapeutic effect. In terms of bone regeneration, In our previous study, a bone scaffold composed of ceramic and polymer was fabricated through cryogenic 3D printing for repairing the bone defect, and it shows great potential in bone regeneration since it has good mechanical properties and sustainable peptide release profile; We also prepared ZIF- 8: Ce nanoparticles with therapeutic effect on periodontitis. In this proposal, we will prepare a multi-gradient "bionic bone" using multi-channel biological 3D printing technology. The "bionic bone" are designed to fabricate from cell inks containing cells and autologous platelet-rich fibrin and pH-responsive hydrogel which designed to release ZIF-8: Ce in a lower pH micro-environment. The optimized multi-channel 3D printing strategy for the "bionic bone" from three aspects of structure, mechanical strength, and biological activity. The effect of "bionic bone" on stem cells and macrophages was studied in vitro. An animal model of bone defect with acute periodontitis after immediate implant placement was established, and the function and mechanism of "bionic bone" to promote bone healing were verified in vivo. The structural design and optimization of bionic bone were more comprehensively considered from the perspective of gradient ordered structure, cell therapy, and smart drug release. This “bionic bone” propose a new solution for oral implantation in patients with periodontitis and bone defects, and to provide a theoretical basis for bone regeneration under the state of periodontitis from the perspective of immune regulation mechanisms.