双环分层支架控释IL-17抗体促进伴糖尿病牙周骨再生的作用和机制研究

糖尿病患者的过度炎症反应是牙槽骨愈合困难的重要因素，其体内IL-17的水平与骨破坏的程度呈正相关，是抗炎的关键靶点之一。基于血糖响应体系合理控释IL-17抗体是促进骨愈合的新方向。但目前该体系血糖响应灵敏度不足、药物活性不易保存且存在突释现象，本课题拟采用直接光处理3D生物打印技术来构建新型双环分层壳聚糖-生物玻璃支架，通过打印纤维环固定葡萄糖氧化酶体系并负载IL-17抗体，以期提高血糖响应性、抗体活性和改善突释等。重点考察酶活性、血糖响应性、释药曲线等关键参数；建立骨髓间充质干细胞高糖炎症模型，检测体系对细胞抗炎和成骨水平的作用；建立血糖控制不良的大鼠牙槽骨缺损模型，评价体系对骨缺损愈合的影响。本课题有望得到一种实时响应血糖控释IL-17抗体的载药体系，通过抑制局部炎症促进牙槽骨愈合，为糖尿病患者牙周或种植体周等裂隙型骨缺损提供符合临床实际的治疗策略，有助于探讨糖尿病牙槽骨愈合的机制。

The excessive inflammatory response in diabetic patients is a key factor for periodontal bone healing. IL-17 is identified as one of the significant anti-inflammatory targets, the level of which and bone destruction have a positive correlation. Rational controlled release of IL-17 antibody based on glucose response system provides a new way to promote bone healing. However, the system still exists some drawbacks such as insufficient glucose responsiveness, difficulty in long-term preservation of drug activity and burst release. In this study, a novel dual-looped layered chitosan-bioglass scaffold will be fabricated using direct light processing(DLP) 3D bio-printing technology. Specifically, the glucose oxidase system and IL-17 antibody will be fixed and loaded respectively by layered fibrous loops, in order to improve the glucose responsiveness, the activity of the antibody and avoid burst release. And then, firstly, the key parameters such as enzyme activity, glucose response and drug release curve will be investigated. After that, the scaffold will be co-cultured with bone marrow mesenchymal stem cells in the hyperglycemic inflammation medium to investigate on anti-inflammation and osteogenic process. At last, the model of diabetic rats with poor glucose control will be established. The scaffold will be implanted into the periodontal bone defect to evaluate the effect on bone healing. The aim of this study is to obtain a real-time glucose responsive drug delivery system to release IL-17 antibody, which is expected to promote periodontal bone healing by inhibiting local inflammation. This system provides a promising clinical strategy for fracturing type of bone defects of periodontal tissue or peri-implant, which is helpful to explore the mechanism of healing of alveolar bone in diabetes.