GTF响应型控释体系的构建及其修复牙体硬组织缺损的机制研究

Tooth defect is the most common disease in dental treatment, and the dominant reason is believed to be the cariogenic effect of S. mutans. S. mutans could secrete an enzyme called GTF that facilitates the adherence, colonization and acid production of bacteria, thus leading to tooth defect. Therefore, there is high clinical significance in early specific recognition of S. mutans, early intervention and interruption of caries development and simultaneous repair of the tooth defect. Our study intends to establish the GTF-responsive drug controlled release system through using sucrose analogs (3-deoxysucrose) as the gatekeeper, and MSN as the nanocarrier for EGCG (antibacterial) and PAH-ACP (precursor of remineralization). During the early stage of caries development, the GTF secreted by S. mutans specifically recognizes and cuts 3-deoxysucrose to open the gate, releasing EGCG which could kill bacteria and protect dentin collagen effectively and PAH-ACP which facilitates the remineralization of demineralized dentin. The GTF-responsive drug controlled release system has various advantages, such as specific recognition of cariogenic bacteria, drug release as needed and in situ recovery. This system will renovate the existing defect repairing strategy, and provide new technical support and guarantee for the exploration of caries early prevention, secondary caries repair and prolongation of dentin bonding durability.

牙体缺损是口腔临床最常见的疾病，S.mutans致龋是其最主要的病因。S.mutans分泌GTF促进细菌的粘附、定植和产酸，从而破坏牙体硬组织，导致牙体缺损。如何在龋损早期特异性识别S.mutans、介入并中断其进一步发展，同时修复缺损具有重要的临床意义。本课题拟利用蔗糖类似物（3-脱氧蔗糖）为门控，以介孔硅为纳米载体，负载EGCG和PAH-ACP，构建GTF响应型智能药物控释系统。在龋损发生早期，口腔内微环境发生改变，S.mutans释放的GTF可特异性识别切断3-脱氧蔗糖，打开门控，释放能够高效杀菌并保护牙本质胶原的药物EGCG，并且释放矿化前驱体PAH-ACP促进牙本质再矿化。该系统具有特异性识别致龋菌、按需释放、原位修复的优点，将革新现有的缺损后修复策略，为早期预防龋损发生、修复继发龋坏、提高粘接修复耐久性等方面的探索提供新的技术支持和保障。

项目背景：牙体缺损是口腔临床最常见的疾病，S.mutans致龋是其最主要的病因。S.mutans分泌GTF促进细菌的粘附、定植和产酸，从而破坏牙体硬组织，导致牙体缺损。目前龋病的药物治疗多为使用涂剂、漱口水等或将抗菌药物掺入充填材料，但仍存在药物释放不持久、特异性不强等缺陷。如何在龋损早期特异性识别S.mutans、介入并中断其进一步发展，同时修复缺损具有重要的临床意义。.主要研究内容：第一部分：（1）酶响应型智能水凝胶的合成；（2）智能药物控释凝胶材料的性能表征、特异性降解特性及生物安全性评价；（3）酶响应型智能凝胶材料药物控释能力及释放药物的生物活性评价。第二部分：（1）细菌响应型胶束双载药控释系统的构建；（2）智能胶束材料性能表征、药物控释能力、牙表面黏附性评价；（3）智能胶束材料抗生物膜能力、促釉质矿化修复效果的体外研究；（4）智能胶束材料对大鼠龋损模型的预防龋齿及促釉质修复体内研究；（5）细菌响应型胶束双载药控释材料生物相容性及维持体内微生物多样性研究。.重要结果和关键数据：本课题组合成了酶响应降解的智能药物控释水凝胶材料，研究证实其具有良好的亲水性、大孔径、高孔隙率、酶特异性降解及生物安全性。此外，针对龋损酸性微环境，构建了细菌响应型胶束双载药控释系统。该系统能黏附于牙表面，并在酸性pH下快速释放药物。性能表征和体外评价证实了该材料具有效的抗菌黏附性、抗致龋生物膜能力、抑制釉质脱矿并促其再矿化、并恢复其机械性能的效果。体内评价也证实了其具有良好的体内预防龋齿及促釉质修复效果。此外，该系统具有良好的生物相容性，且能维持口腔微生物多样性。.科学意义：本研究成功合成了酶响应型智能水凝胶材料，在药物控释和组织再生方面具有良好的潜力；本研究成功构建了细菌响应型胶束双载药控释系统，通过特异性识别致龋菌、按需释放、原位修复，为预防龋齿、修复牙齿缺损、对抗口腔生物膜等方面的探索提供新的技术支持和理论保障。