核壳结构CHX-ACP纳米微球及MSNs联合改性口腔复合树脂的基础研究

Secondary caries and restoration fracture are the main reasons for the failure of dental resin restorations. The modification by functional components can endow the resin with excellent antibacterial property, remineralization property or mechanical property, which is the important means to extend the clinical lifetime of the resin restorations. Studies reported that amorphous calcium phosphate (ACP) slowly released calcium and phosphate ions to mineralize the demineralized teeth tissue, although the mechanical properties of the resin modified by ACP are not always ideal. Chlorhexidine (CHX) can kill several kinds of oral bacteria. However, the long-term antibacterial property of the modified resin is weakened due to its burst effect. Mesoporous silica nanoparticles (MSNs) can improve the mechanical properties of composite resin and release CHX slowly. However, the modified resin still lack the mineralization ability. There is still no research on whether the combined application of the CHX-ACP nanosphere with core-shell structure and MSNs can endow composite resin with excellent antibacterial property, mineralization property and mechanical properties to improve its clinical lifetime. In this project, CHX-ACP nanosphere with core-shell structure and MSNs will be prepared as the active filler. Traditional composite resin will be modified by them in order to possess excellent antibacterial property, mineralization property and mechanical properties and maintain its basic properties such as biocompatibility. Then the effects of preventing microleakage, reducing secondary caries and improving restoration bonding durability based on novel multifunction resin will be investigated through the teeth model in vitro and animal model. This project provides a new strategy to lengthen the clinical lifetime of dental resin restorations.

继发龋和修复体断裂是造成口腔树脂修复失败的主要原因。功能成分可赋予树脂优良的抗菌、再矿化及机械性能，是延长树脂修复临床寿命的重要手段。研究发现无定形磷酸钙（ACP）可缓释钙磷离子促进脱矿牙体组织矿化，但其改性树脂机械性能常不理想；氯己定（CHX）可杀灭多种口腔致病菌，但其突释效应削弱了改性树脂的远期抗菌性能；介孔硅纳米颗粒（MSNs）可提高复合树脂的机械性能并缓释CHX，但其改性树脂仍缺乏矿化能力。核壳结构CHX-ACP纳米微球及MSNs联合应用可否同时赋予复合树脂优良的抗菌、再矿化及机械性能以提高其临床寿命目前尚无研究。本项目拟制备核壳结构CHX-ACP纳米微球及MSNs共同改性口腔复合树脂，赋予其优良的抗菌、再矿化及机械性能，维持其生物相容性等基本性能；进而通过离体牙模型和动物模型评价该树脂预防微渗漏、减少继发龋及提高修复体粘接持久性的效果，为延长口腔树脂修复体临床寿命提供新策略。

继发龋和修复体断裂是造成口腔树脂修复失败的主要原因，功能成分可赋予树脂优良的抗菌、再矿化及机械性能，是延长树脂修复临床寿命的重要手段。因此，本课题先将核壳结构CHX-ACP纳米微球引入树脂体系中，合成了一种新型抗菌再矿化口腔复合树脂。结果表明本研究成功制备了直径约100nm的核壳结构CHX-ACP纳米球，该纳米球具有缓释钙、磷离子及CHX的功能，且对变形链球菌的最低抑菌浓度（MIC）和最低杀菌浓度（MBC）分别为25和50μg/mL。添加5wt%CHX-ACP纳米球改性的口腔复合树脂（5-0组）抗菌性能优良（即刻及老化抗菌率均>92%），钙、磷离子及CHX的缓释可持续28天以上，固化深度4.50mm，双键转化率（DC）>65%，溶解率<0.5%，吸水率<2%，挠曲强度>90MPa，压缩强度>110MPa，且在模拟体液中浸泡1、7天后表面可形成磷酸钙沉积物。为了进一步提高复合树脂的机械强度及抗菌性能，我们制备了负载CHX的MSNs（CHX/MSNs）并将其引入上述复合树脂中，合成了另一种新型抗菌再矿化口腔复合树脂。结果表明20mg/mL氯己定溶液中制备的CHX/MSNs可在14天内持续缓释CHX，且其释放量最大，其对变形链球菌的MIC和MBC分别为50和100μg/mL。5wt%CHX/MSNs联合5wt%CHX-ACP纳米球共同改性的口腔复合树脂（5-5组）具有更强的抗菌性能，固化深度>4mm，吸水率及溶解率略高于对照组（分别为2.57%和0.63%），但且其挠曲强度和压缩强度与对照组相当。以上结果表明本研究所制备的核壳状CHX-ACP纳米球及CHX/MSNs具有缓释钙、磷离子及CHX的能力及优良的抗菌性能。两者各添加5wt%联合改性的口腔复合树脂具有更加优良的抗菌性能、与对照组相当的机械强度、满足临床需求的固化深度和溶解率、吸水率，为延长口腔树脂修复体临床寿命提供新策略。