Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510030, People's Republic of China.
Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, 510515, People's Republic of China.
Int J Nanomedicine. 2023 Sep 4;18:4933-4947. doi: 10.2147/IJN.S418465. eCollection 2023.
Dentin caries remains a significant public concern, with no clinically viable material that effectively combines remineralization and antimicrobial properties. To address this issue, this study focused on the development of a bio-inspired multifunctional nanogel with both antibacterial and biomineralization properties.
First, p(NIPAm-co-DMC) (PNPDC) copolymers were synthesized from N-isopropylacrylamide (NIPAm) and 2-methacryloyloxyethyl-trimethyl ammonium chloride (DMC). Subsequently, PNPDC was combined with γ-polyglutamic acid (γ-PGA) through physical cross-linking to form nanogels. These nanogels served as templates for the mineralization of calcium phosphate (Cap), resulting in Cap-loaded PNPDC/PGA nanogels. The nanogels were characterized using various techniques, including TEM, particle tracking analysis, XRD, and FTIR. The release properties of ions were also assessed. In addition, the antibacterial properties of the Cap-loaded PNPDC/PGA nanogels were evaluated using the broth microdilution method and a biofilm formation assay. The remineralization effects were examined on both demineralized dentin and type I collagen in vitro.
PNPDC/PGA nanogels were successfully synthesized and loaded with Cap. The diameter of the Cap-loaded PNPDC/PGA nanogels was measured as 196.5 nm at 25°C and 162.3 nm at 37°C. These Cap-loaded nanogels released Ca and PO ions quickly, effectively blocking dental tubules with a depth of 10 μm and promoting the remineralization of demineralized dentin within 7 days. Additionally, they facilitated the heavy intrafibrillar mineralization of type I collagen within 3 days. Moreover, the Cap-loaded nanogels exhibited MIC and MIC values of 12.5 and 50 mg/mL against , respectively, with an MBC value of 100 mg/mL. At a concentration of 50 mg/mL, the Cap-loaded nanogels also demonstrated potent inhibitory effects on biofilm formation by while maintaining good biocompatibility.
Cap-loaded PNPDC/PGA nanogels are a multifunctional biomimetic system with antibacterial and dentin remineralization effects. This strategy of using antibacterial nanogels as mineral feedstock carriers offered fresh insight into the clinical management of caries.
牙本质龋仍然是一个重大的公共卫生问题，目前还没有一种临床可行的材料能够有效地结合再矿化和抗菌性能。为了解决这个问题，本研究专注于开发一种具有抗菌和生物矿化性能的仿生多功能纳米凝胶。
首先，由 N-异丙基丙烯酰胺（NIPAm）和 2-甲基丙烯酰氧乙基三甲基氯化铵（DMC）合成 p（NIPAm-co-DMC）（PNPDC）共聚物。随后，PNPDC 通过物理交联与γ-聚谷氨酸（γ-PGA）结合形成纳米凝胶。这些纳米凝胶作为磷酸钙（Cap）矿化的模板，形成负载 Cap 的 PNPDC/PGA 纳米凝胶。使用 TEM、粒子跟踪分析、XRD 和 FTIR 等多种技术对纳米凝胶进行了表征。还评估了离子的释放特性。此外，使用肉汤微量稀释法和生物膜形成测定法评估了负载 Cap 的 PNPDC/PGA 纳米凝胶的抗菌性能。在体外对脱矿质牙本质和 I 型胶原蛋白进行了再矿化效果的检测。
成功合成了负载 Cap 的 PNPDC/PGA 纳米凝胶。在 25°C 时，负载 Cap 的 PNPDC/PGA 纳米凝胶的直径为 196.5nm，在 37°C 时为 162.3nm。这些负载 Cap 的纳米凝胶快速释放 Ca 和 PO 离子，有效封闭深度为 10μm 的牙本质小管，并在 7 天内促进脱矿质牙本质的再矿化。此外，它们在 3 天内促进 I 型胶原蛋白的纤维内重矿化。此外，负载 Cap 的纳米凝胶对 的 MIC 和 MIC 值分别为 12.5 和 50mg/mL，MBC 值为 100mg/mL。在 50mg/mL 的浓度下，负载 Cap 的纳米凝胶对 的生物膜形成也具有很强的抑制作用，同时保持良好的生物相容性。
负载 Cap 的 PNPDC/PGA 纳米凝胶是一种具有抗菌和牙本质再矿化作用的多功能仿生系统。使用具有抗菌作用的纳米凝胶作为矿物原料载体的策略为龋病的临床管理提供了新的思路。
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