Biomineralization-Inspired Anti-Caries Strategy Based on Multifunctional Nanogels as Mineral Feedstock Carriers

Abstract

Rui Yuan,1,* Yuwen Zhang,1,* Liqiong Liao,2 Yige Ge,1 Weichang Li,1 Qinghui Zhi1 1Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510030, People’s Republic of China; 2Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qinghui Zhi, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, Guangdong, 510055, People’s Republic of China, Email [email protected] Weichang Li, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, Guangdong, 510055, People’s Republic of China, Email [email protected]: 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.Methods: 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.Results: 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 Ca2+ and PO43- 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 MIC50 and MIC90 values of 12.5 and 50 mg/mL against Streptococcus mutans, 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 Streptococcus mutans while maintaining good biocompatibility.Conclusion: 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.Graphical Abstract: Keywords: nanomaterial, mineralization, antibacterial materials, dentinal tubule occlusion, caries

Keywords

• nanomaterial
• mineralization
• antibacterial materials
• dentinal tubule occlusion
• caries