Visual Antimicrobial Gold Nanocluster Hydrogel with Inflammation-Responsive and Time-Regulated Swelling/Degradation for Regenerative Endodontic Procedures.

Beibei Xie, Chunyun Liang, Cong Liu, Xu Wang, Hailun Zhou, Jun Zhou, Kangjing Li, Huasheng Xu, Xiaoping Su, Ying Luo, Hao Zhang, Dan Liang, Ao Long, Shufang Zhuo, Xuan He, Dan Lin, Zhiyong Chen, Wenxia Chen, Yaling Wang, Xinglu Jiang
Author Information
  1. Beibei Xie: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China.
  2. Chunyun Liang: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China.
  3. Cong Liu: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China.
  4. Xu Wang: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China.
  5. Hailun Zhou: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China.
  6. Jun Zhou: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China.
  7. Kangjing Li: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China.
  8. Huasheng Xu: Stomatology Department, Affiliated Minzu Hospital of Guangxi Medical University, Guangxi, Nanning, Guangxi 530001, China.
  9. Xiaoping Su: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China.
  10. Ying Luo: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China.
  11. Hao Zhang: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China.
  12. Dan Liang: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China.
  13. Ao Long: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China.
  14. Shufang Zhuo: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China.
  15. Xuan He: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China.
  16. Dan Lin: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China.
  17. Zhiyong Chen: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China.
  18. Wenxia Chen: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China.
  19. Yaling Wang: New Cornerstone Science Laboratory, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Chinese Academy of Sciences, Beijing 100190, China. ORCID
  20. Xinglu Jiang: Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College & Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi 530021, China. ORCID

Abstract

Regenerative endodontic procedures (REPs) have become the primary therapy for immature permanent teeth. Double antibiotic (DA, ciprofloxacin, and metronidazole) is recommended as the intracanal medicament in REPs. However, it has several limitations, such as toxicity to stem cells, short-term antibacterial efficacy, and inability to be visualized radiographically. In this study, a method is induced to construct an antimicrobial Gold nanocluster (Au NC) hydrogel loading DA (DA@Au NCs) via electrostatic interactions and disulfide bond generation for REPs. As exposed to interstitial fluid from root canal infection, DA@Au NCs can swell and fill the canal to thoroughly contact with bacteria in its biofilm. The increasing interstitial fluid and its internal protease can trigger the degradation of DA@Au NC hydrogel to release DA, and it has been found that the cross-linking time of hydrogel can regulate its degradation time because of the positive correlation between them. Au NC hydrogel has the characteristics of radiographical visualization to track the drug location and release dynamics. These properties can improve the antimicrobial efficiency, achieve long-term antibacterial effects, and reduce cells toxicity. Moreover, the hydrogel can also kill planktonic bacteria and biofilm, even penetrating dentin tubules. Attributed to the introduction of Au NCs, it also supports stem cell proliferation, migration, adhesion, and mineralization by regulating the expression of alkaline phosphatase (ALP). The in vivo experiments also verified that the multiple properties of DA@Au NC hydrogel offer a solution to address the problem of REPs.

Keywords

MeSH Term

Gold
Hydrogels
Metal Nanoparticles
Animals
Anti-Bacterial Agents
Regenerative Endodontics
Biofilms
Humans
Ciprofloxacin
Inflammation
Metronidazole
Microbial Sensitivity Tests
Mice
Cell Proliferation

Chemicals

Gold
Hydrogels
Anti-Bacterial Agents
Ciprofloxacin
Metronidazole

Word Cloud

Created with Highcharts 10.0.0hydrogelcanREPsNCDA@AuDAantimicrobialAuNCsalsoRegenerativeendodonticprocedurestoxicitystemcellsantibacterialgoldinterstitialfluidcanalbacteriabiofilmdegradationreleasetimepropertiesbecomeprimarytherapyimmaturepermanentteethDoubleantibioticciprofloxacinmetronidazolerecommendedintracanalmedicamentHoweverseverallimitationsshort-termefficacyinabilityvisualizedradiographicallystudymethodinducedconstructnanoclusterloadingviaelectrostaticinteractionsdisulfidebondgenerationexposedrootinfectionswellfillthoroughlycontactincreasinginternalproteasetriggerfoundcross-linkingregulatepositivecorrelationcharacteristicsradiographicalvisualizationtrackdruglocationdynamicsimproveefficiencyachievelong-termeffectsreduceMoreoverkillplanktonicevenpenetratingdentintubulesAttributedintroductionsupportscellproliferationmigrationadhesionmineralizationregulatingexpressionalkalinephosphataseALPvivoexperimentsverifiedmultipleoffersolutionaddressproblemVisualAntimicrobialGoldNanoclusterHydrogelInflammation-ResponsiveTime-RegulatedSwelling/DegradationEndodonticProceduresnanoclustersinflammationresponsiveregenerative

Similar Articles

Cited By

No available data.