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

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.