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Keeping sodium hypochlorite (NaOCl) within the root canal is challenging in regenerative endodontics. In this study, we developed a drug delivery system using a gelatin methacryloyl (GelMA) hydrogel incorporated with aluminosilicate clay nanotubes (HNTs) loaded with NaOCl. Pure GelMA, pure HNTs, and NaOCl-loaded HNTs carrying varying concentrations were assessed for chemo-mechanical properties, degradability, swelling capacity, cytocompatibility, antimicrobial and antibiofilm activities, and in vivo for inflammatory response and degradation. SEM images revealed consistent pore sizes of 70–80 µm for all samples, irrespective of the HNT and NaOCl concentration, while HNT-loaded hydrogels exhibited rougher surfaces. The hydrogel’s compressive modulus remained between 100 and 200 kPa, with no significant variations. All hydrogels demonstrated a 6–7-fold mass increase and complete degradation by the seventh day. Despite an initial decrease in cell viability, all groups recovered to 65–80% compared to the control. Regarding antibacterial and antibiofilm properties, 12.5 HNT(Double) showed the highest inhibition zone on agar plates and the most significant reduction in biofilm compared to other groups. In vivo, the 12.5 HNT(Double) group displayed partial degradation after 21 days, with mild localized inflammatory responses but no tissue necrosis. In conclusion, the HNT-NaOCl-loaded GelMA hydrogel retains the disinfectant properties, providing a safer option for endodontic procedures without harmful potential.

This study was aimed at engineering photocrosslinkable azithromycin (AZ)-laden gelatin methacryloyl fibers via electrospinning to serve as a localized and biodegradable drug delivery system for endodontic infection control. AZ at three distinct amounts was mixed with solubilized gelatin methacryloyl and the photoinitiator to obtain the following fibers: GelMA+5%AZ, GelMA+10%AZ, and GelMA+15%AZ. Fiber morphology, diameter, AZ incorporation, mechanical properties, degradation profile, and antimicrobial action against Aggregatibacter actinomycetemcomitans and Actinomyces naeslundii were also studied. In vitro compatibility with human-derived dental pulp stem cells and inflammatory response in vivo using a subcutaneous rat model were also determined. A bead-free fibrous microstructure with interconnected pores was observed for all groups. GelMA and GelMA+10%AZ had the highest fiber diameter means. The tensile strength of the GelMA-based fibers was reduced upon AZ addition. A similar pattern was observed for the degradation profile in vitro. GelMA+15%AZ fibers led to the highest bacterial inhibition. The presence of AZ, regardless of the concentration, did not pose significant toxicity. In vivo findings indicated higher blood vessel formation, mild inflammation, and mature and thick well-oriented collagen fibers interweaving with the engineered fibers. Altogether, AZ-laden photocrosslinkable GelMA fibers had adequate mechanical and degradation properties, with 15%AZ displaying significant antimicrobial activity without compromising biocompatibility.

The impact of oral microbial dysbiosis on Alzheimer’s disease (AD) remains controversial. Building off recent studies reporting that various microbes might directly seed or promote amyloid β (Aβ) deposition, we evaluated the effects of periodontal bacteria (Porphyromonas gingivalis, Treponema denticola) and supragingival commensal (Streptococcus gordonii) oral bacterial infection in the APP-transgenic CRND8 (Tg) mice model of AD. We tracked bacterial colonization and dissemination, and monitored effects on gliosis and amyloid deposition. Chronic oral infection did not accelerate Aβ deposition in Tg mice but did induce alveolar bone resorption, IgG immune response, and an intracerebral astrogliosis (GFAP: glial fibrillary acidic protein). In contrast, intracerebral inoculation of live but not heat-killed P. gingivalis increased Aβ deposition and Iba-1 (ionized calcium-binding adaptor-1) microgliosis after 8 weeks of bacterial infection but not at 4 days. These data show that there may be differential effects of infectious microbes on glial activation and amyloid deposition depending on the species and route of inoculation, and thereby provide an important framework for future studies. Indeed, these studies demonstrate marked effects on amyloid β deposition only in a fairly non-physiologic setting where live bacteria is injected directly into the brain.