RESUMEN
INTRODUCTION: Recognizing the necessity of novel disinfection strategies for improved bacterial control to ultimately favor tissue regeneration, this study developed and characterized antibiotics-laden silk fibroin methacrylated (SilkMA) scaffolds for regenerative endodontics. METHODS: SilkMA-based solutions (10% w/v) containing Clindamycin (CLI) or Tinidazole (TIN) (0 - control; 5, 10, or 15% w/w) or the combination of both drugs (BiMix CLI/TIN 10%) were electrospun and photocrosslinked. Morphology and composition were assessed using scanning electron microscopy and Fourier-transform infrared spectroscopy. Additionally, swelling and degradation profiles were also determined. Cytotoxicity was evaluated in stem cells from apical papilla. Antibacterial efficacy was tested using direct and indirect contact assays against Aggregatibacter actinomycetemcomitans/Aa, Actinomyces naeslundii/An, Enterococcus faecalis/Ef, and Fusobacterium nucleatum/Fn. E. faecalis biofilm inhibition on dentin discs was specifically evaluated for BiMix-laden scaffolds. Data were statistically analyzed with a significance level of 5%. RESULTS: Scanning electron microscopy revealed that all scaffolds had similar characteristics, including fiber morphology and bead absence. Fourier-transform infrared spectroscopy showed the incorporation of CLI and TIN into the fibers and in BiMix scaffolds. Antibiotic-laden scaffolds exhibited lower swelling capacity than the control and were degraded entirely after 45 days. Scaffolds laden with CLI, TIN, or BiMix throughout all time points did not reduce stem cells from apical papilla's viability. CLI-laden scaffolds inhibited the growth of Aa, An, and Ef, while TIN-laden scaffolds inhibited Fn growth. BiMix-laden scaffolds significantly inhibited Aa, An, Ef, and Fn in direct contact, and their aliquots inhibited An and Fn through indirect contact, with additional biofilm inhibition against Ef. CONCLUSIONS: BiMix-laden SilkMA scaffolds are cytocompatible and exhibit antimicrobial effects against endodontic pathogens, indicating their therapeutic potential as a drug delivery system for regenerative endodontics.
RESUMEN
BACKGROUND: The effects of ethylenediaminetetraacetic acid (EDTA) on regenerative endodontic procedures (REPs) are controversial, because, despite releasing growth factors from dentine, some studies show negative effects on cell behaviour. OBJECTIVES: The aim of the study was to investigate the influence of the use of EDTA in REP on the growth factors' release, cell behaviour and tissue regeneration. METHODS: A systematic search was conducted (PubMed/Medline, Scopus, Cochrane Library, Web of Science, Embase, OpenGrey and reference lists) up to February 2021. Only in vivo and in vitro studies evaluating the effects of EDTA on the biological factors of dentine, pulp/periapical tissues and cell behaviour were eligible. Studies without a control group or available full text were excluded. The growth factors' release was the primary outcome. Risk of bias in the in vitro and in vivo studies was performed according to Joanna Briggs Institute's Checklist and SYRCLE's RoB tool, respectively. RESULTS: Of the 1848 articles retrieved, 36 were selected. Amongst these, 32 were in vitro, three animal studies and one with both models. The EDTA concentrations ranged from 3% to 15%, at different times. Regarding growth factors' release (17 studies), 15 studies found significant transforming growth factor (TGF)-ß release after dentine conditioning with EDTA, and most found no influence on vascular endothelial growth factor release. Regarding cell behaviour (26 studies), eight studies showed no influence of EDTA-treated dentine on cell viability, whereas, five, nine and six studies showed higher cell migration, adhesion and differentiation respectively. No influence of EDTA conditioning was observed in animal studies. In vitro studies had a low risk of bias, whereas animal studies had high risk of bias. Meta-analysis was unfeasible. DISCUSSION: This review found that EDTA increased TGF-ß release and improved cell activity. However, well-designed histological analyses using immature teeth models are needed. CONCLUSIONS: High-quality in vitro evidence suggests that EDTA-treated dentine positively influences TGF-ß release, cell migration, attachment and differentiation; further research to evaluate its influence on tissue regeneration is necessary due to low methodological quality of the animal studies.