A Bi-Mix Antibacterial Drug-Delivery System for Regenerative Endodontics

poster abstractTraumatic injuries to immature teeth have traditionally been managed via apexification therapy with intracanal calcium hydroxide/Ca(OH)2. Recently, the use of a bi-mix (metronidazole-MET and ciprofloxacin-CIP) paste appears to provide more predictable results. The objective of this study was to fabricate/characterize polydioxanone (PDSII®)-based electrospun bi-mix drug-delivery systems incorporated with the combination of MET and CIP. The antibacterial property of the released media was tested against Enterococcus faecalis (Ef), Porphyromonas gingivalis (Pg) , Aggregatibacter actinomycetemcomitans (Aa). PDSII® was dissolved in HFP to obtain a 10wt.% solution. Either MET, CIP or distinct drug combinations were added into the solution followed by homogenization overnight. Six groups of study were employed: Control-100%PDS, G1-100%MET, G2-75%MET+25%CIP, G3- 50%MET+50%CIP, G4-25%MET+75%CIP and G5-100%CIP. Electrospinning was done based on optimized parameters to fabricate the distinct samples. Uniaxial microtensile testing (n=10), Fourier transform infrared spectroscopy/FTIR, scanning electron microscopy (SEM), and agar diffusion assay were used to characterize mechanical, chemical and antibacterial properties. One-way ANOVA (only for fiber diameter), Kruskal-Wallis and Mann-Whitney tests were performed (α=0.05). The results showed that uniaxial tensile strength was not significantly decreased compared to the control except G3. Average fiber diameters were in the nano-scaled range and significantly lower then the control. SEM imaging indicated a submicron fibrous morphology. FTIR confirmed the characteristic peaks for PDS as well as for the employed drugs. Agar diffusion assay suggested that the higher the CIP concentration the greater the antibacterial property against Ef, Pg and Aa. The results indicated that higher amount of CIP (G4 & G5) did not compromise mechanical properties of nanofibers and showed the highest bacterial inhibition against Ef, Pg and Aa. Optimization of the physical-mechanical properties, kinetics of drug release, and the effect of released drugs on dental pulp stem cells are currently being pursued. Partially funded by American Association of Endodontists/AAE (M.C.B.)

Bimix antimicrobial scaffolds for regenerative endodontics

INTRODUCTION: Eliminating and/or inhibiting bacterial growth within the root canal system has been shown to play a key role in the regenerative outcome. The aim of this study was to synthesize and determine in vitro both the antimicrobial effectiveness and cytocompatibility of bimix antibiotic-containing polydioxanone-based polymer scaffolds. METHODS: Antibiotic-containing (metronidazole [MET] and ciprofloxacin [CIP]) polymer solutions (distinct antibiotic weight ratios) were spun into fibers as a potential mimic to the double antibiotic paste (DAP, a MET/CIP mixture). Fiber morphology, chemical characteristics, and tensile strength were evaluated by scanning electron microscopy, Fourier transform infrared spectroscopy, and tensile testing, respectively. Antimicrobial efficacy was tested over time (aliquot collection) against Enterococcus faecalis (Ef), Porphyromonas gingivalis (Pg), and Fusobacterium nucleatum (Fn). Similarly, cytotoxicity was evaluated in human dental pulp stem cells. Data were statistically analyzed (P < .05). RESULTS: Scanning electron microscopy and Fourier transform infrared spectroscopy confirmed that electrospinning was able to produce antibiotic-containing fibers with a diameter mostly in the nanoscale. The tensile strength of 1:1MET/CIP scaffolds was significantly (P < .05) higher than pure polydioxanone (control). Meanwhile, all other groups presented similar strength as the control. Aliquots obtained from antibiotic-containing scaffolds inhibited the growth of Ef, Pg, and Fn, except pure MET, which did not show an inhibitory action toward Pg or Fn. Antibiotic-containing aliquots promoted slight human dental pulp stem cell viability reduction, but none of them were considered to be cytotoxic. CONCLUSIONS: Our data suggest that the incorporation of multiple antibiotics within a nanofibrous scaffold holds great potential toward the development of a drug delivery system for regenerative endodontics

Doxycycline-Encapsulated Nanotube-Modified Dentin Adhesives

This article presents details of fabrication, biological activity (i.e., anti-matrix metalloproteinase [anti-MMP] inhibition), cytocompatibility, and bonding characteristics to dentin of a unique doxycycline (DOX)-encapsulated halloysite nanotube (HNT)-modified adhesive. We tested the hypothesis that the release of DOX from the DOX-encapsulated nanotube-modified adhesive can effectively inhibit MMP activity. We incorporated nanotubes, encapsulated or not with DOX, into the adhesive resin of a commercially available bonding system (Scotchbond Multi-Purpose [SBMP]). The following groups were tested: unmodified SBMP (control), SBMP with nanotubes (HNT), and DOX-encapsulated nanotube-modified adhesive (HNT+DOX). Changes in degree of conversion (DC) and microtensile bond strength were evaluated. Cytotoxicity was examined on human dental pulp stem cells (hDPSCs). To prove the successful encapsulation of DOX within the adhesivesbut, more important, to support the hypothesis that the HNT+DOX adhesive would release DOX at subantimicrobial levelswe tested the antimicrobial activity of synthesized adhesives and the DOX-containing eluates against Streptococcus mutans through agar diffusion assays. Anti-MMP properties were assessed via -casein cleavage assays. Increasing curing times (10, 20, 40 sec) led to increased DC values. There were no statistically significant differences (p > .05) in DC within each increasing curing time between the modified adhesives compared to SBMP. No statistically significant differences in microtensile bond strength were noted. None of the adhesives eluates were cytotoxic to the human dental pulp stem cells. A significant growth inhibition of S. mutans by direct contact illustrates successful encapsulation of DOX into the experimental adhesive. More important, DOX-containing eluates promoted inhibition of MMP-1 activity when compared to the control. Collectively, our findings provide a solid background for further testing of encapsulated MMP inhibitors into the synthesis of therapeutic adhesives that may enhance the longevity of hybrid layers and the overall clinical performance of adhesively bonded resin composite restorations