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UVA-activated riboflavin promotes collagen crosslinking to prevent root caries.

ABSTRACT: Root caries is an increasingly problem in aging societies with severe implications for the general health and wellbeing of large numbers of people. Strengthening type-I collagen, a major organic component of human dentin, has proved effective in preventing root caries. This study sought to determine whether exposure to riboflavin followed by UVA irradiation (RF/UVA) could promote additional collagen crosslinking, and thus improve the acid and enzymatic resistance of human dentin under simulated oral environments. If so, it could offer potential for treatment of the intractable problem of root caries. The greatest flexural strengths were found in dentin exposed to a 0.1% riboflavin solution for 1?minute followed by 1,600 mW/cm2 UVA irradiation for 10?minutes. Mineral loss and lesion depth were significantly lower in the RF/UVA group than in the control group. The microstructures of dentinal tubules and collagen networks after RF/UVA treatment retained their original forms after acidic and enzymatic degradation. In conclusion, RF/UVA treatment may be a new method for preventing root caries with promising prospects for clinical application.

SUBMITTER: Uemura R

PROVIDER: S-EPMC6362121 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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UVA-activated riboflavin promotes collagen crosslinking to prevent root caries.

Uemura R R Miura J J Ishimoto T T Yagi K K Matsuda Y Y Shimizu M M Nakano T T Hayashi M M

Scientific reports 20190204 1

Root caries is an increasingly problem in aging societies with severe implications for the general health and wellbeing of large numbers of people. Strengthening type-I collagen, a major organic component of human dentin, has proved effective in preventing root caries. This study sought to determine whether exposure to riboflavin followed by UVA irradiation (RF/UVA) could promote additional collagen crosslinking, and thus improve the acid and enzymatic resistance of human dentin under simulated ...[more]

PMID: 30718745

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Project description:Corneal collagen cross-linking (CXL) halts human corneal ectasias progression by increasing stromal mechanical stiffness. Although some reports describe that this procedure is effective in dealing with some infectious and immunologic corneal thinning diseases, there is a need for more animal models whose corneal thickness more closely resemble those occurring in these patients. To meet this need, we describe here high-intensity protocols that are safe and effective for obtaining CXL in rat corneas. Initially, a range of potentially effective UVA doses were evaluated based on their effectiveness in increasing tissue enzymatic resistance to dissolution. At UVA doses higher than a threshold level of 0.54 J/cm2, resistance to enzymatic digestion increased relative to that in non-irradiated corneas. Based on the theoretical threshold CXL dose, a CXL regimen was established in which the UVA tissue irradiance was 9 mW/cm2, which was delivered at doses of either 2.16, 2.7 or 3.24 J/cm2. Their dose dependent effects were evaluated on ocular surface morphological integrity, keratocyte apoptotic frequency, tissue thickness and endothelial cell layer density. Doses of 2.16 and 2.7 J/cm2 transiently decreased normal corneal transparency and increased thickness. These effects were fully reversed after 14 days. In contrast, 3.24 J/cm2 had more irreversible side effects. Three days after treatment, apoptotic frequency in the CXL-2.16 group was lower than that at higher doses. Endothelial cell losses remained evident only in the CXL-3.24 group at 42 days posttreatment. Stromal fiber thickening was evident in all the CXL-treated groups. We determined both the threshold UVA dose using the high-intensity CXL procedure and identified an effective dose range that provides optimal CXL with minimal transient side effects in the rat cornea. These results may help to provide insight into how to improve the CXL outcome in patients afflicted with a severe corneal thinning disease.

Project description:PurposePreviously, we found norepinephrine (NE) could affect the corneal epithelial integrity, herein we investigated the feasibility and safety of NE serving as a chemical enhancer to promote corneal penetration of riboflavin during transepithelial corneal crosslinking (CXL).MethodsThe dosage of NE that could promote riboflavin diffusion through the healthy epithelial barrier without inducing epithelial damage in C57BL/6 mice was determined. The safety of NE treatment was confirmed by morphological and histological examinations of the whole cornea. The efficacy of NE in promoting riboflavin penetration was verified by slit lamp and scanning electron microscope (SEM), and corneal biomechanical measurement after CXL. To better fit the clinical scenario, increased NE dosage and shortened riboflavin infiltration time were further evaluated.ResultsThe lowest dosage of NE (1 mg/mL) that facilitated transepithelial riboflavin permeation was 2 µL. No visible corneal structure alteration was observed after NE treatment. SEM indicated dissociation of intercellular junctions among corneal epithelial cells. Homogenous distribution of riboflavin throughout corneal stroma was observed. NE-treated corneas reached comparable biomechanical properties after CXL, including stress-relaxation curve and elastic modulus, with corneas treated with the commercially available transepithelial drug Peschke TE. To better fit the clinical scenario, increasing NE up to 5.5 µL helped riboflavin infiltrate the corneal stroma within 30 minutes. After CXL with 9 mW/cm2 ultraviolet-A (UVA) for 2.5 minutes, the cornea showed significantly enhanced corneal biomechanical properties with undisturbed corneal endothelium.ConclusionsNE serves as an effective enhancer in increasing riboflavin diffusion with limited impairment on corneal epithelium and has great potential for clinical application.Translation relevanceNE serves as an effective enhancer for riboflavin penetration and clinical transepithelial CXL.

Project description:ObjectiveTo assess the effectiveness of lasers (at sub-ablative parameters) in reducing caries incidence compared with traditional prophylactic interventions (TPIs) when used alone or together with other TPIs such as pits and fissures sealant or fluoride gels or varnishes.DesignA systematic review. Data sources include Medline (via PubMed), Embase, Web of Science and the Cochrane Library (December 2019).Eligibility criteriaOnly randomised trials (RCTs) and controlled clinical trials (CCTs) dealing with prophylactic lasers use (vs TPI or untreated teeth) were considered as eligible. We excluded in vitro and ex vivo studies.Data extractionEligible studies were selected and data extracted independently by two reviewers. Risk of bias was assessed adopting the Cochrane Risk of Bias tool. Data on caries incidence, sealant retention, fluoride uptake, adverse events, treatment duration, patients' discomfort and cost-effectiveness ratio was extracted.Data analysisExtracted data were presented narratively due to the heterogeneity of included studies.ResultsSeven RCTs and two CCTs, all with an evident risk of bias, met inclusion criteria, pooling together 269 individuals and 1628 teeth. CO2, neodymium-doped yttrium aluminium garnet, erbium-doped yttrium aluminum garnet (Er:YAG), erbium, chromium: yttrium scandium gallium garnet (Er,Cr:YSGG) and Argon lasers were used. In the permanent dentition, lasers only when used in combination with TPIs were effective in reducing caries when compared with untreated teeth (risk ratio (RR)=0.44 (0.20-0.97); Er:YAG laser) or with TPIs used alone (RR=0.39 (0.22-0.71); CO2 laser). Moreover, Argon laser significantly improved the fluoride uptake into the enamel surfaces (ANalysis Of VAriance (ANOVA) tests: 95%, p<0.0001). Likewise, sealant retention improved when acid etching was performed on previously irradiated enamel fissures by CO2 laser (RR=0.63 (0.38-1.04)) or Er:YAG laser (RR=0.54 (95% CI: 0.34 to 0.87)). In addition, laser resulted safe and well tolerated by patients.ConclusionDespite some positive indications, an inadequate level of evidence was found in the included studies concerning the lasers' effectiveness in preventing caries. Further studies with a higher methodological quality level are required.

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UVA-activated riboflavin promotes collagen crosslinking to prevent root caries.

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UVA-activated riboflavin promotes collagen crosslinking to prevent root caries.

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