Optical penetration models for practical prediction of femtosecond laser ablation of dental hard tissue.

OBJECTIVES: To develop and practically test high-precision femtosecond laser ablation models for dental hard tissue that are useful for detailed planning of automated laser dental restorative treatment. METHODS: Analytical models are proposed, derived, and demonstrated for practical calculation of ablation rates, ablation efficiency and ablated morphology of human dental enamel and dentin using femtosecond lasers. The models assume an effective optical attenuation coefficient for the irradiated material. To achieve ablation, it is necessary for the local energy density of the attenuated pulse in the hard tissue to surpass a predefined threshold that signifies the minimum energy density required for material ionization. A 1029 nm, 40 W carbide 275 fs laser was used to ablate sliced adult human teeth and generate the data necessary for testing the models. The volume of material removed, and the shape of the ablated channel were measured using optical profilometry. RESULTS: The models fit with the measured ablation efficiency curve against laser fluence for both enamel and dentin, correctly capturing the fluence for optimum ablation and the volume of ablated material per pulse. The detailed shapes of a 400-micrometer wide channel and a single-pulse width channel are accurately predicted using the superposition of the analytical result for a single pulse. CONCLUSIONS: The findings have value for planning automated dental restorative treatment using femtosecond lasers. The measurements and analysis give estimates of the optical properties of enamel and dentin irradiated with an infrared femtosecond laser at above-threshold fluence and the proposed models give insight into the physics of femtosecond laser processing of dental hard tissue.

Investigation of laser wavelength effect on the ablation of enamel and dentin using femtosecond laser pulses.

We investigated the effect of femtosecond (fs) laser ablation of enamel and dentin for different pulse wavelengths: infrared (1030 nm), green (515 nm), and ultra-violet (343 nm) and for different pulse separations to determine the optimal irradiation conditions for the precise removal of dental hard tissues with the absence of structural and compositional damage. The ablation rates and efficiencies were established for all three laser wavelengths for both enamel and dentin at room temperature without using any irrigation or cooling system, and the surfaces were assessed with optical and scanning electron microscopy, optical profilometry, and Raman spectroscopy. We demonstrated that 515 nm fs irradiation provides the highest rate and efficiency for ablation, followed by infrared. Finally, we explored the temperature variations inside the dental pulp during the laser procedures for all three wavelengths and showed that the maximum increase at the optimum conditions for both infrared and green irradiations was 5.5 °C, within the acceptable limit of temperature increase during conventional dental treatments. Ultra-violet irradiation significantly increased the internal temperature of the teeth, well above the acceptable limit, and caused severe damage to tooth structures. Thus, ultra-violet is not a compatible laser wavelength for femtosecond teeth ablation.

Mechanical and Metallurgical Characterization of Nickel-Titanium Wire Types for Rotary Endodontic Instrument Manufacture.

This study aimed to evaluate and compare the effects of ambient temperature and post-manufacture heat-treatment on the mechanical behavior of nickel-titanium (NiTi) wires. Four types of commercial NiTi variants (Stock NiTi, heat treated "Blue", "Gold", "Superflex", all Dentsply Maillefer, Ballaigues, Switzerland) were stressed in a tensile testing machine in a temperature-controlled water bath at three different temperatures. Stress and strain values were extrapolated from the raw data, and 2-way ANOVA and Tukey's test for multiple comparisons were performed to compare the differences of the mechanical constants. Differential scanning calorimetry (DSC) tests established the martensitic transformation starting (Ms), finishing (Mf) and austenitic (reverse-martensitic) starting (As) and finishing (Af) points. Austenitic modulus of elasticity and transformation stress values increased with temperature for all NiTi groups. The martensitic modulus of elasticity, maximum transformation strain and ultimate tensile stress were not significantly affected by temperature changes. Stock NiTi and Gold wire samples presented with clearly delineated austenitic and martensitic transformations in the DSC experiments. Differences in manufacturing/heat treatment conditions and ambient temperature affect the mechanical behavior of nickel-titanium and may have clinical implications. Further improvements to the experimental setup could be considered to provide more accurate measurements of strain.

Finite element analysis of rotary nickel-titanium endodontic instruments: A critical review of the methodology.

Finite element analysis has been a valuable research tool for rotary nickel-titanium endodontic files over the last two decades. This review aims to summarise and critique the methodology as used in currently available endodontic literature for finite element analysis of rotary nickel-titanium instruments. An electronic literature research in PubMed and Scopus databases was performed using the appropriate search terms, and the titles and abstracts were screened for relevance. The review revealed an inconsistent approach to the finite element method, particularly with regards to the boundary conditions in which the instruments are tested. Moreover, there is a lack of experimental data to validate in silico findings. A standardised protocol to finite element analysis of rotary endodontic instruments could be considered for future studies.

Efficient transfection and long-term stability of rno-miRNA-26a-5p for osteogenic differentiation by large pore sized mesoporous silica nanoparticles.

MicroRNA (miRNA) based therapy for bone repair has shown promising results for regulating stem cell proliferation and differentiation, an efficient and stable vector for delivery of microRNA delivery is needed. The present study explored the stability and functionality of lyophilized mesoporous silica nanoparticles with core-cone structure and coated with polyethylenimine (MSN-CC-PEI) as a system for delivering Rattus norvegicus (rno)-miRNA-26a-5p into rat marrow mesenchymal cells (rBMSCs) to promote their osteogenic differentiation. We assessed the cellular uptake and transfection efficiency of nanoparticles loaded with labelled miRNA using confocal laser scanning microscopy and flow cytometry, and the cell viability using the MTT assay. The expression levels of osteogenic genes after one and two weeks were analysed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Extracellular matrix deposition and mineralization at 3 weeks were evaluated using Picro Sirius red and Alizarin red staining. We also assessed the performance of the delivery system after long term storage, by freeze drying rno-miRNA-26a-5p@MSN-CC-PEI with 5% trehalose and keeping them at -30 °C for 3 and 6 months. Osteogenic differentiation, matrix deposition, and mineralization were all significantly increased by rno-miRNA-26a-5p. In addition, this enhancement was not significantly altered by lyophilization and storage. Overall, these findings support the concept of MSN-CC-PEI as a delivery system for gene therapy. The complex of rno-miRNA-26a-5p@MSN-CC-PEI could efficiently transfect rBMSCs and enhance their osteogenic differentiation. In addition, the lyophilized complexes remain functional after 6 months of storage.

Laser-assisted nucleic acid delivery: A systematic review.

Gene therapy has become an effective treatment modality for some conditions. Laser light may augment or enhance gene therapy through photomechanical, photothermal, and photochemical. This review examined the evidence base for laser therapy to enhance nucleic acid transfection in mammalian cells. An electronic search of MEDLINE, Scopus, EMBASE, Web of Science, and Google Scholar was performed, covering all available years. The preferred reporting items for systematic reviews and meta-analyses guideline for systematic reviews was used for designing the study and analyzing the results. In total, 49 studies of laser irradiation for nucleic acid delivery were included. Key approaches were optoporation, photomechanical gene transfection, and photochemical internalization. Optoporation is better suited to cells in culture, photomechanical and photochemical approaches appear well suited to in vivo use. Additional studies explored the impact of photothermal for enhancing gene transfection. Each approach has merits and limitations. Augmenting nucleic acid delivery using laser irradiation is a promising method for improving gene therapy. Laser protocols can be non-invasive because of the penetration of desirable wavelengths of light, but it depends on various parameters such as power density, treatment duration, irradiation mode, etc. The current protocols show low efficiency, and there is a need for further work to optimize irradiation parameters.

Oral HPV16 DNA as a screening tool to detect early oropharyngeal squamous cell carcinoma.

Given that oropharyngeal squamous cell carcinoma (OPSCC) have now surpassed cervical cancer as the most common human papillomavirus (HPV)-driven cancer, there is an interest in developing non-invasive predictive biomarkers to early detect HPV-driven OPSCC. In total, 665 cancer-free individuals were recruited from Queensland, Australia. Oral HPV16 DNA positivity in those individuals was determined by our in-house developed sensitive PCR method. Individuals with (n = 9) or without (n = 12) oral HPV16 infections at baseline were followed for a median duration of 24 mo. Individuals with persistent oral HPV16 infection (≥ 30 mo) were invited for clinical examination of their oral cavity and oropharynx by an otolaryngologist. Oral HPV16 DNA was detected in 12 out of 650 cancer-free individuals (1.8%; 95% confidence interval [CI]: 1.0-3.2). Of the 3 individuals with persistent oral HPV16 infection, the first individual showed no clinical evidence of pathology. The second individual was diagnosed with a 2 mm invasive squamous cell carcinoma (T1N0M0) positive for both p16INK4a expression and HPV16 DNA. The third individual was found to have a mildly dysplastic lesion in the tonsillar region that was negative for p16INK4a expression and HPV16 DNA and she continues to have HPV16 DNA in her saliva. Taken together, our data support the value of using an oral HPV16 DNA assay as a potential screening tool for the detection of microscopic HPV-driven OPSCC. Larger multicenter studies across various geographic regions recruiting populations at a higher risk of developing HPV-driven OPSCC are warranted to extend and confirm the results of the current investigation.

An Occult HPV-Driven Oropharyngeal Squamous Cell Carcinoma Discovered Through a Saliva Test.

Oropharyngeal cancer (OPC) caused by human papillomavirus (HPV) is a rising global concern. Early lesions are small and are often located in difficult to access areas (such as the crypts of the tonsils or base of tongue). Unlike cervical cancer, there is no standard or routine screening program for HPV-driven OPC. HPV DNA from OPC tumors may shed directly into saliva, and this can be used as a biomarker for early diagnosis. In this study, we report the first-ever clinically occult OPC in an asymptomatic patient discovered through a saliva test. This case relied upon serial measurements of HPV-16 DNA in saliva, which fell to undetectable levels following low morbidity, curative treatment.

Oral HPV16 Prevalence in Oral Potentially Malignant Disorders and Oral Cavity Cancers.

The role of human papillomavirus type 16 (HPV16) in oral potentially malignant disorders (OPMD) and oral cavity carcinoma (OC) is still under debate. We investigated HPV16 prevalence in unstimulated saliva, oral rinse samples, oral swabs and tumour biopsies collected from OPMD (n = 83) and OC (n = 106) patients. HPV16 genotype, viral load, physical status (episomal vs. integrated) and tumour p16INK4a expression were determined. Oral HPV16 prevalence was higher in OC than in OPMD, but this difference was not statistically significant (7.5% (8/106) versus 3.6% (3/83), odds ratio (OR): 2.18, 95% confidence interval (CI): 0.56, 8.48, p = 0.26). There was a significant association (p < 0.05) between oral HPV16 infection and heavy tobacco consumption. Real-time PCR results indicated that no integration events occurred in either OPMD or OC cases based on the HPV16 E2/E6 ratio. HPV16 positive OPMD and OC patients had similar HPV16 E2 and E6 viral loads. The inter-rater agreement between tumour p16INK4a expression and oral HPV16 infection was considered as fair (k = 0.361) for OC. Our data suggest that the involvement of HPV16 in oral carcinogenesis is limited.

Effect of polyphenol-rich cranberry extracts on cariogenic biofilm properties and microbial composition of polymicrobial biofilms.

OBJECTIVE: To investigate the effect of cranberry extracts on saliva-derived polymicrobial biofilms with regards to biofilm biomass, acidogenicity, exopolysaccharide (EPS)/microbial biovolumes, colony forming unit (CFU) counts, and the relative abundance of specific caries- and health-associated bacteria. METHODS: Saliva-derived polymicrobial biofilms were grown for 96 h in a cariogenic environment and treated for 2 min every 12 h over the entire biofilm growth period with 500 µg/mL cranberry extract or vehicle control. The effect of the cranberry extract on biofilm behaviour was evaluated using different assays and its influence on key cariogenic and health-associated bacterial populations was assessed with a microarray real-time quantitative PCR method. RESULTS: Cranberry-treated biofilms showed significant drops in biomass (38% reduction, P < 0.001), acidogenicity (44% reduction, P < 0.001), EPS/microbial biovolume ratios (P = 0.033), and CFU counts (51% reduction, P = 0.001). Furthermore, the cranberry extracts effected a significantly lower relative abundance of caries-associated Streptococcus sobrinus (fold change 0.004, P = 0.002) and Provotella denticola (0.002, P < 0.001), and a significantly higher relative abundance of the health-associated Streptococcus sanguinis (fold change 90.715, P = 0.001). CONCLUSIONS: The cranberry extract lowered biofilm biomass, acidogenicity, EPS/microbial biovolumes, CFU counts, and modulated a beneficial microbial ecological change in saliva-derived polymicrobial biofilms.

Cranberry Polyphenols: Natural Weapons against Dental Caries.

Bioactive polyphenol components of cranberry (Vaccinium macrocarpon) are known to have virulence attenuating effects against several cariogenic virulence properties responsible for dental caries pathogenesis. In particular, cranberry A-type proanthocyanidins and flavonols have demonstrated potent inhibitory effects against cariogenic virulence targets such as bacterial acidogenicity, aciduricity, glucan synthesis, and hydrophobicity. Cranberry phenols have the ability to disrupt these cariogenic virulence properties without being bactericidal, a key quality essential for retaining the benefits of the symbiotic resident oral microbiome and preventing the emergence of resistant microbes. This review discusses the cariostatic mechanisms of specific cranberry phytochemicals and their potential use as therapeutic agents against cariogenic bacteria in the prevention and control of dental caries.

Polyphenol-Rich Cranberry Extracts Modulate Virulence of Streptococcus mutans-Candida albicans Biofilms Implicated in the Pathogenesis of Early Childhood Caries.

Purpose: The purpose of this study was to investigate the effects of polyphenol-rich cranberry extracts on dual-species Streptococcus mutans-Candida. albicans biofilms implicated in contributing to the severity of early childhood caries. Methods: S. mutans-C. albicans biofilms were grown on saliva-coated hydroxyapatite discs (s-HA) mounted on the high-throughput Amsterdam Active Attachment model. The s-HA discs were treated with the cranberry extracts/vehicle control for five minutes just before biofilm growth and subsequently, for similar exposure times, after 12 hours and 24 hours of biofilm growth. The treated 24-hour-old biofilms were then assessed for acidogenicity, metabolic activity, exopolysaccharide (EPS)/microbial biovolumes, structural organization, and colony forming unit (CFU) counts. Results: Treatment with 500 to 1,000 µg/mL of the cranberry extracts produced significant reductions in acidogenicity and metabolic activity (P<0.0001) compared to the control-treated biofilms. A significant decrease in biovolumes of the EPS (P=0.003) and microbial biofilm components (P=0.007) was also seen. Qualitative assessment of confocal biofilm images revealed that the cranberry extract disrupted biofilm structural architecture. Finally, significantly fewer S. mutans (P=0.006) and C. albicans (P=0.036) CFUs were recovered from the cranberry-treated biofilms than from the control-treated bio-films. Conclusions: Cranberry extracts inhibited cariogenic virulence properties of S. mutans-C. albicans dual-species biofilms in an in vitro model.

The Effect of Heating to Intracanal Temperature on the Stability of Sodium Hypochlorite Admixed with Etidronate or EDTA for Continuous Chelation.

INTRODUCTION: Tetrasodium etidronate (Na4 etidronate) and tetrasodium EDTA (Na4 EDTA) are chelators that can combine with sodium hypochlorite (NaOCl) as a 1-mix endodontic irrigant in a process called continuous chelation. The therapeutic window of these mixtures is determined by the chemical reaction between NaOCl and the chelator. At room temperature, this window is 60 minutes for Na4 etidronate and 30 minutes for Na4 EDTA. Because reaction kinetics are influenced by heat, this study assesses the influence of heating to an intracanal temperature of 35°C on the therapeutic window in continuous chelation. METHODS: The loss of free available chlorine (FAC) in NaOCl mixtures with Na4 etidronate or Na4EDTA was determined by iodometric titration at 23°C ± 0.7°C (23°C) and 34.6°C ± 0.3°C (35°C) at 1, 20, 40, and 60 minutes after mixing. The pH and temperature of the mixtures were measured. RESULTS: At 23°C, 18% Na4 etidronate/5% NaOCl solutions at 20, 40, and 60 minutes lost 4%, 9% and 18% FAC, and at 35°C, they lost 20%, 68% and 92% FAC; 5% Na4 EDTA/2.5% NaOCl solutions at 20, 40, and 60 minutes at 23°C lost 88%, 94%, and 97% FAC, and at 35°C, they lost 96%, 99%, and 100%. Decreases in FAC were accompanied by pH declines. CONCLUSIONS: The effect of heating to 35°C from a room temperature of 23°C on 18% Na4 etidronate/5% NaOCl solutions reduces its therapeutic window to 20 minutes. Solutions of 5% Na4 EDTA/2.5% NaOCl are not useful in the continuous chelation technique. Tracking pH changes could be used to estimate NaOCl degradation.

Inhibitory effects of fruit berry extracts on Streptococcus mutans biofilms.

Dark-colored fruit berries are a rich source of polyphenols that could provide innovative bioactive molecules as natural weapons against dental caries. High-quality extracts of cranberry, blueberry, and strawberry, and a combination of the three berry extracts (Orophenol), were used to treat 24-h-old Streptococcus mutans biofilms. The grown biofilms were treated with the berry extracts at concentrations ranging from 62.5 to 500 µg ml-1 . Treated biofilms were assessed for metabolic activity, acidogenicity, biovolumes, structural organization, and bacterial viability. The biofilms treated with the cranberry and Orophenol extracts exhibited the most significant reductions in metabolic activity, acid production, and bacterial/exopolysaccharide (EPS) biovolumes, while their structural architecture appeared less compact than the control-treated biofilms. The blueberry extract produced significant reductions in metabolic activity and acidogenicity only at the highest concentration tested, without significantly affecting bacterial/EPS biovolumes or biofilm architecture. Strawberry extracts had no significant effects on S. mutans biofilms. None of the berry extracts were bactericidal for S. mutans. The results indicate that cranberry extract was the most effective extract in disrupting S. mutans virulence properties without significantly affecting bacterial viability. This suggests a potential ecological role for cranberry phenols as non-bactericidal agents capable of modulating pathogenicity of cariogenic biofilms.

Pulp Stones, Prevalence and Distribution in an Iranian Population.

AIM: This study determined the prevalence and distribution of pulp stones in the permanent dentition of an adult population using their periapical radiographs. MATERIALS AND METHODS: The study followed a cross-sectional design. A total of 800 periapical radiographs collected from 412 patients attending dental clinics in Kerman, Islamic Republic of Iran, were examined using magnification. RESULTS: Pulp stones were present in 9.6% of all permanent teeth examined, being most common in maxillary first and second molars, followed by mandibular first and second molars. They were present in 31.5% of all adult patients, with a significantly increased prevalence in females compared with males (40.5 vs 23.9%, chi-squared test p < 0.001). There was also an increased prevalence with age. CONCLUSION: Based on the results of this study, clinicians should expect to encounter pulp stones most commonly in the pulp chambers of maxillary first and second molars, particularly in older female patients. CLINICAL SIGNIFICANCE: Pulp stones depending on their size and location can pose challenges to endodontic treatment. They obstruct access to the canal orifices and thus complicate endodontic treatment. Knowing where and when pulp stones are likely to occur improves the quality of root canal treatments.

Pulpal response following photo-biomodulation with a 904-nm diode laser: a double-blind clinical study.

The aim of this study was to evaluate pulpal responses in healthy human teeth to photo-biomodulation therapy (PBMT) with 904-nm GaAs diode laser. The study followed a double-blind split mouth design, with a randomly selected maxillary first premolar acting as a sham-irradiated control tooth, and the contralateral tooth receiving active laser treatment. Two coded but otherwise identical laser probes (Irradia™, SpectraMedics Ltd., NC, USA) were used to deliver the sham (placebo) and laser radiation, with both the operator and patient unaware of each probe's identity. The selection of teeth for sham or laser irradiation was randomised for each treatment. Pulpal responses were assessed using electric pulp testing (EPT), 2 min prior to exposure, and immediately after laser irradiation (60 s, 30 mW average power, 25 Hz pulse frequency, 3.6 J/cm2). Treatment effects were analysed using the Wilcoxon-signed rank test. A total of 30 participants provided written informed consent. Majority of the participants (66.7 %) demonstrated an analgesic effect following PBMT (elevated EPT scores); however, nine participants (30 %) reported the lower EPT scores than the control. Both the treatment effects (stimulation and analgesia) were significant compared to the placebo. In most individuals, PBMT of healthy teeth with a 904-nm GaAs diode laser can induce analgesia, as witnessed by elevated EPT scores. A converse effect can occur in a minority of subjects.

Assessment of Er:YAG laser for cavity preparation in primary and permanent teeth: a scanning electron microscopy and thermographic study.

PURPOSE: Most studies of cavity preparation using Er:YAG lasers have employed permanent teeth. This study's purpose was to compare the cutting efficiency of an Er:YAG laser versus diamond burs in primary and permanent teeth in order to measure thermal effects on the pulp and evaluate lased surfaces using scanning electron microscopy (SEM). METHODS: A total of 80 primary and permanent teeth were used. Crater depths and mass loss were measured after delivering laser pulses at varying energies onto sound or carious enamel or dentin using the Key-3 laser. Control samples were cut using diamond burs in an air turbine handpiece. Thermal changes were measured using miniature thermocouples placed into the pulp chamber. Lased surfaces were evaluated using SEM. RESULTS: Laser ablation crater-like defects were deeper in dentin than enamel at the same pulse energy. Greater ablation rates for dentin and enamel and significantly more efficient removal of carious tooth structure by laser was present in primary teeth. Temperature rises in the pulp did not exceed the 5.5 degrees Celsius threshold in any teeth during laser ablation. CONCLUSIONS: The Er:YAG laser is an efficient device for cavity preparations in primary teeth, with no unacceptable increases in temperature detected in this model.

Treatment of root canal biofilms of Enterococcus faecalis with ozone gas and passive ultrasound activation.

INTRODUCTION: Biofilms of resistant species such as Enterococcus faecalis pose a major challenge in the treatment of root canals with established periapical disease. This study examined the effects of gaseous ozone delivered into saline on biofilms of E. faecalis in root canals of extracted teeth with and without the use of passive ultrasonic agitation. METHODS: Biofilms of E. faecalis were established over 14 days in 70 single roots that had undergone biomechanical preparation followed by gamma irradiation. The presence and purity of biofilms were confirmed using scanning electron microscopy and culture. Biofilms were treated with saline (negative control), 1% sodium hypochlorite for 120 seconds (positive control), ozone (140 ppm ozone in air at 2 L/min delivered into saline using a cannula for 120 seconds), saline with passive ultrasonic activation (70 kHz and 200 mW/cm(2) applied to an ISO 15 file held passively within the canal, for 120 seconds), and ozone followed immediately by ultrasonic agitation. After treatment, samples were taken from the biofilm and serially diluted for plate counting. RESULTS: Analysis revealed that 1% sodium hypochlorite was the most effective disinfecting agent followed by ozone combined with ultrasonic agitation, ozone alone, and finally ultrasonic alone. CONCLUSIONS: Although none of the treatment regimes were able to reliably render canals sterile under the conditions used, ozone gas delivered into irrigating fluids in the root canal may be useful as an adjunct for endodontic disinfection.

Accelerated wound healing phenotype in Interleukin 12/23 deficient mice.

BACKGROUND: The concept that a strong inflammatory response involving the full complement of cytokines and other mediators is critical for unimpaired healing has been challenged by wound healing studies using transgenic and knockout (KO) mice. The present study explored the effect of abrogation of the p40 subunit, which is shared by the pro-inflammatory cytokines interleukin (IL)-12 and IL-23, on wound closure of excisional oral mucosal wounds. METHODS: Double IL-12 and IL-23 KO mice and C57BL / 6J wildtype mice were wounded on the dorsal surface of the tongue using a 2 mm biopsy punch. The degree of epithelialization was examined histologically. At specific timepoints wounds were examined for cellular and molecular markers for inflammation and angiogenesis using 1) immunohistochemistry; 2) analysis of RNA expression; and 3) flow cytometric analysis. RESULTS: Compared to wild type controls, KO mice displayed enhanced healing, which was driven by a greater influx of neutrophils and macrophages during the early stages of wound healing, and increased induction of messenger RNA (mRNA) for endothelial derived neutrophil attractant (ENA78) chemokine and macrophage inflammatory protein-2 alpha (MIP-2α). Increased mRNA for monocyte-attracting chemokines including monocyte chemoattractant protein (MCP)-1 and MCP-3 was seen from day 1, together with higher levels of IL-1ß and IL-6 within 24 hours after wounding. In addition, mRNA for vascular endothelial growth factor (VEGF)-A was upregulated in KO mice within 2 hours after injury, and higher expression of this mediator was confirmed by immunohistochemistry. CONCLUSION: Overall, the accelerated oral mucosal wound healing seen in IL-12/IL-23p40 KO compared to wildtype mice was associated with the early establishment of an inflammatory response and vascularization.