An omicron-specific neutralizing antibody test predicts neutralizing activity against XBB 1.5.

Introduction: Understanding the immune status of an individual using neutralizing antibody testing is complicated by the continued evolution of the SARS-CoV-2 virus. Previous work showed that assays developed against the wildtype strain of SARS-CoV-2 were insufficient predictors of neutralization of omicron variants, thus we developed an omicron-specific flow cytometry-based neutralizing antibody test and performed experiments to assess how well it compared to an omicron-specific PRNT assay (gold standard) and whether it could predict neutralizing activity to more recent omicron subvariants such as XBB.1.5. Methods: Accuracy of a novel flow cytometry-based neutralizing antibody (FC-NAb) assay was determined by comparison with an omicron-specific PRNT assay. A series of samples were evaluated in both the omicron FC-NAb assay and a second test was designed to assess neutralization of XBB.1.5. Results: Good concordance between the omicron FC-NAb test and the omicron PRNT was demonstrated (AUC = 0.97, p <0.001; sensitivity = 94%, specificity = 100%, PPV = 100%, and NPV = 97%). A strong linear relationship between the omicron FC-NAb and neutralization of XBB1.5 was observed (r = 0.83, p<0.001). Additionally, the omicron FC-NAb test was a very strong predictor of positive XBB1.5 NAb activity (AUC = 0.96, p<0.001; sensitivity = 94%, specificity = 90%, positive predictive value = 90%, and negative predictive values = 94%). Discussion: Our data suggest that despite continued evolution of the SARS-CoV-2 spike protein, the omicron FC-NAb assay described here is a good predictor of XBB1.5 neutralizing activity, as evidenced by a strong correlation and good predictive performance characteristics.

A mathematical model of the within-host kinetics of SARS-CoV-2 neutralizing antibodies following COVID-19 vaccination.

Compelling evidence continues to build to support the idea that SARS-CoV-2 Neutralizing Antibody (NAb) levels in an individual can serve as an important indicator of the strength of protective immunity against infection. It is not well understood why NAb levels in some individuals remain high over time, while in others levels decline rapidly. In this work, we present a two-state mathematical model of within-host NAb dynamics in response to vaccination. By fitting only four host-specific parameters, the model is able to capture individual-specific NAb levels over time as measured by the AditxtScore™ for NAbs. The model can serve as a foundation for predicting NAb levels in the long-term, understanding connections between NAb levels, protective immunity, and breakthrough infections, and potentially guiding decisions about whether and when a booster vaccination may be warranted.

Simultaneous measurement of multiple variant-specific SARS-CoV-2 neutralizing antibodies with a multiplexed flow cytometric assay.

Introduction: Neutralizing antibodies (NAbs) have been recognized as surrogates of protection against SARS-CoV-2; however, the emergence of variants/subvariants escaping neutralization suggests that laboratory assessments of NAbs against the ancestral/wild type (WT) antigens likely overestimate the degree of protection. Methods: A novel flow cytometry-based multiplex test system was developed for the simultaneous detection of NAbs of multiple SARS-CoV-2 variants. SARS-CoV-2 antibodies (Abs) including IgG, IgM, IgA isotypes were measured in the same system. Samples from negative, convalesced, vaccinated, boosted, and breakthrough infection (BTI) populations were tested for both NAbs and Abs. Results: NAbs induced by WT showed neutralization activity that correlated strongly to all variants (R2 > 0.85) except omicron BA.1/BA.2 (R2 <0.50). Two doses of vaccine elicited very little protective immunity against BA.1/BA.2, though a booster dose significantly improved NAbs for all variants. NAbs/Abs increased more following BTI than after a booster, suggesting that hybrid immunity (vaccination + natural immunity) was more robust to all variants including BA.1/BA.2. BTIs occurring in the omicron era led to stronger NAb responses against BA.1/BA.2 than did older BTIs. In all comparisons, the RBD antigens demonstrated greater differences between WT and BA.1/BA.2 than the spike antigens. Discussion: Taken together, we demonstrated that both Ab and NAb against multiple SARS-CoV-2 variants/subvariants can be reliably detected on the same multiplex platform. Distinguishing NAbs to the appropriate antigenic target of prevalent variants offers the best correlate of protection and aids individual decisions about the appropriateness and cadence of vaccine boosters and other exposure mitigation strategies.

Reversal of Hyperglycemia and Suppression of Type 1 Diabetes in the NOD Mouse with Apoptotic DNA Immunotherapy™ (ADi™), ADi-100.

The antigen-specific apoptotic DNA immunotherapeutic, ADi-100, is designed to suppress type 1 diabetes and consists of two DNA plasmids encoding genetic sequences of the apoptosis-inducing molecule, BAX, and the secreted form of the autoantigen, glutamic acid decarboxylase 65, that is CpG hyper-methylated to avoid inflammatory signaling (msGAD55). Upon a four-day treatment with ADi-100 of young female non-obese diabetic (NOD) mice, the frequency of various tolerogenic dendritic cell populations increased in draining lymph nodes; these cells lost the capacity to stimulate glutamic acid decarboxylase (GAD)-specific CD4+ T lymphocytes and were associated with the previously demonstrated enhancement of GAD-specific regulatory T cells. The efficacy of two ADi-100 formulations containing different proportions of BAX and msGAD55, 1:4 (10/40 µg) and 1:2 (17/33 µg), was evaluated in mildly hyperglycemic pre-diabetic NOD female mice. Both formulations suppressed the incidence of diabetes by 80% in an antigen-specific manner, while all untreated mice developed diabetes. However, treatment of pre-diabetic mice with significantly higher hyperglycemia, denoting progressive disease, showed that ADi-100 1:2 strongly suppressed diabetes incidence by 80% whereas the ADi-100 1:4 was less effective (50%). As an antigen-specific monotherapy, ADi-100 is highly efficacious in reversing elevated hyperglycemia to prevent diabetes, in which increasing apoptosis-inducing BAX content is a promising immune tolerance feature.

Regenerative Endodontic Treatment in Immature Noninfected Ferret Teeth Using Blood Clot or SynOss Putty as Scaffolds.

INTRODUCTION: SynOss Putty (Collagen Matrix, Oakland, NJ) has shown the formation of mineralized tissues when used as a scaffold in regenerative endodontic treatment (RET) in immature human teeth. The aim of this study was to compare the outcome of RET in immature ferret teeth using 2 scaffolds: a blood clot and SynOss Putty. METHODS: Thirty-two immature canine teeth in 8 ferrets (95-105 days old) were divided into 4 groups: group 1, no treatment (positive control, n = 8); group 2, full pulpectomy with no further treatment (negative control, n = 8); group 3, revascularization using a blood clot (n = 8); and group 4, revascularization using a SynOss Putty scaffold (n = 8). After 3 months, the animals were euthanized, and the newly formed tissues were examined histologically. The data were statistically analyzed using chi-square and Fisher exact tests. RESULTS: Normal pulps were found in group 1. No pulp tissue was found in teeth in group 2. In group 3, the pulp tissue and the odontoblastic layer were absent, and the root canal spaces were filled with a hard tissue characterized as bonelike and cementumlike tissues. All teeth except 1 in group 4 showed no hard tissue formation and intracanal/periapical inflammation. SynOss Putty was significantly associated with a lack of tissue formation and intracanal/periapical inflammation (P < .05). CONCLUSIONS: Intracanal hard tissue formation was observed in immature teeth after RET using a blood clot. No tissue regeneration was found in the majority of samples using SynOss Putty as a scaffold.

A Mathematical Model for DC Vaccine Treatment of Type I Diabetes.

Type I diabetes (T1D) is an autoimmune disease that can be managed, but for which there is currently no cure. Recent discoveries, particularly in mouse models, indicate that targeted modulation of the immune response has the potential to move an individual from a diabetic to a long-term, if not permanent, healthy state. In this paper we develop a single compartment mathematical model that captures the dynamics of dendritic cells (DC and tDC), T cells (effector and regulatory), and macrophages in the development of type I diabetes. The model supports the hypothesis that differences in macrophage clearance rates play a significant role in determining whether or not an individual is likely to become diabetic subsequent to a significant immune challenge. With this model we are able to explore the effects of strengthening the anti-inflammatory component of the immune system in a vulnerable individual. Simulations indicate that there are windows of opportunity in which treatment intervention is more likely to be beneficial in protecting an individual from entering a diabetic state. This model framework can be used as a foundation for modeling future T1D treatments as they are developed.

Effect of Residual Dental Pulp Tissue on Regeneration of Dentin-pulp Complex: An In Vivo Investigation.

INTRODUCTION: Current pulp revascularization procedures in teeth with necrotic pulps and open apices have produced histologic evidence of connective tissue growth, cementum, and bone within the root canals of experimental animals. This study aims to investigate the effect of maintaining uninflamed residual apical pulp tissue on the histologic outcome of pulp-dentin complex regeneration after a revascularization procedure in immature ferret cuspid teeth. METHODS: Twenty-eight cuspid teeth from 7 young male ferrets were used in this experiment. Seven teeth were reserved to serve as positive control samples without any treatment. In another 7 teeth, the pulp was completely extirpated (negative control), whereas the pulp of the remaining 14 teeth were removed to either 1-2 mm short of the apex (7 samples) or 2-4 mm short of the apex (7 samples). Blood clots were covered with mineral trioxide aggregate at the cementoenamel junction level of each tooth. Three months later, block sections were removed for histologic evaluations, and the data were statistically analyzed with the chi-square test (P < .05). RESULTS: All teeth with complete pulp extirpation showed the presence of bone inside the root canal. In contrast, the root canals for most teeth with pulp amputation 1-4 mm from the radiographic apex were filled with normal pulp, which extended coronally to the mineral trioxide aggregate, where hard tissue bridges had formed. CONCLUSIONS: Based on these results, we concluded that regeneration of the pulp-dentin complex is possible when the apical 1-4 mm of the apical pulp remains intact in immature teeth.

Application of Enamel Matrix Derivative (Emdogain) in Endodontic Therapy: A Comprehensive Literature Review.

INTRODUCTION: Enamel matrix derivative (EMD) is a protein extract used for the treatment of periodontal defects and soft tissue recession. Its use in endodontics has been a subject of exploration, especially in regenerative procedures. The aim of this review was to evaluate the current literature available on the application of EMD in the field of endodontics. METHODS: An initial literature search of databases using different combinations of the search terms yielded 1089 articles. From the 29 qualified studies, there were 17 animal studies and 12 human case series and clinical trials. RESULTS: The evidence for the application of EMD as a direct pulp capping agent was relatively dichotomous. In determining the possible effect of EMD on pulpotomy procedures, only 1 animal study qualified under the criteria set forth previously. When comparing EMD against calcium hydroxide (Ca[OH]2), Portland cement, and mineral trioxide aggregate (MTA), Ca(OH)2 induced more histologic hard tissue formation, whereas MTA performed best clinically and radiographically. The scientific literature available is inconclusive on the effectiveness of EMD in preventing root resorption. In regeneration, EMD treatment induced mainly the formation of a cementumlike tissue at the apical region of the root's external surface and showed an ingrowth of newly formed hard tissues into the root canal space. CONCLUSIONS: The results of EMD application in endodontic treatments are highly variable, warranting additional research, specifically in the subjects of replantation and regeneration/revascularization.

Effect of apex size on the leakage of gutta-percha and sealer-filled root canals.

OBJECTIVES: There are no data comparing coronal leakage of teeth prepared to different apical sizes and obturated with gutta-percha and sealer. The aim of this study was to investigate the effect of apical preparation size on the leakage of obturated root canals. Large apical openings are encountered as a result of pulp necrosis in immature teeth, apical resorption, or over-enlargement of the apical foramen. Complete cleaning, shaping, obturation, and apical seal of root canal systems are essential for the success of root canal treatment. METHOD AND MATERIALS: One hundred twenty-five extracted human teeth were divided into groups containing 25 samples each and prepared to apical file sizes 30, 40, 50, 60, and 70. Twenty teeth served as positive and negative controls. Obturation was completed with gutta-percha and sealer via warm vertical compaction. Bacterial leakage was investigated after 112 days using Proteus vulgaris. Data were analyzed via independent-samples Kruskal-Wallis test. RESULTS: The average time for leakage of apical preparation sizes 30, 40, 50, 60, and 70 were 57.5, 52.4, 47.2, 37.5, and 28.4 days, respectively. Significant differences in leakage were observed between apical preparation sizes 70 versus 30, 70 versus 40, 70 versus 50, as well as 60 versus 30. A trend for more leakage occurred when apical preparation sizes exceeded size 60. CONCLUSIONS: Based on these results, it appears leakage of gutta-percha and sealer as obturation materials increases when apical preparation size exceeds 60. Consideration should be given to using sealing materials other than gutta-percha and sealer when the apex size exceeds 60.

Histologic examination of teeth with necrotic pulps and periapical lesions treated with 2 scaffolds: an animal investigation.

INTRODUCTION: Traditional pulp regeneration procedures that use a blood clot as a scaffold have produced histologic evidence of bone, cementum, and connective tissue growth within the root. Platelet-rich plasma (PRP) is a bioactive scaffold containing growth factors that enhance wound healing. AIM: The aim of this study was to histologically compare the tissues generated when PRP or a blood clot is placed into teeth with preexisting necrotic pulps and periapical lesions. METHODS: Twenty-four canine teeth from 6 immature ferrets were used. Two ferrets served as positive controls. Sixteen experimental canine teeth from 4 ferrets were infected, debrided, treated with a triple antibiotic paste, and randomly distributed to the following groups: group 1 (blood clot/Gelfoam), group 2 (PRP), and group 3 (no scaffold). At 3 months, the ferrets were sacrificed, and the tissues were evaluated histologically. Data were analyzed by using the Fisher exact test (P < .05). RESULTS: In 3 of 6 teeth in the PRP group, 2 of 6 teeth in the blood clot group, and 1 of 4 teeth in the no scaffold group, an ingrowth of hard tissues was observed in the apical third of the roots. When using PRP or a blood clot as a scaffold, we found significantly more apical narrowing and hard tissue deposition in comparison to not using a scaffold (P < .05). CONCLUSIONS: The use of PRP or blood clots as scaffolds results in the ingrowth of bone-like, cementum-like, and connective tissue in the apical third of the roots at inconsistent rates.

Histologic examinations of teeth treated with 2 scaffolds: a pilot animal investigation.

INTRODUCTION: A growing body of evidence is building a case for the possibility of tissue regeneration within the root canal of necrotic teeth, allowing for continued root development. However, it remains unknown what type of tissue is produced after regenerative endodontics. The purpose of this study was to use blood clots and platelet-rich plasma (PRP) as scaffolds in regenerative endodontics under ideal conditions in a ferret model to examine the tissues generated within the root canals. METHODS: The pulps of 21 canine teeth from 7 young ferrets were extirpated using broaches without filing the canal walls. Bleeding was stimulated from the periapical tissues, and a blood clot was induced in the canal space to the level of the cementoenamel junction in 12 teeth. PRP was prepared and placed in the canals to the level of the cementoenamel junction in 9 teeth. The coronal access was sealed with mineral trioxide aggregate. Seven canines were not operated on and served as controls. Three months later, block sections including each canine and its surrounding tissues were removed for histologic evaluation. The tissues found in the canals of experimental teeth were compared with those in the control teeth. RESULTS: Almost all of the experimental teeth showed the presence of intracanal bonelike tissue. No evidence of dentinal wall thickening or apical narrowing was noted in the experimental teeth. CONCLUSIONS: In this experimental model, the use of either PRP or blood clots during regenerative endodontics leads to the formation of intracanal bonelike tissue without continual root maturation.

Comparison of efficacy of pulverization and sterile paper point techniques for sampling root canals.

INTRODUCTION: The purpose of this study was to compare the efficacy of the pulverization and sterile paper point techniques for sampling root canals using 5.25% NaOCl/17% EDTA and 1.3% NaOCl/MTAD (Dentsply, Tulsa, OK) as irrigation regimens. METHODS: Single-canal extracted human teeth were decoronated and infected with Enterococcus faecalis. Roots were randomly assigned to 2 irrigation regimens: group A with 5.25% NaOCl/17% EDTA (n = 30) and group B with 1.3% NaOCl/MTAD (n = 30). After chemomechanical debridement, bacterial samplings were taken using sterile paper points and pulverized powder of the apical 5 mm root ends. RESULTS: The sterile paper point technique did not show growth in any samples. The pulverization technique showed growth in 24 of the 60 samples. The Fisher exact test showed significant differences between sampling techniques (P < .001). The sterile paper point technique showed no difference between irrigation regimens. However, 17 of the 30 roots in group A and 7 of the 30 roots in group B resulted in growth as detected by pulverization technique. Data showed a significant difference between irrigation regimens (P = .03) in pulverization technique. CONCLUSIONS: The pulverization technique was more efficacious in detecting viable bacteria. Furthermore, this technique showed that 1.3% NaOCl/MTAD regimen was more effective in disinfecting root canals.

Treatment options: apexogenesis and apexification.

This article will describe requirements for case selection and review the procedures for apexogenesis and apexification in immature permanent teeth. Nonclinical and clinical data will be presented to support the recommendations, and outcomes will be presented from clinical studies. The dental pulp is an ectomesenchymally derived connective tissue with certain unique properties such as being encased in hard tissues, which limits its collateral circulation. The pulp provides a matrix for binding of its cells and provides support allowing communication between the cells. In addition to immune cells, the dental pulp contains odontoblasts, which are specialized cells capable of producing dentin. In the absence of a vital pulp, dentin deposition is arrested. When an immature tooth is affected by caries or trauma, the pulp requires proper management according to the degree of inflammation and its vitality. Maintenance of pulp vitality will allow continued root development along the entire root length. If the pulp is irreversibly inflamed or necrotic, root-end closure procedures are required when the apex has not fully formed.

Treatment options: apexogenesis and apexification.

This article will describe requirements for case selection and review the procedures for apexogenesis and apexification in immature permanent teeth. Nonclinical and clinical data will be presented to support the recommendations, and outcomes will be presented from clinical studies. The dental pulp is an ectomesenchymally derived connective tissue with certain unique properties such as being encased in hard tissues, which limits its collateral circulation. The pulp provides a matrix for binding of its cells and provides support allowing communication between the cells. In addition to immune cells, the dental pulp contains odontoblasts, which are specialized cells capable of producing dentin. In the absence of a vital pulp, dentin deposition is arrested. When an immature tooth is affected by caries or trauma, the pulp requires proper management according to the degree of inflammation and its vitality. Maintenance of pulp vitality will allow continued root development along the entire root length. If the pulp is irreversibly inflamed or necrotic, root-end closure procedures are required when the apex has not fully formed.

An animal model to study regenerative endodontics.

INTRODUCTION: A growing body of evidence is demonstrating the possibility for regeneration of tissues within the pulp space and continued root development in teeth with necrotic pulps and open apices. There are areas of research related to regenerative endodontics that need to be investigated in an animal model. The purpose of this study was to investigate ferret cuspid teeth as a model to investigate factors involved in regenerative endodontics. METHODS: Six young male ferrets between the ages of 36-133 days were used in this investigation. Each animal was anesthetized and perfused with 10% buffered formalin. Block sections including the mandibular and maxillary cuspid teeth and their surrounding periapical tissues were obtained, radiographed, decalcified, sectioned, and stained with hematoxylin-eosin to determine various stages of apical closure in these teeth. RESULTS: The permanent mandibular and maxillary cuspid teeth with open apices erupted approximately 50 days after birth. Initial signs of closure of the apical foramen in these teeth were observed between 90-110 days. Complete apical closure was observed in the cuspid teeth when the animals were 133 days old. CONCLUSIONS: Based on the experiment, ferret cuspid teeth can be used to investigate various factors involved in regenerative endodontics that cannot be tested in human subjects. The most appropriate time to conduct the experiments would be when the ferrets are between the ages of 50 and 90 days.

Recent patents on immunoregulatory DNA vaccines for autoimmune diseases and allograft rejection.

The goal of immunoregulatory DNA vaccination is the antigen- and tissue-specific suppression of pathological inflammation that underlies immune-mediated inflammatory disorders like autoimmune diseases and allograft rejection. Recent patents and patent applications have applied immunoregulatory DNA vaccines in rodent model systems and human clinical trials using plasmid DNA coding for autoantigens such as insulin and glutamic acid decarboxylase for type 1 diabetes, myelin-associated proteins for multiple sclerosis, and heat-sock protein 60 for rheumatoid arthritis. In these cases, the objective is to induce a homeostatic-like regulatory immune response to suppress pathological inflammation. In addition, patent applications have disclosed the use of DNA vaccines encoding the pro-inflammatory MIF cytokine and the CD25 IL-2 receptor subunit to interfere with the inflammatory process. Approaches have also been taken to improve DNA vaccination efficacy, including covalent modification of plasmid DNA, engineering secretion of vaccine-encoded antigen, and co-delivery of DNA coding for anti-inflammatory cytokines, a mutant co-stimulatory molecule, a growth factor, or a pro-apoptotic protein. Furthermore, a patent application has disclosed the use of a DNA vaccine previously shown to treat successfully an autoimmune disease to prolong allograft survival. Taken together, these patents and patent applications indicate a promising bench-to-bedside potential for immunoregulatory DNA vaccination applied to autoimmune diseases and allograft rejection.

Minimum contact time and concentration of sodium hypochlorite required to eliminate Enterococcus faecalis.

INTRODUCTION: The purpose of this investigation was to determine the concentration of sodium hypochlorite and the irrigation time required to disinfect dentin cylinders infected with Enterococcus faecalis. METHODS: Four hundred fifty dentin cylinders (5 mm in diameter and 4 mm in height) with a lumen (2-3 mm in width) were prepared from freshly extracted bovine incisors. The cementum and predentin were then removed. The tubules were opened by using a 4-minute application with 17% ethylenediaminetetraacetic acid and 5.25% NaOCl and then exposed to E. faecalis (ATCC 4082) for 3 weeks in brain-heart infusion broth. The cylinders were then divided into 3 groups, and a 1.3%, 2.5%, or 5.25% concentration of NaOCl was applied in 5-, 10-, 15-, 20-, 25-, 30-, 35-, and 40-minute intervals for a total of 30 subgroups including positive and negative controls. Each test sample was placed into a tube of 2 mL brain-heart infusion broth and incubated for 72 hours. Absence of turbidity demonstrated no bacterial growth, whereas turbidity indicated presence of remaining viable bacteria. RESULTS: The most effective irrigation regimen was 5.25% at 40 minutes, whereas irrigation with 1.3% and 2.5% NaOCl for this same time interval was ineffective in removing E. faecalis from infected dentin cylinders. CONCLUSIONS: High concentration and long exposure to NaOCl are needed for elimination of E. faecalis contaminated dentin.

Outcomes of nonsurgical retreatment and endodontic surgery: a systematic review.

INTRODUCTION: The purpose of this systematic review was to compare the clinical and radiographic outcomes of nonsurgical retreatment with those of endodontic surgery to determine which modality offers more favorable outcomes. METHODS: The study began with targeted electronic searches of MEDLINE, PubMed, and Cochrane databases, followed with exhaustive hand searching and citation mining for all articles reporting clinical and/or radiographic outcomes for at least a mean follow-up of 2 years for these procedures. Pooled and weighted success rates were determined from a meta-analysis of the data abstracted from the articles. RESULTS: A significantly higher success rate was found for endodontic surgery at 2-4 years (77.8%) compared with nonsurgical retreatment for the same follow-up period (70.9%; P < .05). At 4-6 years, however, this relationship was reversed, with nonsurgical retreatment showing a higher success rate of 83.0% compared with 71.8% for endodontic surgery (P < .05). Insufficient numbers of articles were available to make comparisons after 6 years of follow-up period. Endodontic surgery studies showed a statistically significant decrease in success with each increasing follow-up interval (P < .05). The weighted success for 2-4 years was 77.8%, which declined at 4-6 years to 71.8% and further declined at 6+ years to 62.9% (P < .05). Conversely, the nonsurgical retreatment success rates demonstrated a statistically significant increase in weighted success from 2-4 years (70.9%) to 4-6 years (83.0%; P < .05). CONCLUSIONS: On the basis of these results it appears that endodontic surgery offers more favorable initial success, but nonsurgical retreatment offers a more favorable long-term outcome.

The effect of hyperglycemia on pulpal healing in rats.

Diabetes mellitus (DM) may impede healing of dental pulps. In this study, the effect of hyperglycemia on pulpal healing was determined in exposed rat pulps capped with mineral trioxide aggregate. Two groups of 11 rats received injections of saline (control group) or streptozotocin to induce hyperglycemia (DM group). The pulps of the maxillary first molars of all rats were exposed and capped. Intact teeth and teeth with exposed pulps without restorations served as positive and negative controls, respectively. Histologic samples were prepared and evaluated for dentin bridge formation and pulpal inflammation. Data were analyzed by using Fisher exact, Mann-Whitney U, and Spearman correlation tests. Dentin bridge formation was inhibited in diabetic rats (p = 0.029) along with more inflammation in these pulps (p = 0.005). There was an inverse association between dentin bridge formation and inflammatory cell infiltration (p = 0.001). Based on these results, it appears that hyperglycemia adversely affects pulpal healing in rats.