Faculty Bibliography

INTRODUCTION: Regenerative endodontic procedures (REPs) are usually used to treat human immature permanent teeth with necrotic pulps and/or apical periodontitis. Successful REPs result in the elimination of clinical signs/symptoms, the resolution of apical periodontitis, and, in some cases, thickening of the canal walls and/or continued root development with or without apical closure. REPs can restore the vitality of tissue in the canals of immature permanent teeth previously destroyed by infection or trauma. Vital tissue is inherited with immune defense mechanisms to protect itself from foreign invaders. Recently, REPs have also been used to successfully treat human mature permanent teeth with necrotic pulps and apical periodontitis. The purpose of this case series was to present the potential of using REPs for mature permanent teeth with necrotic pulps and apical periodontitis. METHODS: This case series consisted of 6 patients, 4 females and 2 males. The patients' ages ranged from 8-21 years old. Seven permanent teeth, 4 anterior and 3 molar teeth, with necrotic pulps and apical periodontitis were treated using REP. Radiographically, the root development of all teeth was almost completed except the apices of 2 molars, which showed slightly open. Complete chemomechanical debridement of the canals of the teeth was performed, and the canals were dressed with Metapaste (Meta Biomed Co, Ltd, Chungbuk, Korea) during treatment visits. Periapical bleeding into the canals was induced at the last treatment visit by placing a hand #20 or #25 K-file with the tip slightly bent through the apical foramina into the periapical tissues. A 3-mm thickness of mineral trioxide aggregate was placed into the coronal canals over semicoagulated blood. The access cavities were restored with either composite resin or amalgam. RESULTS: Follow-ups of the 7 teeth ranged from 8 to 26 months. The periapical lesions of 2 teeth were considered healed, and 5 teeth revealed healing. Clinical signs/symptoms were absent in all teeth at follow-up visits at different time points. None of the treated teeth responded to cold and electric pulp tests. CONCLUSIONS: This case series shows the potential of using REPs for mature teeth with necrotic pulp and apical periodontitis.

The goal of regenerative endodontics is to reinstate normal pulp function in necrotic and infected teeth that would result in reestablishment of protective functions, including innate pulp immunity, pulp repair through mineralization, and pulp sensibility. In the unique microenvironment of the dental pulp, the triad of tissue engineering would require infection control, biomaterials, and stem cells. Although revascularization is successful in resolving apical periodontitis, multiple studies suggest that it alone does not support pulp-dentin regeneration. More recently, cell-based approaches in endodontic regeneration based on pulpal mesenchymal stem cells (MSCs) have demonstrated promising results in terms of pulp-dentin regeneration in vivo through autologous transplantation. Although pulpal regeneration requires the cell-based approach, several challenges in clinical translation must be overcome-including aging-associated phenotypic changes in pulpal MSCs, availability of tissue sources, and safety and regulation involved with expansion of MSCs in laboratories. Allotransplantation of MSCs may alleviate some of these obstacles, although the long-term stability of MSCs and efficacy in pulp-dentin regeneration demand further investigation. For an alternative source of MSCs, our laboratory developed induced MSCs (iMSCs) from primary human keratinocytes through epithelial-mesenchymal transition by modulating the epithelial plasticity genes. Initially, we showed that overexpression of DeltaNp63alpha, a major isoform of the p63 gene, led to epithelial-mesenchymal transition and acquisition of stem characteristics. More recently, iMSCs were generated by transient knockdown of all p63 isoforms through siRNA, further simplifying the protocol and resolving the potential safety issues of viral vectors. These cells may be useful for patients who lack tissue sources for endogenous MSCs. Further research will elucidate the level of potency of these iMSCs and assess their transdifferentiation capacities into functional odontoblasts when transplanted into the root canal microenvironment.

INTRODUCTION: Regenerative endodontic therapy (RET) is currently used to treat immature teeth with necrotic pulp and/or apical periodontitis. However, recently RET has been used to treat mature teeth with necrotic pulp and/or apical periodontitis and resulted in regression of clinical signs and/or symptoms and resolution of apical periodontitis. The purpose of this case report was to describe the potential of using RET to treat 2 mature teeth with persistent apical periodontitis after root canal therapy using RET. METHODS: Two male patients, one 26-year old and another 12-year old, presented for retreatment of persistent apical periodontitis after root canal treatment of 2 mature teeth (#9 and #19). The gutta-percha fillings in the canals of teeth #9 and #19 were removed with Carvene gutta-percha solvent (Prevest DenPro, Jammu, India) and ProTaper Universal rotary retreatment files (Dentsply Maillefer, Ballaigues, Switzerland). The canals of both teeth were further chemomechanically debrided with rotary retreatment files and copious amounts of sodium hypochlorite irrigation and dressed with Metapaste (Meta Biomed, Chungbuk, Korea). RET was performed on teeth #9 and #19. Periapical bleeding was provoked into the disinfected root canals. The blood clots were covered with mineral trioxide aggregate plugs, and the access cavities were restored with intermediate restorative material. RESULTS: Teeth #9 and #19 showed regression of clinical signs and/or symptoms and healing of apical periodontitis after 13-month and 14-month follow-ups, respectively. Tooth #9 revealed narrowing of the canal space and apical closure by deposition of hard tissue. CONCLUSIONS: RET has the potential to be used to retreat teeth with persistent apical periodontitis after root canal therapy.

Endodontics is a specialized discipline in dentistry that concerns the morphology, physiology, and pathology of the pulp-dentin complex, root, and peri-radicular tissues. [...].

BACKGROUND AND AIM: Many studies have examined the nature of tissue formed in the canals of immature necrotic teeth, following revascularization in animals and humans. While speculations have been made that regeneration of the pulp tissue might take place in the canal, the tissue has been found to be cementum-like, bone-like, and periodontal ligament-like. The purpose of this study was to histologically examine the tissue in the root canals in immature dog teeth that had been artificially infected and then revascularized. METHODS: Two 4- to 5-month-old mongrel dogs with immature teeth were used in the study. In one dog, four maxillary and four mandibular anterior teeth, and in another dog, four maxillary and five mandibular anterior teeth were used in the experiment. Pulp infection was artificially induced in the immature teeth. Revascularization was performed on all teeth by disinfecting the root canals with sodium hypochlorite irrigation and triple antibiotic intracanal dressing, completed with induction of intracanal bleeding, and sealed with an MTA plug. The access cavity was restored with silver amalgam. The animals were sacrificed 3 months after revascularization procedures. The revascularized teeth and surrounding periodontal tissues were removed and prepared for histological examination. RESULTS: Besides cementum-like, bone-like, and periodontal ligament-like tissues formed in the canals, residual remaining pulp tissue was observed in two revascularized teeth. In four teeth, ingrowth of alveolar bone into the canals was seen; presence of bone in the root canals has the potential for ankylosis. CONCLUSIONS: Within the limitation of this study, it can be concluded that residual pulp tissue can remain in the canals after revascularization procedures of immature teeth with artificially induced pulp infection. This can lead to the misinterpretation that true pulpal regeneration has occurred. Ingrowth of apical bone into the root canals undergoing revascularization can interfere with normal tooth eruption if ankylosis occurs.

Aim: The impact of tenofovir disoproxil fumarate (TDF) on lipid profile in chronic hepatitisB(CHB) patients is unknown. Data from GSUS- 174-0149, a clinical trial evaluating pegylated interferon alfa-2a (PEG) +/- TDF combination therapy in non-cirrhotic CHB patients, were analyzed for impact of antiviral treatment on fasting lipid profile. Methods: 570 subjects with fasting baseline and week 24 total cholesterol, LDL, HDL, and triglyceride were included. Regression analyses of on-treatment changes in lipid profile were examined, adjusted for baseline lipid values, age, sex, race, and BMI. Results: Comparing baseline and week 24 results, TDF monotherapy was significantly associated with reductions in total cholesterol, LDL, and HDL (-25.6 mg/dL, -16.4 mg/dL, and, -9.6 mg/dL, respectively, P<0.05) with no significant change in triglyceride or total cholesterol/HDL ratio (p-values > 0.05). Moreover, TDF + PEG x 48 weeks combination therapy was significantly associated with an even greater reductions in total cholesterol, LDL, and HDL, and a moderate triglyceride increase (-42.5 mg/dL, -29.0 mg/dL, and -18.1 mg/dL, +18.8 mg/dL, respectively, p-values<0.05) compared to baseline. The changes were also significant relative to either monotherapy. In patients, who were on (TDF + PEG) x 16 weeks then continuing on TDF, the lipid impact of PEG lessened after its discontinuation. Only minor cardiovascular events, mostly palpitations, occurred up to Week 72. Conclusion: TDF monotherapy was associated with significant improvements in total cholesterol and LDL in CHB patients. PEG + TDF x 48 weeks was associated with greater changes in lipid profile than either monotherapy

INTRODUCTION: Regenerative endodontic therapy is currently used to treat immature permanent teeth with necrotic pulp and/or apical periodontitis. However, mature teeth with necrotic pulp and apical periodontitis have also been treated using regenerative endodontic therapy. The treatment resulted in resolution of apical periodontitis, regression of clinical signs and symptoms but no apparent thickening of the canal walls, and/or continued root development. A recent study in an animal model showed that the tissues formed in the canals of mature teeth with apical periodontitis after regenerative endodontic therapy were cementumlike, bonelike, and periodontal ligament-like tissue with numerous blood vessels. These tissues are similar to the tissues observed in immature permanent teeth with apical periodontitis after regenerative endodontic therapy. METHODS: A 23-year-old woman had a history of traumatic injury to her upper anterior teeth when she was 8 years old. Subsequently, #8 developed pulp necrosis and an acute apical abscess and #7 symptomatic apical periodontitis. The apex of #8 was slightly open, and the apex of #7 was completely formed. Instead of nonsurgical root canal therapy, regenerative endodontic therapy was attempted, including complete chemomechanical debridement on #8 and #7. This was based on the premise that filling of disinfected root canals with the host's biological vital tissue might be better than filling with foreign materials. RESULTS: After regenerative endodontic therapy of #8 and #7, there was radiographic evidence of periapical osseous healing and regression of clinical signs and symptoms. The pulp cavity of #8 decreased in size, and the apex closed. The pulp cavity of #7 appeared to be obliterated by mineralized tissue. These indicated ingrowth of new vital tissue into the chemomechanically debrided canals. CONCLUSIONS: Regenerative endodontic therapy of mature teeth with apical periodontitis and apical abscess can result in the regression of clinical signs and/or symptoms and healing of apical periodontitis but no apparent thickening of the canal walls or continued root development. Filling of the disinfected canals with the host's vital tissue may be better than with foreign materials because vital tissue has innate and adaptive immune defense mechanisms.

INTRODUCTION: Revascularization treatment is rapidly becoming an accepted treatment alternative for the management of endodontic pathology in immature permanent teeth with necrotic dental pulps. However, the success and timing of clinical resolution of symptoms, and radiographic outcomes of interest, such as continued hard tissue deposition within the root, are largely unknown. METHODS: In this prospective cohort study, 20 teeth were treated with a standardized revascularization treatment protocol and monitored for clinical and radiographic changes for 1 year. Standardized radiographs were collected at regular intervals, and radiographic changes were quantified. RESULTS: All 20 treated teeth survived during the 12-month follow-up period, and all 20 also met the clinical criteria for success at 12 months. As a group, the treated teeth showed a statistically significant increase in radiographic root width and length and a decrease in apical diameter, although the changes in many cases were quite small (such that the clinical significance is unclear). The within-case percent change in apical diameter after 3 months was 16% and had increased to 79% by 12 months, with 55% (11/20) showing complete apical closure. The within-case percent change in root length averaged less than 1% at 3 months and increased to 5% at 12 months. The within-case percent change in root thickness averaged 3% at 3 months and 21% at 12 months. CONCLUSIONS: Although clinical success was highly predictable with this procedure, clinically meaningful radiographic root thickening and lengthening are less predictable after 1-year of follow-up. Apical closure is the most consistent radiographic finding.

IL-17 is one of the most potent and most actively investigated proinflammatory cytokines. In this study, we examined the effect of IL-17 on mesenchymal stem cells (MSCs) under the influence of inflammatory cytokines. Ironically, IL-17 dramatically enhanced the immunosuppressive effect of MSCs induced by IFNgamma and TNFalpha, revealing a novel role of IL-17 in immunosuppression. Interestingly, we found that this action of IL-17 was dependent on the promoted expression of a key immune suppressive molecule, inducible nitric oxide synthase (iNOS), in MSCs. In a concanavalin A (ConA)-induced hepatitis mouse model, we found that IL-17 also enhanced the in vivo immunosuppressive effect of MSCs in an iNOS-dependent manner. Moreover, this promoting effect of IL-17 was found to be exerted through enhancing mRNA stability by modulating the protein level of ARE/poly(U)-binding/degradation factor 1 (AUF1), a well-known factor that promotes mRNA decay. In auf1(-/-) MSCs, IFNgamma and TNFalpha could induce maximal immunosuppressive effect, both in vitro and in vivo, without the need for IL-17. Thus, our studies demonstrated that in the presence of MSCs, IL-17 promotes immunosuppression.

OBJECTIVES: Conceptually, two types of tertiary dentine may be produced in response to caries and environmental irritations: "reactionary dentine" that is secreted by existing primary odontoblasts and "reparative dentin", formed after the death of the odontoblasts by proliferation and differentiation of progenitor cells into odontoblast-like cells. Because histologic evidence for tubular dentine generated by newly-differentiated odontoblast-like cells is lacking in human teeth, the present study examined pulpal cellular changes associated with caries/restorations, in the presence or absence of pulpal exposures. METHODS: Ninety-six extracted human teeth were histologically processed and serial sectioned for light microscopy: 65 contained untreated enamel/dentine caries; 20 were heavily-restored and 11 had carious exposures managed by direct pulp-capping. RESULTS: Sparsely-distributed, irregularly-arranged dentinal tubules were identified from the tertiary dentine formed in teeth with unexposed medium/deep caries and in restored teeth; those tubules were continuous with the tubules of secondary dentine; in some cases, tubules were absent. The palisade odontoblast layer was reduced to a single layer of flattened cells. In direct pulp-capping of pulp exposures, the defects were repaired by the deposition of an amorphous dystrophic calcified tissue that resembled pulp stones more than dentine, sometimes entrapping pulpal remnants. This atubular hard tissue was lined by fibroblasts and collagen fibrils. CONCLUSIONS: Histological evidence from the present study indicates that reparative dentinogenesis cannot be considered as a regenerative process since the so-formed hard tissue lacks tubular features characteristic of genuine dentine. Rather, this process represents a repair response that produces calcified scar tissues by pulpal fibroblasts.