Penn Dental Medicine
Established in 1878, Penn Dental Medicine is among the oldest university-affiliated dental schools in the nation. The school's mission is to transform global oral health and well-being through exceptional clinical care, innovation, education, and research.
PublicationNovel Endodontic Disinfection Approach Using Nanotechnology(2016-08-09) Bukhari, Sarah; Karabucak, Bekir; Koo, HyunThe aim of this in vitro investigation was to use a recently developed Enterococcus faecalis infection model using root canal for evaluating iron oxide (Fe3O4) nanoparticles (NP) with biomimetic (catalytic) properties as a new antimicrobial endodontic treatment. We compared iron oxide NP bioactivity with currently used chemical modalities using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) as analytical tools. We hypothesized that iron oxide NP with enzyme-like (peroxidase) activity catalyzes H2O2 to promote bacterial killing within dentinal tubules (DT) via in situ production of free radicals. We further hypothesized that the NP is more effective than the conventional treatments (irrigants) used in the clinical endodontic practice. Because iron oxides can be used as food additives, and iron oxide NP formulations are low-cost and FDA-approved for human use, it could be a safe and feasible approach to potentiate the effects of a commonly used antiseptic. PublicationEpigenetic Changes in the Innate Response of Gingival Epithelium(2014-05-28) Abdolhosseini, MahsaIn this study we showed TLR2 CpG promoter methylation in periodontitis affected human gingival tissues and in primary human gingival epithelial cells chronically stimulated with P. gingivalis that may instigate epithelial dysbiosis that may create a unique pathogen niche in the gingival crevice and susceptibility to periodontitis. PublicationINCIDENCE OF DENTAL IMPLANT FAILURE IN ACADEMIC SETTING - A CLINICAL RETROSPECTIVE STUDY PART ONE: PATIENT LEVEL(2021-06-17) Hakim Shoushtari, RezaAim: The aim of this retrospective study was to determine the implant failure rate and associated factors in the academic setting by using electronic health records (Axium) and hard copies of patients who received dental implants at in Penn Dental Medicine (PDM) and at Penn Dental Faculty Ppractices (PDFP) ofat the University of Pennsylvania from 06/01/2016 to 08/31/201920. In addition, evaluation of electronic health records and hard copies were reviewed for patients who had implants removed due to bone loss or lack of osseointegration atin PDM and Faculty practicesPDFP of the University of Pennsylvania from 06/01/2016 to 02/29/2020. Secondary objective was to investigate the co-contributing factors for implant failure at the patient level. Method and Material: Electronic health records and hard copies of patients who had implants placed and removed due to bone loss or lack of osseointegration atin PDM and Faculty practicesPDFP of the University of Pennsylvania from 06/01/2016 to 02/29/2020 were analyzed. Results: Data was evaluated at patient count and implant count for this retrospective study. 1609 patients received implants. 883 patients had implant placement at PDM and 726 patients had implant placement at PDFP. Of the total patients, 3180 implants were placed during the study period. 2162 implants were placed at PDM and 1018 implants were placed at PDFP. The total patient failure rate was 4.97% and the failure rate was of 6.0% and 3.7% for PDM and PDFP, respectively. The total implant failure rate was 3.49% and the implant failure rate was 3.7% and 3% for PDM and PDFP, respectively. Based on the chi-square test results, patients with bisphosphonate IV+PO (12%, P-value=0.004) were significantly overrepresented in the failure group. In contrast, patients with no bisphosphonate use (4.60%, P-value=0.004) were significantly underrepresented in the failure group. No overrepresentation (or underrepresentation) of patients with different gender, different age group, diabetes mellitus, history of periodontal disease, current smoking status, penicillin allergy, and recall were noted amongst failures. Based on the chi-square test, implants for bisphosphonate IV variable (11.5%, P-value=0.025) were significantly overrepresented in the failure group. In contrast, implants for no bisphosphonate use (3.20%, P-value<0.001) were significantly underrepresented in the failure group. No overrepresentation (or underrepresentation) of implants for different gender, different age group, diabetes mellitus, history of periodontal disease, current smoking status, penicillin allergy, and recall was noted amongst failures. Based on the multivariate conditional logistic regression, estimated odds of implant failure in participants with multiple implants were about three times than the participants with single implant (Adj OR=2.99, P-value=0.002); estimated odds of implant failure for bisphosphonate use of IV and PO was about four times that of the participants with no bisphosphonate use (Adj. OR=4.09, P-value=0.003). Diabetes and history of failed implants did not show any significant association with implant failure (with P-values>0.05). Conclusion: This study concluded that bisphosphonate use and patients with multiple implants were shown to have a significant contribution to implant failure. There was no difference in the failure rate of patients with different gender, different age group, diabetes mellitus, history of periodontal disease, current smoking status, penicillin allergy, and recallamongst failures. It is important to note that due to limitations and the retrospective nature of this study, only the co-contributing factors were evaluated and not the etiology of the implant failure. To further investigate the etiology, randomized clinical trial should be conducted. PublicationThe Role of Specific Integrase Strand Transfer Inhibitors (INSTIs) in the Alteration of Oligodendrocyte Maturation and Myelination in Hand(2019-03-13) Zidane, Bassam NCurrently, thirty-seven million people are infected with human immunodeficiency virus-1 (HIV-1) worldwide. Thankfully, the development of combined antiretroviral therapy (cART) regimens has decreased mortality and significantly improved the overall quality of life for these patients. However, approximately half of all patients clinically manifest with HIV-associated neurocognitive disorder (HAND), a spectrum of cognitive, motor, and behavioral abnormalities which histologically present as non-specific gliosis, synaptodendritc damage and loss of white matter and myelin. Furthermore, the severity of white matter damage correlates with the length of ART duration. However, almost no studies have been performed to determine how the myelin sheath or the oligodendrocytes that synthesize the sheath are damaged. Thus, we hypothesized that the administration of ART contributed in part to the myelin loss in the CNS of HIV-positive patients. Previously, we have reported that the protease inhibitor class of ART drugs hampered the in vitrodifferentiation of oligodendrocytes. Given that the new US guidelines for treating HIV patients recommends anew class of drugs, the integrasestrand transferinhibitors(INSTIs)as front-line therapy, we examined if two specific INSTIs, Elvitegravir (EVG) and raltegravir (RAL), altered the survival and/or maturation of developing oligodendrocytes in vitroand in vivo. We found that treatment of oligodendrocyte precursor cells (OPCs) with EVG, but not RAL, during differentiation reduced the number of cells positive for immature oligodendrocyte marker galactosylceramide (GalC) and mature oligodendrocyte marker myelin basic protein (MBP) in vitro, as well as the synthesis of myelin proteins. However, neither EVG or RAL induced cell loss or apoptosis, as determined by cell counts and TUNEL assays, suggesting that EVG does not affect OPC viability but instead, inhibits differentiation. EVG-induced oligodendrocyte differentiation deficits could be reversed by pre-treating the cells with a drug that pharmacologically inhibits the phosphorylation of eukaryotic initiation factor 2α(eIF2α) throughthe cellular integrated stress response (ISR). Finally, in vivo,mice receiving EVG/COBI failed to remyelinate the corpus callosum during the three week recovery period following demyelination, after cuprizone treatment. Although EVG/COBI treatment by itself did not cause overt white matter loss in this brain region. Our study demonstrates that EVG, but not RAL, inhibits oligodendrocyte precursor cell differentiation both in vitroand in vivo. Furthermore, EVG may be inhibiting oligodendrocyte precursor cell differentiation though activation of the ISR. Also, we found thatthe effects of EVG on oligodendrocyte differentiation could be attenuated in vitroby inhibiting the ISR. These studies suggest that ART may contribute to cognitive impairment by inhibiting renewal and replacement of oligodendrocytes in adults or development of oligodendrocytes in children. Further, our results suggest an ISR inhibitor might attenuate the negative effect of EVG on the maturation of oligodendrocytes. Our findings also suggest that development of less toxic ART compounds and adjunctive therapies are needed to minimize the side effects of ART on the CNS. PublicationDo Buffered Local Anesthetics Provide More Successful Anesthesia Over Non-Buffered Solutions in Patients Requiring Dental Therapy? – A Systematic Review & Meta-Analysis.(2017-05-18) Kattan, Sereen; Karabucak, Bekir; Hersh, Elliot V; Korostoff, Johnathan M; Hunter, PaulBackground: The pH of commercially available local anesthetics (LAs) is purposefully low (pH 3–4). Decreasing the pH extends the shelf life of the solution and prevents its early oxidation. However, a low pH may produce a burning sensation on the injection site, a slower onset of anesthesia, and a decrease in its clinical efficacy. Buffering of local anesthetics (alkalinization) by adding sodium bicarbonate has been suggested to achieve better pain control, reduce the pain of injection and produce a faster onset of local anesthetics. The aim of this review is to utilize a systematic review to collate evidence on the use of buffering agents with local anesthetics and its effect on causing profound pulpal anesthesia in patients requiring dental therapy and its side effects. Methods: Electronic searches were conducted in MEDLINE, Scopus, Cochrane Library, and ClinicalTrials.gov, World Health Organization (WHO) International Trials Registry Platform, OpenGrey & Google Scholar beta. Hand searching of two books “Handbook of Local Anesthesia” & “Successful Local Anesthesia for Restorative Dentistry and Endodontics” was conducted. Also, the reference lists of all included and excluded studies were checked to identify any further trials. Weighted anesthesia success rates and 95% confidence intervals (CIs) were estimated and compared by using a random-effects model. Results: 14,011 studies were initially identified from the search; 5 double-blind, randomized clinical trials met the inclusion criteria. For combined studies, buffered local anesthetics were more likely than non-buffered solutions to achieve successful anesthesia (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.11–4.71; P = 0.0232; I2 = 66%). Conclusion: This systematic review of double-blind, randomized clinical trials comparing the use of buffered and non-buffered local anesthetics in patients requiring dental therapy provides level ‘A’ evidence that is based on the criteria given by the Strength of Recommendation Taxonomy (SORT). In conclusion, the present meta-analysis showed that in patients receiving dental therapy, buffered local anesthetics are more effective than non-buffered solutions when used for mandibular or maxillary anesthesia. Buffering local anesthetics has 2.29 times greater likelihood of achieving successful anesthesia. PublicationGingival MSCs Improve Bone Phenotype in Ovariectomy-Induced Osteoporosis via Programmed Cell Death Pathway(2019-12-19) Alghaithi, SultanEstrogen deficiency-related osteoporosis is a skeletal system disorder that affects women after menopause taking a toll on financial and health institutions. Gingival Mesenchymal Stem cells (GMSCs) are a distinctive population of dental tissue-derived stem cells that possess uniquely high proliferation abilities and are capable of self-maintenance and multipotent differentiation. Their use has been investigated in different disease model applications, including cutaneous wound healing models, colitis, and allergy-related inflammatory disease models, but their effect on the bone phenotype of ovariectomy-induced osteoporosis hasn’t been explored. In our study, we show that a single systemic infusion of GMSCs elevated the bone mass reduction caused by Ovariectomy (OVX)-induced osteoporosis in both the femurs and mandibles of OVX mice, they also successfully rescued the function of the defective endogenous population of Bone Marrow Mesenchymal Stem Cells (BMMSCs). We saw that the systemic infusion of GMSCs exerted an immunomodulatory effect on the host, leading to the elevation of T-regulatory lymphocytes (T-regs) and the downregulation of T helper type 1 lymphocytes (Th1) levels in recipient OVX mice. Mechanistically, PD-1/PD-L1 is a popular cellular death pathway being heavily investigated in multiple research fields, In our study, we found that GMSC expresses PD-L1 and that the improved bone phenotype resulting from the GMSC infusion was via the programmed cell death (PD-1/PD-L1) pathway triggering activated T-cell apoptosis in the OVX mice, eventually resulting in an improvement of the bone phenotype. PublicationIn Vitro Comparative Study Between Full-Arch Conventional Implant Impressions and Full-Arch Digital Implant Impressions with Snap-on Scan Bodies(2022-06-24) Yoo, Thomas H.Statement of Problem: Digital impression techniques are widely used in everyday cases. There is sufficient evidence to support this technique in partially edentulous patients but the evidence supporting the use of intraoral scanners (IOS) in restorative digital workflows for edentulous patients is still limited. Purpose: The aim of the present in vitro study was to measure and compare the accuracy of full- arch conventional implant impressions with open and closed-trays, full-arch digital implant impressions with intraoral scanners (IOS), and three-dimensional (3D) printed casts from the full-arch digital implant impressions. Material and methods: Six implants were placed into a mandibular model. Snap-on scan bodies were inserted into the implants and scanned with a high-resolution reference scanner and exported in standard tessellation language (.STL) format (Group Control). Splinted open-tray impressions (Group 1, n=5) and closed-tray impressions (Group 2, n=5) were made and stone casts were fabricated. Digital impressions (Group 3, n=5) were made with an intra-oral scanner and the .STL files were exported to fabricate 3D printed casts. Snap-on scan bodies were inserted into analogs in Groups 1, 2, and 3 and scanned with the reference scanner. Using a 3D inspection software, impression techniques were compared to the control. Root mean square (RMS) values were calculated from the control and superimposed digitized casts from different impression techniques. Results: Group 3 had the lowest mean dimensional difference when superimposed with Group Control, then Groups 4, 1, and 2. Significant differences were found in RMS values between Group Control and digitized models fabricated from different techniques (P<0.05). Post Hoc (Tukey) test revealed that Group 3 (P<0.001) was significantly different from other groups while no significant difference was found between Groups 1, 2, and 4 (P>0.001). Conclusions: 3D printed models from full-arch digital impression of Snap-on scan bodies seem to be as accurate as stone models fabricated from full-arch conventional impression techniques. Closed-tray full-arch impression technique using dual-functioning Snap-on scan bodies seem to be as accurate as the splinted open-tray full-arch technique. Publication18F-FDG-PET/CT in Radiation Therapy-Induced Cerebellar Inflammation(2022-06-22) Abu Kar, Mohammad; Alavi, Abass; Korostoff, Johnathan M; Fiorellini, Joseph P; Chang, Yu-ChengABSTRACT Background 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG- PET/CT) is used in the clinical diagnosis and management of oncologic and inflammatory pathologies. It may also have utility in detecting tissue damage induced by radiotherapy (RT) used to treat various types of cancer. The aim of the present study was to use 18FDG-PET/CT to evaluate the effect of RT on the uptake of 18FDG by the cerebellum. Methods Thirty patients with head and neck cancer (HNC) were included in this retrospective study. The patients were treated with photon, proton, or combined photon/proton RT, in addition to chemotherapy. All patients received 18FDG- PET/CT imaging pre-treatment and 3 months post-treatment. The global mean standardized uptake value (SUVmean) of the cerebellum was determined for every patient by global assessment of 18FDG activity using OsiriX MD software. A two-tailed paired t-test was used to compare global SUVmean pre- and post-RT. Results The pre-treatment and post-treatment global SUVmean for the photon group were 5.26 and 5.51 (p: 0.42), respectively. As for the proton only group, the pre- and post-treatment global SUVmeans were 7.06 and 6.05, respectively. In the combined RT group, the pre- and post-treatment global SUVmeans were 6.14 and 6.19 respectively (p: 0.92). The differences between the pre- and post-treatment values failed to reach statistical significance for any of the treatment groups but it should be noted that there was a trend of increased 18FDG uptake in the cerebellum following photon therapy. This trend was not clear in the combined group. As for the proton group, p-value was not calculated as only two patients were included. Conclusion Although not statistically significant, the results showed an incremental increase in global SUVmean following treatment with photon RT likely reflecting the presence of mild radiation-induced inflammation in the cerebellum. PublicationThe Change of Alveolar Bone Thickness on Mandibular Central Incisors of Skeletal Class II Patients After Orthodontic Treatment Using Cone-Beam Computed Tomography.(2019-05-17) Matsumoto, Kensuke; Sherrill-Mix, Scott; Boucher, Normand; Tanna, NipulObjective: To test the null hypothesis that orthodontic tooth movement does not create dehiscences and the sagittal width dimension of alveolar bone is maintained. Materials and Methods: In 60 skeletal class II patients, CBCT images at pre- (T1) and post-orthodontic treatment (T2) were obtained and the presence of dehiscences was recorded. Based on the presence of dehiscences at T1 and T2, the patients were divided into four groups. The alveolar bone thickness at the level of 2 (CEJ2), 5 (CEJ5), 10 (CEJ10), and 15 (CEJ15) mm from the cementoenamel junction (CEJ) was measured on CBCT images in cross section along the long axis on the central incisors. CBCT-synthesized lateral cephalometric images were analyzed. Statistical analysis and the Pearson correlation analyses were utilized at a pResults: CBCT imaging showed that 27.1% of the mandibular central incisors had dehiscences at T1. With pre-existing dehiscence, the incidence of dehiscence increased to 50% at T2. Patients that developed dehiscences after orthodontic treatment showed the highest percentage of alveolar bone loss (-23.7% at CEJ2, -19.9% at CEJ5 at T2). In the group where patients developed dehiscences after orthodontic treatment, there was statistically significant mean increase of L1-NB (3.1mm) and IMPA (9.8°) (pConclusions: When camouflaging skeletal Class II patients, the limits of mandibular anterior incisor forward movement might be less than previously thought. In order to prevent the development of inadvertent dehiscences during the orthodontic treatment, careful diagnosis with CBCT images is recommended. Furthermore, when excessive protrusion and/or proclination is planned, additional treatment modalities such as orthognathic surgery, tooth extraction, and partial corticotomy with bone grafting should be considered. PublicationTHE ROLE OF LGR5+ EPITHELIAL STEM-LIKE CELLS IN 3D-ORGANOID MODELING AND PATHOGENESIS OF AMELOBLASTOMA(2020-04-16) Chang, Ting-HanAmeloblastoma (AM) is a benign yet locally aggressive tumor with high recurrences. Currently, the underlying pathophysiology remains elusive and radical surgery remains the most definitive treatment with severe morbidities. Our group first reported that AM harbors a subpopulation of tumor epithelial stem-like cells (AM-EpiSCs). Herein, this study further explored whether LGR5+ epithelial cells in AM possess unique stem-like cell properties and their potential contribution to the pathogenesis and recurrence of AM. Our findings demonstrated that LGR5 and stem cell-related genes were simultaneously expressed in a subpopulation of AM epithelial cells, both in vivo and in vitro, which were markedly enriched under the 3D-spheroid culture condition. As compared to LGR5- counterparts, LGR5+ AM epithelial cells showed increased expression of several critical genes involved in the regulation of epithelial-mesenchymal transition (EMT) and stem cell pluripotency, and functionally, exhibited enhanced capacity to form 3D-spheroids and generate human tumor 3D-organoids, which recapitulated characteristic histopathologic features of distinct subtypes of solid AM. Interestingly, AM derived mesenchymal stromal cells (AM-MSCs) and their secretomes or extracellular vesicles (EVs) significantly promoted the generation of LGR5+ AM-EpiSCs both in vitro and in vivo. Furthermore, treatment with a selective BRAFV600E inhibitor, Vemurafenib, unexpectedly enriched the proportion of LGR5+ AM-EpiSCs in AM 3D-organoids, which may explain the therapeutic resistant and recurrent properties of AM conferred by this unique subpopulation of AM-EpiSCs. Therefore, the tumor 3D-organoids generated by LGR5+ AM-EpiSCs provided a novel ex vivo platform for mechanistic studies of human AM and high throughput screening of targeted therapeutic drugs. These findings suggest that LGR5+ AM-EpiSCs play a pivotal role in pathogenesis and progression of AM and targeted inhibition of both BRAF and LGR5 potentially serves a novel non-surgical adjuvant therapeutic approach for this benign yet aggressively destructive jaw tumor.