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.
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Publication IMPACT OF SINTERING PROTOCOL AND YTTERIA CONTENT ON THE INTERNAL AND MARGINAL ADAPTATION OF 3-UNIT MONOLITHIC ZIRCONIA FIXED DENTAL PROSTHESIS(2025) Victoria Tiange HuDigital dentistry has revolutionized single-day dental prosthetic treatments, significantly improving efficiency and precision. Compared to conventional convection furnaces, high-speed sintering furnaces drastically reduce sintering time from several hours to minutes. However, variations in sintering time and temperature may alter material characteristics, affecting the dimensional stability and fit of fixed dental prosthetics. Previous studies on internal fit and marginal adaptation have yielded conflicting results, primarily focusing on single-unit restorations. This study investigates the effects of sintering protocols and yttria content on the internal fit and marginal adaptation of 3-unit monolithic zirconia fixed dental prostheses (FDPs). FDPs were fabricated using 3Y-TZP, 4Y-TZP, and 5Y-TZP zirconia under three sintering protocols: conventional sintering (CS), high-speed sintering (HS), and an optimized speed sintering (OS) protocol developed in-house to improve translucency while maintaining efficiency. A silicone impression method was used to quantify marginal and internal discrepancies. Results indicate that both sintering protocol and yttria content significantly affect adaptation. 3Y-PSZ exhibited the smallest marginal and internal gaps across all conditions, with CS yielding the highest precision. 4Y-PSZ demonstrated intermediate adaptation, while 5Y-PSZ showed the largest discrepancies, particularly under HS, where some gaps exceeded clinically acceptable thresholds. A statistically significant interaction between yttria content and sintering protocol was observed, with adaptation accuracy decreasing as yttria content increased. HS resulted in the largest variation, highlighting its limitations in maintaining precise adaptation, while OS provided a more clinically acceptable balance between speed and fit. These findings emphasize the need for material-specific sintering strategies. CS remains the most reliable method for optimal adaptation, particularly for zirconia with higher translucency. OS presents a viable alternative for achieving clinically acceptable results with reduced processing time, making it suitable for chairside workflows. However, HS, while time-efficient, introduces greater dimensional instability, necessitating further optimization. This study contributes to the growing body of knowledge in digital dentistry, offering valuable insights into material selection and sintering protocols for zirconia FDPs. By refining sintering parameters, future advancements may enhance chairside zirconia restoration workflows, improving efficiency, precision, and long-term clinical outcomes.Publication LGBT Oral Health Disparities: A Review of Oral Health Needs, Barriers to Care, and Culturally Competent Practices(2025-01-22) Yu, ClaireIn the realm of health disparities, the unique challenges faced by the LGBT community, particularly within dentistry, remain largely underexplored. Marginalized and often facing significant societal prejudice, members of the LGBT community have a higher propensity for risk behaviors such as tobacco and alcohol use and a greater susceptibility to substance use disorders. These behaviors directly influence their oral health, increasing their risk for oral cancers, periodontal disease, and other oral health problems. The broader impact of these health disparities affects every facet of LGBT individuals' well-being, including their oral health. These disparities include limited access to dental care, higher rates of discrimination and mistreatment, inadequate health insurance coverage, and elevated dental fear. Intertwined with social and psychological stressors, these issues create a complex web of factors contributing to the observed oral health disparities in the LGBT community. Despite the urgency and significance of these issues, there is a substantial gap in our understanding of LGBT health overall. Comprehensive, population-specific research is vital to delve deeper into these disparities and design effective strategies that foster health equity within oral healthcare. A narrative review of peer-reviewed articles was conducted using databases like PubMed, Cochrane Library, and Scopus, focusing on keywords related to LGBT and oral health. This research would greatly contribute to improving the oral and overall health of the LGBT population, thereby promoting a broader sense of inclusivity and well-being in healthcare.Publication An update on periodontal inflammation and bone loss(Frontiers Media SA, 2024) Zhang, Mingzhu; Liu, Yali; Afzali, Hamideh; Graves, Dana T.Periodontal disease is a chronic inflammatory condition that affects the supporting structures of the teeth, including the periodontal ligament and alveolar bone. Periodontal disease is due to an immune response that stimulates gingivitis and periodontitis, and its systemic consequences. This immune response is triggered by bacteria and may be modulated by environmental conditions such as smoking or systemic disease. Recent advances in single cell RNA-seq (scRNA-seq) and in vivo animal studies have provided new insight into the immune response triggered by bacteria that causes periodontitis and gingivitis. Dysbiosis, which constitutes a change in the bacterial composition of the microbiome, is a key factor in the initiation and progression of periodontitis. The host immune response to dysbiosis involves the activation of various cell types, including keratinocytes, stromal cells, neutrophils, monocytes/macrophages, dendritic cells and several lymphocyte subsets, which release pro-inflammatory cytokines and chemokines. Periodontal disease has been implicated in contributing to the pathogenesis of several systemic conditions, including diabetes, rheumatoid arthritis, cardiovascular disease and Alzheimer’s disease. Understanding the complex interplay between the oral microbiome and the host immune response is critical for the development of new therapeutic strategies for the prevention and treatment of periodontitis and its systemic consequences. Copyright © 2024 Zhang, Liu, Afzali and Graves.Publication Osteoimmunology in Periodontitis and Orthodontic Tooth Movement(Springer Publishing, 2023-04) Alghamdi, Bushra; Jeon, Hyeran Helen; Ni, Jia; Qiu, Dongxu; Liu, Alyssia; Hong, Julie J.; Ali, Mamoon; Wang, Albert; Troka, Michael; Graves, Dana T.Purpose of Review: To review the role of the immune cells and their interaction with cells found in gingiva, periodontal ligament, and bone that leads to net bone loss in periodontitis or bone remodeling in orthodontic tooth movement. Recent Findings: Periodontal disease is one of the most common oral diseases causing inflammation in the soft and hard tissues of the periodontium and is initiated by bacteria that induce a host response. Although the innate and adaptive immune response function cooperatively to prevent bacterial dissemination, they also play a major role in gingival inflammation and destruction of the connective tissue, periodontal ligament, and alveolar bone characteristic of periodontitis. The inflammatory response is triggered by bacteria or their products that bind to pattern recognition receptors that induce transcription factor activity to stimulate cytokine and chemokine expression. Epithelial, fibroblast/stromal, and resident leukocytes play a key role in initiating the host response and contribute to periodontal disease. Single-cell RNA-seq (scRNA-seq) experiments have added new insight into the roles of various cell types in the response to bacterial challenge. This response is modified by systemic conditions such as diabetes and smoking. In contrast to periodontitis, orthodontic tooth movement (OTM) is a sterile inflammatory response induced by mechanical force. Orthodontic force application stimulates acute inflammatory responses in the periodontal ligament and alveolar bone stimulated by cytokines and chemokines that produce bone resorption on the compression side. On the tension side, orthodontic forces induce the production of osteogenic factors, stimulating new bone formation. A number of different cell types, cytokines, and signaling/pathways are involved in this complex process. Summary: Inflammatory and mechanical force-induced bone remodeling involves bone resorption and bone formation. The interaction of leukocytes with host stromal cells and osteoblastic cells plays a key role in both initiating the inflammatory events as well as inducing a cellular cascade that results in remodeling in orthodontic tooth movement or in tissue destruction in periodontitis. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Publication An IL-10/DEL-1 axis supports granulopoiesis and survival from sepsis in early life(Nature Portfolio, 2024-12) Vergadi, Eleni; Kolliniati, Ourania; Lapi, Ioanna; Ieronymaki, Eleftheria; Lyroni, Konstantina; Alexaki, Vasileia Ismini; Diamantaki, Eleni; Vaporidi, Katerina; Hatzidaki, Eleftheria; Papadaki, Helen A.; Galanakis, Emmanouil; Hajishengallis, George; Chavakis, Triantafyllos; Tsatsanis, ChristosThe limited reserves of neutrophils are implicated in the susceptibility to infection in neonates, however the regulation of neutrophil kinetics in infections in early life remains poorly understood. Here we show that the developmental endothelial locus (DEL-1) is elevated in neonates and is critical for survival from neonatal polymicrobial sepsis, by supporting emergency granulopoiesis. Septic DEL-1 deficient neonate mice display low numbers of myeloid-biased multipotent and granulocyte-macrophage progenitors in the bone marrow, resulting in neutropenia, exaggerated bacteremia, and increased mortality; defects that are rescued by DEL-1 administration. A high IL-10/IL-17A ratio, observed in newborn sepsis, sustains tissue DEL-1 expression, as IL-10 upregulates while IL-17 downregulates DEL-1. Consistently, serum DEL-1 and blood neutrophils are elevated in septic adult and neonate patients with high serum IL-10/IL-17A ratio, and mortality is lower in septic patients with high serum DEL-1. Therefore, IL-10/DEL-1 axis supports emergency granulopoiesis, prevents neutropenia and promotes sepsis survival in early life. © 2024, The Author(s).Publication Distinct fibroblast progenitor subpopulation expedites regenerative mucosal healing by immunomodulation(Rockefeller University Press, 2023-06-03) Ko, Kang I.; Dergarabedian, Brett P.; Chen, Zhaoxu; Debnath, Rahul; Ko, Annette; Link, Brittany N.; Korostoff, Jonathan M.; Graves, Dana T.Injuries that heal by fibrosis can compromise organ function and increase patient morbidity. The oral mucosal barrier has a high regenerative capacity with minimal scarring, but the cellular mechanisms remain elusive. Here, we identify distinct postnatal paired-related homeobox-1+ (Prx1+) cells as a critical fibroblast subpopulation that expedites mucosal healing by facilitating early immune response. Using transplantation and genetic ablation model in mice, we show that oral mucosa enriched with Prx1+ cells heals faster than those that lack Prx1+ cells. Lineage tracing and scRNA-seq reveal that Prx1+ fibroblasts exhibit progenitor signatures in physiologic and injured conditions. Mechanistically, Prx1+ progenitors accelerate wound healing by differentiating into immunomodulatory SCA1+ fibroblasts, which prime macrophage recruitment through CCL2 as a key part of pro-wound healing response. Furthermore, human Prx1+ fibroblasts share similar gene and spatial profiles compared to their murine counterpart. Thus, our data suggest that Prx1+ fibroblasts may provide a valuable source in regenerative procedures for the treatment of corneal wounds and enteropathic fibrosis. © 2022 Ko et al.Publication Mechanical Regulation of Oral Epithelial Barrier Function(MDPI, 2023-05) Lee, Eun-Jin; Kim, Yoontae; Salipante, Paul; Kotula, Anthony P.; Lipshutz, Sophie; Graves, Dana T.; Alimperti, StellaEpithelial cell function is modulated by mechanical forces imparted by the extracellular environment. The transmission of forces onto the cytoskeleton by modalities such as mechanical stress and matrix stiffness is necessary to address by the development of new experimental models that permit finely tuned cell mechanical challenges. Herein, we developed an epithelial tissue culture model, named the 3D Oral Epi-mucosa platform, to investigate the role mechanical cues in the epithelial barrier. In this platform, low-level mechanical stress (0.1 kPa) is applied to oral keratinocytes, which lie on 3D fibrous collagen (Col) gels whose stiffness is modulated by different concentrations or the addition of other factors such as fibronectin (FN). Our results show that cells lying on intermediate Col (3 mg/mL; stiffness = 30 Pa) demonstrated lower epithelial leakiness compared with soft Col (1.5 mg/mL; stiffness = 10 Pa) and stiff Col (6 mg/mL; stiffness = 120 Pa) gels, indicating that stiffness modulates barrier function. In addition, the presence of FN reversed the barrier integrity by inhibiting the interepithelial interaction via E-cadherin and Zonula occludens-1. Overall, the 3D Oral Epi-mucosa platform, as a new in vitro system, will be utilized to identify new mechanisms and develop future targets involved in mucosal diseases. © 2023 by the authors.Publication Illuminating the oral microbiome and its host interactions: animal models of disease(Oxford University Press, 2023-05-01) Hajishengallis, GeorgePeriodontitis and caries are driven by complex interactions between the oral microbiome and host factors, i.e. inflammation and dietary sugars, respectively. Animal models have been instrumental in our mechanistic understanding of these oral diseases, although no single model can faithfully reproduce all aspects of a given human disease. This review discusses evidence that the utility of an animal model lies in its capacity to address a specific hypothesis and, therefore, different aspects of a disease can be investigated using distinct and complementary models. As in vitro systems cannot replicate the complexity of in vivo host–microbe interactions and human research is typically correlative, model organisms—their limitations notwithstanding—remain essential in proving causality, identifying therapeutic targets, and evaluating the safety and efficacy of novel treatments. To achieve broader and deeper insights into oral disease pathogenesis, animal model-derived findings can be synthesized with data from in vitro and clinical research. In the absence of better mechanistic alternatives, dismissal of animal models on fidelity issues would impede further progress to understand and treat oral disease. © The Author(s) 2023. Published by Oxford University Press on behalf of FEMS. All rights reserved.Publication Oral polymicrobial communities: Assembly, function, and impact on diseases(Elsevier, 2023-04-12) Hajishengallis, George; Lamont, Richard J.; Koo, HyunOral microbial communities assemble into complex spatial structures. The sophisticated physical and chemical signaling systems underlying the community enable their collective functional regulation as well as the ability to adapt by integrating environmental information. The combined output of community action, as shaped by both intra-community interactions and host and environmental variables, dictates homeostatic balance or dysbiotic disease such as periodontitis and dental caries. Oral polymicrobial dysbiosis also exerts systemic effects that adversely affect comorbidities, in part due to ectopic colonization of oral pathobionts in extra-oral tissues. Here, we review new and emerging concepts that explain the collective functional properties of oral polymicrobial communities and how these impact health and disease both locally and systemically. © 2023 Elsevier Inc.Publication Advanced Imaging in Dental Research: From Gene Mapping to AI Global Data(Sage Publishing, 2024-12) Graves D.T.; Uribe S.E.Advances in imaging technologies combined with artificial intelligence (AI) are transforming dental, oral, and craniofacial research. This editorial highlights breakthroughs ranging from gene expression mapping to visualizing the availability of global AI data, providing new insights into biological complexity and clinical applications. © The Author(s) 2024.