• The Effect of Processing Techniques for rhBMP-2 Coated Titanium Implants on Alveolar Augmentation and Osseointegration in the Canine Supraalveolar Peri-Implant Defect Model

      Decker, John; Department of Oral Biology (9/5/2014)
      A current paradigm-shift in implant dentistry places restorative factors associated with esthetics and function in front of implant site selection based on bone quantity and quality. Marginal bone loss after implant placement, resorption of the edentulous alveolar ridge, bone defects from periodontal disease, and ridge aberrations due to trauma all challenge implant treatment driven by esthetics and function. Clinicians compensate for bone loss using bone augmentation procedures including bone grafts, bone materials, biologic mediators, barrier devices, or combinations thereof. The search for treatment modalities to address implant placement into compromised sites has lead to the development of a variety of products designed to replace or induce bone formation. Some believe an ideal material could be coated onto implants, to promote osseointegration, induce local bone formation, while not requiring adjunctive biomaterials, or procedures including placement of allogeneic and xenogeneic biomaterials, or autograft bone.
    • Evaluation of a Novel Compression Resistant Matrix for Recombinant Human Bone Morphogenetic Protein-2 (RHBMO-2) for Onlay Graft Indications

      Lu, Sheldon; Department of Oral Biology (6/4/2014)
      The discovery and subsequent characterization of endogenous signaling peptides known as bone morphogenetic proteins (BMPs) capable of inducing de novo bone formation in postfetal life represents a critical advancement in the understanding of tissue morphogenesis and has become an incentive to develop additional growth factor based tissue engineering strategies (Wozney & Seeherman 2004). Because BMPs act locally, a suitable carrier system must be used to ensure effective presentation of an adequate dose to a target site (Mont et al. 2004). A number of candidate biomaterials have thus been tested as potential carrier technologies (Huang et al. 2008). Currently, recombinant human BMP-2 (rhBMP-2) coupled with an absorbable collagen sponge (ACS) manufactured from bovine Achilles tendon Type 1 collagen is the only FDA approved device for orthopedic and craniofacial indications. Although the rhBMP-2/ACS construct has demonstrated clinical efficacy for indications including spine fusion, long bone fracture healing, sinus and alveolar augmentation, the ACS’s inability to resist tissue compression limits its use for onlay indications (Wikesjö et al. 2007).
    • EFFECT OF MATRIX-BOUND BISPHOSPHONATES ON MONOCYTE DIFFERENTIATION AND OSTEOCLAST FUNCTION

      Abraham, Pheba; Abraham, Pheba; Department of Oral Biology (5/1/2017)
      This study was to explore the effect of local, matrix-bound bisphosphonates to monocytedifferentiation and osteoclast function in vitro. Experiments were designed using osteoassay plates. Cell-viability, differentiation, resorption pits and gene expression were analyzed to see the effect of matrix-bound BPs on monocyte differentiation and osteoclast function. EDTA was used as a chelating agent to remove the bound BPs. There was a dose dependent response in the differentiation and resorption pits. With chelation, there was increase in differentiation, resorption pits and increase in the calcium and PYD in the supernatant. Thus, matrix-bound Bisphosphonatesare biologically active and they inhibit monocyte differentiation and osteoclast function. Thereby removal of this matrix-bound drug can rescue osteoclast differentiation and function.
    • Inherent Gene Expression and Protein Profile Differences Between Alveolar and Basal Bone

      Alotaibi, Fawwaz; Department of Oral Biology (5/1/2015)
      The mandible is composed to two bone types: alveolar and basal. Previous studies on the mandible have shown that the alveolar bone resorbs more than the basal bone after tooth extraction or as a result of tooth movement. Reasons for why the resorption rates are different is not well understood. This research begins exploring the differences of the alveolar and basal bone by using comparison characteristics such as bone mineral density (BMD), gene expression, protein profiles, and number of osteocytes. The research investigates these characteristics by using Real time RCR to study the differences in gene expression and protein profiles of the alveolar and basal bone. Micro-CT was used in comparing density and bone architecture characteristics of the alveolar and basal bone. Immunohistochemistry was used to better understand how osteocytes are different between the two bone types in hopes of later being able to understand the differences in resorption rates. The real time PCR showed that four genes are expressed significantly higher in basal bone than alveolar bone: SOST, E-11, DMP-1, MEPE. Three of which are associated with mature osteocytes indicating that basal bone has more mature osteocyte phenotypes. Micro-CT data indicated that the basal bone is denser and less porous than alveolar bone. There was no significant difference in immunohistochemistry and further quantitative testing is needed to draw and significant correlation.
    • Marker Co-Expression Analysis of Initial Cellular Events in the Critical-Size Rat Calvarial Defect Model and the Effect of Bone Morphogenetic Protein-2 (rhBMP-2)

      Capetillo, Joseph F.; Department of Oral Biology (4/15/2016)
      Craniofacial defects can result from congenital malformations, trauma, tumor resection,periodontal disease, post-extraction ridge remodeling, and peri-implantitis. Regenerationof bone is critical to achieving functional and esthetic outcomes in the rehabilitation ofsuch defects. Traditional strategies for osseous regeneration include a multiple ofsurgical techniques utilizing autologous bone, cadaver-sourced allogeneic or xenogeneicbone, synthetic bone biomaterials, barrier membranes, or combinations thereof(Wikesjö, Qahash 2009). The need to enhance the predictability of regeneration inespecially large defects that cannot heal adequately without intervention (critical-sizedefects) has led to recent development of protein- and cell-based technologies.[Introduction, first paragraph]
    • The role of Toll-like receptor (TLR) 2 in the systemic immune response profile of mice induced to develop squamous cell carcinoma of the upper aerodigestive tract

      El-Shafey, Sally; El-Shafey, Sally; Department of Oral Biology (4/1/2017)
      Background Head and necksquamous cell carcinomais associated with immunosuppression, a state in which the progression of cancer is associated with disturbances in the immune system functions. Emerging studies suggest a fundamental role for the innate immune system, particularly Toll-like receptor 2 (TLR2), in this process.QuestionsIn this study, we investigated the potential roles of TLR2 on systemic immune profile in a mouse model of headand necksquamous cell carcinoma.MethodsTwo different protocols of a mouse model of 4-nitroquinoline 1-oxide and ethanol-induced carcinogenesis to induce head and neck squamous cell carcinoma were used. To evaluate the systemic immune profiles, total RNA wasisolated from the spleens of four groups of animals, including carcinogen-treated and control untreated wild-type and toll-like receptor 2-deficient animals. Quantitative real-time PCR was performed forgenesrepresentative of house-keeping genes, type 1 and type 2 immune responses, regulatory T and B cells, and adenosine receptors.Results and ConclusionIn the standard protocol of 4-nitroquinoline 1-oxide and ethanol-induced carcinogenesis, there was asignificant upregulation of adenosine receptor A2a in the spleens of wild type iiimice treatedwith4-nitroquinoline 1-oxide and ethanolrelative to wild type untreatedanimals. In the standard protocol of carcinogenesis, there was a significant upregulation of CD39 in the spleens of TLR2-koanimalstreated with 4-nitroquinoline 1-oxide and ethanol relative to untreated TLR2-ko mice. These results suggest that carcinogenesis in the upper aerodigestive tract is associated with alterations in the systemic immune profile reflected in the spleen. However, the specific impact on the immune profiles appears to be affected by the presence or absence of TLR2.
    • Changes in the RANK/RANKL/OPG Signaling System as a Mechanism of Zoledronate-Induced Osteonecrosis of the Jaw

      Lane, Jonathan; Department of Oral Biology (3/22/2016)
      Bisphosphonates (BPs) are widely used for the treatment of osteoporosis, hypercalcemia of malignancy, skeletal-related events associated with bone metastases, and for managing lytic lesions of multiple myeloma. A serious risk associated with the use of BPs is the development of Bisphosphonate Related Osteonecrosis of the Jaw (BRONJ), a painful and inflamed area of exposed bone in the oral cavity that fails to heal after 6-8 weeks. The cause of BRONJ is unknown, but it is believed to be due primarily to a longterm suppression of bone remodeling, caused by BP’s potent inhibition of osteoclastic activity. At the cellular level, it is generally accepted that bisphosphonates are taken in by osteoclasts at sites of relatively greater bone remodeling, owing to the strong affinity of bisphosphonates for the mineralized matrix and the increased activity of osteoclasts at active sites of resorption. The accumulation of intracellular bisphosphonates ultimately leads to osteoclast dysfunction or apoptosis through the formation of nonhydrolyzable ATP-analogues, or due to inhibition of the mevalonate pathway responsible for synthesis of sterols and lipids necessary for proper cellular membrane structure. However, the refined details of the pathophysiology of BRONJ remain elusive. The RANK/RANKL/OPG system is a well-known signaling pathway for the recruitment and differentiation of osteoclasts. RANK is a surface-bound receptor on osteoclasts, and requires binding of its ligand, RANKL, for cell activation and ultimately resorption of bone. On the other hand, OPG is a soluble decoy receptor for RANKL. Therefore, osteoclastic activity is effectively regulated by the ratio of RANKL to OPG. For years, it has been generally accepted that osteoblasts are the primary source of both RANKL and OPG. However, it is now recognized that the master orchestrator of bone activity, the osteocyte, contributes to the pathway. Furthermore, it has been shown that in localized tissue damage or hypoxia, such as in a dental extraction, immediately adjacent surviving nonapoptotic osteocytes upregulate RANKL and downregulate OPG. It is unknown to what extent BPs may alter the normal osteocyte response to injury and hypoxia or, ultimately, the dynamics of the RANK/RANKL/OPG system. Furthermore, the extent to which this could contribute to the development of BRONJ is unexplored.There is a paucity of studies concerning how the fundamental system responsible for bone remodeling, RANK/RANKL/OPG, is effected by BPs. It may be that changes in this system, especially in signals derived from the osteocyte, contribute to the pathophysiology of BRONJ.
    • Dendritic Cell Derived Exosomes Loaded with Immunoregulatory Cargo Reprogram local Immune Responses and Inhibit Degenerative Bone Disease In vivo

      Elashiry, Mahmoud; Biomedical Sciences (Augusta University, 2020-12)
      Background: Histopathological study of periodontitis (PD) lesions at sites of bone loss reveals infiltration with dendritic cells (DC) CD4+ T cell clusters and other inflammatory cells. DCs can direct bone protective T-regulatory cell (Tregs) responses, or bone destructive T-helper 17 (Th17). The use of exosomes (EXO), natural nanoparticles released by DCs and other cells, are under intense scrutiny in clinical trials for autoimmune diseases and cancer, but no studies to date have harnessed DC-derived EXO to regulate alveolar bone loss in PD. Aim: To determine the ability of custom DC-derived EXO to reprogram immune cell functions of recipient DCs and T cells and mitigate inflammatory bone loss in mice. Methods: Murine bone marrow derived donor DC subtypes, including immune regulatory DCs (regDC), immature DCs (iDC) and immune stimulatory (stimDC) DCs were the source of purified DC EXO. Reg DC EXO were actively loaded with TGFB1/IL10 using ultrasonication. Preliminary in vitro studies of EXO cargo, stability and resistance of cytokine cargo to proteolysis, as well as immune functions and osteoclastogenesis was investigated. The following DC EXO subtypes were then tested in vivo in six groups of mice, in the ligature induced PD model: Group 1, no ligature, Groups 2, 3, 4, 5 and 6, 8 ligature plus gingival injection of, respectively, PBS, regDC EXO, iDC EXO, stimDC EXO and free TGFB1/IL10. Biodistribution and in vivo uptake of EXO by gingival recipient DCs and T cells were tracked. The ability of DC EXO to modulate gingival recipient DC and CD4 T cells and cytokine expression was confirmed. TRAP staining of histological sections measured osteoclast number, while bone loss volume was measured in 3-D by micro-CT. Results: Injected EXO showed a high affinity for gingival site of inflammatory bone loss. RegDC EXO containing TGFb/IL-10 cargo, protected cargo against proteolytic degradation and were taken up by recipient DCs and T cells in vivo, promoting Tregs, while inhibiting Th17 recruitment and inhibiting bone loss. In contrast, EXO subtypes lacking TGFb/IL-10 or free TGFB/IL-10 did not shift the Treg-Th17 balance and did not inhibit bone loss. Mechanistically, a key role for TGFb1 in induction of Tregs by regDC EXO was found using blocking antibodies to TGFb and/or IL-10. T.E.M. analysis revealed TGFb1 localized in the EXO lumen and in the transmembrane domain, which sustained signaling in recipient DCs. Blocking experiments revealed that sustainable prolonged TGFb1 signaling required initial interaction between regDCs EXO and TGFBR1 complex on acceptor cells, followed by internalization of regDC EXO with TGFB1-TGFBR1 complex for sustained SMAD2/3 phosphorylation. Conclusion: This is the first study to demonstrate the efficacy of DCs exosomes for inhibition of experimental bone loss and the cellular immune mechanisms involved. This provides the basis for a future novel immunotherapeutic strategy for PD in humans.
    • The Application of Low-Cost, Close-Range Photogrammetry in Dentistry

      Patel, Mohit; Mettenburg, D.; Biological Sciences, Restorative Sciences (Augusta University Libraries, 2020-05-05)
      This item presents the abstract for a poster presentation at the 21st Annual Phi Kappa Phi Student Research and Fine Arts Conference.
    • Efficacy of Epigallocatechin-3-gallate-palmitate as a Virucidal Compound Against Norovirus

      Widjaja, Nicole; Department of Oral Biology and Diagnostic Sciences (Augusta University, 2020-05)
      Norovirus is a highly infectious, non-enveloped virus found to be the leading cause of global gastroenteritis outbreaks. Every year within the United States, this virus is responsible for an average of 19-21 million cases of acute gastroenteritis, approximately 570-800 deaths, and has been the cause of 1.7 to 1.9 million outpatient visits. On a global scale, healthcare costs and lost productivity are estimated to $60 billion due to illnesses and outbreaks caused by the burden of norovirus. Unfortunately, current measures to prevent the transmission of norovirus remain insufficient as the Center for Disease Control and Prevention (CDC) can only recommend hand washing with soap and water as the best preventative measure. The only other hand hygiene method available is alcohol-based hand sanitizers, but the CDC states that they are not effective in inactivating norovirus particles and warns that it should not be considered a substitute to hand washing. Recently, epigallocatecin-3-gallate (EGCG) a major component extracted from the leaves of Camellia sinensis, also commonly known as tea plant, has shown potential to be the next viable candidate as an antiviral solution. Lipid derivatives of EGCG, most notably EGCGpalmitate, has shown to express potent antiviral properties and has showed to play a crucial role in the fight against other non-enveloped viruses such as poliovirus and adenovirus. In this study, we determined the efficacy of EGCG-palmitate in novel formulations against human norovirus surrogates by utilizing the EU international standards for hand hygiene in vitro studies against norovirus. Evidence is provided determining the virucidal activity of alcohol-based ProtecTeaV formulations containing EGCG-palmitate as well as the potential for EGCG-palmitate as a persistent residual virucidal activity against norovirus surrogates, feline calicivirus (FCV) and murine norovirus-1 (MNV-1). By creating an effective, environmentally friendly, non-toxic and long lasting solution composed of EGCG-palmitate, the results of this innovative approach would expand the options available to reduce the transmission of norovirus essentially bridging the gap for a new preventative hand hygiene and ultimately impacting the spread of norovirus on a worldwide scale.
    • The Clinical Aspects of Hypophosphatasia

      Baker, Abby; Simpson, Sage; Dental Hygiene (2020-02-13)
      OBJECTIVES: The purpose of this research is to educate the dental community on the effects of hypophosphatasia and the clinical manifestations it presents throughout the body and the oral cavity. METHODS: Hypophosphatasia is a rare inherited metabolic disorder that has a wide spectrum of disease presentation. Due to 300 types of ALP mutations, HPP has six different major forms: perinatal lethal, prenatal benign, infantile, childhood, adulthood, and odotohypophosphatasia. There are clinical signs presented throughout the body and the oral cavity. Premature exfoliation of primary dentition is the first clinical sign of hypophosphatasia in childhood. Two different studies were reviewed in order to compare similar symptoms of hypophosphatasia. RESULTS: In one case study there were 38 patients who reported similar symptoms. In 15 (39%) of the patients a history of fractures was present. In the same study 21 (55%) of the patients had recurring headaches, 4 (11%) of the patients experienced severe muscle weakness, 23 (61%) experienced recurring muscle pain, and 18 (47%) of the patients exhibited dental abnormalities. In another case study there were 9 patients that reported only dental signs of hypophosphatasia. Dental signs of HPP were shown in childhood in 8 (88%) of the patients. The premature loss of the primary dentition was shown in 7 (77%) of the patients, absent primary dentition in 1 (11%) of the patients, and delayed loss of primary teeth in 1 (11%) of the patients. CONCLUSIONS: Since hypophosphatasia is so rare, more studies are needed on the diagnosis, preventative methods, and treatments. The majority of HPP cases are diagnosed in adulthood which ensures the disorder could have been present during childhood and was overlooked. In order to diagnose the disorder promptly, there should be a thorough medical history and clinical signs must be evaluated. There is no cure or long term prognosis for the hypophosphatasia disorder.
    • Incidence of Emergence Delirium following administration of Midazolam in female patients

      Ibrahim, Chris; James, Jeffrey; Oral Surgery (2020-02)
      Emergence delirium is a disturbing complication in the female population after the administration of midazolam. This study is constructed to determine incidence of female patients undergoing the side effect of emergence delirium and to observe common variables that may make individuals more susceptible to the post-operative emergence phenomenon.
    • Is there a Correlation Between Weather and Head & Neck Fascial Space Infections?

      Frazier, Kyle; James, Jeffrey; Faigen, Alex; Looney, Stephen W.; Sinha, Arnoneel; Oral Surgery (2020-02)
      The purpose of this study was to compare the CBSE scores of Oral & Maxillofacial Surgery residency candidates that matched to 4-year and 6-year tracts in the 2019-2020 application cycle.
    • Alteration of the VDO of an existing RPD with Composite Resin

      Shepherd, Kevin A.; Restorative Sciences (2020-02)
      1. Can composite resin be added to an RPD to test a new proposed VDO and it hold up over the course of treatment? 2. Can a flange and teeth be added chairside to an existing RPD? 3. Can a treatment plan that involves alteration of VDO, implant therapy, fixed prosthodontics, and removable prosthodontics be simplified by the use of a prototype?
    • How effective is manual debridement on exposed dental implant threads?

      Sellers, Brian; Oral Surgery (2020-02)
      Evaluate manual debridement of periosteal dental implants with high speed hand piece and diamond burrs.