Autologous platelet concentrates represent promising innovative tools in the field of regenerative medicine and are successfully used in oral surgery. Several commercial systems exist that generate various forms of platelet concentrates including Platelet-rich plasma (PRP) and Platelet-rich fibrin (PRF). The alpha- granules of entrapped platelets release a variety of peptide growth factors that promotes healing. Usually PRP is a suspension that can be injected into the site of injury or used as a gel with the addition of thrombin (PRP-gel). In contrast Choukroun’s L-PRF is a dense fibrin based biomaterial enriched with platelets and growth factors. The physical state of these natural biomaterials especially L-PRF permits manual handling and suturing onto the tissue bead to improve healing. However, our knowledge about the mechanical characteristic of L-PRF is quite limited and a good understanding of material properties will enable expansion of current clinical applications. This study demonstrates the techniques to identify L-PRF’s mechanical properties (uniaxial tensile testing and suture retention strength); morphology (scanning electron microscope); biological stability and cytocompatibility.

PURPOSE: The aim of this study is to examine the healing of intact extraction sockets grafted with leukocyte-platelet rich fibrin (L-PRF) as compared to sockets grafted with freeze-dried bone allograft (FDBA) and a resorbable collagen barrier membrane (RCM). METHODS: This prospective randomized, examiner blinded pilot study included 17 subjects randomized to two treatment groups. Serum total cholesterol, low density lipoprotein (LDL), 25-hydroxyvitamin-D3, and platelet counts were determined preoperatively in all subjects. The experimental arm consisted of 8 posterior tooth-bounded intact extraction sites receiving L-PRF plugs. The control group consisted of 9 posterior tooth-bounded intact extraction sites receiving FDBA and RCM. An acrylic stent was fabricated to take duplicate clinical and CBCT measurements immediately post-extraction and at time of implant placement. A repeat-measures analysis of variance was utilized for statistical analysis. RESULTS: The study failed to detect a clinical or radiographic difference between treatment groups in horizontal or vertical ridge dimension changes. Serum cholesterol, LDL, 25-hydroxyvitamin-D3, and buccal plate thickness had a non-significant effect on outcome measurements, although there was a high prevalence of hyperlidpidemia and hypovitaminosis in the study population. CONCLUSIONS: The alveolar ridge dimension changes in intact posterior extraction sockets may be similar when either L-PRF or FDBA and RCM are utilized as socket grafting material. Although there was a high prevalence of high cholesterol and low 25-hydroxyvitamin-D3 levels in the population, this study failed to detect a significant correlation between preoperative serum levels and postoperative ridge dimension changes.

AIM: This study aims to determine what portion of specific autoantibody phenotypes are genetically determined by using a twin model. METHODS: This study specifically examines Anti-Ro(SSA), Anti-La (SSB), Anti-Sn/RNP, Anti-Sm, Anti-Jo-1, Anti-Scl-70, Anti-Tg & Anti-TPO, Anti-dsDNA, Anti-PS, and Anti-cardiolipin antibodies for their heritability. This study examined 104 same-sex adult twins (66 monozygous, 38 dizygous) for the above mentioned autoantibody values. The serum autoantibody values in each subject were quantified using automated ELISA. Descriptive statistics including, distributions, quantiles, and moments were calculated by zygosity for continuous antibody values, subject ages, gender, race and smoking status. Categorical antibody levels were used to determine twin pair concordance rates. Continuous and rank ordered autoantibody values were used to determine the presence and portion of a genetic component. To evaluate how strongly the antibody values in each twin group resembled each other, the intraclass correlation was calculated for each antibody by zygosity. The genetic variances, environmental variances, and heritability were estimated using path models with maximum likelihood estimation techniques. The phenotypic variance was modeled as a linear function of underlying additive genetic (A), dominant genetic (D), common environmental (C), and random environmental (E) effects. RESULTS: Several antibodies demonstrated a genetic component in our study population. Anti-cardiolipin had a genetic component with an estimated 69% heritability. Anti-dsDNA yielded a genetic component with a heritability estimate of 55-62%. Anti-Jo-1 presented a genetic component with the heritability estimate to be 41-51%. Anti-SCL-70 demonstrated a genetic component with a heritability estimate of 42-59%. Anti-PL had a genetic component with a heritability estimate of 52-54%. Several antibodies did not have a measurable genetic component. These included anti-Sm, anti-Ro(SSA), anti-La(SSB), anti-sn/RNP, anti-Tg, and anti-TPO. Some possibilities for the lack of a measureable genetic component may be due to the limited number of discordant twin pairs and/or the small number of subjects with higher levels of antibodies. CONCLUSION: The results of this study suggest several clinically relevant markers of auto-immunity may be partially genetically determined. These include: anti-cardiolipin, anti-dsDNA, anti-Jo-1, anti-SCL-70, and anti-phospholid.

AbstractINTERLEUKIN-6 LEVELS IN GENERALIZED AND LOCALIZED AGGRESSIVE PERIODONTITIS PATIENTSBy Bindu Reddy, D.D.S.A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at the Virginia Commonwealth UniversityVirginia Commonwealth University, 2004Major Director: Joseph V. Califano, D.D.S., Ph.D.Associate Professor, Department of Periodontics Periodontitis is an inflammatory disease involving the supporting structures of the dentition. Many studies have shown that there is a relationship between periodontal disease, the presence of pro-inflammatory cytokines, and systemic disease such as cardiovascular disease and diabetes mellitus. The purpose of this study was to measure serum Interleukin-6 levels in generalized and localized aggressive periodontitis and non-periodontitis patients and look for relationships with measures of disease severity. We also examined variables known to have a relationship with IL-6. A total of 172 subjects, comprising three periodontal subgroups, non-periodontitis (NP=61), generalized aggressive periodontitis (GAP=77), and localized aggressive periodontitis (LAP= 34), had serum samples evaluated for IL-6 levels using a highly sensitive ELISA test. The IL-6 levels were compared with clinical and demographic data including age, race, gender, number of teeth, probing depth, attachment loss, bleeding index, plaque index, gingival index, cotinine levels, smoking status, and CRP levels. Using multiple regression analysis, smoking status (p=0.0015) was the only variable found to have a significant relationship with IL-6 levels for all three groups.

Clinicians have described the success rates of dental implants. The use of implants is projected to increase in the future. With a 5-10% failure rate, it is unclear the exact factors that are associated with implant failures. To improve upon these success rates, it is critical to understand parameters associated with implant failure including: periodontitis, peri-implantitis, systemic diseases, site preparation, dental history of the implant site, bone quality, materials, occlusion, and treatment timelines. While bone quality is associated with failure, objective measures to assess bone quality and characteristics are scarce. Therefore, the aim of this study is to determine whether possible comorbidities, associated dental parameters, and measurable bone quality are possible predictors of implant failure. In this study, we utilized the electronic health record system axiUm® to retrospectively investigate non-failed (NF) and failed (F) dental implants from a patient cohort with 149 implants placed between 2012-2015 at Virginia Commonwealth University School of Dentistry. A chart review was conducted extracting information on age, gender, systemic diseases, smoking, occlusal trauma, parafunction, bone grafting history, treatment timelines, implant site/type/placement protocol, infection, torque at placement, bone quality and microarchitecture assessed by the novel, innovative technology: trabecular bone score (TBS). A total of 149 implants, 46 failures and 105 non-failed controls, were selected based on similar implant sites. Preliminary data obtained from analysis suggests that average time from implant placement to failure was 6.6 months (0.55 years). Parafunction habit (p=0.0202) and increased number of implants (p=0.0478) were found to be associated with increased implant failure.

Purpose: To determine the characteristics influencing periodontal practices in Virginia and report on the anticipated changes in practice. Methods: A REDCap survey was emailed to Virginia based American Academy of Periodontology (AAP) members assessing personal and practice demographics, trends in dental treatment and practice models, and how periodontists will adjust to account for these trends. Results: The response rate was 31% (n=46). Respondents report greater referrals from more experienced general practitioners (GPs). Student debt was associated with age. Respondents ranked biologic advances, treatment of peri-implantitis, digital dentistry, development of corporate and group practice models, and GPs incorporating more periodontal services in their practices as most likely to impact periodontal practices. The most reported periodontal practice adjustments included expansion of existing services, increasing the number of periodontists in the practice, and joining with other specialists or GPs to create group practices. Conclusions: Periodontists perceive the need to expand services, increase number of providers in their practices or create group practice models as future practice adjustments.

Periodontitis is an inflammatory disease of the oral cavity induced by anaerobic bacteria, that remains to be the primary cause of tooth loss in adults worldwide. Finding an anti-microbial therapeutic to selectively target periodontal pathogens has proven to be difficult, and current treatment modalities only provide a transient benefit. Amixicile is a non-toxic, readily bioavailable novel antimicrobial that targets strict anaerobes through inhibition of the activity of Pyruvate Ferredoxin Oxidoreductase (PFOR), a major enzyme mediating oxidative decarboxylation of pyruvate, a critical step in metabolism. Our study aimed to evaluate the efficacy of amixicile in inhibiting the growth of bacteria harvested from the complex sub-gingival biofilm of patients with chronic periodontitis. We hypothesize that amixicile will selectively inhibit pathogenic anaerobic bacteria collected from patients, with the same efficacy as metronidazole, the current accepted treatment modality. Plaque samples were harvested from patients with severe chronic periodontitis and cultured under anaerobic conditions. The microbiomes were grown in the presence of amixicile and metronidazole and the growth was compared to that of bacteria grown in the absence of the antimicrobials. Following 24 hour incubation, bacterial DNA was isolated and bacterial quantity was evaluated by quantitative PCR (qPCR) using primers specific for 12 bacterial species: P. gingivalis (Pg), P. intermedia (Pi), F.nucleatum (Fn), S.gordonii (Sg), S. anginosus (Sa), V. atypical (Va), L. acidophilus (La), A.actinomycetemcomitans (Aa), T.denticola (Td), S.mutans (Sm), S.sanguis (Ss), and 16s. Individual qPCR runs were combined to represent an overall average of CT value differences. Amixicile treatment groups exhibited statistical significant reductions (PP. intermedia, F. nucleatum and Veillonella atypical. When comparing amixicile to metronidazole, amixicile performed with similar efficacy with the largest effect seen for PFOR bacteria. Our conclusion supports amixicile as a potent inhibitor of anaerobic bacteria, and could be a potential new therapeutic antimicrobial in the treatment of periodontal disease

Background: Exosomes have great potential in regenerative medicine through the transfer of their bioactive cargos, such as RNA. tRF RNA and tiRNA are tRNAderived non-coding RNA. Here, we sought to identify the tRF/tiRNA profile in human mesenchymal stem cell (hMSC) exosomes. Methods: Bone marrow hMSCs were cultured with/without osteogenic differentiation medium and exosomes were harvested. RNA was extracted from: 1) control cells (Cell-NT); 2) control exosomes (EXO-NT); 3) differentiated cells (Cell-OM); 4) exosomes produced by differentiated cells (EXO-OM). RNA was sequenced to profile the small RNA with a focus on tRF/tiRNA. Results: tRF/tiRNA was highly enriched in hMSC exosomes. Less diversity was seen in the tRF/tiRNA profile in exosomes than that in parent cells. Selective tRF/tiRNA were packed into MSC exosomes and their profile is dependent on the cell maturation status. Conclusions: Our results suggest that tRF/tiRNA may play a role in mediating the function of exosomes in tissue regeneration.

The purpose of this study was to investigate if the addition of biologic materials and/or oral steroids would affect horizontal bone gain, or the bone density of the grafted bone in horizontal alveolar ridge augmentations. A retrospective chart review was completed to assess the clinical and radiographic outcomes of 53 ridge augmentation patients. An average bone gain of 3.6mm of width was found in our study based on radiographic analysis. There were no statistically significant differences found in the linear bone gain with the addition of biologic materials and steroids. A marginally statistically significant difference was found in the bone density when biologics were added (p-value=0.0653). No statistically significant difference found in the bone density with the addition of oral steroids. The use of tenting screws and resorbable occlusive membranes and a combination of allograft and xenograft bone materials provides significant clinical and radiographic dimensional changes in alveolar ridge width.

Periodontitis is a chronic inflammatory disease caused by pathogenic bacteria residing in a complex biofilm within a susceptible host. Amixicile is a non-toxic, readily bioavailable novel antimicrobial that targets strict anaerobes through inhibition of the activity of Pyruvate Ferredoxin Oxidoreductase (PFOR), a major enzyme mediating oxidative decarboxylation of pyruvate. Our study aimed to evaluate the efficacy of amixicile, when compared to metronidazole, in inhibiting the growth of bacteria present in a microbiome harvested from patients with chronic periodontitis. Plaque samples were harvested from patients with severe chronic periodontitis and cultured under anaerobic conditions. The microbiomes were grown in the presence of amixicile and metronidazole and the growth was compared to that of bacteria grown in the absence of the antimicrobials. Following 24 hour growth the bacterial DNA was analyzed using quantitative PCR (qPCR) using primers specific for 12 bacterial species: P. gingivalis (Pg), P. intermedia (Pi), F.nucleatum (Fn), S.gordonii (Sg), S. anginosus (Sa), V. atypical (Va), L. acidophilus (La), A.actinomycetemcomitans (Aa), T.denticola (Td), S.mutans (Sm), and S.sanguis (Ss). Both drug treatment groups yielded a statistical significant reduction for several anaerobic bacteria: Pi (P