Publications by authors named "Larry F Wolff"

39 Publications

Association between Periodontal Disease and Systemic Inflammatory Conditions Using Electronic Health Records: A Pilot Study.

Antibiotics (Basel) 2021 Apr 4;10(4). Epub 2021 Apr 4.

Division of Periodontology, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA.

Aims: To investigate the association between periodontal disease and systemic inflammatory conditions and examine the link between medical conditions and the extent of missing teeth in a large population.

Methods: In this retrospective study, a total of 4890 randomly selected patients who had attended the University of Minnesota dental clinics were analyzed. Severity of periodontal disease was determined based on the percentage of bone loss, evaluated through the examination of a full-mouth intraoral series of radiographs. The number of missing teeth was calculated from the examined radiographs, while ten systemic inflammatory conditions were extracted from patients' self-reported medical histories.

Results: Moderate bone loss was observed in 730 (14.9%) and severe in 323 (6.6%) patients of the total population, while the mean number of missing teeth was 3.54 ± 3.93. The prevalence of systemic conditions and tobacco use were gender-dependent ( < 0.05). Regression analysis showed that hypertension, arthritis, asthma, diabetes and HIV were associated significantly with the severity of bone loss, while diabetes and lupus with the extent of missing teeth.

Conclusions: The findings reported in our study add to this body of knowledge, strengthening the association between periodontal disease with systemic inflammatory conditions.
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http://dx.doi.org/10.3390/antibiotics10040386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066908PMC
April 2021

Peri-Implant Diseases: Diagnosis, Clinical, Histological, Microbiological Characteristics and Treatment Strategies. A Narrative Review.

Antibiotics (Basel) 2020 Nov 22;9(11). Epub 2020 Nov 22.

Division of Periodontology, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA.

Since the use of dental implants is continuously increasing, it is imperative for dental practitioners to understand the nature and treatment of peri-implant diseases. The purpose of this manuscript is to comprehensively review peri-implant diseases, their characteristics, as well as their non-surgical and surgical treatment. To that end, the current literature was searched and a narrative review was conducted. It is essential that the case definitions described in the 2017 World Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions are used to diagnose and classify peri-implant health, peri-implant mucositis and peri-implantitis. While recent epidemiologic studies on peri-implant diseases exist, there is great heterogeneity in the definition of these conditions. Several risk factors and indicators are reported in the literature, with smoking and diabetes being the most universally accepted. In peri-implant mucositis, non-surgical treatment seems to be sufficient. However, for the treatment of peri-implantitis, a surgical approach, which includes open-flap debridement, apically positioned flap and guided bone regeneration, is considered more appropriate. A great variety of adjuncts to mechanical treatment have been reported with controversial results. Finally, studies comparing results from different peri-implantitis treatments are warranted in randomized controlled clinical trials in order to provide stronger evidence-based approaches.
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http://dx.doi.org/10.3390/antibiotics9110835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700146PMC
November 2020

Sclerostin and WNT-5a gingival protein levels in chronic periodontitis and health.

J Periodontal Res 2019 Oct 14;54(5):555-565. Epub 2019 Apr 14.

Division of Periodontology, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, Minnesota.

Background And Objective: Wnt signaling pathways regulate osteoblast differentiation and bone formation and are associated with inflammatory responses driven by innate and adaptive immunity via the NF-κB pathway. The aim of this study was to compare the levels of sclerostin (SOST), WNT-5a, and TNF-α between chronic periodontitis and periodontally healthy sites and determine their value as diagnostic markers of chronic periodontitis.

Material And Methods: In a cross-sectional assessment 25 chronic periodontitis cases and 25 periodontally healthy controls were selected upon clinical and radiographic periodontal evaluation. Gingival crevicular fluid (GCF) was collected cross-sectionally from diseased and healthy sites in periodontitis patients and from healthy sites in each control subject. In a subgroup analysis, ten patients with generalized moderate and severe chronic periodontitis and ten generalized periodontally healthy individuals were included. The protein levels of SOST, WNT-5a, and TNF-α in GCF were measured by sandwich ELISA. The Shapiro-Wilk test was utilized to assess the normality of the distribution and non-parametric comparisons were performed.

Results: The protein levels of SOST were significantly higher in the generalized moderate and severe chronic periodontitis subgroup when compared to the generalized healthy (P = 0.002), while the WNT-5a and TNF-α GCF total amounts were similar (P > 0.05). Diseased sites in the periodontitis patients exhibited significantly higher total protein levels of WNT-5a than in healthy sites (P = 0.017), whereas no differences were detected for SOST and TNF-α (P > 0.05). The total protein levels of SOST, WNT-5a, and TNF-α in GCF were similar in periodontitis and non-periodontitis patients (P > 0.05).

Conclusions: Sclerostin and WNT-5a gingival protein levels demonstrated a high diagnostic value for generalized moderate and severe chronic periodontitis, while a low accuracy was detected for localized chronic periodontitis.
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http://dx.doi.org/10.1111/jre.12659DOI Listing
October 2019

Patients' Socio-Economic Status, Tobacco and Medical History Associated with Implant Failure.

Acta Stomatol Croat 2018 Sep;52(3):175-183

Division of Periodontology, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN USA.

Objective: To examine the potential association between patients' characteristics that experienced implant failure and those who had successful implant treatment.

Materials And Methods: This retrospective case-control study is based on 186 dental records of implant failure and 186 age and gender matched successful treatments for a total of 372 patients. Age at the time of the procedure, gender, medical history, tobacco use, dental insurance status, ZIP code and type of treatment provided (implant failure/successful implant treatment) were recorded.

Results: The population consisted of 47.6% females, 48.9% individuals with dental insurance and 9.7% self-reported tobacco users. A statistically significant association (p≤0.05) was found between implant failure and successful implant treatment in regards to tobacco use, socio-economic status and medical history. Insurance status and implant location (region, arch) did not affect significantly (p>0.05) the outcome of implant therapy.

Conclusions: Within the limitation of this retrospective case-control study, individuals with high socio-economic status, no history of tobacco use and history of heart attack were more likely to have a successful implant treatment than those with a low socio-economic status, tobacco users and without history of heart attack.
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http://dx.doi.org/10.15644/asc52/3/1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238874PMC
September 2018

Systemic medical conditions and periodontal status in older individuals.

Spec Care Dentist 2018 Nov 1;38(6):373-381. Epub 2018 Sep 1.

Division of Periodontology, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN, USA.

Aims: The purposes of this study are to: (1) assess the prevalence of systemic and periodontal disease in older individuals, (2) compare periodontal conditions between four age cohorts, and (3) investigate the relationship between periodontal disease and systemic medical conditions.

Methods: Electronic records from a total of 5,000 adults were randomly selected from the University of Minnesota School of Dentistry database. Individuals ≥60 years of age, with at least six remaining teeth in their dentition with a complete medical history and full-mouth series of radiographs were included in the study to determine the severity of periodontal disease based on the percentage of radiographic bone loss.

Results: A total of 2,163 patients were included in the final analysis. The multivariable regression analysis showed that patients self-reported tobacco use and diabetes were significantly associated with moderate and severe bone loss than none to mild, whereas the opposite was found for those with joint replacement, past use of steroids and acid reflux/GERD.

Conclusion: A number of systemic medical conditions and tobacco use are associated with periodontitis. This reflects the importance of an interdisciplinary interaction between dental and medical professionals.
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http://dx.doi.org/10.1111/scd.12319DOI Listing
November 2018

Symptoms of temporomandibular disorder, self-reported bruxism, and the risk of implant failure: A retrospective analysis.

Cranio 2020 Jan 9;38(1):50-57. Epub 2018 Jul 9.

Department of Developmental and Surgical Sciences, Division of Periodontology, School of Dentistry, University of Minnesota , Minneapolis, MN, USA.

Objective: To investigate the association between symptoms of temporomandibular disorder and self-reported bruxism with the risk of implant failure.

Methods: This retrospective study is based on 2127 records of patients who had 4519 implants placed and restored at the University of Minnesota School of Dentistry. Patient and implant level information were retrieved from each dental record: age, gender, implant location, as well as history of clicking, pain, difficulty opening, difficulty chewing, and clenching or grinding.

Results: A total of 51 implant failures were identified in the sample. This corresponded to a failure rate of 1.1% at the implant level and 1.7% at the patient level. Among all the patient and implant level variables, the binary logistic regression showed that none of them were significantly associated with implant failure ( > 0.05).

Discussion: The identification of risk indicators for implant loss can foster long-term implant survival, peri-implant health, and ultimately, implant prosthesis survival.
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http://dx.doi.org/10.1080/08869634.2018.1491097DOI Listing
January 2020

Validity of self-reported periodontal measures, demographic characteristics, and systemic medical conditions.

J Periodontol 2018 08;89(8):924-932

Division of Periodontology, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN.

Background: The objective of the present study was to assess self-reported periodontal screening questions, demographic characteristics, systemic medical conditions, and tobacco use for predicting periodontal disease among individuals seeking dental therapy in a university dental clinic.

Methods: In this retrospective study, a total of 4,890 randomly selected dental charts were evaluated from among patients who had attended the University of Minnesota School of Dentistry clinics for treatment. Radiographic bone loss measurements were used to assess the severity of periodontal disease. Demographic characteristics as well as medical history of the patients were also recorded. Five self-reported periodontal screening questions were included, with answers limited to Yes/No. Generalized logit models were used to assess the association between bone loss and the predictors.

Results: The sample's mean age was 54.1 years and included 52.6% males and 14.9% smokers, with a mean of 3.5 missing teeth. Self-reported tooth mobility, history of "gum treatment," and the importance of retaining teeth as well as age, tobacco use, and cancer were statistically significant predictors (P < 0.05) of a radiographic diagnosis of moderate and severe periodontal disease. With respect to severe periodontal disease, significant associations (P < 0.05) were also found with "bleeding while brushing," gender, diabetes, anxiety, and arthritis.

Conclusions: Self-reported periodontal screening questions as well as demographic characteristics, smoking, and systemic medical conditions were significant predictors of periodontal disease, and they could be used as valid, economic, and practical measures.
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http://dx.doi.org/10.1002/JPER.17-0586DOI Listing
August 2018

Implant and root canal treatment: Survival rates and factors associated with treatment outcome.

J Dent 2018 04 27;71:61-66. Epub 2018 Feb 27.

Department of Developmental and Surgical Sciences, Division of Periodontology, School of Dentistry, University of Minnesota, 515 Delaware Street SE, Minneapolis, MN, 55455, USA.

Objectives: To assess and compare the survival rates of implant and root canal treatment as well as to investigate the effect of patient and tooth related variables on the treatment outcome in a large-scale population-based study.

Methods: Dental records of patients who received root canal treatment and implant therapy were retrieved from the electronic records of the University of Minnesota School of Dentistry. Demographic characteristics, dental insurance status, socioeconomic status as well as medical history and tobacco use were recorded. The treatment outcome was included as a binary variable (survival/failure).

Results: A total of 13,434 records of patients who had implant (33.6%) or root canal therapy (66.4%) were included. The survival rate analysis and Kaplan-Meier table revealed the majority of the implants were removed within the first year (58.8%), while only 35.2% of the root canal treatments failed in the same time period. The overall survival rate was significantly (p < 0.001) higher for implant therapy (98.3%) compared to root canal treatment (72.7%). A statistically significant association was found between treatment (p 
Clinical Significance: Clinicians are in an increased dilemma that affects the decision-making process due to the inadequate evidence in regards to the question of retention or extraction of a tooth in the natural dentition. This study demonstrated that both root canal and implant treatments are sound options with high survival rates; however, root canal therapy exhibited a significantly higher failure rate.
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http://dx.doi.org/10.1016/j.jdent.2018.02.005DOI Listing
April 2018

Implant failure and history of failed endodontic treatment: A retrospective case-control study.

J Clin Exp Dent 2017 Nov 1;9(11):e1322-e1328. Epub 2017 Nov 1.

MS, PhD, DDS, Professor, Division of Periodontology, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, 515 Delaware St. SE, Minneapolis, MN 55455.

Background: Residual bacterial biofilm and/or bacteria in planktonic form may be survived in the bone following an extraction of an infected tooth that was endodontically treated unsuccessfully Failed endodontic treatment may be associated with failure of implants to osseointegrate in the same sites. Therefore, the aim of this retrospective case-control study is to examine the risk of implant failure in previous failed endodontic sites.

Material And Methods: This retrospective case-control study is based on 94 dental records of implants placed at the University of Minnesota School of Dentistry. Dental records of patients who received an implant in sites with previously failed endodontic therapy in the dental school were identified from the electronic database, while control subjects were obtained from the same pool of patients with the requirement to have received an implant in a site that was not endodontically treated.

Results: The mean age of the population was 62.89±14.17 years with 57.4% of the sample being females and 42.6% of them being males. In regards to the socio-economic status and dental insurance, 84.0% of this population was classified as low socio-economic status and 68.1% had dental insurance. Tobacco use was self-reported by 9.6% and hypercholesterolemia was the most prevalent systemic medical condition. Dental implant failure was identified in two of the included records (2.1%), both of which were placed in sites with a history of failed endodontic treatment.

Conclusions: Within the limitations of this retrospective case-control study, further investigation with a larger population group into implant failure of sites that previously had unsuccessful endodontic treatment would be warranted. Implant failure may be associated with a history of failed endodontic treatment. Implantology, endodontics, osseointegration, treatment outcome, case-control study.
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http://dx.doi.org/10.4317/jced.54277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741846PMC
November 2017

Prevalence of temporomandibular symptoms and parafunctional habits in a university dental clinic and association with gender, age, and missing teeth.

Cranio 2019 May 16;37(3):159-167. Epub 2017 Nov 16.

a Department of Developmental and Surgical Sciences, Division of Periodontology, School of Dentistry , University of Minnesota , Minneapolis , MN , USA.

Objective To assess the prevalence of symptoms of temporomandibular disorder (TMD) and parafunctional habits as well as to investigate their association with age, gender, and number of missing teeth. Methods This retrospective study is based on 4204 randomly selected patients who were examined to determine their symptoms of TMD, such as clicking, difficulty chewing, difficulty opening/closing, as well self-reported joint pain and parafunctional habits. Results Clenching/grinding was reported by 26.5% of the examined population, clicking by 14.8%, and difficulty chewing and closing by 3.6%. Significant associations between the number of missing teeth with clenching/grinding (p = 0.05) and difficulty chewing (p < 0.001) were detected. Age and gender showed significant effects on the examined parameters (p < 0.05). Discussion Understanding the TMD subjective symptoms in relation to age, gender, and tooth loss would be of great value for treatment planning and could provide other perspectives to establish preventive measures.
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http://dx.doi.org/10.1080/08869634.2017.1399649DOI Listing
May 2019

Implant and endodontic treatment selection are influenced by patients' demographic characteristics, insurance status, and medical history: A retrospective cohort study.

Quintessence Int 2017 ;48(9):753-764

Objective: The aim of this study was to examine any potential association between demographic characteristics, socioeconomic status, dental insurance, and medical and tobacco history between patients that received endodontic treatment or extraction and implant treatment in a university dental clinic.

Method And Materials: Dental charts of patients who received root canal treatment and implant therapy were retrieved from the University of Minnesota School of Dentistry records. Age at the time of the procedure, gender, medical history, tobacco use, dental insurance status, zip code, and type of treatment provided were recorded. Patients who had both treatment modalities were excluded from the analysis.

Results: A total of 8,540 records of patients with a mean age of 50.66 years who have received either endodontic treatment (73.6%) or implant therapy (26.4%) were included. A statistically significant (P < .05) association was found between endodontic treatment or implant treatment as related to age, socioeconomic status, high blood pressure, asthma, thyroid disorders, arthritis, artificial joint, osteoporosis, depression, anxiety, cancer, and cancer treatment. Nonsmokers were significantly more likely to select a treatment plan with implants rather than an endodontic therapy.

Conclusion: Within the limitations of this retrospective study, demographic parameters, insurance status, smoking, and medical history significantly affected the treatment selection between implant and endodontic treatment in a university setting.
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http://dx.doi.org/10.3290/j.qi.a38907DOI Listing
October 2018

Systematic review of cyclosporin A-induced gingival overgrowth and genetic predisposition.

Quintessence Int 2017 ;48(9):711-724

Objective: This systematic review aimed to investigate the influence of gene polymorphisms on the development of gingival overgrowth in renal transplant patients treated with cyclosporin A.

Method And Materials: Electronic and hand literature searches were conducted by two independent reviewers in MEDLINE-Pubmed, Cochrane Library, ISI Web of Science, and SCOPUS Elsevier for prospective (case-control studies, cohort studies), cross-sectional, and retrospective studies published up to June 2016 (first week) in any language. Data were reviewed and extracted in duplicate independently. Methodologic quality assessment of the included studies was performed during the data extraction process.

Results: Due to the estimated high risk of bias and the heterogeneity of the included studies in regards to the variety of medications administered to study patients, a systematic review of the literature and not a meta-analysis of the data was performed. Fourteen articles meeting study inclusion criteria were selected for data extraction that examined the association between various genetic polymorphisms and gingival overgrowth in kidney transplant patients receiving cyclosporin A. Interleukin-1A, interleukin-10, transforming growth factor-β1 and androgen receptor gene polymorphisms may have a significant effect on an individual susceptibility to cyclosporin A-induced gingival overgrowth in renal transplant patients.

Conclusion: Genetic polymorphisms seem to affect the development of cyclosporin A-induced gingival overgrowth in renal transplant patients. Pharmacogenetics and pharmacogenomics have the potential to determine the clinical outcome of a medication, the drug efficacy, and adverse drug reactions such as gingival overgrowth.
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http://dx.doi.org/10.3290/j.qi.a38120DOI Listing
October 2018

In vitro immunological and biological evaluations of the angiogenic potential of platelet-rich fibrin preparations: a standardized comparison with PRP preparations.

Int J Implant Dent 2015 Dec 27;1(1):31. Epub 2015 Nov 27.

Division of Periodontology, Institute of Medicine and Dentistry, Niigata University, Niigata, Japan.

Background: Platelet-rich fibrin (PRF), a platelet-rich plasma (PRP) derivative mainly composed of fibrin networks, has been increasingly demonstrated to be effective in wound healing in clinical and pre-clinical animal studies. However, there has still been a concern that major growth factors may significantly be loss from PRF during its preparation through the slow clotting process. To address this concern, we compared the angiogenic potential of PRF and PRP by standardization of procedures based on volume ratios.

Methods: PRP, PRF, and platelet-poor plasma (PPP) were prepared from the peripheral blood of healthy donors. PRF preparations were squeezed or homogenized to produce exudate (PRFexu) or extract (PRFext), respectively. Concentrations of the angiogenic factors and their bioactivities were determined using ELISA kits, a scratch assay using endothelial cells and a chicken chorioallantoic membrane (CAM) assay.

Results: In PRP and PRF preparations, both VEGF and PDGF-BB were significantly more concentrated than PPP. In the scratch assay, PRFexu and PRFext were the most effective for wound closure. In the CAM assay, PRF membranes were the most effective for neovascularization.

Conclusions: It is suggested that PRF preparations efficiently preserve the angiogenic factors and function not only as a scaffolding material but as a reservoir of angiogenic factors in wound healing.
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http://dx.doi.org/10.1186/s40729-015-0032-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5005601PMC
December 2015

Gingival crevicular blood as a source to screen for diabetes control in a dental office setting.

Am J Dent 2015 Apr;28(2):63-7

Unlabelled: screen for diabetes control, this study compared glycosylated hemoglobin (HbAlc) levels found in GCB and serum. Methods: Patients diagnosed (n= 29), with diabetes received a venipuncture on the finger and serum blood (METHODS) obtained was tested for HbAlc status chair-side. GCB (test) was collected at site(s) with evidence of bleeding after probing and the HbAlc value was determined in the same manner as with the serum blood. Results: There was a significant correlation between serum blood and GCB using the HbAlc test. The Pearson

Results: tion was 0.98 (P< 0.0001). The Altman-Bland bias was -0.21 (P= 0.0095), indicating that on average, the GCB method slightly underestimated the venipuncture serum (control) method for determining HbA1c values. The Altman-Bland 95% agreement interval ranged from -1.02 to 0.6. Furthermore, the HbAlc values were independent of the gingival sites used for collection with intra-patient GCB values exhibiting a correlation value between sites of 0.91 (P< 0.0001).
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April 2015

Diabetes and periodontal disease.

Authors:
Larry F Wolff

Am J Dent 2014 Jun;27(3):127-8

With the increasing incidence of diabetes in our patient population, the dental professional needs to be vigilant in recognizing the oral manifestations of diabetes and also be prepared to monitor and treat the diabetic patient who presents to their office for dental care.
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June 2014

The heat-compression technique for the conversion of platelet-rich fibrin preparation to a barrier membrane with a reduced rate of biodegradation.

J Biomed Mater Res B Appl Biomater 2015 May 14;103(4):825-31. Epub 2014 Aug 14.

Division of Oral Bioengineering, Institute of Medicine and Dentistry, Niigata University, Niigata, 951-8514, Japan.

Platelet-rich fibrin (PRF) was developed as an advanced form of platelet-rich plasma to eliminate xenofactors, such as bovine thrombin, and it is mainly used as a source of growth factor for tissue regeneration. Furthermore, although a minor application, PRF in a compressed membrane-like form has also been used as a substitute for commercially available barrier membranes in guided-tissue regeneration (GTR) treatment. However, the PRF membrane is resorbed within 2 weeks or less at implantation sites; therefore, it can barely maintain sufficient space for bone regeneration. In this study, we developed and optimized a heat-compression technique and tested the feasibility of the resulting PRF membrane. Freshly prepared human PRF was first compressed with dry gauze and subsequently with a hot iron. Biodegradability was microscopically examined in vitro by treatment with plasmin at 37°C or in vivo by subcutaneous implantation in nude mice. Compared with the control gauze-compressed PRF, the heat-compressed PRF appeared plasmin-resistant and remained stable for longer than 10 days in vitro. Additionally, in animal implantation studies, the heat-compressed PRF was observed at least for 3 weeks postimplantation in vivo whereas the control PRF was completely resorbed within 2 weeks. Therefore, these findings suggest that the heat-compression technique reduces the rate of biodegradation of the PRF membrane without sacrificing its biocompatibility and that the heat-compressed PRF membrane easily could be prepared at chair-side and applied as a barrier membrane in the GTR treatment.
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http://dx.doi.org/10.1002/jbm.b.33262DOI Listing
May 2015

Tissue-engineered cultured periosteum sheet application to treat infrabony defects: case series and 5-year results.

Int J Periodontics Restorative Dent 2013 May-Jun;33(3):281-7

Department of Oral Biological Science, Division of Periodontology, Institute of Medicine and Dentistry, Niigata University, Niigata, Japan.

One-year data after autologous grafting of infrabony periodontal defects with human cultured periosteum sheets in combination with platelet-rich plasma and hydroxyapatite granules have shown favorable clinical and radiographic results. A 5-year follow-up evaluation of 22 selected patients indicated that treated infrabony defects remained stable. Radiographically, there was an increase in osseous radiopacity and bone trabeculation suggesting further bone maturation. This novel tissue-engineered periodontal treatment approach has resulted in significant clinical improvement, and defects remained stable after 5 years.
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http://dx.doi.org/10.11607/prd.1545DOI Listing
March 2014

An improved freeze-dried PRP-coated biodegradable material suitable for connective tissue regenerative therapy.

Cryobiology 2013 Jun 17;66(3):223-32. Epub 2013 Feb 17.

Division of Oral Bioengineering, Department of Tissue Regeneration and Reconstitution, Institute of Medicine and Dentistry, Niigata University, Niigata, Japan.

We previously published an investigation indicating freeze-dried platelet-rich plasma (PRP)-coated polyglactin mesh was a promising wound-dressing material. However, one of its disadvantages was the inflammatory nature due to degradation of the polyglactin. Therefore, in this study, we investigated the use of a collagen sponge as the carrier for PRP. When implanted subcutaneously in nude mice, the PRP-coated sponge alone rapidly induced angiogenesis and infiltration of surrounding connective tissue without inducing appreciable inflammation. Moreover, addition of periosteal fibroblastic cells substantially augmented the angiogenic response. With in vitro studies, the PRP-coated sponge provided various major growth factors at high levels to stimulate the proliferation of cells cultured on plastic dishes, but did not stimulate the proliferation of cells inoculated into the PRP-coated sponge. Cells were embedded in the fibrin mesh and maintained their spherical shape without stretching. The atomic force microscopic analysis demonstrated that the fibrin gel formed on the PRP-coated sponge was much softer (approx. 22 kPa) than the cross-linked collagen that formed the sponge base (appox. 1.9 MPa). Because insoluble matrices have recently and increasingly been considered important regulatory factors of cellular behavior, as are soluble growth factors, it is suggested that this soft fibrin mesh possibly suppresses cell survival. Overall, our investigation has successfully demonstrated improved wound-healing and regenerative potential of the PRP-coated mesh by combining it with the collagen sponge. In the clinical setting, this PRP-coated collagen sponge is a promising material for connective tissue regenerative therapy, such as periodontal therapy, burn victim treatment and in cosmetic or plastic surgery.
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http://dx.doi.org/10.1016/j.cryobiol.2013.01.006DOI Listing
June 2013

A proposed protocol for the standardized preparation of PRF membranes for clinical use.

Biologicals 2012 Sep 28;40(5):323-9. Epub 2012 Jul 28.

Division of Oral Bioengineering, Department of Tissue Regeneration and Reconstitution, Institute of Medicine and Dentistry, Niigata University, 2-5274 Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan.

Upon clinical application, thick platelet-rich fibrin (PRF) is usually compressed to fit the implantation site. However, it is speculated that the preservation of platelets and plasma content depends on the compression methods used. To accurately evaluate the clinical outcome of PRF, the preparation protocol should be standardized. Freshly prepared PRF clots were compressed into a thin membrane by our novel PRF compression device. The localization of platelets was examined by SEM and immunostaining. Growth factor levels were evaluated by bioassays and cytokine-antibody array techniques. The angiogenic activity was examined by the chick chorioallantoic membrane assay and the scratch assay using HUVEC cultures. Platelets were concentrated on the surface of the region adjacent to the red thrombus and this region was subjected to the experiments. Compared to the PRF membrane compressed by dry gauze (G-PRF), the preservation of the plasma content, 3D-fibrin meshwork, and platelets was more intact in the compressor-prepared PRF membrane (C-PRF). Among the growth factors tested, C-PRF contained PDGF isoforms at higher levels, and significantly stimulated cell proliferation and neovascularization. C-PRF may be useful for grafting while minimizing the loss of bioactive factors. This C-PRF preparation protocol is proposed as a standardized protocol for PRF membrane preparation.
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http://dx.doi.org/10.1016/j.biologicals.2012.07.004DOI Listing
September 2012

A short-term preservation of human cultured periosteal sheets, osteogenic grafting materials, using a commercial preservation solution containing epigallocatechin-3-gallate (Theliokeep(®)) under hypothermic conditions.

Biopreserv Biobank 2012 Jun;10(3):245-52

1 Division of Oral Bioengineering, Department of Tissue Regeneration and Reconstitution, Institute of Medicine and Dentistry, Niigata University , Niigata, Japan .

In the past decade, it has increasingly been reported that epigallocatechin-3-gallate (EGCG), a major catechin derivative extracted from Green tea, has various bioactivities, including a cell-protective action on mammalian cells and tissues. In this study, we have tested a commercial preservation solution containing EGCG (Theliokeep(®)) in both two- and three-dimensional cultures of human periosteal sheets, which have been used as an osteogenic grafting material for periodontal regenerative therapy. When periosteal sheets were 3D-cultured on collagen mesh, cell viability was maintained for 2 days using the hypothermic EGCG preservation solution. Replenishment of EGCG solution with 2-day intervals prevented the time-dependent decline in cell viability at 3 days and later. As observed in nonpreserved control cultures, most cells were positive for proliferating cell-nuclear antigen (PCNA) in the cultures preserved at 4°C in the EGCG solution, whereas PCNA-negative cells were increased in the cultures preserved at 4°C in the MesenPRO medium. In periosteal sheets 2D-cultured in plastic dishes, the EGCG solution occasionally was associated with vacuole formation in the cytoplasm, but cells could again expand in the culture medium at 37°C. As observed in the nonpreserved periosteal sheets control, the osteogenic induction upregulated alkaline phosphatase in those cells and tissues preserved in the EGCG solution. The EGCG solution protected cells from the cold shock-induced membrane phospholipid peroxidation. Our data suggest that the EGCG solution acts as an antioxidant to protect periosteal cells from cold shock and preserves cells under chilled conditions. The limited period of preservation time could be expanded by repeating replenishment of the EGCG solution or by optimizing the formula to be more favorable for human periosteal sheets without sacrificing cell viability. This methodology of preserving human cultured periosteal sheets with EGCG would be expected to support and spread the clinical use of regenerative therapy with autologous periosteal sheets.
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http://dx.doi.org/10.1089/bio.2011.0051DOI Listing
June 2012

Bioactivity of freeze-dried platelet-rich plasma in an adsorbed form on a biodegradable polymer material.

Platelets 2012 24;23(8):594-603. Epub 2012 Jan 24.

Division of Oral Bioengineering, Department of Tissue Regeneration and Reconstitution, Institute of Medicine and Dentistry, Niigata University, Niigata, Japan.

Owing to the necessity for the immediate preparation from patients' blood, autologous platelet-rich plasma (PRP) limits its clinical applicability. To address this concern and respond to emergency care and other unpredictable uses, we have developed a freeze-dried PRP in an adsorbed form on a biodegradable polymer material (Polyglactin 910). On the polymer filaments of PRP mesh, which was prepared by coating the polymer mesh with human fresh PRP and subsequent freeze-drying, platelets were incorporated, and related growth factors were preserved at high levels. This new PRP mesh preparation significantly and reproducibly stimulated the proliferation of human periodontal ligament cells in vitro and neovascularization in a chorioallantoic membrane assay. A full-thickness skin defect model in a diabetic mouse demonstrated the PRP mesh, although prepared from human blood, substantially facilitated angiogenesis, granulation tissue formation, and re-epithelialization without inducing severe inflammation in vivo. These data demonstrate that our new PRP mesh preparation functions as a bioactive material to facilitate tissue repair/regeneration. Therefore, we suggest that this bioactive material, composed of allogeneic PRP, could be clinically used as a promising alternative in emergency care or at times when autologous PRP is not prepared immediately before application.
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http://dx.doi.org/10.3109/09537104.2011.645923DOI Listing
April 2013

In-vivo near-infrared optical imaging of growing osteosarcoma cell lesions xenografted in mice: dual-channel quantitative evaluation of volume and mineralization.

Acta Radiol 2011 Nov 3;52(9):978-88. Epub 2011 Oct 3.

Division of Oral Bioengineering, Department of Tissue Regeneration and Reconstitution, Institute of Medicine and Dentistry, Niigata University, Niigata, Japan.

Background: In a previous study using a rodent osteosarcoma-grafted rat model, in which cell-dependent mineralization was previously demonstrated to proportionally increase with growth, we performed a quantitative analysis of mineral deposit formation using (99m)Tc-HMDP and found some weaknesses, such as longer acquisition time and narrower dynamic ranges (i.e. images easily saturated). The recently developed near-infrared (NIR) optical imaging technique is expected to non-invasively evaluate changes in living small animals in a quantitative manner.

Purpose: To test the feasibility of NIR imaging with a dual-channel system as a better alternative for bone scintigraphy by quantitatively evaluating mineralization along with the growth of osteosarcoma lesions in a mouse-xenograft model.

Material And Methods: The gross volume and mineralization of osteosarcoma lesions were evaluated in living mice simultaneously with dual-channels by NIR dye-labeled probes, 2-deoxyglucose (DG) and pamidronate (OS), respectively. To verify these quantitative data, retrieved osteosarcoma lesions were then subjected to ex-vivo imaging, weighing under wet conditions, microfocus-computed tomography (μCT) analysis, and histopathological examination.

Results: Because of less scattering and no anatomical overlapping, as generally shown, specific fluorescence signals targeted to the osteosarcoma lesions could be determined clearly by ex-vivo imaging. These data were well positively correlated with the in-vivo imaging data (r > 0.8, P < 0.02). Other good to excellent correlations (r > 0.8, P < 0.02) were observed between DG accumulation and tumor gross volume and between OS accumulation and mineralization volume.

Conclusion: This in-vivo NIR imaging technique using DG and OS is sensitive to the level to simultaneously detect and quantitatively evaluate the growth and mineralization occuring in this type of osteosarcoma lesions of living mice without either invasion or sacrifice. By possible mutual complementation, this dual imaging system might be useful for accurate diagnosis even in the presence of overlapping tissues.
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http://dx.doi.org/10.1258/ar.2011.110131DOI Listing
November 2011

Collagen-coated poly(L-lactide-co-ɛ-caprolactone) film: a promising scaffold for cultured periosteal sheets.

J Periodontol 2010 Nov 14;81(11):1653-62. Epub 2010 Jul 14.

Division of Oral Bioengineering, Department of Tissue Regeneration and Reconstitution, Institute of Medicine and Dentistry, Niigata University, Niigata, Japan.

Background: We previously demonstrated that human periosteal sheets prepared on culture dishes function as an osteogenic "graft material" applicable to periodontal regenerative therapy. However, a lower level of initial adhesion of the excised periosteum tissue segments to culture dishes was a critical point that compromised the successful preparation of functional periosteal sheets. To improve on this weakness, we developed a transparent, biodegradable poly(L-lactide-co-ɛ-caprolactone) (LCL) film and tested its function as a scaffold and carrier of periosteal sheets.

Methods: Human periosteum tissue segments excised from alveolar bone of healthy donors were cultured on type I atelocollagen-coated LCL films. Initial adhesion was examined by simple agitation. Cell outgrowth and in vitro mineralization were cytohistochemically examined. Osteogenic activity was histochemically examined in an animal implantation model using nude mice.

Results: Surface collagen-coating modified the hydrophobic nature of LCL and substantially improved the initial adhesion. Compared to cultures in plastic dishes, the growth rate was delayed in non-coated films, but not in collagen-coated films. In the trimming process for animal implantation, periosteal sheets were frequently detached from non-coated films, but not from collagen-coated films. Regardless of collagen-coating, LCL films did not cause any significant infiltration of inflammatory cells, or negatively impact mineralized tissue formation.

Conclusions: Collagen-coating improved the initial adhesion of periosteum segments, which facilitated cell outgrowth and also handling efficiency on implantation. Therefore, we believe that once evaluated in human studies, our collagen-coated LCL film will contribute to improving the periodontal regenerative methodology with the application of cultured autologous periosteal sheets.
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http://dx.doi.org/10.1902/jop.2010.100194DOI Listing
November 2010

Human periosteum-derived cells combined with superporous hydroxyapatite blocks used as an osteogenic bone substitute for periodontal regenerative therapy: an animal implantation study using nude mice.

J Periodontol 2010 Mar;81(3):420-7

Division of Oral Bioengineering, Department of Tissue Regeneration and Reconstitution, Institute of Medicine and Dentistry, Niigata University, Niigata, Japan.

Background: A superporous (85%) hydroxyapatite (HA) block was recently developed to improve osteoconductivity, but it was often not clinically successful when used to treat periodontal osseous defects. The primary purpose of this study is to develop a clinically applicable tissue-engineered bone substitute using this HA block and human alveolar periosteum-derived cells.

Methods: Commercially available superporous HA blocks were acid treated and subjected to a three-dimensional (3D) culture for periosteal cell cultivation. Cells in the pore regions of the treated HA block were observed on the fracture surface by scanning electron microscopy. After osteogenic induction, the cell-HA complexes were implanted subcutaneously in nude mice. Osteoid formation was histologically evaluated.

Results: Acid treatment enlarged the interconnections among pores, resulting in the deep penetration of periosteal cells. Under these conditions, cells were maintained for >2 weeks without appreciable cell death in the deep pore regions of the HA block. The cell-HA complexes that received in vitro osteogenic induction formed osteoids in pore regions of the treated HA blocks in vivo. In contrast, most pore regions in the non-pretreated, cell-free HA blocks that were evaluated in vivo remained cell free.

Conclusions: Our findings suggest that an acid-treated HA block could function as a better scaffold for the 3D high-density culture of human periosteal cells in vitro, and this cell-HA complex had significant osteogenic potential at the site of implantation in vivo. Compared with the cell-free HA block, our cell-HA complex using periosteal cells, which are the most accessible for clinical periodontists, showed promising results as a bone substitute in periodontal regenerative therapy.
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http://dx.doi.org/10.1902/jop.2009.090523DOI Listing
March 2010

Evaluation by bone scintigraphy of osteogenic activity of commercial bioceramics (porous beta-TCP and HAp particles) subcutaneously implanted in rats.

J Biomater Appl 2010 May 2;24(8):751-68. Epub 2009 Sep 2.

Division of Oral Bioengineering, Department of Tissue Regeneration and Reconstitution, Institute of Medicine and Dentistry, Niigata University, Niigata 951-8514, Japan.

Osteogenic potential of biomaterials used in bone regenerative therapy has been mainly examined in an animal-implantation study. We have here evaluated the applicability of bone scintigraphy in imaging ectopic bone formation, especially its initial phase, by beta-tricalcium phosphate (beta-TCP) particles that were implanted in rat dorsal subcutaneous tissues. In implanted osteogenic osteosarcoma cells used as a positive control, osteoid formation was found by histological examination and bone scintigraphy using (99m)Tc- hydroxymethyl diphosphonate (HMDP) at 2 and 3 weeks post-implantation, respectively, while the microfocuscomputed tomography (muCT) system required further mineralization, which occurred at 4 weeks. Implantation of beta-TCP particles alone induced only faint biomineralization inside the particles, which could be microscopically detected by calcein chelation at 2 weeks post-implantation, but not by other histological examinations (e.g., HE staining) or muCT. However, the bone scintigraphy successfully detected this microscopic change at 1 week. Implanted hydroxyapatite (HAp) particles alone used as a negative control did not induce mineralization at microscopic levels, and therefore nothing was detected by either calcein chelation or bone scintigraphy. In conclusion, the bone scintigraphic methodology, although exhibiting less quantitation and resolution, would be applicable as a non-invasive, highly sensitive methodology in detecting the initial, microscopic changes associated with mineralization.
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http://dx.doi.org/10.1177/0885328209341845DOI Listing
May 2010

A pilot study of glycosylated hemoglobin levels in periodontitis cases and healthy controls.

J Periodontol 2009 Jul;80(7):1057-61

University of Minnesota School of Dentistry, Minneapolis, MN, USA.

Background: Periodontitis is associated with glycemic control in patients with diabetes. The purpose of this study was to determine if glycosylated hemoglobin is elevated in patients with periodontitis who have not been diagnosed with diabetes.

Methods: Glycosylated hemoglobin (HbA1c) was assessed using a chairside test in 59 adults without diabetes but with periodontitis (having at least five teeth with probing depth [PD] > or =5 mm, bleeding on probing [BOP], and clinical attachment or radiographic bone loss) and 53 healthy controls (PDs < or =4 mm and BOP < or =15%). Groups were compared using the t test and linear regression. Patients with HbA1c levels > or =6% were compared using the Fisher exact test and logistic regression.

Results: Periodontitis cases were more likely than controls to be male (68% versus 38%; P = 0.002) and current or former smokers (P = 0.002). Cases had significantly higher body mass index (BMI) than controls (27.6 kg/m(2) versus 25.5 kg/m(2); P = 0.018) but were of similar age (51.3 years versus 50.9 years; P = 0.89). Unadjusted mean HbA1c levels did not differ significantly between cases and controls (5.66% +/- 0.56% versus 5.51% +/- 0.44%; P = 0.12). After adjustments for age, gender, BMI, and current smoking, mean HbA1c was significantly higher in cases (between-group difference, 0.21%; P = 0.046). A higher proportion of cases (27.3%) than controls (13.2%) had HbA1c values > or =6%, although this difference was not statistically significant (P >0.1).

Conclusions: Periodontitis is associated with a slight elevation in glycosylated hemoglobin. The clinical significance of this difference remains to be determined. This preliminary finding is consistent with earlier reports that periodontitis is associated with elevated blood glucose in adults without diabetes and may increase one's risk for type 2 diabetes.
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http://dx.doi.org/10.1902/jop.2009.080664DOI Listing
July 2009

Root coverage with cultured gingival dermal substitute composed of gingival fibroblasts and matrix: a case series.

Int J Periodontics Restorative Dent 2008 Oct;28(5):461-7

Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Cultured gingival dermal substitute (CGDS), composed of gingival fibroblasts and matrix and fabricated using tissue-engineering techniques, has been used for root coverage procedures. Fourteen sites from four patients with > or = 2 mm of Miller Class I or II facial gingival tissue recession were treated. The autologous CGDS sheet, prepared prior to surgical treatment, was grafted over the teeth with gingival recession and then covered with a coronally positioned flap. Vertical and horizontal recession was measured at baseline (prior to the surgical procedure) and 13 to 40 weeks (average: 30.7 +/- 9.6 weeks) after surgery. The average vertical and horizontal root coverage after surgery was 79.1% +/- 25.7% and 75.2% +/- 31.4%, respectively. Moreover, there was a significant increase of keratinized and attached gingival tissue at the final clinical evaluation compared with preoperative measurements (P < .05). These results demonstrate CGDS as a promising grafting material for use with root coverage procedures in periodontal therapy.
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October 2008

Tissue-engineered cultured periosteum used with platelet-rich plasma and hydroxyapatite in treating human osseous defects.

J Periodontol 2008 May;79(5):811-8

Division of Periodontology, Department of Oral Biological Science, Course for Oral Life Science, Institute of Medicine and Dentistry, Niigata University, 52374 Chuo-ku, Gakkocho-dori 2-bancho, Niigata, Japan.

Background: The aim of the present controlled clinical study was to compare the clinical response of human cultured periosteum (HCP) sheets in combination with platelet-rich plasma (PRP) and porous hydroxyapatite (HA) granules to a mixture of PRP and HA in the treatment of human infrabony periodontal defects.

Methods: Thirty interproximal infrabony osseous defects in 30 healthy, non-smoking subjects diagnosed with chronic periodontitis were included in this study. The subjects were randomly assigned to the test group (HCP sheets combined with PRP and HA) or the control group (PRP with HA). Clinical and radiographic measurements were made at baseline and the 12-month post-surgical evaluation.

Results: Compared to baseline, the 12-month results indicated that both treatment modalities resulted in statistically significant changes (P <0.01) in the gingival index, bleeding on probing, probing depth, clinical attachment level, and radiographic infrabony defect depth. Compared to the control group, the test group exhibited a statistically significantly more favorable change in clinical attachment gain (3.9 +/- 1.6 mm versus 2.7 +/- 1.3 mm; P <0.05), vertical relative attachment gain (83.5% +/- 31.7% versus 55.0% +/- 21.9%; P <0.05), and radiographic infrabony defect fill (4.9 +/- 1.2 mm versus 3.2 +/- 1.1 mm; P <0.01).

Conclusions: Compared to PRP with HA, treatment with a combination of HCP sheets, PRP, and HA led to a significantly more favorable clinical improvement in infrabony periodontal defects. A factor likely contributing to these favorable clinical results is the presence of osteogenic cells in the HCP sheets, which provided greater regeneration potential.
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http://dx.doi.org/10.1902/jop.2008.070518DOI Listing
May 2008

Platelet-rich plasma combined with a porous hydroxyapatite graft for the treatment of intrabony periodontal defects in humans: a comparative controlled clinical study.

J Periodontol 2005 Jun;76(6):890-8

Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Background: The aim of the present controlled clinical study was to compare platelet-rich plasma (PRP) combined with a biodegradable ceramic, porous hydroxyapatite (HA) with a mixture of HA and saline in the treatment of human intrabony defects.

Methods: Seventy interproximal intrabony osseous defects in 70 healthy, non-smoking subjects diagnosed with chronic periodontitis were included in this study. Thirty-five subjects each were randomly assigned to either the test group (PRP and HA) or control group (HA with saline). Clinical and radiographic measurements were determined at baseline and the 12-month evaluation.

Results: When compared to baseline, the 12-month results indicated that, while both treatment modalities resulted in significant changes in all clinical parameters (gingival index, bleeding on probing, probing depth, clinical attachment level, and intrabony defect fill; P <0.001), the test group exhibited statistically significant changes compared to the control sites in probing depth reduction: 4.7 +/- 1.6 mm versus 3.7 +/- 2.0 mm (P <0.05); clinical attachment gain: 3.4 +/- 1.7 mm versus 2.0 +/- 1.2 mm (P <0.001); and vertical relative attachment gain: 70.3% +/- 23.4% versus 45.5% +/- 29.4% (P <0.001).

Conclusion: Treatment with a combination of PRP and HA compared to HA with saline led to a significantly more favorable clinical improvement in intrabony periodontal defects.
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http://dx.doi.org/10.1902/jop.2005.76.6.890DOI Listing
June 2005

The surface free energy of dental gold-based materials.

Dent Mater 2005 Mar;21(3):272-7

Minnesota Dental Research Center for Biomaterials and Biomechanics, University of Minnesota, School of Dentistry, 16-212 Moos Tower, 515 Delaware Street SE, Minneapolis, MN 55455, USA.

Objective: A gold composite material (Captek) has been developed which is claimed to resist plaque deposition. This study's aim was to compare the surface free energy (SFE) of this composite material with that of a type III casting gold.

Methods: Contact angle measurements, using the Wilhelmy technique, were made on four bar-shaped samples of each material, using five test liquids (diiodomethane, ethylene glycol, formamide, glycerol and water) and four measurements per sample per liquid. For each material, the dispersive, Lewis acid and Lewis base components of SFE (gamma(S)D, gamma(S)+, gamma(S)-, respectively) were estimated by least squares analysis and also by a Bayesian method.

Results: The gold composite material and the type III casting gold did not differ significantly in their gamma(S)D values (95% confidence interval for gold composite minus type III gold, -5.0 to +2.7). Both materials had low gamma(S)+ values in common with most solids. The gold composite had a significantly lower Lewis base component of SFE than the type III gold-8.4 mN/m for the former material compared to 19.1 mN/m for the latter (95% confidence interval for gold composite minus type III gold, -16.4 to -4.9). The difference between materials could be related to the lack of non-precious metals and the structure of the gold composite material.

Conclusions: It is hypothesized that difference in gamma(S)- components of SFE may be an important parameter in predicting bacterial adhesion and plaque resistance. Methods that only determine SFE as a single parameter may be unable to differentiate adequately between dental restorative materials.
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http://dx.doi.org/10.1016/j.dental.2004.06.002DOI Listing
March 2005
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