Search

Background: This study aims to investigate and compare the major Australian government research funding schemes for oral health science with other disciplines from the burden of disease perspective. Methods: Major government research funding scheme outcomes were identified. An innovative index of Fair Research Funding (FRF) was developed to examine the extent to which National Health and Medical Research Council funding is aligned with the disease burden. In addition to comparing different diseases, overall governmental research funding for different areas of oral health sciences was explored. Results: Oral disorders with $15 million NHMRC grant funds (2017–2021) and FRF of 10.7 has the lowest and most inequitable amount of Australian government support in relation to disease burden. The share of oral health science in the Australian Research Council and Medical Research Future Fund was very minimal, with $3.43 and $1.88 million respectively. Conclusion: Governmental research funding for oral health sciences is inequitable according to the disease burden. More dedicated oral health sciences research funding schemes are essential. Funding for prevention‐focused public oral health programmes is a vital requirement towards reducing the inequalities in population oral health. [ABSTRACT FROM AUTHOR]

Background: Periodontal treatment may be a useful adjunct to medical management of diabetes; however, oral health has not been integrated into multidisciplinary diabetes care in Australia. This study aimed to understand the needs of patients and staff at a diabetes clinic to inform a prototype of integrated dental and diabetes care. Methods: Quantitative and qualitative data were collected from patients and staff at West Moreton Diabetes Clinic (WMDC) between September‐October 2019. Clinical information, survey responses and dental screening results were analysed for 41 patients. Semi‐structured interviews were held with six patients and a focus group with seven staff. Results: Most patients (83%) had not seen a dentist in the previous year. Of the 37 patients with remaining natural teeth, 84% required periodontal assessment and 46% had multiple carious lesions. Unmet treatment needs and rates of access were similar for private and public dental patients. Staff and patients reported high levels of support for incorporation of dental care at WMDC. Conclusions: Integrating oral health into diabetes management is well‐supported by patients and staff to address significant unmet dental needs for both public and private dental patients. Incorporating dental screening/services within diabetes clinics may increase uptake and improve awareness of its importance in diabetes management. [ABSTRACT FROM AUTHOR]

Background: It is now generally accepted that the response to a particular signal, such as the surgical trauma following implant placement, is not the result of a single linear signalling pathway, but rather reflects pathway integration, which can occur at multiple levels. Although it is well documented that both SLA and SLActive surfaces are able to promote bone formation and osseointegration, it is still unclear which are the key signalling pathways involved and how surface hydrophilicity/hydrophobicity might affect pathway integration. Objective: To combine gene and protein data from in vivo studies applying titanium hydrophobic (Sandblasting, Large‐grit, Acid‐etching, SLA) and hydrophilic (SLActive) surfaces to understand the molecular mechanisms responsible for the pro‐osteogenic properties of these surfaces. Methods: The Kyoto Encyclopedia of Genes and Genomes (KEGG®) pathway database and the Ingenuity® Pathway Analysis (IPA®) software were applied to the genomic and proteomic data of previous in vivo studies applying SLA and SLActive surfaces, with the specific aim to focus on bone formation‐related signalling pathways. While gene data were derived from a human study on osseointegration, protein data originated from a preclinical study in rabbits. Data were available for the 4, 7 and 14 days of healing periods. Results: Both genomic and proteomic data showed that the osteogenesis process takes place mainly at 7 and 14 days of healing on both SLA and SLActive surfaces. Surface hydrophilicity enhances bone formation at multiple levels, by directly promoting an earlier expression of pathways involved in cell proliferation and osteoblast precursor differentiation (eg, mitogen‐activated protein kinase, phosphoinositide‐3 kinase‐AKT, Wnt, Notch, transforming growth factor‐β), but also by positively regulating angiogenesis, bone mineralization and bone remodelling. Conclusion: This study combined, for the first time, different ‘omics’ outputs to get new insights on the molecular mechanisms behind the influence of surface hydrophilicity on osseointegration/bone formation. Specific signalling pathways, such as Wnt, vascular endothelial growth factor and mitogen‐activated protein kinase, were identified as differentially modulated by titanium surface hydrophilicity both at a genomic and proteomic level. These findings may be used in the future to monitor/predict the bone formation/osseointegration process, or as a screening tool towards the manufacture of new pro‐osteogenic implant surfaces. In order to take into account the full complexity and interplay of cell signalling during bone formation, powerful bioinformatics tools integrating different ‘omics’ data and predicting signalling pathways trends should be applied by future studies. [ABSTRACT FROM AUTHOR]

Background: Osteonecrosis of the jaw (ONJ) is a serious complication of both radiation and antiresorptive therapies. This study aimed to determine how many patients have been treated for medication-related osteonecrosis of the jaws (MRONJ) and osteoradionecrosis (ORN), and whether the number of diagnoses has decreased over time with improved awareness and preventative measures.Methods: Medical records at the Royal Brisbane and Women's Hospital, Gold Coast University Hospital and Robina Hospital were reviewed to identify patients diagnosed with MRONJ and ORN between January 2003 and May 2017. Data on patient demographics, year of admission and primary disease were analysed.Results: Two hundred and thirty-eight patients were diagnosed with ONJ, of which 74.4% were ORN and 25.6% were MRONJ. Tongue (24.6%), floor of mouth (17.3%) and tonsillar (15.1%) squamous cell carcinomas were the most common primary diseases associated with ORN, with a strong male predominance (80%). Of patients diagnosed with MRONJ, 52.5% were taking low-dose antiresorptives for osteoporosis (44.2%), rheumatoid arthritis (4.6%) or Paget's disease (3.3%), while 47.5% were oncology patients receiving high-dose antiresorptives.Conclusions: The number of patients diagnosed with MRONJ and ORN has trended upwards since 2003. ORN affected three times more patients than MRONJ, and patients on low-dose antiresorptives accounted for over half of the MRONJ cases. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify the patient populations at risk of medication‐related osteonecrosis of the jaw (MRONJ) and determine which medical and dental comorbidities are significant risk factors for this disease. An electronic search of Embase, MEDLINE, Cochrane Central Register of Controlled Trials, WHO International Clinical Trials Registry Platform and ProQuest Dissertations and Theses Global was conducted to identify all human studies that reported risk factors for MRONJ. Only a qualitative analysis was performed due to significant heterogeneity in the collected data. The search strategy identified 2872 records, of which 219 studies were eligible for inclusion. A total of 4106 patients with MRONJ were identified, 39 different systemic diseases were implicated, and 14 medical and 11 dental risk factors were reported, although no statistical analysis of the significance of each of these factors was possible. The clinical reach of MRONJ may be wider than anticipated, and more data on the significance of each potential risk factor are needed to guide the identification and management of at‐risk patients. [ABSTRACT FROM AUTHOR]

The aim of this review was to evaluate the outcomes of preclinical trials that assessed the use of melatonin as a pro-osteogenic agent in the field of oral implantology. Melatonin is a hormone that has been shown to have beneficial antioxidant and bone-metabolic effects. A number of experimental studies have analysed its effect in promoting osseointegration around dental implants in animals. A bibliographic search in PubMed, Scopus and EBSCOhost was performed. Animal studies that quantitatively analysed the pro-osteogenic effect of melatonin were included. Quality assessment of the included studies was performed using the ARRIVE guidelines. Eight studies met the inclusion criteria. The experimental animals used were dogs, rabbits and rats. Melatonin was used in a lyophilized powdered form, an injectable form or as a dipping solution. Six of the eight studies included showed a statistically significant positive effect of melatonin on bone-implant contact and various other histomorphometric parameters. The ARRIVE criteria were generally well reported by the included studies (17.5 ± 1.60/24), although several criteria (including randomization and blinding) were poorly documented, with most of the studies showing a high/unclear risk of bias. The majority of the studies included showed a statistically significant positive effect of melatonin on bone formation around implants. However, the clinical significance of this effect was unclear given the high/unclear risk of bias in the majority of included studies. Given the limited amount of data available, further research should be conducted to evaluate the clinical potential of this pineal hormone in clinically relevant situations, such as compromised sites or patients. [ABSTRACT FROM AUTHOR]

Attainment of periodontal regeneration is a significant clinical goal in the management of advanced periodontal defects arising from periodontitis. Over the past 30 years numerous techniques and materials have been introduced and evaluated clinically and have included guided tissue regeneration, bone grafting materials, growth and other biological factors and gene therapy. With the exception of gene therapy, all have undergone evaluation in humans. All of the products have shown efficacy in promoting periodontal regeneration in animal models but the results in humans remain variable and equivocal concerning attaining complete biological regeneration of damaged periodontal structures. In the early 2000s, the concept of tissue engineering was proposed as a new paradigm for periodontal regeneration based on molecular and cell biology. At this time, tissue engineering was a new and emerging field. Now, 14 years later we revisit the concept of tissue engineering for the periodontium and assess how far we have come, where we are currently situated and what needs to be done in the future to make this concept a reality. In this review, we cover some of the precursor products, which led to our current position in periodontal tissue engineering. The basic concepts of tissue engineering with special emphasis on periodontal tissue engineering products is discussed including the use of mesenchymal stem cells in bioscaffolds and the emerging field of cell sheet technology. Finally, we look into the future to consider what CAD/ CAM technology and nanotechnology will have to offer. [ABSTRACT FROM AUTHOR]

Augmentation of the extraction socket (ridge preservation) is increasingly being advocated in anticipation of implant placement. The aim of this article is to review the available evidence with regards to ridge preservation procedures, investigating whether these techniques improve dental implant treatment outcomes. Evidence is examined to compare these techniques to other treatment alternatives such as implant placement with simultaneous lateral augmentation. An electronic PubMed search was conducted using search terms relevant to assessing treatment outcomes in association with ridge preservation. Titles were screened and full text obtained where relevant. Further full text articles were obtained from analysis of those papers yielded from the original search. Twenty-two papers were finally selected for analysis. Ridge preservation techniques are effective in minimizing post-extraction alveolar ridge contraction. However, there is insufficient evidence to suggest that the use of these techniques in conjunction with dental implant treatment improves implant treatment outcomes. Furthermore, ridge preservation does not necessarily eliminate the need for further simultaneous augmentation at the time of implant placement. The delayed healing associated with ridge preservation using socket grafting necessitates a commitment to a delayed placement protocol. The extended treatment time, compromised healing and expense related to ridge preservation suggests a more cautious approach with regards to the indication of such techniques. [ABSTRACT FROM AUTHOR]

The prolonged use of bisphosphonates has been shown to cause a condition termed 'bisphosphonate related osteonecrosis of the jaws' ( BRONJ). BRONJ is a disease entity which has only been described relatively recently, and its multi-factorial aetiology is yet to be fully elucidated. Therefore, the treatment of BRONJ lesions remains a challenge, and animal models are necessary to assist researchers in better understanding the disease. This has led to the recent publication of a number of studies utilising a variety of animal models of BRONJ. This review outlines the factors to be considered when selecting an animal model for BRONJ and discusses the current literature in this rapidly progressing field of research. It is important to consider the applicability of a given model to the clinical condition presenting in humans, and to this end, thorough characterisation of the clinical, histological, radiographic and systemic features is necessary. The development of a clinical lesion is an important consideration in terms of choosing a relevant model, and it appears clear that surgical manipulation, generally involving tooth extraction, is necessary for successful induction of the classic 'clinical' lesion of BRONJ. [ABSTRACT FROM AUTHOR]

Oral Diseases (2012) 18, 494-500 Objective: Platelet-rich plasma (PRP) has been proposed as a method of delivering growth factors to enhance regeneration. The aim of this study was to investigate the use of autogenous and allogenic PRP and platelet-poor plasma (PPP) on migration and proliferation of human gingival fibroblasts in vitro. Methods: Various concentrations of PRP, as well as PPP, were prepared from autologous and allogenic sources and applied to primary gingival fibroblasts. Migration was determined by assessing the fibroblast response to a concentration gradient. 3H-thymidine incorporation and crystal violet colorimetric assays were utilized to assess DNA synthesis and proliferation. Results: Platelet-rich plasma provides a significant migratory stimulus to gingival fibroblasts. Furthermore, the various concentrations of PRP (50%, 20% and 10%) do not promote DNA synthesis in the short term (24 h), but over the longer term (5 days) they stimulate an increase in cell proliferation. Compared with PPP, PRP was superior in terms of encouraging migration, but was inferior in terms of promoting DNA synthesis and cell proliferation. No difference was noted between the autologous and allogenic PRP preparations on cell function. Conclusion: Both PPP and PRP promote gingival fibroblast migration and proliferation in vitro, without differences between preparations obtained from autologous and allogenic sources. [ABSTRACT FROM AUTHOR]

To determine the temporal gene expression profile associated with the early healing events during osseointegration in a human model. Nine solid screw-type cylindrical titanium implants, 4 mm long and 2.8 mm wide, with a chemically modified surface (SLActive) were surgically inserted in the retromolar area of nine human volunteers. The devices were removed using a trephine following 4, 7 and 14 days of healing. The tissue surrounding the implant was harvested, total RNA was extracted and microarray analysis was carried out to identify the differences in the transcriptome between days 4, 7 and 14. Gene ontology (GO) analysis of the temporal transcriptional changes was characteristic of a maturing, osteogenic process over the course of the study (4-14 days). At day 4, a gene expression profile associated with proliferation and immuno-inflammatory processes was predominant. However, by day 14, by far the most predominant mechanisms were associated with skeletogenesis, with the GO categories of skeletal system development, bone development and ossification being predominant, with the majority of changes occurring between days 7 and 14. Furthermore, the biological processes of angiogenesis and neurogenesis were also predominant by day 14. In terms of signal transduction, I-κB kinase/NF-κB cascade was predominant at day 4, whereas TGF-β/BMP, Wnt and Notch signalling were all associated with the osteogenic process over the duration of the study. Furthermore, Ras and Rho protein signal transduction was regulated throughout the osseointegration process. The temporal transcriptional changes during osseointegration involve the expression of proliferation and immuno-inflammatory response associated genes during the early stages of osseointegration, which are ultimately replaced by genes associated with the biological processes of skeletogenesis, angiogenesis and neurogenesis. The early immuno-inflammatory changes appear to be regulated via the I-κB kinase/NF-κB cascade, whereas the later osteogenesis-related mechanisms are regulated by TGF-β/BMP, Notch and Wnt signaling. Ivanovski S, Hamlet S, Salvi GE, Huynh-Ba G, Bosshardt DD, Lang NP, Donos N. Transcriptional profiling of osseointegration in humans. Clin. Oral Impl. Res. , 2011; 273-281. doi: 10.1111/j.1600-0501.2010.02112.x [ABSTRACT FROM AUTHOR]

Guided bone regeneration (GBR) is a commonly utilized surgical technique in the craniofacial region. The transcriptional mechanisms associated with this type of bone regeneration are not well understood. The aim of this study was to characterize the transcriptome associated with GBR of a critical-size calvarial defect in the rat. Critical-size calvarial defects were created in six Wistar strain rats and treated according to the principles of GBR. The tissue filling the regenerating defect was harvested at 7 and 14 days. Total RNA was extracted and microarray analysis was carried out to identify the differences in the transcriptome between days 7 and 14. Gene ontology (GO) analysis of the genes up-regulated at day 7 showed that immature wound healing-related mechanisms, such as protein metabolism and cell proliferation, were up-regulated at this time point. Furthermore, the immuno-inflammatory process was also up-regulated at the earlier time point. In contrast, by day 14, GO groups consistent with wound maturation, such as extracellular matrix formation, anatomical structure development and cell differentiation, were up-regulated. Furthermore, the functionally important GO categories of skeletal development, ossification and bone mineralization were up-regulated at day 14. Genes of interest that belonged to this group and were up-regulated at day 14 included growth and differentiation factors (Bmp2, Bmp3, Tgfb3), extracellular matrix proteins (osteocalcin, osteomodulin, stenniocalcin 1) and transcription factors (Runx2, Sox6, Satb2). Furthermore, a number of genes associated with Tgfβ/Bmp and Wnt signalling were also up-regulated. Besides skeletogenesis, genes associated with angiogenesis and neurogenesis were also up-regulated at day 14. The transcriptome associated with a maturing GBR-treated craniofacial bone defect is characterized by the down-regulation of the immuno-inflammatory response and up-regulation of skeletogeneis-, angiogenesis- and neurogenesis-associated genes. The Tgfβ/Bmp and Wnt signalling pathways play an important role in the regenerative process. Ivanovski S, Hamlet S, Retzepi M, Wall I, Donos N. Transcriptional profiling of 'guided bone regeneration' in a critical size calvarial defect. Clin. Oral Impl. Res. , 2011; 382-389. [ABSTRACT FROM AUTHOR]

To determine the gene expression profile characteristic of 'guided bone regeneration' associated with a microrough titanium surface. Critical-size calvarial defects were treated with the principle of 'guided bone regeneration,' whereby the extracranial barriers were either polished (SMO) or microrough (SLA) titanium disks. After 7 and 14 days, the contents of the regenerating defect were collected, RNA was extracted and microarray analysis was carried out. At each time point, the healing associated with the microrough surface was compared with that associated with the polished titanium surface. On comparing the SLA and SMO profiles, there were few genes different at day 7 (∼250), whereas there were a large number of genes different at day 14 (∼6500). At day 14, the list of genes that were differentially regulated in response to the SMO and SLA surfaces had an over-representation of genes associated with the functionally relevant gene ontology categories of regeneration, skeletogenesis, mesenchymal cell differentiation, angiogenesis and neurogenesis. There were a greater number of genes within each of these functionally relevant categories that were up-regulated on the SLA surface compared with the SMO surface. The main signalling pathway that was differentially regulated between the two surfaces at day 14 was the Wnt signaling pathway. Minimal difference was observed between the SMO and the SLA samples at day 7, whereas significant differences were noted at day 14, including genes associated with a number of functionally relevant gene ontology groups. The differentially regulated biological processes provide an insight into the influence of surface topography on 'guided bone regeneration' at the cellular and molecular level. Donos N, Retzepi M, Wall I, Hamlet S, Ivanovski S. In vivo gene expression profile of guided bone regeneration associated with a microrough titanium surface. Clin. Oral Impl. Res. , 2011; 390-398. [ABSTRACT FROM AUTHOR]

To compare the gene expression profile of osseointegration associated with a moderately rough and a chemically modified hydrophilic moderately rough surface in a human model. Eighteen solid screw-type cylindrical titanium implants, 4 mm long and 2.8 mm wide, with either a moderately rough (SLA) or a chemically modified moderately rough (SLActive) surface were surgically inserted in the retromolar area of nine human volunteers. The devices were removed using a trephine following 4, 7 and 14 days of healing. The tissue surrounding the implant was harvested, total RNA was extracted and microarray analysis was carried out to identify the differences in the transcriptome between the SLA and SLActive surfaces at days 4, 7 and 14. There were no functionally relevant gene ontology categories that were over-represented in the list of genes that were differentially expressed at day 4. However, by day 7, osteogenesis- and angiogenesis-associated gene expression were up-regulated on the SLActive surface. Osteogenesis and angiogenesis appeared to be regulated by BMP and VEGF signalling, respectively. By day 14, VEGF signalling remains up-regulated on the SLActive surface, while BMP signalling was up-regulated on the SLA surface in what appeared to be a delayed compensatory response. Furthermore, neurogenesis was a prominent biological process within the list of differentially expressed genes, and it was influenced by both surfaces. Compared with SLA, SLActive exerts a pro-osteogenic and pro-angiogenic influence on gene expression at day 7 following implant insertion, which may be responsible for the superior osseointegrative properties of this surface. Donos N, Hamlet S, Lang NP, Salvi GE, Huynh-Ba G, Bosshardt DD, Ivanovski S. Gene expression profile of osseointegration of a hydrophilic compared with a hydrophobic microrough implant surface. Clin. Oral Impl. Res. , 2011; 365-372. [ABSTRACT FROM AUTHOR]

Aims The aim of this paper is to define the key competencies (knowledge, skills, attitudes and values) in the field of implant dentistry, necessary for graduating general practitioners in Australia. The authors have produced a headline reference guide to outline the necessary educational outcomes which can be targeted by the undergraduate curricula in dental schools of Australian universities. This paper focuses on competencies and aims to clarify curricula ‘endpoints’ rather than processes. The process towards achieving these outcomes and the instructional methods and strategies might vary among universities. The authors acknowledge that there are different ways to reach the targeted learning outcomes and that there is a diversity of curricular approaches, structures and methodologies among Australian dental schools, which are enriching and desirable educationally. Specific educational strategies also with regards to the teaching of implant dentistry have been addressed in previous work and will not be covered in this paper. This paper will not address extracurricular courses, special degrees or training after graduation. [ABSTRACT FROM AUTHOR]

Aims of This Paper This paper aims to: (1) Describe the educational requirements of general practitioners who want to safely and effectively introduce implant dentistry procedures to their practice. (2) Define the necessary competencies and level of complexity that would need to be attained in a postgraduate implant dentistry programme for general dental practitioners. (3) Discuss the programme structures which universities can utilize in order to provide quality education in implant dentistry for general practitioners. (4) Provide guidelines for the resources, content, course format and instructional methods which could be well suited to the educational requirements of such programmes. The authors intend to produce a headline reference guide to outline the necessary educational structures for postgraduate pathways aimed at facilitating the continuous professional development of general practitioners within implant dentistry. This paper does not address issues concerning specialist training or higher research degrees. [ABSTRACT FROM AUTHOR]

The article presents a discussion of implant dentistry during the Australian Consensus Workshop on Implant Dentistry University Education to be held at Gold Coast, Queensland on February 4-6, 2010.

The ultimate goal of periodontal therapy is the regeneration of the tissues destroyed as a result of periodontal disease. Currently, two clinical techniques, based on the principles of “guided tissue regeneration” (GTR) or utilization of the biologically active agent “enamel matrix derivative” (EMD), can be used for the regeneration of intrabony and Class II mandibular furcation periodontal defects. In cases where additional support and space-making requirements are necessary, both of these procedures can be combined with a bone replacement graft. There is no evidence that the combined use of GTR and EMD results in superior clinical results compared to the use of each material in isolation. Great variability in clinical outcomes has been reported in relation to the use of both EMD and GTR, and these procedures can be generally considered to be unpredictable. Careful case selection and treatment planning, including consideration of patient, tooth, site and surgical factors, is required in order to optimize the outcomes of treatment. There are limited data available for the clinical effectiveness of other biologically active molecules, such as growth factors and platelet concentrates, and although promising results have been reported, further clinical trials are required in order to confirm their effectiveness. Current active areas of research are centred on tissue engineering and gene therapy strategies which may result in more predictable regenerative outcomes in the future. [ABSTRACT FROM AUTHOR]

Background: There have been numerous reports evaluating clinical outcomes of implants placed in institutional settings, but there are few studies relating to implants placed in private practice. The aim of this retrospective study was to analyse the clinical outcomes of 1000 consecutively placed Straumann implants in private specialist periodontal practice. Methods: A hand-search of patient records was undertaken to identify 1000 consecutively placed implants. Data extracted included patient demographics, details of implants placed, implant sites, timing of placement after extraction, hard and soft tissue augmentation procedures, loading protocols, type of prostheses and treatment outcomes (implant survival, implant success and complications). Results: The majority of implants (71.5 per cent) placed in patients aged 40 to 69, and the majority of patients (88.6 per cent) received 1 or 2 implants. During the period of the study, 9 implants were lost and 45 presented with complications requiring chairside intervention. A life table analysis showed 5 and 10-year cumulative survival rates of 99.2 per cent and 98.4 per cent respectively, and 5 and 10-year cumulative success rates of 93.1 per cent and 90.9 per cent respectively. Conclusions: With careful treatment planning and adherence to recommended surgical and prosthetic protocols, high implant survival and success rates can be achieved in a private practice setting. [ABSTRACT FROM AUTHOR]

Background and Objective: Platelet-rich plasma is used to deliver growth factors, in a safe and convenient manner, for enhancing bone and periodontal regeneration. However, conflicting reports regarding its effectiveness suggest that further study of the relevant cellular mechanisms is required. The aim of this study was to investigate the in vitro effect of platelet-rich plasma on osteoblasts and periodontal ligament cell function. Material and Methods: Various concentrations of platelet-rich plasma (100, 50, 20 and 10%) and platelet-poor plasma, obtained from human donors, were applied to primary cultures of human osteoblasts and periodontal ligament cells. [3H]-Thymidine incorporation, crystal violet staining and MTT assays were utilized to assess DNA synthesis and proliferation. Migration was determined by assessing the cell response to a concentration gradient, while differentiation was assessed using Alazarin Red staining. Results: Platelet-rich plasma and platelet-poor plasma had stimulatory effects on the migration of both human osteoblasts and periodontal ligament cells. At 24 h, DNA synthesis was suppressed by the application of the various concentrations of platelet-rich plasma, but over a 5-d period, a beneficial effect on proliferation was observed, especially in response to 50% platelet-rich plasma. Platelet-poor plasma resulted in the greatest enhancement of cellular proliferation for both cell types. At a concentration of 50%, platelet-rich plasma and platelet-poor plasma facilitated differentiation of both cell types. Conclusion: Platelet-rich plasma can exert a positive effect on osteoblast and periodontal ligament cell function, but this effect is concentration specific with maximal concentrations not necessarily resulting in optimal outcomes. Platelet-poor plasma also appears to have the ability to promote wound healing-associated cell function. [ABSTRACT FROM AUTHOR]

Introduction: Porphyromonas gingivalis is an important periodontopathic bacterium that is strongly associated with periodontal disease and is part of human dental plaque. Periodontal disease results from the interaction of the host with bacterial products, and T-cell-derived cytokines remain critical in the immunoregulation of periodontal disease. Methods: The aim of this study was to examine the role of T helper type 1 [interleukin-12p40 (IL-12p40), interferon- γ, tumour necrosis factor (TNF)] and type 2 (IL-4, IL-10) cytokines in the immune response to a subcutaneous challenge with P. gingivalis using a well-established murine abscess model, in genetically modified cytokine-specific knockout mice. Results: IL-12p40−/− mice exhibited more advanced tissue destruction and a reduced inflammatory cell infiltrate after subcutaneous P. gingivalis challenge. Deficiency of IL-4 or IL-10 did not result in increased susceptibility to P. gingivalis-mediated tissue destruction. Furthermore, TNF deficiency appeared to reduce local tissue destruction. Interestingly, serum-specific antibodies suggested a strong T helper type 2 response. Conclusion: The results of our study indicate an important role for IL-12 in a primary P. gingivalis subcutaneous challenge. [ABSTRACT FROM AUTHOR]

Background and Objective: The role of cytokines in bone loss is important in the context of periodontitis, where inflammation-induced bone destruction is a major manifestation. Numerous cytokines have been implicated as mediators of bone resorption. The purpose of this study was to observe the impact of targeted gene deletion of T helper 1 (Th1) and T helper 2 (Th2) cytokines on naturally occurring alveolar bone loss in genetically modified mice. Material and Methods: Alveolar bone loss was measured histomorphometrically in interleukin-4, interleukin-10, interleukin-12p40, interferon-γ (IFN-γ) and tumor necrosis factor (TNF) knockout mice at 6, 16 and 30 wk of age. Results: Both Th1 (interleukin-12p40, IFN-γ, TNF) and Th2 (interleukin-10, interleukin-4) knockout mice exhibited significantly more alveolar bone loss than their respective wild-type control mice ( p < 0.001). Interleukin-10–/– and interleukin-12p40–/– mice exhibited a three-fold increase in alveolar bone loss at 30 wk of age, whereas bone loss in IFN-γ–/–, TNF–/– and interleukin-4–/– mice was 1.5- to two-fold higher compared with wild-type control mice. Conclusion: The results of the present study indicate that both Th1 and Th2 cytokines play an important role in maintaining alveolar bone homeostasis. The kinetics of alveolar bone loss seen in cytokine gene knockout mice indicates that bone loss is age dependent and late in onset. [ABSTRACT FROM AUTHOR]

Periodontitis is a chronic inflammatory disease that results in extensive soft and hard tissue destruction of the periodontium. Porphyromonas gingivalis possesses an array of virulence factors and has been shown to induce expression of inducible nitric oxide synthase (iNOS) in inflammatory cells. The aim of this study was to investigate the effect of eliminating iNOS in a murine model of P. gingivalis infection. This was achieved by utilizing a P. gingivalis-induced skin abscess model, and an alveolar bone loss model employing an oral infection of P. gingivalis in iNOS knockout mice. The results indicated that iNOS knockout mice exhibit more extensive soft tissue damage and alveolar bone loss in response to P. gingivalis infection compared to wild-type mice. The local immune response to P. gingivalis in iNOS knockout mice was characterized by increased numbers of polymorphonuclear monocytes, while the systemic immune response was characterized by high levels of interleukin-12. The iNOS is required for an appropriate response to P. gingivalis infection. [ABSTRACT FROM AUTHOR]

The ability to identify and manipulate stem cells has been a significant advancement in regenerative medicine and has contributed to the development of tissue engineering-based clinical therapies. Difficulties associated with achieving predictable periodontal regeneration, means that novel techniques such as tissue engineering need to be developed in order to regenerate the extensive soft and hard tissue destruction that results from periodontitis. One of the critical requirements for a tissue engineering approach is the delivery of ex vivo expanded progenitor populations or the mobilization of endogenous progenitor cells capable of proliferating and differentiating into the required tissues. By definition, stem cells fulfill these requirements and the recent identification of stem cells within the periodontal ligament represents a significant development in the progress toward predictable periodontal regeneration. In order to explore the importance of stem cells in periodontal wound healing and regeneration, this review will examine contemporary concepts in stem cell biology, the role of periodontal ligament progenitor cells in the regenerative process, recent developments in identifying periodontal stem cells and the clinical implications of these findings. [ABSTRACT FROM AUTHOR]

Background: Growth hormone (GH) is a potent regulator of bone formation. The proposed mechanism of GH action is through the stimulation of osteogenic precursor cell proliferation and, following clonal expansion of these cells, promotion of differentiation along the osteogenic lineage. Objectives: We tested this hypothesis by studying the effects of GH on primary cell populations of human periodontal ligament cells (PLC) and alveolar bone cells (ABC), which contain a spectrum of osteogenic precursors. Methods: The cell populations were assessed for mineralization potential after long-term culture in media containing β-glycerophosphate and ascorbic acid, by the demonstration of mineral deposition by Von Kossa staining. The proliferative response of the cells to GH was determined over a 48-h period using a crystal violet dye-binding assay. The profile of the cells in terms of osteogenic marker expression was established using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for alkaline phosphatase (ALP), osteopontin, osteocalcin, bone sialoprotein (BSP), as well as the bone morphogenetic proteins BMP-2, BMP-4 and BMP-7. Results: As expected, a variety of responses were observed ranging from no mineralization in the PLC populations to dense mineralized deposition observed in one GH-treated ABC population. Over a 48-h period GH was found to be non-mitogenic for all cell populations. Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) BSP mRNA expression correlated well with mineralizing potential of the cells. The change in the mRNA expression of the osteogenic markers was determined following GH treatment of the cells over a 48-h period. GH caused an increase in ALP in most cell populations, and also in BMP expression in some cell populations. However a decrease in BSP, osteocalcin and osteopontin expression in the more highly differentiated cell populations was observed in response to GH. Conclusion: The response of the... [ABSTRACT FROM AUTHOR]

The expression of hard tissue associated proteins may be used to identify periodontal fibroblasts with the capability to facilitate periodontal regeneration. The aim of this study was to describe, by immunohistochemistry, the distribution of osteocalcin, osteopontin, bone sialoprotein and bone morphogenic proteins-2 and -4 (BMP-2 and BMP-4) within the human periodontiuin. Furthermore, the expression of mRNA for the above proteins and alkaline phosphatase by gingival and periodontal ligament fibroblasts fri vitro was also assessed by reverse transcriptase polymerase chain reaction (RT-PCR). Localization of osteopontin, osteocalcin, BMP-2 and BMP-4 within sections of human periodontal structures was stronger in the periodontal ligament compared to the gingiva. Bone sialoprotein was not detected in either of the soft tissues but, along with osteopontin and osteocalcin, it was localized in the cementum and bone. In vitro, both the gingival and periodontal ligament fibroblasts expressed mRNA for alkaline phosphatase, BMP-2, BMP-4 and osteopontin. Although there were no differences in the expression of alkaline phosphatase and BMP-4 mRNA between the two cell types, we noted significantly higher mRNA levels of osteopontin in the periodontal ligament and BMP-2 in the gingival fibroblasts. Osteocalcin and bone sialoprotein mRNA expression was only noted in the cultured periodontal ligament fibroblasts. From these results, it can be concluded that distinct differences exist between the two fibroblast populations in terms of the localization and mRNA expression of the majority of the hard tissue associated proteins. Furthermore, the elevated in vitro mRNA expression for osteocalcin, osteopontin and bone sialoprotein may be used to identify cells with the potential to facilitate hard tissue formation and hence periodontal regeneration. [ABSTRACT FROM AUTHOR]

Guided tissue regeneration (GTR) is a clinical procedure developed to facilitate periodontal regeneration by using barrier membranes to selectively promote the repopulation of a periodontal defect by periodontal ligament and bone cells at the expense of epithelial and gingival connective tissue cells. The aim of this study was to gain insight into the biological events occurring during membrane mediated periodontal wound healing by examining the immunohistochemical expression of a number of extracellular matrix components in tissues treated via the GTR technique. Experimental periodontal defects were created around the second premolar tooth in 4 dogs and wound closure was achieved by application of expanded polytetrafluoroethylene membranes around each tooth and flap positioning coronal to the cemento-enamel junction. The dogs were sacrificed after a 4-wk healing period, block dissections of the part of the mandible containing the experimental tooth were obtained and paraiffin sections were prepared. Using standard immunohistochemical techniques, the sections were stained with a monoclonal antibody against bone morphogenetic proteins 2 and 4 (BMP-2 and -4) and polyclonal antibodies against collagen I. collagen III, decorin, biglycan, bone sialoprotein, osteopontin and osteocalcin. Collagen I was predominantly localized within the regenerating bone, whereas collagen III staining was more abundant in the soft connective tissues of the defect. Decorin and biglycan staining was faint within the extracellular matrix of the regenerating defect, although both proteoglycans exhibited intense intracellular localization within some of the ceils inhabiting the defect. The staining for BMP-2 and -4 was weak within the bone but strong within the extracellular matrix of the regenerating soft tissue. Osteopontin and bone sialoprotein were strongly localized in the regenerating bone and cementum found within the defect. Osteocalcin staining was present in both the regenerating and mature cementum and associated cementoblasts, and it was relatively weaker in the regenerating bone compared to the mature bone. The observed pattern of immunolocalization of the extracellular matrix macromolecules suggests that the heterogeneous cell population filling the GTR wound had created an environment that was conducive to periodontal regeneration. [ABSTRACT FROM AUTHOR]

A specific collagenous cementum attachment protein (CAP) has been identified in human cementum which promotes selective cell migration towards and attachment of various periodontal derived cell populations to root surfaces in vitro. The CAP is known to support attachment of periodontal-derived cell via an RGD motif, which suggests an integrin-mediated mode of attachment. The purpose of the present study was to ascertain which integrin(s) are involved in the attachment of periodontal-derived cells to CAP. The integrins examined comprised subunits of the major receptors for fibronectin (α 5) and collagen (α2, α3), as well as the common β1 subunit which is present in many extracellular matrix receptors. The wells of 48-well non-tissue culture treated plates were coated with CAP (2 μg/ml). For negative and positive controls the wells were coated with bovine serum albumin and fibronectin (5 μg/ml), respectively. Human gingival fibroblasts and periodontal ligament fibroblasts were labeled with [³H]-proline, incubated with anti-integrin antibodies and added to the precoated wells. Attachment was assessed after incubating the cells for 1 h at 37°C in the presence of the antibodies. Antibodies to α5 and β1 inhibited the attachment of both human gingival fibroblasts and human periodontal ligament fibroblasts to CAP, while anti α2 and α3 antibodies did not affect the attachment. The binding of the fibroblasts to fibronectin was also inhibited by anti-α 5 and β1 antibodies, both of which are components of the "classical" fibronectin receptor and remained unaffected by the addition of anti-α2 and α3 antibodies. Proteins migrating in SDS-polyacrylamide gels in positions similar to the α 5 and β1 integrin subunits were present in fractions bound to a column of CAP coupled to Sepharose CL-4B. These results indicate that the attachment to CAP of the periodontal-derived cells, human gingival fibroblasts and human periodontal ligament fibroblasts, is mediated primarily via the integrin α 5 β1. [ABSTRACT FROM AUTHOR]

An abstract of the article "Confirmation of protein expression encoded by transcripts that are differentially expressed in periodontal regeneration" by S. Ivanovski, A. M. Lichanska, and M. J. Waters is presented.

The article discusses the gene programs involved in periodontal regeneration. The study aims to identify the gene expression profiles that are responsible for the distinct nature of regenerating tissue-derived cells (RTC), when compared to gingival fibroblasts and periodontal ligament cells (PLC). Hierarchical clustering was used in order to determine which variables had a dominant effect on gene expression. Functional classification of the differentially regulated genes in RTC was carried out using the gene ontology annotation tools. Since the RTC are derived from a PLC sub-population, these changes are important for understanding of the mechanisms involved in progenitor cell activity during regeneration.

The article discusses the role of nitric oxide synthases (NOS) in Porphyromonas gingivalis induced alveolar bone loss. There are numerous studies which have indicated an increased local production of Nitric oxide (NO) and increased expression of iNOS in gingivitis and periodontitis, relative to healthy controls. It has been reported that NO retards the growth and survival of periodontopathic bacteria and can prevent excessive bone resorption. The mere increase of NO aids in the elimination of periodontopathic bacteria or contributes to tissue destruction.

The article discusses the immune response to Porphyromonas gingivalis in the periodontal tissues of cytokine-specific knockout mice. With increased bacterial challenge, neutrophils under the influence of pro-inflammatory cytokines and chemokines migrate to the gingival tissues and exert a protective effect. The main aim of the study was to determine the response of alveolar bone to Porphyromonas gingivalis in an experimental murine model, using genetically-modified cytokine-specific knockout mice. The study could not clarify the actual mechanisms of bone loss but it appears that the presence of Porphyromonas gingivalis plays a central role in regulating this response in this model.

An abstract of the article "Technique for specific sampling of cementoblasts using laser capture microdissection (LCM)" by A. Jang, S. Ivanovski, C. S. Farah, M. Jones, and A. Chan is presented.

Aim: To evaluate the effect of non-surgical periodontal therapy (NSPT) on salivary histone deacetylases (HDACs) gene expression in patients with Stage III-IV periodontitis at baseline and at 3 and 6 months post NSPT treatment., Materials and Methods: Twenty patients completed the study. Periodontitis (as well as the corresponding staging and grading) was diagnosed according to the 2017 World Workshop Classification. Clinical measures were recorded and whole unstimulated saliva was collected at baseline and at 3 and 6 months after NSPT. The expression of 11 HDACs was determined using reverse-transcription PCR, and the respective changes over time were evaluated., Results: Six months after NSPT, significant improvements in all clinical periodontal parameters were observed, concomitant with significant up-regulation of HDAC2, 4, 6, 8, 9 and 11 expressions. Subgroup analyses of non-responders and responders revealed no significant differences in HDACs mRNA expression between groups at any time point., Conclusions: This prospective clinical study identified longitudinal changes in salivary HDACs expression in response to NSPT, which provides new insights into the epigenetic mechanisms underlying the pathobiology of periodontitis and creates avenues for the discovery of novel biomarkers., (© 2024 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Periodontitis is a chronic inflammatory disease caused by dysbiotic biofilms and destructive host immune responses. Extracellular vesicles (EVs) are circulating nanoparticles released by microbes and host cells involved in cell-to-cell communication, found in body biofluids, such as saliva and gingival crevicular fluid (GCF). EVs are mainly involved in cell-to-cell communication, and may hold promise for diagnostic and therapeutic purposes. Periodontal research has examined the potential involvement of bacterial- and host-cell-derived EVs in disease pathogenesis, diagnosis, and therapy, but data remains scarce on immune cell- or microbial-derived EVs. In this narrative review, we first provide an overview of the role of microbial and host-derived EVs on disease pathogenesis. Recent studies reveal that Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans-derived outer membrane vesicles (OMVs) can activate inflammatory cytokine release in host cells, while M1 macrophage EVs may contribute to bone loss. Additionally, we summarised current in vitro and pre-clinical research on the utilisation of immune cell and microbial-derived EVs as potential therapeutic tools in the context of periodontal treatment. Studies indicate that EVs from M2 macrophages and dendritic cells promote bone regeneration in animal models. While bacterial EVs remain underexplored for periodontal therapy, preliminary research suggests that P. gingivalis OMVs hold promise as vaccine candidates. Finally, we acknowledge the current limitations present in the field of translating immune cell derived EVs and microbial derived EVs in periodontology. It is concluded that microbial and host immune cell-derived EVs have a role in periodontitis pathogenesis and hence may be useful for studying disease pathophysiology, and as diagnostic and treatment monitoring biomarkers., (Journal of Periodontal Research© 2024 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Objective: To enrich and compare three extracellular vesicles-EV subtypes (apoptotic bodies, microvesicles and small EV) from three periodontal cells (periodontal ligament cells-PDLCs, alveolar bone-derived osteoblasts-OBs and gingival fibroblasts-GFs), and assess uptake and cell function changes in buccal fat pad-derived mesenchymal stromal cells (BFP-MSCs)., Background: Periodontal cells such as PDLCs, OBs and GFs have the potential to enhance bone and periodontal regeneration, but face significant challenges, such as the regulatory and cost implications of in vitro cell culture and storage. To address these challenges, it is important to explore alternative 'cell-free' strategies, such as extracellular vesicles which have emerged as promising tools in regenerative medicine, to facilitate osteogenic differentiation and bone regeneration., Methods and Materials: Serial centrifuges at 2600 and 16 000 g were used to isolate apoptotic bodies and microvesicles respectively. Small EV-sEV was enriched by our in-house size exclusion chromatography (SEC). The cellular uptake, proliferation, migration and osteogenic/adipogenic differentiation genes were analysed after EVs uptake in BFP-MSCs., Results: Three EV subtypes were enriched and characterised by morphology, particle size and EV-associated protein expression-CD9. Cellular uptake of the three EVs subtypes was observed in BFP-MSCs for up to 7 days. sEV from the three periodontal cells promoted proliferation, migration and osteogenic gene expression. hOBs-sEV showed superior levels of osteogenesis markers compared to that hPDLCs-sEV and hGFs-sEV, while hOBs-16k EV promoted adipogenic gene expression compared to that from hPDLCs and hGFs., Conclusions: Our proof-of-concept data demonstrate that hOBs-sEV might be an alternative cell-free therapeutic for bone tissue engineering., (© 2023 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Oral biofilms are three-dimensional (3D) complex entities initiating dental diseases and have been evaluated extensively in the scientific literature using several biofilm models and assessment techniques. The list of biofilm models and assessment techniques may overwhelm a novice biofilm researcher. This narrative review aims to summarize the existing literature on biofilm models and assessment techniques, providing additional information on selecting an appropriate model and corresponding assessment techniques, which may be useful as a guide to the beginner biofilm investigator and as a refresher to experienced researchers. The review addresses previously established 2D models, outlining their advantages and limitations based on the growth environment, availability of nutrients, and the number of bacterial species, while also exploring novel 3D biofilm models. The growth of biofilms on clinically relevant 3D models, particularly melt electrowritten fibrous scaffolds, is discussed with a specific focus that has not been previously reported. Relevant studies on validated oral microcosm models that have recently gaining prominence are summarized. The review analyses the advantages and limitations of biofilm assessment methods, including colony forming unit culture, crystal violet, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt assays, confocal microscopy, fluorescence in situ hybridization, scanning electron microscopy, quantitative polymerase chain reaction, and next-generation sequencing. The use of more complex models with advanced assessment methodologies, subject to the availability of equipment/facilities, may help in developing clinically relevant biofilms and answering appropriate research questions., (© 2023 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

Objective: The objective of the study was to profile the expression level of histone deacetylase enzymes (HDACs) in human saliva in periodontal health, gingivitis and periodontitis., Background: HDACs are epigenetic modulators and a group of enzymes that catalyse the removal of acetyl functional groups from the lysine residues of both histone and nonhistone proteins. HDACs have been detected in gingival tissues and may provide valuable insight into the periodontal inflammatory response. However, no studies have investigated the expression of HDACs in saliva from periodontitis-affected individuals and their capacity for periodontal diagnostics and screening., Materials and Methods: Whole unstimulated saliva was collected from 53 participants (17 healthy, 14 gingivitis and 22 stages III/IV periodontitis). The expression of 11 HDACs in saliva samples was determined using RT-qPCR and diagnostic power was calculated using the receiver operating characteristic (ROC) curves and area under the ROC Curve (AUC)., Results: Relative to health, the expression of HDAC4, 8 and 10 was downregulated in gingivitis, and the expression of HDAC4, 6, 8 and 9 was downregulated in periodontitis. Increased HDAC1 and decreased HDAC9 expression were observed in periodontitis compared to gingivitis. Higher HDAC1 and lower HDAC6 and 9 expression was observed in periodontitis compared to non-periodontitis (combining health and gingivitis). Expression of HDAC3, 4, 8, 9 and 10 was significantly decreased in periodontal disease (combining gingivitis and periodontitis) compared to health. HDAC4 and 8 exhibited an excellent diagnostic capacity for distinguishing gingivitis and periodontal disease from health (AUC 0.79-0.86). HDAC9 showed an acceptable power in discriminating periodontitis from health, gingivitis and non-periodontitis (AUC 0.76-0.80). Salivary HDAC enzyme activity showed no significant difference among the groups., Conclusion: This pilot study has demonstrated the differential expression of HDACs in human saliva for the first time and identified HDAC4, 8 and 9 as potential biomarkers in periodontal diagnosis., (© 2023 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Background: Growing evidence suggests that excessive inflammation hampers the regenerative capacity of periodontal ligament cells (PDLCs) and that activation of the Wnt/β-catenin pathway is crucial in suppressing immune dysregulation., Objective: This study aimed to establish the role of the Wnt/β-catenin in regulating the immune microenvironment and its subsequent impact on periodontal regeneration., Methods: Lithium chloride (LiCl, Wnt activator) was administered daily into the standard periodontal defects created in 12-week-old Lewis rats. Harvested at 1-week and 2-week post-surgery, samples were then subjected to histological and immunohistochemical evaluation of macrophage distribution and phenotype (pro-inflammatory M1 and anti-inflammatory M2). A murine macrophage cell line, RAW 264.7, was stimulated with LiCl to activate Wnt/β-catenin. Following treatment with the conditioned medium derived from the LiCl-activated macrophages, the expression of bone- and cementum-related markers of the PDLCs was determined. The involvement of Wnt/β-catenin in the immunoregulation and autophagic activity was further investigated with the addition of cardamonin, a commercially available Wnt inhibitor., Results: A significantly increased number of macrophages were detected around the defects during early healing upon receiving the Wnt/β-catenin signaling cue. The defect sites in week 2 exhibited fewer M1 and more M2 macrophages along with an enhanced regeneration of alveolar bone and cementum in the Wnt/β-catenin activation group. LiCl-induced immunomodulatory effect was accompanied with the activation Wnt/β-catenin signaling, which was suppressed in the presence of Wnt inhibitor. Exposure to LiCl could induce autophagy in a dose-dependent manner, thus maintaining macrophages in a regulatory state. The expression level of bone- and cementum-related markers was significantly elevated in PDLCs stimulated with LiCl-activated macrophages., Conclusion: The application of Wnt activator LiCl facilitates the recruitment of macrophages to defect sites and regulates their phenotypic switching in favor of periodontal regeneration. Suppression of Wnt/β-catenin pathway could attenuate the LiCl-induced immunomodulatory effect. Taken together, the Wnt/β-catenin pathway may be targeted for therapeutic interventions in periodontal diseases., (© 2022 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Objective: To investigate the effect of Hfe gene mutation on the distribution of iron and periodontal bone loss in periodontal tissues., Background Data: It remains unclear how tissue iron loading affects the periodontium architectures in a genetic animal model of hereditary haemochromatosis (HH)., Methods: Male C57BL/6 Hfe -/- (8 weeks old) and wild-type (WT) mice were utilized to examine the iron distribution in periodontal tissues, as well as periodontal tissues changes using micro-computed tomography and histomorphometric analysis. Furthermore, tissue inflammatory mediators, bone markers and periodontal pathogens were carried out in PFA-fixed paraffin-embedded tissues using ELISA, RT-qPCR and genomic DNA qPCR, respectively., Results: Excessive iron deposition was found in the periodontal ligament, gingiva and alveolar bone in Hfe -/- mice relative to their WT counterparts. This, in turn, was associated with significant periodontal bone loss, increased cemento-enamel junction-alveolar bone crest distance and decreased expression of molecules involved in bone development and turnover. Furthermore, the pro-inflammatory cytokine - interleukin 6 and periodontal bacteria - Campylobacter rectus were significantly increased in Hfe -/- mice compared with WT controls., Conclusion: Our results suggest that the iron loading in a mouse model of HH decreases alveolar bone formation and leads to alterations in the inflammatory state in the periodontium. Periodontal health should be assessed during the clinical assessment of HFE-HH patients., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Periodontitis is a highly prevalent multifactorial chronic inflammatory disease associated with a destructive host immune-inflammatory response to microbial dysbiosis. Current clinical diagnosis is reliant on measuring past periodontal tissue loss, with a lack of molecular biomarkers to accurately diagnose periodontitis activity in 'real-time'. Thus, discovery of new classes of diagnostic biomarkers is of critical importance in periodontology. Small extracellular vesicles (<200 nm in diameter; sEVs) from oral biofluids (saliva and gingival crevicular fluid-GCF) are lipid-encapsulated bilayered vesicles and have recently emerged as a potential source of biomarkers for periodontal disease (gingivitis and periodontitis), due to the cargo of protein, genetic material and lipids derived from their parent cells. There is limited information on the isolation and characterisation methods of saliva/GCF-sEVs or the characterisation of sEVs cargo as biomarkers for periodontitis. In this review, we detail the composition of sEVs and summarise their isolation and characterisation from saliva and GCF. The potential role of saliva and GCF-derived sEVs in periodontitis diagnosis is also explored. It is proposed that sEVs cargo, including protein, microRNA, message RNA and DNA methylation, are potential biomarkers for periodontitis with good diagnostic power (area under the curve-AUC > 0.9)., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The periodontium is a highly hierarchically organized organ composed of gingiva, alveolar bone, periodontal ligament and cementum. Periodontitis leads to the destruction of hard and soft tissues ultimately leading to a loss of the teeth supporting apparatus. Current treatments are capable of limiting the disease progression; however, true regeneration, characterized by perpendicularly oriented periodontal ligament fibre attachment to cementum on the root surface remains challenging. Tissue engineering approaches have been developed to enhance regeneration via micro-engineered topographical features, purposely designed to guide the insertion of the regenerated ligament to the root surface. This review reports on the recent advancements in scaffold manufacturing methodologies for generating fibre guiding properties and provides a critical insight in the current limitations of these techniques for the formation of functional periodontal attachment., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objective: The study compared clinical and patient-centered outcomes of subepithelial connective tissue graft (CTG) with and without enamel matrix derivative (EMD) in the treatment of Class I-II Miller periodontal recession defects., Material and Methods: This prospective clinical study evaluated 80 patients over a 3 years follow-up in a private periodontal practice. A total of 144 maxillary and mandibular anterior teeth were divided into two groups: group 1 (CTG with EMD-80 teeth) and group 2 (CTG only-64 teeth). Recession (REC), keratinized tissue (KT) width, % root overage, patient-centered outcomes, and pain visual analog scale (P-VAS) were compared between the two groups., Results: At 3 years follow-up at a patient level, statistically significant changes in REC were achieved in both group 1 (4.65 ± 1.84 to 0.39 ± 0.19 mm) and group 2 (4.43 ± 1.11 to 0.92 ± 0.43 mm). Complete root coverage (CRC) was achieved in 66.4% of group 1 and 50.1% of group 2. At both patient and tooth level, the 3-year outcomes were superior for group 1 compared with group 2 in terms of % root coverage, REC, and KT width. Clinical attachment loss (CAL) was reduced in group 1 compared with group 2 at the tooth level analysis only (<.01). Significantly less pain was reported using the pain visual analog Scale (P < .001) at the two weeks follow-up post-surgery in group 1., Conclusions: Addition of EMD results in improved root coverage outcomes and higher amounts of keratinized tissue width 36 months after treatment of multiple adjacent recessions on maxillary and mandibular anterior teeth. The adjunctive use of EMD also resulted in significantly reduced pain 14 days after the surgery., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: To evaluate the influence of systemic zoledronate administration on the osseointegration of titanium implants with different surface topography in rat maxillae., Methods: Twenty Sprague-Dawley rats were divided into two groups-test (bisphosphonate) and control (healthy). Bisphosphonate administration began three weeks prior to implant placement, and the animals received zoledronate (66 μg/kg) three times per week. Forty endosseous implants with a moderately rough (20 implants) or a turned surface (20 implants) were immediately placed bilaterally into extraction sockets of maxillary first molars. Animals were sacrificed after 14 and 28 days of healing, and en bloc specimens were harvested for histological and histomorphometric analysis. Osseointegration was quantified by measuring the percentage of bone-to-implant contact., Results: Bone-to-implant contact (BIC) (mean ± SD) values of moderately rough and turned implants at day 14 in test group were 17.62 ± 6.68 and 10.69 ± 1.48, respectively, while in the control group, they were 46.36 ± 5.08 and 33.29 ± 8.89, respectively. At day 28, BIC values of moderately rough and turned implants in the test group were 25.94 ± 7.87 and 7.83 ± 4.30, respectively, while in the control group, they were 72.99 ± 6.60 and 47.62 ± 18.19, respectively. Statistically significant higher BIC values were measured on moderately rough implants compared to turned implants at 28 days, and the control group compared to the test group for both implant surfaces. Histological observations for the control and the test groups demonstrated initial bone formation around moderately rough implants not only on the surface of the parent bone, as was the case with the turned surfaced implants, but also along the implant surface itself., Conclusions: Systemic zoledronate administration negatively influences osseointegration. Osseointegration was enhanced adjacent to moderately rough compared to turned implants in both the presence and absence of systemic zoledronate administration. Therefore, topographical surface modification may partially offset the negative impact of zoledronate administration., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: The aim of the present study was to investigate the diagnosis, treatment, and referral patterns of periodontal patients by general dental practitioners (GDP)., Methods: A questionnaire was mailed to registered GDP with publicly-listed postal addresses in Tasmania, Australia. Information was collected on demographics, training and professional development, examination, diagnosis and referral patterns, and periodontal treatment patterns., Results: Seventy-seven (44.5%) questionnaires were completed. Over 85% always or usually screened for periodontal disease. On average, 0 to ≤7 patients were diagnosed with periodontal disease. GDP were always or usually confident in treating gingivitis (100%), mild (98.7%) and moderate periodontitis (73.7%), and rarely or never confident in treating severe (81.6%) and aggressive periodontitis (86.8%). Over 38% frequently referred to periodontists, 35.5% sometimes, 21.1% rarely, and 5.3% never. Clinical factors associated with referral were periodontal pocketing of ≥6 mm, tooth mobility, no improvement following treatment, and a complex medical history., Conclusions: Most GDP performed periodontal screening and diagnosis. They were confident in treating gingivitis and mild-to-moderate periodontitis. Referral to a periodontist was associated with disease severity, tooth mobility, a complex medical history, or unsuccessful treatment., (© 2019 John Wiley & Sons Australia, Ltd.)

Background: Physiological bone formation and bone regeneration occurring during bone repair can be considered distinct but similar processes. Mesenchymal stem cells (MSC) and associated biologic factors are crucial to both bone formation and bone regeneration., Aim: To perform a narrative review of the current literature regarding the role of MSC and biologic factors in bone formation with the aim of discussing the clinical relevance of in vitro and in vivo animal studies., Methods: The literature was searched for studies on MSC and biologic factors associated with the formation of bone in the mandible and maxilla. The search specifically targeted studies on key aspects of how stem cells and biologic factors are important in bone formation and how this might be relevant to bone regeneration. The results are summarized in a narrative review format., Results: Different types of MSC and many biologic factors are associated with bone formation in the maxilla and mandible., Conclusion: Bone formation and regeneration involve very complex and highly regulated cellular and molecular processes. By studying these processes, new clinical opportunities will arise for therapeutic bone regenerative treatments., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: The purpose of this retrospective study was to investigate the influence of implant placement timing on the esthetic outcomes for single implants in the anterior maxilla., Materials and Methods: One hundred and ten patients (48 males; 62 females) who received a single-tooth implant after extraction either immediately (Type 1); after 4-8 weeks (Type 2); after 8-16 weeks (Type 3); or more than 16 weeks (Type 4) were evaluated in terms of esthetic outcomes after a mean post-placement interval of 26.3 months (range 12-116). Esthetic outcomes were measured using the Pink and White Esthetic Score (PES; WES). Stepwise regression analysis was performed to analyze the effect of timing of placement, as well as patient demographics and other clinical parameters on the esthetic outcomes., Results: No statistically significantly differences in PES were found between the various treatment modalities with Type 1 implants (n = 33) scoring 10.58 ± 1.65 (median: 11), followed by 10.36 ± 2.09 (median: 10.5), 9.68 ± 2.43 (median: 10), and 9.63 ± 2.21 (median: 10) for Type 2 (n = 14), Type 3 (n = 19), and Type 4 (n = 44), respectively. For immediate implants, a trend towards better esthetic outcomes was observed when implant placement was done flaplessly in cases with intact buccal bone (Type 1A, median PES 11) as compared to cases with partial/complete missing buccal plates where a flap was raised (Type 1B, median PES 10). Overall, the only parameter that influenced esthetic outcomes (as measured by PES) was gender, with females having significantly superior results. The median WES was 8 and 96% of the crowns were deemed esthetically acceptable, with crowns placed by specialist prosthodontists yielding higher scores than those placed by general practitioners., Conclusions: Single tooth implants in the anterior maxilla showed satisfactory outcomes when measured with objective esthetic criteria. Timing of implant placement did not significantly influence the esthetic outcomes, although a trend towards better outcomes was seen with immediate implant placement as observed by higher median PES values., Clinical Significance: Single tooth implant placement in the anterior maxilla is a predictable treatment modality for achieving acceptable esthetic outcomes regardless of the timing of placement., (© 2018 Wiley Periodicals, Inc.)

Aim: To evaluate the effect of decellularized tissue engineered constructs on cell differentiation in vitro and periodontal regeneration in vivo., Materials and Methods: Periodontal ligament cell (PDLC) sheets were loaded on polycaprolactone (PCL) scaffolds and then decellularized. Constructs were assessed for their effect on allogenic PDLC and mesenchymal stem cell (MSC) differentiation in vitro, as evaluated by gene expression of bone and periodontal ligament tissue markers post-seeding. Expression of MSC marker STRO-1 was assessed by immunostaining. Decellularized constructs were evaluated in a rat periodontal defect model to assess their biocompatibility and tissue integration. Microcomputed topography (μCT) and histological assessment were performed to assess the regenerative potential of the constructs at 2 and 4 weeks postoperatively., Results: There was upregulation of bone marker gene expression by PDLCs especially on the 14th day. MSCs lacked bone markers expression, but showed increased collagen I marker expression on day 14. STRO-1 expression by the MSCs decreased over the three timepoints when seeded on decellularized sheets. Histological assessment demonstrated the biocompatibility of the decellularized constructs in vivo. More new attachment formation was observed on the decellularized constructs compared to scaffold only controls., Conclusion: Decellularized tissue engineered constructs are capable of inducing cell differentiation in vitro and have the potential to facilitate periodontal regeneration in vivo., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: This systematic review aimed to determine the optimum dose and duration of amoxicillin-plus-metronidazole prescribed as an adjunct to non-surgical treatment of periodontitis., Methods: Electronic searching identified 376 records, of which 18 were eligible blinded, randomized placebo-controlled trials. The primary outcomes assessed were periodontal pocket depth and clinical attachment level at 3 months, and secondary outcomes were adverse events and compliance. Subgroup analyses were conducted to compare lower and higher doses, and 7- and 14-day courses., Results: Meta-analysis showed a small beneficial effect of adjunctive amoxicillin-plus-metronidazole for each primary outcome, but there was <0.1 mm variation with antibiotic dose or duration. Risk differences for adverse events in the higher dose and longer duration groups were minimally greater (0.04 and 0.05, respectively), and there was one report of anaphylaxis; 1.3% of patients were not fully compliant., Conclusion: There was no clinically meaningful difference between different doses or duration of amoxicillin-plus-metronidazole at 3 months post-treatment. Without compelling evidence to suggest that any one regimen performed superiorly, principles of responsible antibiotic use generally recommend the highest dose for the shortest duration of time to reduce the risk of antibiotic resistance. Therefore, a 7-day regimen of 500/500 mg or 500/400 mg of amoxicillin and metronidazole would be most appropriate., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: Alveolar bone regeneration remains a significant clinical challenge in periodontology and dental implantology. This study assessed the mineralized tissue forming potential of 3-D printed medical grade polycaprolactone (mPCL) constructs containing osteoblasts (OB) encapsulated in a hyaluronic acid (HA)-hydrogel incorporating bone morphogenetic protein-7 (BMP-7)., Materials and Methods: HA-hydrogels containing human OB ± BMP-7 were prepared. Cell viability, osteogenic gene expression, mineralized tissue formation and BMP-7 release in vitro, were assessed by fluorescence staining, RT-PCR, histological/μ-CT examination and ELISA respectively. In an athymic rat model, subcutaneous ectopic mineralized tissue formation in mPCL-hydrogel constructs was assessed by μ-CT and histology., Results: Osteoblast encapsulation in HA-hydrogels did not detrimentally effect cell viability, and 3-D culture in osteogenic media showed mineralized collagenous matrix formation after 6 weeks. BMP-7 release from the hydrogel was biphasic, sustained and increased osteogenic gene expression in vitro. After 4 weeks in vivo, mPCL-hydrogel constructs containing BMP-7 formed significantly more volume (mm 3 ) of vascularized bone-like tissue., Conclusions: Functionalized mPCL-HA hydrogel constructs provide a favourable environment for bone tissue engineering. Although encapsulated cells contributed to mineralized tissue formation within the hydrogel in vitro and in vivo, their addition did not result in an improved outcome compared to BMP-7 alone., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)