P4 Medicine as a model for precision periodontal care.

OBJECTIVES: P4 Medicine is based on a proactive approach for clinical patient care incorporating the four "pillars" of prediction, prevention, personalization, and participation for patient management. The purpose of this review is to demonstrate how the concepts of P4 medicine can be incorporated into the management of periodontal diseases (particularly periodontitis) termed P4 periodontics. METHODS: This is a narrative review that used current literature to explore how P4 periodontics can be aligned with the 2018 Classification of Periodontal Diseases, current periodontal treatment paradigms, and periodontal regenerative technologies. RESULTS: The proposed model of P4 periodontics is highly aligned with the 2018 Classification of Periodontal Diseases and represents a logical extension of this classification into treatment paradigms. Each stage of periodontitis can be related to a holistic approach to clinical management. The role of "big data" in future P4 periodontics is discussed and the concepts of a treat-to-target focus for treatment outcomes are proposed as part of personalized periodontics. Personalized regenerative and rejuvenative periodontal therapies will refocus our thinking from risk management to regenerative solutions to manage the effects of disease and aging. CONCLUSIONS: P4 Periodontics allows us to focus not only on early prevention and intervention but also allow for personalized late-stage reversal of the disease trajectory and the use of personalized regenerative procedures to reconstruct damaged tissues and restore them to health. CLINICAL SIGNIFICANCE: P4 Periodontics is a novel means of viewing a holistic, integrative, and proactive approach to periodontal treatment.

Localisation of citrullinated and carbamylated proteins in inflamed gingival tissues from rheumatoid arthritis patients.

OBJECTIVES: It has been proposed that citrullination and carbamylation occur in the inflamed periodontium and could be the plausible mechanisms for the generation of antigens involved in the development and progression of RA. The purpose of this study was to determine the presence and location of citrullinated and carbamylated proteins in the gingival tissues and compare their abundance in periodontitis (PD) patients with or without RA. MATERIALS AND METHODS: Gingival tissue samples of healthy (n = 5), PD with RA (n = 5) and PD without RA (n = 5) were collected. Specimens were formalin fixed, paraffin embedded and sectioned at 4 µm. The tissue sections were analysed for the presence of citrullinated and carbamylated proteins by immunohistochemistry. Semi-quantitative analysis was performed to quantify and compare the protein abundance between groups. RESULTS: The number of cells containing citrullinated and carbamylated proteins with higher intensity was markedly increased in gingival tissues from PD with or without RA in comparison with healthy controls. CONCLUSION: Inflamed gingival tissue is a potential source of citrullinated and carbamylated proteins other than synovial tissues. The extent to which the local accumulation of these proteins contributes to the pathogenesis of RA needs further elucidation. CLINICAL RELEVANCE: If PD is a potential source of post-translationally modified proteins, untreated PD should not be taken lightly in the context of RA. Hence, addressing gingival inflammation should be viewed as an important preventive measure in the general population not only for the progression of periodontal disease but also reducing the risk of developing extra-oral comorbidities.

Biological factors involved in alveolar bone regeneration: Consensus report of Working Group 1 of the 15th European Workshop on Periodontology on Bone Regeneration.

BACKGROUND AND AIMS: To describe the biology of alveolar bone regeneration. MATERIAL AND METHODS: Four comprehensive reviews were performed on (a) mesenchymal cells and differentiation factors leading to bone formation; (b) the critical interplay between bone resorbing and formative cells; (c) the role of osteoimmunology in the formation and maintenance of alveolar bone; and (d) the self-regenerative capacity following bone injury or tooth extraction were prepared prior to the workshop. RESULTS AND CONCLUSIONS: This summary information adds to the fuller understanding of the alveolar bone regenerative response with implications to reconstructive procedures for patient oral rehabilitation. The group collectively formulated and addressed critical questions based on each of the reviews in this consensus report to advance the field. The report concludes with identified areas of future research.

Lifestyle and periodontitis: The emergence of personalized periodontics.

Personalized medicine is a medical model that involves the tailoring of healthcare - with medical decisions, practices, and/or products being customized to an individual patient. In this model, diagnostic testing is often employed for selecting appropriate and optimal therapies based on the context of a patient's genetic content or other epidemiologic, sociologic, molecular, physiologic, or cellular analyses. With the advent of major advances in periodontal medicine, including genomic discoveries and greater understanding of the multifactorial nature of periodontitis, it seems that the time is ripe to use personalized medicine as a model for personalized periodontics. This volume of Periodontology 2000 explores how new advances in our understanding of periodontitis within a medical model can evolve into new treatment strategies tailor-made for individual patients and not merely based on wholesale treatment paradigms.

Periodontal complications of prescription and recreational drugs.

Drug use for both therapeutic and recreational purposes is very widespread in most societies. The range of drugs used, the variations in response to these drugs and other health and behavioral confounders mean that drug use may be an important contributor to individualized periodontal diagnoses. In this narrative review, we review the main reported effects of drugs on the periodontal tissues and periodontal disease processes. Although some of the more common adverse drug reactions on periodontal tissues are well described, in many other cases the evidence for these drug effects is quite limited and based on small case series or isolated reports. Prescription drugs are responsible for a range of effects, including drug-induced gingival overgrowth and increased gingival bleeding, and influence periodontal inflammation and periodontal breakdown. The effects of recreational drugs on the periodontal tissues is less well researched, perhaps for the obvious reason that assembling large cohorts of recreational drug users presents particular challenges. Use of nearly all of these substances is associated with poorer periodontal and dental health, although there is almost certainly a large degree of behavioral confounding in these findings. Overall, further studies of adverse drug reactions on the periodontal tissues are required as this continues to be an important and increasing factor in periodontal health determination.

Periodontal health.

OBJECTIVES: To date there is a paucity of documentation regarding definitions of periodontal health. This review considers the histological and clinical determinants of periodontal health for both intact and reduced periodontium and seeks to propose appropriate definitions according to treatment outcomes. IMPORTANCE: Defining periodontal health is can serve as a vital common reference point for assessing disease and determining meaningful treatment outcomes. FINDINGS: The multifactorial nature of periodontitis is accepted, and it is recognized that restoration of periodontal health will be defined by an individual's response to treatment, taking into account allostatic conditions. CONCLUSIONS: It is proposed that there are 4 levels of periodontal health, depending on the state of the periodontium (structurally and clinically sound or reduced) and the relative treatment outcomes: (1) pristine periodontal health, with a structurally sound and uninflamed periodontium; (2) well-maintained clinical periodontal health, with a structurally and clinically sound (intact) periodontium; (3) periodontal disease stability, with a reduced periodontium, and (4) periodontal disease remission/control, with a reduced periodontium.

Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions.

Periodontal health is defined by absence of clinically detectable inflammation. There is a biological level of immune surveillance that is consistent with clinical gingival health and homeostasis. Clinical gingival health may be found in a periodontium that is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodontium in either a non-periodontitis patient (e.g. in patients with some form of gingival recession or following crown lengthening surgery) or in a patient with a history of periodontitis who is currently periodontally stable. Clinical gingival health can be restored following treatment of gingivitis and periodontitis. However, the treated and stable periodontitis patient with current gingival health remains at increased risk of recurrent periodontitis, and accordingly, must be closely monitored. Two broad categories of gingival diseases include non-dental plaque biofilm-induced gingival diseases and dental plaque-induced gingivitis. Non-dental plaque biofilm-induced gingival diseases include a variety of conditions that are not caused by plaque and usually do not resolve following plaque removal. Such lesions may be manifestations of a systemic condition or may be localized to the oral cavity. Dental plaque-induced gingivitis has a variety of clinical signs and symptoms, and both local predisposing factors and systemic modifying factors can affect its extent, severity, and progression. Dental plaque-induced gingivitis may arise on an intact periodontium or on a reduced periodontium in either a non-periodontitis patient or in a currently stable "periodontitis patient" i.e. successfully treated, in whom clinical inflammation has been eliminated (or substantially reduced). A periodontitis patient with gingival inflammation remains a periodontitis patient (Figure 1), and comprehensive risk assessment and management are imperative to ensure early prevention and/or treatment of recurrent/progressive periodontitis. Precision dental medicine defines a patient-centered approach to care, and therefore, creates differences in the way in which a "case" of gingival health or gingivitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys. Thus, case definitions of gingival health and gingivitis are presented for both purposes. While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing. Here we classify gingival health and gingival diseases/conditions, along with a summary table of diagnostic features for defining health and gingivitis in various clinical situations.

Compromised inflammatory cytokine response to P. gingivalis LPS by fibroblasts from inflamed human gingiva.

OBJECTIVES: The aims of this study were to compare the in vitro cytokine response of gingival fibroblasts (GF's) from healthy and inflamed human gingival tissues and to assess whether GF's from inflamed gingivae are capable of mounting a secondary inflammatory response after exposure to P. gingivalis LPS. MATERIALS AND METHODS: GF's were obtained from healthy donors and periodontitis patients and cultured in vitro. Cells were exposed to P. gingivalis LPS for 24h before measurement of MCP-1, GRO, IL-6, IL-8 and VEGF using a bead-based multiplex assay. Statistical comparisons were made between LPS-exposed GF's and unstimulated cells as well as the two patient groups by two-way ANOVA. RESULTS: GF's exposed to P. gingivalis LPS significantly increased their production of MCP-1, GRO, IL-6, IL-8 and VEGF compared to unstimulated cells. GF's isolated from inflamed tissue from periodontitis patients demonstrated consistently less cytokine production after exposure to P. gingivalis LPS, most notably for GRO and IL-6. CONCLUSIONS: The current study demonstrates that GF's play an active role in the inflammatory response in periodontal disease by producing a number of chemokines and cytokines. Furthermore, inflamed GF's may be compromised in their ability to mount an adequate secondary immune response in relation to chemokine/cytokine production. CLINICAL RELEVANCE: The compromised inflammatory cytokine response of inflamed human gingival fibroblasts to P. gingivalis LPS may impact on their ability to recruit and activate inflammatory cells while maintaining persistent inflammation, a key feature of periodontal disease.

Host modulation: controlling the inflammation to control the infection.

Historically, periodontal disease (gingivitis and periodontitis) has been recognized as being primarily of bacterial origin. However, recent evidence indicates that while bacteria are necessary for disease development they are not sufficient for the clinical manifestation of the many and varied forms of periodontal disease. It is becoming increasingly apparent that it is the host inflammatory response to the subgingival bacteria that is responsible for the tissue damage and, most likely, progression of the disease. We explore the concept that it is the subgingival microenvironment modified by the inflammatory response that leads to a change from a commensal to pathogenic microbiota. In this review, we examine the evidence for the emerging paradigm supporting the central role of inflammation rather than specific microbiota in the pathogenesis of periodontitis, and that by controlling the inflammation, it is possible to control the infection. As an extension of this, we propose a working model for the ongoing monitoring of periodontal patients using the medical model of 'treat to target'.

Implants for the aged patient: biological, clinical and sociological considerations.

Until recently, age, particularly old age, was considered a contraindication to the placement of dental implants. However, this was based largely on anecdotal dogma rather than on empirical information. This review considers the biological, clinical and socio-economic implications of implants placed in the aged population. Aging has been shown to have an influence on the biological aspects of soft- and hard-tissue wound healing and tissue remodeling, which may influence the establishment and maintenance of implant integration. However, information to date indicates that age should not be an a priori contraindication for implant placement and there is good evidence to indicate that dental implants can be placed successfully in the elderly with good clinical and socio-economic outcomes.

Inhibiting histone deacetylase 1 suppresses both inflammation and bone loss in arthritis.

OBJECTIVE: Histone deacetylase 1 (HDAC1) is highly expressed in the synovium of RA patients. Thus we aimed to investigate a novel HDAC inhibitor (HDACi), NW-21, designed to target HDAC1. The effect of NW-21 on osteoclast formation and activity, cytokine and chemokine expression in vitro and arthritis in mice was assessed. METHODS: The effects on human osteoclast formation and activity derived from human blood monocytes stimulated with receptor activator of nuclear factor κB ligand (RANKL) and M-CSF were assessed. The anti-inflammatory activity of NW-21 was assessed using human monocytes stimulated with either TNF-α or lipopolysaccharide for 24 h. mRNA expression of monocyte chemotactic protein 1 (MCP-1), TNF-α, macrophage inflammatory protein 1α (MIP-1α), IL-1 and RANTES (regulated on activation, normal T cell expressed and secreted) was assessed. The effect of NW-21 in the collagen antibody-induced arthritis model was assessed following daily oral administration at 5 mg/kg/day. The HDAC1 inhibitors NW-21 and MS-275 were compared with a broad-acting HDACi, 1179.4b. Effects on inflammation and bone were assessed using paw inflammation scoring, histology and live animal micro-CT. RESULTS: NW-21 suppressed osteoclast formation and activity as well as significantly reducing mRNA expression of MCP-1 and MIP-1α in monocytes stimulated by lipopolysaccharide or TNF-α (P < 0.05) in vitro. Only inhibitors that targeted HDAC1 (NW-21 and MS-275) reduced inflammation and bone loss in the arthritis model. CONCLUSION: The results indicate that inhibitors targeting HDAC1, such as NW-21 and MS-275, may be useful for treating RA, as such drugs can simultaneously target both inflammation and bone resorption.

Influence of periodontitis on the experience of oral mucositis in cancer patients undergoing head and neck radiotherapy: a pilot study.

BACKGROUND AND AIM: Periodontitis and radiation-induced oral mucositis are both inflammatory conditions which may be associated through a common underlying dysregulation of the inflammatory response. This pilot study aimed to determine whether the severity of oral mucositis is associated with the severity of periodontitis in cancer patients undergoing head and neck radiotherapy. MATERIALS AND METHODS: In this pilot study, 41 patients met the inclusion criteria. The severity of oral mucositis was measured according to the WHO system. The severity of periodontitis was assessed clinically and radiographically. Gingival crevicular fluid was sampled and levels of eight cytokines were determined using a multiplexed bead immunoassay. Associations between radiation-induced oral mucositis and periodontitis were analysed using logistic and linear regression. RESULTS: There was a trend towards a greater proportion of periodontitis patients in the mucositis groups (grades = 1-4) than in the non-mucositis group (grade = 0). However, due to the small sample size of this pilot study, these trends were not statistically significant. CONCLUSION: This pilot study did not demonstrate a positive statistical correlation between periodontitis experience and severity of radiation-induced oral mucositis. Nonetheless, a trend towards increased bone loss, pocket depth and clinical attachment levels was noted in patients with mucositis grades 1-4. Larger studies with more stringent inclusion criteria are now required to further investigate this possible relationship between periodontitis experience and severity of radiation-induced oral mucositis.

Human cadaveric histomorphological and metallurgical analysis of dental implants following 12.5 years of service.

OBJECTIVES: To provide a metallurgical and histomorphological analysis of hybrid bridgework and associated dental implants which have been in a clinical load bearing situation for a period of 12.5 years. MATERIAL AND METHODS: The physical integrity of the hybrid framework was examined with stereoimaging microscopy and scanning electron microscopy for signs of wear, fatigue cracks, corrosion. Elemental spectra and maps of the surface were analysed with an EDAX Detecting Unit (AMETEK, Inc, Mahwah, NJ, USA). Similarly, the supporting titanium abutments screwed into the implants were examined for fatigue and corrosion. Bone density scans and bone trabecular patterns were obtained from radiographs. Microcomputer tomography was used to assess the bone-implant interface and bone architecture around the implants. Histological sections were stained with 1% basic fuchsin to assess osseous microdamage. RESULTS: The study demonstrated that the gold alloy framework to be in satisfactory condition with little indication of corrosion or cracking. The interface between the gold alloy and the titanium abutments likewise demonstrated no obvious corrosion cells. No radiographic evidence of any adverse loss of bone around the implants was noted. Bone mineral density was related to implant position, being higher between the implants. Scanning electron micrograph images confirmed the good bone integration with the implant threads with a high level of organisation, maturation and adaptation for the entire length of the implant. There was no evidence of any microdamage. CONCLUSIONS: The implants, abutments and hybrid framework were in remarkably good condition considering their length of service.

Azithromycin suppresses human osteoclast formation and activity in vitro.

Azithromycin is an antibiotic with anti-inflammatory properties used as an adjunct to treat periodontitis, a common inflammatory mediated condition featuring pathologic alveolar bone resorption. This study aimed to determine the effect of azithromycin on human osteoclast formation and resorptive activity in vitro. Osteoclasts were generated from peripheral blood mononuclear cells stimulated with macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B (RANK) ligand. The effects of azithromycin at concentrations ranging from 0.5 to 40 µg/ml were tested. Osteoclast formation and activity, acidification, actin ring formation and expression of mRNA, and protein encoding for key osteoclast genes were assessed. The results demonstrated that azithromycin reduced osteoclast resorptive activity at all concentrations tested with osteoclast formation being significantly reduced at the higher concentrations (20 and 40 µg/ml). mRNA and protein expression of key osteoclast transcription factor Nuclear Factor of Activated T cells (NFATc1) was significantly reduced by azithromycin at later stages of osteoclast development (day 17). Azithromycin also reduced tumor necrosis factor receptor associated factor-6 (TRAF6) mRNA expression at day 14, and cathepsin K mRNA expression at days 14 and 17. Integrin ß3 and MMP-9 mRNA expression was reduced by azithromycin at day 17 in osteoclasts cultured on dentine. The osteoclast proton pump did not appear to be affected by azithromycin, however formation of the actin ring cytoskeleton was inhibited. This study demonstrates that azithromycin inhibits human osteoclast function in vitro, which may account for at least some of the beneficial clinical effects observed with azithromycin treatment in periodontitis.

Information generation and processing systems that regulate periodontal structure and function.

The periodontium is a very dynamic organ that responds rapidly to mechanical and chemical stimuli. It is very complex in that it is composed of two hard tissues (cementum and bone) and two soft connective tissues (periodontal ligament and gingiva). Together these tissues are defined by the molecules expressed by the resident periodontal cells in each compartment and this determines not only the structure and function of the periodontium but also how it responds to infection and inflammation. The biological activity of these molecules is tightly regulated in time and space to preserve tissue homeostasis, influence inflammatory responses and participate in tissue regeneration. In this issue of Periodontology 2000 we explore new experimental approaches and data sets which help to understand the molecules and cells that regulate tissue form and structure in health, disease and regeneration.

Periodontitis: a host-mediated disruption of microbial homeostasis. Unlearning learned concepts.

New concepts evolve when existing ones fail to address known factors adequately or are invalidated by new evidence. For decades periodontitis has been considered to be caused by specific bacteria or groups of bacteria and, accordingly, treatment protocols have largely been based on anti-infective therapies. However, close inspection of current data leads one to question whether these bacteria are the cause or the result of periodontitis. Good evidence is emerging to suggest that it is indeed the host response to oral bacteria that leads to the tissue changes noted in gingivitis. These changes lead to an altered subgingival environment that favors the emergence of 'periodontal pathogens' and the subsequent development of periodontitis if the genetic and external environmental conditions are favorable for disease development. Thus, it seems that it is indeed the initial early host-inflammatory and immune responses occurring during the development of gingivitis, and not specific bacteria or their so-called virulence factors, which determine whether periodontitis develops and progresses. In this review we consider these concepts and their potential to change the way in which we view and manage the inflammatory periodontal diseases.

Immunomodulatory effects of stem cells.

Adult-derived mesenchymal stem cells have received considerable attention over the past two decades for their potential use in tissue engineering, principally because of their potential to differentiate into multiple stromal-cell lineages. Recently, the immunomodulatory properties of mesenchymal stem cells have attracted interest as a unique property of these cells that may be harnessed for novel therapeutic approaches in immune-mediated diseases. Mesenchymal stem cells have been shown to inhibit the proliferation of activated T-cells both in vitro and in vivo but to stimulate T-regulatory cell proliferation. Mesenchymal stem cells are also known to be weakly immunogenic and to exert immunosuppressive effects on B-cells, natural killer cells, dendritic cells and neutrophils through various mechanisms. Furthermore, intravenous administration of allogeneic mesenchymal stem cells has shown a marked suppression of host immune reactions in preclinical animal models of large-organ transplant rejection and in various autoimmune- and inflammatory-based diseases. Some clinical trials utilizing human mesenchymal stem cells have also produced promising outcomes in patients with graft-vs.-host disease and autoimmune diseases. Mesenchymal stem cells identified from various dental tissues, including periodontal ligament stem cells, also possess multipotent and immunomodulatory properties. Hence, dental mesenchymal stem cells may represent an alternate cell source, not only for tissue regeneration but also as therapies for autoimmune- and inflammatory-mediated diseases. These findings have elicited interest in dental tissue mesenchymal stem cells as alternative cell sources for modulating alloreactivity during tissue regeneration following transplantation into human leukocyte antigen-mismatched donors. To examine this potential in periodontal regeneration, future work will need to assess the capacity of allogeneic periodontal ligament stem cells to regenerate periodontal ligament in animal models of periodontal disease. The present review describes the immunosuppressive effects of mesenchymal stem cells on various types of immune cells, the potential mechanisms through which they exert their mode of action and the preclinical animal studies and human clinical trials that have utilized mesenchymal stem cells, including those populations originating from dental structures.

Role of the epithelial cell rests of Malassez in the development, maintenance and regeneration of periodontal ligament tissues.

Periodontitis is a highly prevalent inflammatory disease that results in damage to the tooth-supporting tissues, potentially leading to tooth loss. Periodontal tissue regeneration is a complex process that involves the collaboration of two hard tissues (cementum and alveolar bone) and two soft tissues (gingiva and periodontal ligament). To date, no periodontal-regenerative procedures provide predictable clinical outcomes. To understand the rational basis of regenerative procedures, a better understanding of the events associated with the formation of periodontal components will help to establish reliable strategies for clinical practice. An important aspect of this is the role of the Hertwig's epithelial root sheath in periodontal development and that of its descendants, the epithelial cell rests of Malassez, in the maintenance of the periodontium. An important structure during tooth root development, the Hertwig's epithelial root sheath is not only a barrier between the dental follicle and dental papilla cells but is also involved in determining the shape, size and number of roots and in the development of dentin and cementum, and may act as a source of mesenchymal progenitor cells for cementoblasts. In adulthood, the epithelial cell rests of Malassez are the only odontogenic epithelial population in the periodontal ligament. Although there is no general agreement on the functions of the epithelial cell rests of Malassez, accumulating evidence suggests that the putative roles of the epithelial cell rests of Malassez in adult periodontal ligament include maintaining periodontal ligament homeostasis to prevent ankylosis and maintain periodontal ligament space, to prevent root resorption, to serve as a target during periodontal ligament innervation and to contribute to cementum repair. Recently, ovine epithelial cell rests of Malassez cells have been shown to harbor clonogenic epithelial stem-cell populations that demonstrate similar properties to mesenchymal stromal/stem cells, both functionally and phenotypically. Therefore, the epithelial cell rests of Malassez, rather than being 'cell rests', as indicated by their name, are an important source of stem cells that might play a pivotal role in periodontal regeneration.

Effects of full-mouth scaling on the periodontal health of Indigenous Australians: a randomized controlled trial.

BACKGROUND: Simplified periodontal therapy might be a pragmatic strategy for public health programmes targeting Indigenous Australian adults. The objective of this randomized controlled trial was to evaluate oral health effects of single-visit, non-surgical periodontal therapy compared to no treatment. METHODS: This parallel-group, randomized, open label clinical trial enrolled 273 Indigenous Australians aged ≥18 years with periodontitis. Intervention participants received full-mouth periodontal scaling and root planing during a single visit while the control group received no treatment. Endpoints were summary variables derived from clinical assessments of probing depth, clinical attachment loss, plaque, calculus and gingival bleeding before treatment and 3 months later. RESULTS: Endpoints could be calculated for 169 participants with follow-up data. Compared to the control group, there were statistically significant reductions in extent of shallow pockets: PD ≥4 mm (mean difference -2.86, [95% CI -5.01 to -0.71], p = 0.009) and gingival bleeding (mean difference -0.25, [95% CI -0.43 to -0.08], p = 0.005) but not deeper pockets PD ≥5 mm (mean difference -0.48, [95% CI -1.78 to 0.82], p = 0.468) or plaque scores. CONCLUSIONS: Periodontal therapy produced improvements in shallow periodontal pockets and measures of gingival bleeding in these Indigenous Australians.

Effect of PDGF-BB and beta-tricalcium phosphate (ß-TCP) on bone formation around dental implants: a pilot study in sheep.

OBJECTIVES: The aim of this investigation was to examine the effect of a combination of purified recombinant human platelet-derived growth factor (rhPDGF-BB) mixed with a synthetic beta-tricalcium phosphate (ß-TCP) on bone healing around dental implants with critical size circumferential defects. MATERIAL AND METHODS: Three critical size circumferential defects were prepared in the ilium of six sheep. Three dental implants were placed into the centre of each defect and the 3.25 mm circumferential gap was filled with (a) blood clot alone; (b) ß-TCP; (c) rhPDGF-BB (0.3 mg/ml) with ß-TCP. All the defects in each group were covered with a Bio-Gide(®) resorbable barrier membrane. The sheep were sacrificed at 2 and 4 weeks and histological and histomorphometric analyses were performed to determine the percentage of new mineralized bone formation and residual ß-TCP graft particles in the defects. RESULTS: Defects filled with rhPDGF-BB/ß-TCP showed the highest rate of bone formation after 2 and 4 weeks with limited degradation of the ß-TCP particles over 4 weeks. Defects filled with ß-TCP showed the least bone fill after 2 and 4 weeks, and faster degradation of the ß-TCP particles over 4 weeks compared with defects filled with rhPDGF-BB/ß-TCP. Percentage of new mineralized bone was comparable in defects to blood clot alone and ß-TCP after 4 weeks of healing, but there was a collapse in the defect area in defects with blood clot alone. In comparison, the space was maintained when ß-TCP was used in defects at 4 weeks. CONCLUSIONS: Defects which had ß-TCP alone showed an inhibition in bone healing at 2 and 4 weeks; however, the combination of rhPDGF-BB with ß-TCP enhanced bone regeneration in these peri-implant bone defects at the same time intervals.