A Prospective Clinical Study on Implant Survival at 1-Year Post-Loading of a Bone-Level Tapered Implant in Private Practice: Multicentered Study.

This non-interventional study evaluated the implant survival and success of a new bone-level tapered implant design in seven private dental practices in the United States. One hundred subjects in need of implant(s) were enrolled according to all cleared indications. After implant surgery, subjects were followed for a period of 1-year post-loading. Treatment planning, implant stability, radiographic evaluation of bone levels, soft-tissue characteristics, clinician satisfaction, and adverse events were assessed. A total of 184 implants were placed, of which 172 were evaluable at 1-year follow-up. Of the 172 evaluable implants, 169 survived and were successful at 1-year post-loading. Of 152 implants with radiographs at 1 year, 90% showed no bone remodeling or <1 mm bone loss. Overall clinician satisfaction was high across all centers. Normal soft-tissue profiles were reported around the implants with improvement in color, form, and mucosal attachment at 1 year. In a "real-world" setting this observational study demonstrated high implant survival and success, stable crestal bone levels, high clinician satisfaction, and a low incidence of adverse events.

Design, synthesis and biological activity of N4-phenylsubstituted-7H-pyrrolo[2,3-d]pyrimidin-4-amines as dual inhibitors of aurora kinase A and epidermal growth factor receptor kinase.

Simultaneous inhibition of multiple kinases has been suggested to provide synergistic effects on inhibition of tumour growth and resistance. This study describes the design, synthesis and evaluation of 18 compounds incorporating a pyrrolo[2,3-d]pyrimidine scaffold for dual inhibition of epidermal growth factor receptor kinase (EGFR) and aurora kinase A (AURKA). Compounds 1-18 of this study demonstrate nanomolar inhibition of EGFR and micromolar inhibition of AURKA. Compounds 1-18 allow for a structure-activity relationships (SAR) analysis of the 4-anilino moiety for dual EGFR and AURKA inhibition. Compound 6, a 4-methoxyphenylpyrrolo[2,3-d]pyrimidin-4-amine, demonstrates single-digit micromolar inhibition of both AURKA and EGFR and provides evidence of a single molecule with dual activity against EGFR and AURKA. Compound 2, the most potent inhibitor of EGFR and AURKA from this series, has been further evaluated in four different squamous cell head and neck cancer cell lines for downstream effects resulting from AURKA and EGFR inhibition.

American Academy of Periodontology Best Evidence Consensus Statement on Selected Oral Applications for Cone-Beam Computed Tomography.

BACKGROUND: The American Academy of Periodontology (AAP) recently embarked on a Best Evidence Consensus (BEC) model of scientific inquiry to address questions of clinical importance in periodontology for which there is insufficient evidence to arrive at a definitive conclusion. This review addresses oral indications for use of cone-beam computed tomography (CBCT). METHODS: To develop the BEC, the AAP convened a panel of experts with knowledge of CBCT and substantial experience in applying CBCT to a broad range of clinical scenarios that involve critical structures in the oral cavity. The panel examined a clinical scenario or treatment decision that would likely benefit from additional evidence and interpretation of evidence, performed a systematic review on the individual, debated the merits of published data and experiential information, developed a consensus report, and provided a clinical bottom line based on the best evidence available. RESULTS: This BEC addressed the potential value and limitations of CBCT relative to specific applications in the management of patients requiring or being considered for the following clinical therapies: 1) placement of dental implants; 2) interdisciplinary dentofacial therapy involving orthodontic tooth movement in the management of malocclusion with associated risk on the supporting periodontal tissues (namely, dentoalveolar bone); and 3) management of periodontitis. CONCLUSION: For each specific question addressed, there is a critical mass of evidence, but insufficient evidence to support broad conclusions or definitive clinical practice guidelines.

Accuracy and Reproducibility of Radiographic Images for Assessing Crestal Bone Height of Implants Using the Precision Implant X-ray Locator (PIXRL) Device.

PURPOSE: Assessment of crestal bone levels around implants is essential to monitor success and health. This is best accomplished with intraoral radiographs exposed at 90 degrees to the long axis of the implant, but this can be challenging to achieve clinically. Radiographic paralleling devices produce orthogonal radiographs but traditionally have required access to the implant body for each exposure. This study was conducted to determine if use of the Precision Implant X-ray Locator (PIXRL), a radiographic paralleling device that indexes the implant at the time of surgical placement, can produce orthogonal radiographs of dental implants more accurately than traditional radiologic techniques for assessing crestal bone levels. MATERIALS AND METHODS: Three dental implants were inserted in dry human skulls in supracrestal positions to simulate crestal bone loss (maxillary right first premolar [site 14], maxillary right central incisor [site 11], and mandibular left second premolar [site 35]). The implants were masked with a soft tissue moulage and restored with provisional restorations. Four dental assistants exposed six radiographs using their usual and customary technique and six using the PIXRL device for each implant. A single examiner measured crestal bone levels on the radiographs relative to the implant platform shoulder on the mesial and distal of each implant. Recorded measurements were compared to the known values. Statistical analysis was completed using a generalized linear regression model to analyze the differences, and post-hoc comparisons with pairwise adjustment were applied. RESULTS: The images produced using the PIXRL device were more accurate overall compared to traditional techniques and were also more consistent. The greater degree of accuracy was statistically significant for all sites with the exception of the mesial measurements of the implant at site 11. CONCLUSION: This study demonstrates that the use of the PIXRL device can assist clinicians in obtaining more accurate orthogonal radiographs for assessing crestal bone height and would be a useful tool for researchers utilizing radiographic imaging of implants as a longitudinal measure of implant success and stability.

Emerging regenerative approaches for periodontal reconstruction: a consensus report from the AAP Regeneration Workshop.

BACKGROUND: Historically, periodontal regeneration has focused predominantly on bone substitutes and/or barrier membrane application to provide for defect fill and/or selected cell repopulation of the lesion. More recently, a number of technologies have evolved that can be viewed as emerging therapeutic approaches for periodontal regeneration, and these technologies were considered in the review paper and by the consensus group. The goal of this consensus report on emerging regenerative approaches for periodontal hard and soft tissue reconstruction was to develop a consensus document based on the accompanying review paper and on additional materials submitted before and at the consensus group session. METHODS: The review paper was sent to all the consensus group participants in advance of the consensus conference. In addition and also before the conference, individual consensus group members submitted additional material for consideration by the group. At the conference, each consensus group participant introduced themselves and provided disclosure of any potential conflicts of interest. The review paper was briefly presented by two of the authors and discussed by the consensus group. A discussion of each of the following topics then occurred based on the content of the review: a general summary of the topic, implications for patient-reported outcomes, and suggested research priorities for the future. As each topic was discussed based on the review article, supplemental information was then added that the consensus group agreed on. Last, an updated reference list was created. RESULTS: The application of protein and peptide therapy, cell-based therapy, genetic therapy, application of scaffolds, bone anabolics, and lasers were found to be emerging technologies for periodontal regeneration. Other approaches included the following: 1) therapies directed at the resolution of inflammation; 2) therapies that took into account the influence of the microbiome; 3) therapies involving the local regulation of phosphate and pyrophosphate metabolism; and 4) approaches directed at harnessing current therapies used for other purposes. The results indicate that, with most emerging technologies, the specific mechanisms of action are not well understood nor are the specific target cells identified. Patient-related outcomes were typically not addressed in the literature. Numerous recommendations can be made for future research priorities for both basic science and clinical application of emerging therapies. The need to emphasize the importance of regeneration of a functional periodontal organ system was noted. The predictability and efficacy of outcomes, as well as safety concerns and the cost-to-benefit ratio were also identified as key factors for emerging technologies. CONCLUSIONS: A number of technologies appear viable as emerging regenerative approaches for periodontal hard and soft tissue regeneration and are expanding the potential of reconstructing the entire periodontal organ system. The cost-to-benefit ratio and safety issues are important considerations for any new emerging therapies. Clinical Recommendation: At this time, there is insufficient evidence on emerging periodontal regenerative technologies to warrant definitive clinical recommendations.

Evaluation of a variable-thread tapered implant in extraction sites with immediate temporization: a 3-year multicenter clinical study.

BACKGROUND: The purpose of this clinical study is to evaluate the radiographic bone remodeling, survival rate, and soft tissue health surrounding a variable-thread tapered implant immediately placed in extraction sites. METHODS: Sixty implants were placed in 55 patients at six centers according to a predetermined protocol. All implants were placed in extraction sockets and were subjected to immediate temporization and function. Definitive prostheses (58 single crowns and one two-unit fixed bridge) were placed within the first year. Clinical and radiographic examinations were performed at implant placement and after 3, 6, 12, 24, and 36 months. Measurements of implant stability, papilla index, plaque, peri-implant mucosa, and marginal bone levels were recorded at each visit. RESULTS: Thirty-five implants were evaluated at both implant insertion and 3-year follow-up. Bone levels were observed at 6 months after surgery and yearly intervals thereafter and remained stable throughout the study. There was a slight decrease in mean bone level from -0.68 mm at implant insertion to -0.93 mm at the 6-month recall and then an increase of bone to -0.53 mm from the reference point at the 2-year follow-up (an average increase of 0.15 mm from implant insertion). Bone levels remained steady between the 2-year recall and the 3-year recall. Papilla scores increased significantly (P <0.001; Wilcoxon signed-rank test) from insertion to the 3-year follow-up, with most of the increase occurring during the first year. Patient assessments of function, esthetics, feel of implant, speech, and self-esteem also showed significant improvement over the course of the study. CONCLUSIONS: The results, over 36 months, indicate that the variable-thread tapered implant can be used safely and effectively under demanding conditions as an immediate postextraction tooth replacement. Bone remodeling remained stable with a slight increase, and patients expressed high levels of satisfaction with the restorative results over the course of the study.

Platelet-derived growth factor promotes periodontal regeneration in localized osseous defects: 36-month extension results from a randomized, controlled, double-masked clinical trial.

BACKGROUND: Recombinant human platelet-derived growth factor (rhPDGF) is safe and effective for the treatment of periodontal defects in short-term studies up to 6 months in duration. We now provide results from a 36-month extension study of a multicenter, randomized, controlled clinical trial evaluating the effect and long-term stability of PDGF-BB treatment in patients with localized severe periodontal osseous defects. METHODS: A total of 135 participants were enrolled from six clinical centers for an extension trial. Eighty-three individuals completed the study at 36 months and were included in the analysis. The study investigated the local application of ß-tricalcium phosphate scaffold matrix with or without two different dose levels of PDGF (0.3 or 1.0 mg/mL PDGF-BB) in patients possessing one localized periodontal osseous defect. Composite analysis for clinical and radiographic evidence of treatment success was defined as percentage of cases with clinical attachment level (CAL) ≥2.7 mm and linear bone growth (LBG) ≥1.1 mm. RESULTS: The participants exceeding this composite outcome benchmark in the 0.3 mg/mL rhPDGF-BB group went from 62.2% at 12 months, 75.9% at 24 months, to 87.0% at 36 months compared with 39.5%, 48.3%, and 53.8%, respectively, in the scaffold control group at these same time points (P <0.05). Although there were no significant increases in CAL and LBG at 36 months among all groups, there were continued increases in CAL gain, LBG, and percentage bone fill over time, suggesting overall stability of the regenerative response. CONCLUSION: PDGF-BB in a synthetic scaffold matrix promotes long-term stable clinical and radiographic improvements as measured by composite outcomes for CAL gain and LBG for patients possessing localized periodontal defects ( ClinicalTrials.gov no. CT01530126).

Stem cell-containing allograft matrix enhances periodontal regeneration: case presentations.

Periodontal defects involving either interproximal horizontal bone loss or furcations continue to challenge the regenerative capabilities of the oral cavity. The following case presentations show the successful treatment of these challenging periodontal defects with a novel cellular allograft that contains native mesenchymal stem cells and osteoprogenitor cells.

Histologic and histomorphometric evaluation of an allograft stem cell-based matrix sinus augmentation procedure.

PURPOSE: Long-term success of dental implants has been demonstrated when placed simultaneously with or after a sinus augmentation procedure. However, optimal bone formation can be from 6 to 9 months or longer with grafting materials other than autogenous bone. For this reason, there is interest in any surgical technique that does not require autogenous bone harvesting, yet results in sufficient bone formation within a relatively short time frame. MATERIALS AND METHODS: This study evaluated and compared bone formation following sinus-augmentation procedures using either an allograft cellular bone matrix (ACBM), containing native mesenchymal stem cells and osteoprogenitors, or conventional allograft (CA). RESULTS: Histomorphometric analysis of the ACBM grafts revealed average vital bone content of 32.5% ± 6.8% to residual graft content of 4.9% ± 2.4% for the 21 sinuses in the study, at an average healing period of 3.7 ± 0.6 months. Results for the CA, in the same time frame, were average vital bone content of 18.3% ± 10.6% to residual graft content of 25.8% ± 13.4%. A comparison of ACBM and CA grafts, for both vital and residual bone contents, showed P values of .003 and .002, respectively, indicating a statistically significant difference between the groups. CONCLUSION: The high percentage of vital bone content, after a relatively short healing phase, may encourage a more rapid initiation of implant placement or restoration when a cellular grafting approach is considered.

Histologic evaluation of recombinant human platelet-derived growth factor-BB after use in extraction socket defects: a case series.

Recent advancements in the arena of therapeutic molecular enhancement have shown favorable clinical findings for periodontics. However, further studies to optimize clinical outcomes using this technology are warranted. Twelve premolar extraction sockets were assigned randomly for treatment with 0.3 mg/mL recombinant human platelet-derived growth factor (rhPDGF-BB) combined with either a collagen containing anorganic deproteinized bovine bone (xenograft) or beta-tricalcium phosphate (b-TCP). Histologic evaluation of extraction socket healing was performed at 3 months. Histologic findings were similar with b-TCP and the xenograft, having 21% and 24% vital bone, respectively. The use of rhPDGF-BB with either b-TCP or a xenograft resulted in uneventful socket healing. At reentry, all implants were placed without the need for further grafting, and 100% implant success was recorded at the time of final evaluation (restoration completion).

Histologic evaluation of a stem cell-based sinus-augmentation procedure.

BACKGROUND: Predictability has been demonstrated for the long-term success of dental implants placed simultaneously with or after a sinus-augmentation procedure. However, the time required to obtain optimal bone formation can be from 6 to 9 months or longer with grafting materials other than autogenous bone. For this reason, there is interest in a surgical technique that does not require the harvest of autogenous bone but still results in sufficient bone formation within a relatively short time frame. METHODS: The purpose of this case series was to evaluate the bone formation following sinus-augmentation procedures using an allograft cellular bone matrix containing native mesenchymal stem cells. Biopsy and histologic evaluation were performed after approximately 4 months of healing. RESULTS: Histomorphometric analysis revealed an average vital bone content of 33% (range, 22% to 40%) and an average residual graft content of 6% (range, 3% to 7%) for the five cases reported that had an average healing period of 4.1 months (range, 3 to 4.75 months). CONCLUSION: The high percentage of vital bone content, after a relatively short healing phase, may encourage a more rapid initiation of implant placement or restoration when a cellular grafting approach is considered.

Human histologic evaluation of anorganic bovine bone mineral combined with recombinant human platelet-derived growth factor BB in maxillary sinus augmentation: case series study.

The objective of this proof-of-principle study was to examine the potential for improved bone regenerative outcomes in maxillary sinus augmentation procedures when recombinant human platelet-derived growth factor BB (0.3 mg/mL) is combined with particulate anorganic bovine bone mineral. The surgical outcomes in all treated sites were uneventful at 6 to 8 months, with sufficient regenerated bone present to allow successful placement of maxillary posterior implants. Large areas of dense, well-formed lamellar bone were seen throughout the intact core specimens in more than half of the grafted sites. Abundant numbers of osteoblasts were noted in concert with significant osteoid in all sites, indicating ongoing osteogenesis. A number of cores demonstrated efficient replacement of the normally slowly resorbing anorganic bovine bone mineral matrix particles with newly formed bone when the matrix was saturated with recombinant human platelet-derived growth factor BB.

Bone augmentation techniques.

BACKGROUND: The advent of osseointegration and advances in biomaterials and techniques have contributed to increased application of dental implants in the restoration of partial and completely edentulous patients. Often, in these patients, soft and hard tissue defects result from a variety of causes, such as infection, trauma, and tooth loss. These create an anatomically less favorable foundation for ideal implant placement. For prosthetic-driven dental implant therapy, reconstruction of the alveolar bone through a variety of regenerative surgical procedures has become predictable; it may be necessary prior to implant placement or simultaneously at the time of implant surgery to provide a restoration with a good long-term prognosis. Regenerative procedures are used for socket preservation, sinus augmentation, and horizontal and vertical ridge augmentation. METHODS: A broad overview of the published findings in the English literature related to various bone augmentation techniques is outlined. A comprehensive computer-based search was performed using various databases that include Medline and PubMed. A total of 267 papers were considered, with non-peer-reviewed articles eliminated as much as possible. RESULTS: The techniques for reconstruction of bony defects that are reviewed in this paper include the use of particulate bone grafts and bone graft substitutes, barrier membranes for guided bone regeneration, autogenous and allogenic block grafts, and the application of distraction osteogenesis. CONCLUSIONS: Many different techniques exist for effective bone augmentation. The approach is largely dependent on the extent of the defect and specific procedures to be performed for the implant reconstruction. It is most appropriate to use an evidenced-based approach when a treatment plan is being developed for bone augmentation cases.

Effect of rhPDGF-BB on bone turnover during periodontal repair.

PURPOSE: Growth factors such as platelet-derived growth factor (PDGF) exert potent effects on wound healing including the regeneration of periodontia. Pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a well-known biomarker of bone turnover, and as such is a potential indicator of osseous metabolic activity. The objective of this study was to evaluate the release of the ICTP into the periodontal wound fluid (WF) following periodontal reconstructive surgery using local delivery of highly purified recombinant human PDGF (rhPDGF)-BB. METHODS: Forty-seven human subjects at five treatment centres possessing chronic severe periodontal disease were monitored longitudinally for 24 weeks following PDGF regenerative surgical treatment. Severe periodontal osseous defects were divided into one of three groups and treated at the time of surgery with either: beta-tricalcium phosphate (TCP) osteoconductive scaffold alone (active control), beta-TCP+0.3 mg/ml of rhPDGF-BB, or beta-TCP+1.0 mg/ml of rhPDGF-BB. WF was harvested and analysed for local ICTP levels by radioimmunoassay. Statistical analysis was performed using analysis of variance and an area under the curve analysis (AUC). RESULTS: The 0.3 and 1.0 mg/ml PDGF-BB treatment groups demonstrated increases in the amount of ICTP released locally for up to 6 weeks. There were statistically significant differences at the week 6 time point between beta-TCP carrier alone group versus 0.3 mg/ml PDGF-BB group (p<0.05) and between beta-TCP alone versus the 1.0 mg/ml PDGF-BB-treated lesions (p<0.03). The AUC analysis revealed no statistical differences amongst groups. CONCLUSION: This study corroborates the release of ICTP as a measure of active bone turnover following local delivery of PDGF-BB to periodontal osseous defects. The amount of ICTP released from the WF revealed an early increase for all treatment groups. Data from this study suggests that when PDGF-BB is delivered to promote periodontal tissue engineering of tooth-supporting osseous defects, there is a direct effect on ICTP released from the wound.

Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial.

BACKGROUND: Growth factors are generally accepted to be essential mediators of tissue repair via well-established mechanisms of action that include stimulatory effects on angiogenesis and cellular proliferation, ingrowth, differentiation, and matrix biosynthesis. The aim of this study was to evaluate in a large-scale, prospective, blinded, and randomized controlled clinical trial the safety and effectiveness of purified recombinant human platelet-derived growth factor (rhPDGF-BB) mixed with a synthetic beta-tricalcium phosphate (beta-TCP) matrix for the treatment of advanced periodontal osseous defects at 6 months of healing. METHODS: Eleven clinical centers enrolled 180 subjects, each requiring surgical treatment of a 4 mm or greater intrabony periodontal defect and meeting all inclusion and exclusion criteria. Subjects were randomized into one of three treatment groups: 1) beta-TCP + 0.3 mg/ml rhPDGF-BB in buffer; 2) beta-TCP + 1.0 mg/ml rhPDGF-BB in buffer; and 3) beta-TCP + buffer (active control). Safety data were assessed by the frequency and severity of adverse events. Effectiveness measurements included clinical attachment levels (CAL) and gingival recession (GR) measured clinically and linear bone growth (LBG) and percent bone fill (% BF) as assessed radiographically by an independent centralized radiology review center. The area under the curve (AUC), an assessment of the rate of healing, was also calculated for CAL measurements. The surgeons, clinical and radiographic evaluators, patients, and study sponsor were all masked with respect to treatment groups. RESULTS: CAL gain was significantly greater at 3 months for group 1 (rhPDGF 0.3 mg/ml) compared to group 3 (beta-TCP + buffer) (3.8 versus 3.3 mm; P = 0.032), although by 6 months, this finding was not statistically significant (P = 0.11). This early acceleration of CAL gain led to group 1 exhibiting a significantly greater rate of CAL gain between baseline and 6 months than group 3 as assessed by the AUC (68.4- versus 60.1-mm weeks; P = 0.033). rhPDGF (0.3 mg/ml)-treated sites also had significantly greater linear bone gain (2.6 versus 0.9 mm, respectively; P < 0.001) and percent defect fill (57% versus 18%, respectively; P < 0.001) than the sites receiving the bone substitute with buffer at 6 months. There was less GR at 3 months in group 1 compared to group 3 (P = 0.04); at 6 months, GR for group 1 remained unchanged, whereas there was a slight gain in gingival height for group 3 resulting in comparable GR. There were no serious adverse events attributable to any of the treatments. CONCLUSIONS: To our knowledge, this study is the largest prospective, randomized, triple-blinded, and controlled pivotal clinical trial reported to date assessing a putative periodontal regenerative and wound healing therapy. The study demonstrated that the use of rhPDGF-BB was safe and effective in the treatment of periodontal osseous defects. Treatment with rhPDGF-BB stimulated a significant increase in the rate of CAL gain, reduced gingival recession at 3 months post-surgery, and improved bone fill as compared to a beta-TCP bone substitute at 6 months.