A retrospective analysis of patients referred for implant placement to a specialty clinic: indications, surgical procedures, and early failures

Purpose: This retrospective study analyzed the pool of patients referred for treatment with dental implants over a 3-year period in a referral specialty clinic. Materials and Methods: All patients receiving dental implants between 2002 and 2004 in the Department of Oral Surgery and Stomatology, University of Bern, were included in this retrospective study. Patients were analyzed according to age, gender, indications for implant therapy, location of implants, and type and length of implants placed. A cumulative logistic regression analysis was performed to identify and analyze potential risk factors for complications or failures. Results: A total of 1,206 patients received 1,817 dental implants. The group comprised 573 men and 633 women with a mean age of 55.2 years. Almost 60% of patients were age 50 or older. The most frequent indication for implant therapy was single-tooth replacement in the maxilla (522 implants or 28.7%). A total of 726 implants (40%) were inserted in the esthetically demanding region of the anterior maxilla. For 939 implants (51.7%), additional bone-augmentation procedures were required. Of these, ridge augmentation with guided bone regeneration was performed more frequently than sinus grafting. Thirteen complications leading to early failures were recorded, resulting in an early failure rate of 0.7%. The regression analysis failed to identify statistically significant failure etiologies for the variables assessed. Conclusions: From this study it can be concluded that patients referred to a specialty clinic for implant placement were more likely to be partially edentulous and over 50 years old. Single-tooth replacement was the most frequent indication (> 50%). Similarly, additional bone augmentation was indicated in more than 50% of cases. Adhering to strict patient selection criteria and a standardized surgical protocol, an early failure rate of 0.7% was experienced in this study population

Enhancement of titanium implants via bioengineered periodontal tissues

Osseointegration of titanium dental implants into the jaw bone, which is required for maintenance of the implant in the jaw, results in ankylosis. Dental implants are therefore very unlike natural teeth, which exhibit significant movement in response to mechanical forces. The ability to generate periodontal ligament (PDL) tissues onto dental implants would better mimic the functional characteristics of natural teeth, and would likely improve implant duration and function. OBJECTIVES: The objective of this study was to investigate the feasibility of bioengineering PDL tissues onto titanium implant surfaces. METHODS: Bilateral maxillary first and second molars of 8-week old rats were extracted and used to generate single cell suspensions of PDL tissues, which were expanded in culture. Immunohistochemistry and RT-PCR were used to identify putative PDL progenitor/stem cell populations and characterize stem cell properties, including self-renewal, multipotency and stem cell maker expression. Cultured rPDL cells were harvested at third passage, seeded onto Matrigel-coated titanium implants (1.75 mm x 1 mm), and placed into healed M1/M2 extraction sites. Non-cell seeded Matrigel-coated titanium implants served as negative controls. Implants were harvested after 8, 12, or 18 weeks. RESULTS: Cultured rPDL cells expressed the mesenchymal stem-cell marker STRO-1. Under defined culture conditions, PDL cells differentiated into adipogenic, neurogenic and osteogenic lineages. While control implants were largely surrounded by alveolar bone, experimental samples exhibited fibrous PDL-like tissues, and perhaps cementum, on the surface of experimental implants. CONCLUSIONS: PDL contains stem cells that can generate cementum/PDL-like tissue in vivo. Transplantation of these cells might hold promise as a therapeutic approach for the bioengineering of PDL tissues onto titanium implant. Further refinement of this method will likely result in improved dental implant strategies for use of autologous PDL tissue regeneration in humans. This research was supported by CIMIT, and NIH/NIDCR grant DE016132 (PCY), and TEACRS (YL).

Development of Vapor Deposited Silica Sol-Gel Particles for a Bioactive Materials System to Direct Osteoblast Behavior

Tissue engineering and regenerative medicine have emerged in an effort to generate replacement tissues capable of restoring native tissue structure and function, but because of the complexity of biologic system, this has proven to be much harder than originally anticipated. Silica based bioactive glasses are popular as biomaterials because of their ability to enhance osteogenesis and angiogenesis. Sol-gel processing methods are popular in generating these materials because it offers: 1) mild processing conditions; 2) easily controlled structure and composition; 3) the ability to incorporate biological molecules; and 4) inherent biocompatibility. The goal of this work was to develop a bioactive vaporization system for the deposition of silica sol-gel particles as a means to modify the material properties of a substrate at the nano- and micro- level to better mimic the instructive conditions of native bone tissue, promoting appropriate osteoblast attachment, proliferation, and differentiation as a means for supporting bone tissue regeneration. The size distribution, morphology and degradation behavior of the vapor deposited sol-gel particles developed here were found to be dependent upon formulation (H2O:TMOS, pH, Ca/P incorporation) and manufacturing (substrate surface character, deposition time). Additionally, deposition of these particles onto substrates can be used to modify overall substrate properties including hydrophobicity, roughness, and topography. Deposition of Ca/P sol particles induced apatite-like mineral formation on both two- and three-dimensional materials when exposed to body fluids. Gene expression analysis suggests that Ca/P sol particles induce upregulation osteoblast gene expression (Runx2, OPN, OCN) in preosteoblasts during early culture time points. Upon further modification-specifically increasing particle stability-these Ca/P sol particles possess the potential to serve as a simple and unique means to modify biomaterial surface properties as a means to direct osteoblast differentiation.

Dimensional ridge alterations following immediate implant placement in molar extraction sites: a six-month prospective cohort study with surgical re-entry

AIM: To assess dimensional ridge alterations following immediate implant placement in molar extraction sites. MATERIAL AND METHODS: Twelve subjects received 12 immediate transmucosal implants in molar extraction sites. Peri-implant defects were treated according to the principles of Guided Bone Regeneration by means of a deproteinized bone substitute and a bioresorbable collagen membrane. Changes in vertical (IS-BD, CREST-BD) and horizontal distances (EC-I, IC-I) of alveolar bony walls to the bottom of the defects (BD) and to the implant surfaces (I) were compared between implant placement and surgical re-entry at 6 months. RESULTS: The implant survival rate at 6 months was 100%. Statistically significant differences (P<0.01) were observed in the mean changes in vertical distances IS-BD and CREST-BD between baseline and re-entry. At re-entry, all peri-implant marginal defects assessed from the internal socket wall to the implant surface (IC-I) were healed. The residual combined thickness of the buccal wall with the newly formed peri-implant bone at sites with an initial thickness of 1 mm was statistically significantly smaller (P<0.05) compared with that of sites with an initial buccal thickness of 2 mm (2.50 +/- 0.76 vs. 4+/-0 mm). CONCLUSIONS: The marginal defects around immediate implants placed in molar extraction sites were completely filled after 6 months of healing through de novo bone formation. Bone resorption was observed from the external aspects of the buccal and oral socket walls. Dimensional changes of the external socket walls were mostly pronounced at the buccal aspects.

Soft tissues healing at immediate transmucosal implants placed into molar extraction sites with buccal self-contained dehiscences. A 12-month controlled clinical trial

AIM: To assess soft tissues healing at immediate transmucosal implants placed into molar extraction sites with buccal self-contained dehiscences. MATERIAL AND METHODS: For this 12-month controlled clinical trial, 15 subjects received immediate transmucosal tapered-effect (TE) implants placed in molar extraction sockets displaying a buccal bone dehiscence (test sites) with a height and a width of > or =3 mm, respectively. Peri-implant marginal defects were treated according to the principles of Guided Bone Regeneration (GBR) by means of deproteinized bovine bone mineral particles in conjunction with a bioresorbable collagen membrane. Fifteen subjects received implants in healed molar sites (control sites) with intact buccal alveolar walls following tooth extraction. In total, 30 TE implants with an endosseous diameter of 4.8 mm and a shoulder diameter of 6.5 mm were used. Flaps were repositioned and sutured, allowing non-submerged, transmucosal soft tissues healing. At the 12-month follow-up, pocket probing depths (PPD) and clinical attachment levels (CAL) were compared between implants placed in the test and the control sites, respectively. RESULTS: All subjects completed the 12-month follow-up period. All implants healed uneventfully, yielding a survival rate of 100%. After 12 months, statistically significantly higher (P<0.05) PPD and CAL values were recorded around implants placed in the test sites compared with those placed in the control sites. CONCLUSIONS: The findings of this controlled clinical trial showed that healing following immediate transmucosal implant installation in molar extraction sites with wide and shallow buccal dehiscences yielded less favorable outcomes compared with those of implants placed in healed sites, and resulted in lack of 'complete' osseointegration.

Mammary epithelial-specific knockout of the ephrin-B2 gene leads to precocious epithelial cell death at lactation

The family of Eph receptor tyrosine kinases and their membrane bound ligands, the ephrins, are involved in a wide variety of morphogenic processes during embryonic development and adult tissue homeostasis. Receptor-ligand interaction requires direct cell-cell contact and results in forward and reverse signaling originating from the receptor and ligand, respectively. We have previously shown that EphB4 and ephrinB2 are differentially expressed during the development of the adult mammary parenchyma. Overexpression of EphB4 in the mammary epithelium of transgenic mice leads to perturbations in mammary epithelial morphology, motility and growth. To investigate the role of ephrinB2 signaling in mammary gland biology, we have established transgenic mice exhibiting conditional ephrinB2 knockout in the mammary epithelium. In homozygote double transgenic CreLox mice, specific knockout of ephrinB2 occurred in the mammary epithelium during the first pregnancy-lactating period. Abolishing ephrinB2 function led to severe interference with the architecture and functioning of the mammary gland at lactation. The morphology of the transgenic lactating glands resembled that of involuting controls, with decreased epithelial cell number and collapsed lobulo-alveolar structures. Accordingly, massive epithelial cell death and expression of involution-specific genes were observed. Interestingly, in parallel to cell death, significant cell proliferation was apparent, suggestive of tissue regeneration.

Long-term stability of early implant placement with contour augmentation

In this prospective case series study, 20 patients with an implant-borne single crown following early implant placement with simultaneous contour augmentation were followed for 6 years. Clinical, radiologic, and esthetic parameters were assessed. In addition, cone beam computed tomography (CBCT) was used at 6 years to examine the facial bone wall. During the study period, all 20 implants were successfully integrated, and the clinical parameters remained stable over time. Pleasing esthetic outcomes were noted, as assessed by the pink esthetic scores. None of the implants developed mucosal recession of 1 mm or more. The periapical radiographs yielded stable peri-implant bone levels, with a mean DIB of 0.44 mm at 6 years. The CBCT scans showed that all 20 implants had a detectable facial bone wall at 6 years, with a mean thickness of around 1.9 mm. In summary, this prospective case series study demonstrated stable peri-implant hard and soft tissues for all 20 implants, and pleasing esthetic outcomes overall. The follow-up of 6 years confirmed that the risk for mucosal recession is low with early implant placement. In addition, contour augmentation with guided bone regeneration (GBR) was able to establish and maintain a facial bone wall in all 20 patients.

Long-term stability of contour augmentation with early implant placement following single tooth extraction in the esthetic zone: a prospective, cross-sectional study in 41 patients with a 5- to 9-year follow-up

BACKGROUND Early implant placement with simultaneous contour augmentation is documented with short- and medium-term studies. The long-term stability of contour augmentation is uncertain. METHODS In this prospective, cross-sectional study, 41 patients with an implant-borne single crown were examined twice, in 2006 and 2010. Clinical, radiologic, and esthetic parameters were assessed at both examinations. In addition, a cone beam computed tomographic (CBCT) image was obtained during the second examination to assess the dimensions of the facial bone wall. RESULTS All 41 implants demonstrated ankylotic stability without signs of peri-implant infection at both examinations. The clinical parameters remained stable over time. Satisfactory esthetic outcomes were noted, as assessed by the pink and white esthetic score (PES/WES) indices. Overall, the PES scores were slightly higher than the WES scores. None of the implants developed mucosal recession over time, as confirmed by values of the distance between implant shoulder and mucosal margin and cast measurements. The periapical radiographs yielded stable peri-implant bone levels, with a mean distance between implant shoulder and first visible bone-implant contact value of 2.18 mm. The CBCT analysis demonstrated a mean thickness of the facial bone wall ≈2.2 mm. In two implants (4.9%) no facial bone wall was detectable radiographically. CONCLUSIONS This prospective cross-sectional study demonstrates stable peri-implant hard and soft tissues for all 41 implants examined and satisfactory esthetic outcomes overall. The follow-up of 5 to 9 years confirmed again that the risk for mucosal recession is low with early implant placement. In addition, contour augmentation with guided bone regeneration was able to establish and maintain a facial bone wall in 95% of patients.

NEW TARGET GENES FOR TUMOR SUPPRESSORS p53 AND p73 IN REGENERATING LIVER

The p53-family of proteins regulates expression of target genes during tissue development and differentiation. Within the p53-family, p53 and p73 have hepatic-specific functions in development and tumor suppression. Despite a growing list of p53/p73 target genes, very few of these have been studied in vivo, and the knowledge regarding functions of p53 and p73 in normal tissues remains limited. p53+/-p73+/- mice develop hepatocellular carcinoma (HCC), whereas overexpression of p53 in human HCC leads to tumor regression. However, the mechanism of p53/p73 function in liver remains poorly characterized. Here, the model of mouse liver regeneration is used to identify new target genes for p53/p73 in normal quiescent vs. proliferating cells. In response to surgical removal of ~2/3 of liver mass (partial hepatectomy, PH), the remaining hepatocytes exit G0 of cell cycle and undergo proliferation to reestablish liver mass. The hypothesis tested in this work is that p53/p73 functions in cell cycle arrest, apoptosis and senescence are repressed during liver regeneration, and reactivated at the end of the regenerative response. Chromatin immunoprecipitation (ChIP), with a p73-antibody, was used to probe arrayed genomic sequences (ChIP-chip) and uncover 158 potential targets of p73-regulation in normal liver. Global microarray analysis of mRNA levels, at T=0-48h following PH, revealed sets of genes that change expression during regeneration. Eighteen p73-bound genes changed expression after PH. Four of these genes, Foxo3, Jak1, Pea15, and Tuba1 have p53 response elements (p53REs), identified in silico within the upstream regulatory region. Forkhead transcription factor Foxo3 is the most responsive gene among transcription factors with altered expression during regenerative, cellular proliferation. p53 and p73 bind a Foxo3 p53RE and maintain active expression in quiescent liver. During liver regeneration, binding of p53 and p73, recruitment of acetyltransferase p300, and an active chromatin structure of Foxo3 are disrupted, alongside loss of Foxo3 expression. These parameters of Foxo3 regulation are reestablished at completion of liver growth and regeneration, supporting a temporary suspension of p53 and p73 regulatory functions in normal cells during tissue regeneration.

Endoscopic ultrasonography for the diagnosis of intrathoracic lesions in two dogs.

Endoscopic ultrasound was developed initially in humans to overcome limitations of conventional ultrasound in examining certain internal organs due to intervening bone or air-filled structures. Endoscopic ultrasound has been used most widely in investigation of the gastrointestinal tract in humans, but many intrathoracic applications as well as endoscopic ultrasound-guided techniques have recently been described. Mediastinal and pulmonary structures can be examined with endoscopic ultrasound since a high frequency ultrasound probe can be brought into close contact with the areas of interest via a transesophageal approach. The purpose of this report is to describe the application of endoscopic ultrasound as an aid in the diagnosis of intrathoracic disease in the dog. Two dogs, one with a history of prior esophageal foreign body extraction, the other with apathy, weakness and dyspnea were referred for further investigation. Both dogs had caudal intrathoracic soft tissue opacities diagnosed radiographically, but their origin and nature were difficult to determine. Conventional ultrasound was limiting in both dogs due to their location and superimposition of gas-filled structures. With endosonography lesions were characterized more completely. We have found endoscopic ultrasound to be an elegant diagnostic tool for the investigation of radiographically detected intrathoracic lesions in the dog whose origins are difficult to determine or do not lend themselves to investigation by conventional ultrasound. Endoscopic ultrasound provides valuable diagnostic information complementary to that provided radiographically which aids in therapeutic planning. Endoscopic ultrasound was also more sensitive for detecting mediastinal lymphadenomegaly than radiography in one of the dogs. An additional advantage of endoscopic ultrasound is the fact that US-guided tissue sampling can be performed during the examination.

The secretome of endothelial progenitor cells promotes brain endothelial cell activity through PI3-kinase and MAP-kinase

BACKGROUND Angiogenesis and vascular remodelling are crucial events in tissue repair mechanisms promoted by cell transplantation. Current evidence underscores the importance of the soluble factors secreted by stem cells in tissue regeneration. In the present study we investigated the effects of paracrine factors derived from cultured endothelial progenitor cells (EPC) on rat brain endothelial cell properties and addressed the signaling pathways involved. METHODS Endothelial cells derived from rat brain (rBCEC4) were incubated with EPC-derived conditioned medium (EPC-CM). The angiogenic response of rBCEC4 to EPC-CM was assessed as effect on cell number, migration and tubular network formation. In addition, we have compared the outcome of the in vitro experiments with the effects on capillary sprouting from rat aortic rings. The specific PI3K/AKT inhibitor LY294002 and the MEK/ERK inhibitor PD98059 were used to study the involvement of these two signaling pathways in the transduction of the angiogenic effects of EPC-CM. RESULTS Viable cell number, migration and tubule network formation were significantly augmented upon incubation with EPC-CM. Similar findings were observed for aortic ring outgrowth with significantly longer sprouts. The EPC-CM-induced activities were significantly reduced by the blockage of the PI3K/AKT and MEK/ERK signaling pathways. Similarly to the outcome of the rBCEC4 experiments, inhibition of the PI3K/AKT and MEK/ERK pathways significantly interfered with capillary sprouting induced by EPC-CM. CONCLUSION The present study demonstrates that EPC-derived paracrine factors substantially promote the angiogenic response of brain microvascular endothelial cells. In addition, our findings identified the PI3K/AKT and MEK/ERK pathways to play a central role in mediating these effects.

Thermal processing of bone: in vitro response of mesenchymal cells to bone-conditioned medium

The autoclaving, pasteurization, and freezing of bone grafts to remove bacteria and viruses, and for preservation, respectively, is considered to alter biological properties during graft consolidation. Fresh bone grafts release paracrine-like signals that are considered to support tissue regeneration. However, the impact of the autoclaving, pasteurization, and freezing of bone grafts on paracrine signals remains unknown. Therefore, conditioned medium was prepared from porcine cortical bone chips that had undergone thermal processing. The biological properties of the bone-conditioned medium were assessed by examining the changes in expression of target genes in oral fibroblasts. The data showed that conditioned medium obtained from bone chips that had undergone pasteurization and freezing changed the expression of adrenomedullin, pentraxin 3, BTB/POZ domain-containing protein 11, interleukin 11, NADPH oxidase 4, and proteoglycan 4 by at least five-fold in oral fibroblasts. Bone-conditioned medium obtained from autoclaved bone chips, however, failed to change the expression of the respective genes. Also, when bone-conditioned medium was prepared from fresh bone chips, autoclaving blocked the capacity of bone-conditioned medium to modulate gene expression. These in vitro results suggest that pasteurization and freezing of bone grafts preserve the release of biologically active paracrine signals, but autoclaving does not. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. KEYWORDS: allogeneic bone; augmentation; autoclaving; autologous bone; bone bank; bone grafts; bone regeneration; bone supernatant; bone-conditioned medium; freezing; pasteurization

Periodontal and peri-implant wound healing following laser therapy

Laser irradiation has numerous favorable characteristics, such as ablation or vaporization, hemostasis, biostimulation (photobiomodulation) and microbial inhibition and destruction, which induce various beneficial therapeutic effects and biological responses. Therefore, the use of lasers is considered effective and suitable for treating a variety of inflammatory and infectious oral conditions. The CO2 , neodymium-doped yttrium-aluminium-garnet (Nd:YAG) and diode lasers have mainly been used for periodontal soft-tissue management. With development of the erbium-doped yttrium-aluminium-garnet (Er:YAG) and erbium, chromium-doped yttrium-scandium-gallium-garnet (Er,Cr:YSGG) lasers, which can be applied not only on soft tissues but also on dental hard tissues, the application of lasers dramatically expanded from periodontal soft-tissue management to hard-tissue treatment. Currently, various periodontal tissues (such as gingiva, tooth roots and bone tissue), as well as titanium implant surfaces, can be treated with lasers, and a variety of dental laser systems are being employed for the management of periodontal and peri-implant diseases. In periodontics, mechanical therapy has conventionally been the mainstream of treatment; however, complete bacterial eradication and/or optimal wound healing may not be necessarily achieved with conventional mechanical therapy alone. Consequently, in addition to chemotherapy consisting of antibiotics and anti-inflammatory agents, phototherapy using lasers and light-emitting diodes has been gradually integrated with mechanical therapy to enhance subsequent wound healing by achieving thorough debridement, decontamination and tissue stimulation. With increasing evidence of benefits, therapies with low- and high-level lasers play an important role in wound healing/tissue regeneration in the treatment of periodontal and peri-implant diseases. This article discusses the outcomes of laser therapy in soft-tissue management, periodontal nonsurgical and surgical treatment, osseous surgery and peri-implant treatment, focusing on postoperative wound healing of periodontal and peri-implant tissues, based on scientific evidence from currently available basic and clinical studies, as well as on case reports.

Effects of Prolyl Hydroxylase Inhibitor L-mimosine on Dental Pulp in the Presence of Advanced Glycation End Products

INTRODUCTION Proangiogenic prolyl hydroxylase (PHD) inhibitors represent a novel approach to stimulate tissue regeneration. Diabetes mellitus involves the accumulation of advanced glycation end products (AGEs). Here we evaluated the impact of AGEs on the response of human pulp tissue to the PHD inhibitor L-mimosine (L-MIM) in monolayer cultures of dental pulp-derived cells (DPCs) and tooth slice organ cultures. METHODS In monolayer cultures, DPCs were incubated with L-MIM and AGEs. Viability was assessed based on formazan formation, live-dead staining, annexin V/propidium iodide, and trypan blue exclusion assay. Vascular endothelial growth factor (VEGF), interleukin (IL)-6, and IL-8 production was evaluated by quantitative polymerase chain reaction and immunoassays. Furthermore, expression levels of odontoblast markers were assessed, and alizarin red staining was performed. Tooth slice organ cultures were performed, and VEGF, IL-6, and IL8 levels in their supernatants were measured by immunoassays. Pulp tissue vitality and morphology were assessed by MTT assay and histology. RESULTS In monolayer cultures of DPCs, L-MIM at nontoxic concentrations increased the production of VEGF and IL-8 in the presence of AGEs. Stimulation with L-MIM decreased alkaline phosphatase levels and matrix mineralization also in the presence of AGEs, whereas no significant changes in dentin matrix protein 1 and dentin sialophosphoprotein expression were observed. In tooth slice organ cultures, L-MIM increased VEGF but not IL-6 and IL-8 production in the presence of AGEs. The pulp tissue was vital, and no signs of apoptosis or necrosis were observed. CONCLUSIONS Overall, in the presence of AGEs, L-MIM increases the proangiogenic capacity, but decreases alkaline phosphatase expression and matrix mineralization.