Cellular fluid shear stress on implant surfaces-establishment of a novel experimental set up.

BACKGROUND: Mechanostimuli of different cells can affect a wide array of cellular and inter-cellular biological processes responsible for dental implant healing. The purpose of this in vitro study was to establish a new test model to create a reproducible flow-induced fluid shear stress (FSS) of osteoblast cells on implant surfaces. METHODS: As FSS effects on osteoblasts are detectable at 10 dyn/cm2, a custom-made flow chamber was created. Computer-aided verification of circulation processes was performed. In order to verify FSS effects, cells were analysed via light and fluorescence microscopy. RESULTS: Utilising computer-aided simulations, the underside of the upper plate was considered to have optimal conditions for cell culturing. At this site, a flow-induced orientation of osteoblast cell clusters and an altered cell morphology with cellular elongation and alteration of actin fibres in the fluid flow direction was detected. CONCLUSIONS: FSS simulation using this novel flow chamber might mimic the peri-implant situation in the phase of loaded implant healing. With this FSS flow chamber, osteoblast cells' sensitivity to FSS was verified in the form of morphological changes and cell re-clustering towards the direction of the flow. Different shear forces can be created simultaneously in a single experiment.

Impact of maxillary sinus augmentation on oral health-related quality of life.

BACKGROUND: The aim of this study was to measure the oral health-related quality of life (OHRQoL) after maxillary sinus augmentation to determine the physical and psychological impact of this procedure for the patient. METHODS: Three hundred sixteen patients treated with an external or internal maxillary sinus augmentation and a total of 863 implants in the Department of Oral and Maxillofacial Surgery, Johannes Gutenberg University, Mainz, Germany, between July 2002 and December 2007 were included in this retrospective study. Total implant survival was assessed. Completion of a modified 26-item version of the Oral Health Impact Profile (OHIP-G) for assessing the oral health-related quality of life before and after the treatment was asked for. Subcategories were (1) functional limitations, (2) physical and psychological disabilities, and (3) complaints due to the surgical procedure. In 53 patients available for clinical follow-up examination, assessment of soft tissue parameters was performed. RESULTS: After an average time in situ of 41.2 ± 27 months (3.4 years), the in situ rate was 95.4%. One-year survival rate and five-year survival rate according to Kaplan Meier were 95.4 and 94.4%. Concerning functional limitations, significant better values for OHRQoL after sinus augmentation procedure than before the treatment (p < 0.001) were seen. In the subcategory physical and psychological disabilities, all questions had significant better values after the sinus lift (p < 0.001). Concerning complaints due to the surgical procedure, mean total scores were 5.1 ± 5.4 pre-operative, 6.9 ± 6.1 (0-31) post-operative, and 2.4 ± 3.7 recently. This meant a significant difference between "pre-operative" vs. "post-operative" (p = 0.003), "pre-operative" vs. "recently" (p < 0.001), and "post-operative" vs. "recently" (p < 0.001). Concerning the influence of implant indication, edentulous patients showed the most distinct improvement after the procedure. Clinical assessment showed stable soft tissue parameters. CONCLUSIONS: Evaluation of OHRQoL after sinus augmentation showed a significant improvement indicating a remarkable benefit for the patients through this procedure.

Local and systemic risk factors influencing the long-term success of angular stable alloplastic reconstruction plates of the mandible.

INTRODUCTION: After ablative surgery of the mandible, angular stable alloplastic reconstruction plates are commonly employed. The aim of the study was a long-term evaluation of local anatomical, as looking at systemic factors influencing specific complications and the failure rate of such plates. MATERIALS AND METHODS: In a retrospective study covering an 11-year period, we reviewed the outcomes of angular stable plates of patients who had a segmental resection of the mandible and subsequent alloplastic reconstruction. Complications and failure rates were assessed and local (anatomical size and localization of resection) as well as systemic risk factors (age, sex, radiation therapy, smoking) evaluated. RESULTS: Altogether, 162 plates were reviewed. The overall complication rate was 28% (fractures n = 8, loose screws n = 7, dehiscences n = 31) after an average time of 13 months. Cumulative survival rates of 73% after one, of 67% after 2, of 59% after 3 and of 40% after five years were observed. We found a significant correlation of increasing defect sizes to a rising complication and failure rate. Plate dehiscence occurred more often in defects including the midline (p = 0.005). Though not statistically significant, the occurrence of plate fracture was associated with lateral mandibular defects (7/8, p = 0.113). In smoking patients an earlier failure rate was seen. CONCLUSION: The results clearly indicate that the success of alloplastic reconstruction plates of the mandible is dependent on various risk factors. They should--if possible--be used temporarily only. If not done primarily, a secondary approach with bone reconstruction is recommended.

Multiple primary enoral soft tissue manifestations of a Hodgkin lymphoma--case report and literature review.

BACKGROUND: Hodgkin lymphoma (HL) are lymphoproliferative neoplasms, histologically comprising of mononuclear and multinucleated Hodgkin and Reed Sternberg cells (HRS). About 4 % of all lymphatic malignancies of the head and neck are HL. The typical disease presents itself as a nodal lesion. Extranodal, enoral soft tissue involvement by HL is very rare. CASE REPORT: A 73-year-old man with a suspect, ulcerating lesion in the left retromolar region of the mandible was assigned to our hospital. Prior anti-inflammatory therapy has been without success. Subsequently, three biopsies were taken which could only show inflammation. Finally, two biopsies from the left retromolar region and the left inner cheek showed HRS cells with positive expressions of CD15 and CD30 corresponding to a Hodgkin lymphoma. No lymphatic node or bone involvement could be detected. The patient was designated to receive radio-chemotherapy, but died 3 weeks after diagnosis of multiple organ failure. In a literature review, together with this report, nine cases were found concerning primary HL of the oral mucosa. Accordingly, this is the first case of primary multiple extranodal HL in the oral mucosa in absence of lymphatic node involvement. DISCUSSION: Neither clinical features nor radiological appearances of HL presenting as primary enoral lesions are pathognomonic. Especially when only small biopsy specimens are available, histological diagnosis remains challenging, may lead to a delay in therapy and may result in a significant worse prognosis.

Early implant healing: promotion of platelet activation and cytokine release by topographical, chemical and biomimetical titanium surface modifications in vitro.

OBJECTIVES: Platelet releasate has been shown to promote osteogenetic cell proliferation and differentiation. Topography and chemistry of biomaterials have high impact on platelet activation. More specifically, the bioactive cell adhesive peptide sequence Arg-Gly-Asp (RGD) triggers platelet activation mediated by the α(IIb) ß(3) integrin receptor. Accordingly, topographical, chemical and biomimetical (immobilized RGD peptide) modifications of titanium (Ti) surfaces may enhance early platelet activation and bony healing of implants. Therefore, the aim of the study was to evaluate platelet activation with subsequent platelet-derived cytokine release by accordingly modified Ti surfaces. MATERIALS AND METHODS: Pre-treated (PT; mean roughness [R(a)]=0.04 µm, contact angle [CA]=91°), acid-etched (A, R(a) =0.83 µm, CA=106°), large grit-sandblasted, acid-etched (SLA, R(a) =3.2 µm, CA=109°) as well as hydrophilically modified acid-etched (modA, R(a) =0.83 µm, CA=0) and modified large grit-sandblasted, acid-etched (modSLA, R(a) =3.2 µm; CA=0°) titanium surfaces were investigated. Additionally, RGD peptides were chemically immobilized on PT, A and SLA surfaces (PT-RGD [CA=18°], A-RGD [CA=0°], SLA-RGD [CA=0°]). The different Ti surfaces were incubated with platelet concentrate of three healthy volunteers at room temperature for 15 min and for 30 min. High thrombogenous collagen served as the control group. Out of the supernatant, platelet consumption was assessed via platelet count (PC). Cytokine release was quantified via the level of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). RESULTS: After 15 min, especially the rough SLA surface showed a strong decrease in PC and a strong increase in VEGF and PDGF levels. After 30 min, high platelet consumption as well as high levels of VEGF and PDGF were measured for unspecifically modified (modA) and especially for biomimetic, specifically modified (PT-RGD, A-RGD) surfaces, indicating a delayed effect of the surface modifications on platelet activation. DISCUSSION: Modifications of surface roughness modifications appear to influence early platelet activation and cytokine release after 15 min whereas surface chemistry modifications with increased hydrophilic properties and surface modifications via RGD peptide on plainer surfaces lead to a further, more specific promotion of platelet activation and degranulation after 30 min. The observed effect could be valuable for critical clinical situations like compromised bone sites.

Immobilisation of linear and cyclic RGD-peptides on titanium surfaces and their impact on endothelial cell adhesion and proliferation.

Functional coatings on titanium vascular stents and endosseous dental implants could probably enhance endothelial cell (EC) adhesion and activity with a shortening of the wound healing time and an increase of peri-implant angiogenesis during early bone formation. Therefore, the role of the structure of linear and cyclic cell adhesive peptides Arg-Gly-Asp (l-RGD and c-RGD) on differently pre-treated titanium (Ti) surfaces (untreated, silanised vs. functionalised with l- and c-RGD peptides) on EC cell coverage and proliferation was evaluated. After 24 h and after 3 d, surface coverage of adherent cells was quantified and an alamarBlue® proliferation assay was conducted. After 24 h, l-RGD modified surfaces showed a significantly better coverage of adhered cells than untreated titanium (p=0.01). Differences between l-RGD surfaces and silanised Ti (p=0.066) as well as between l-RGD and c-RGD surfaces (p=0.191) were not significant. After 3 d, c-RGD surfaces showed a significantly higher cell coverage than untreated Ti, silanised and l-RGD titanium surfaces (all p<0.0001). After 24 h, c-RGD modified surfaces showed significant higher cell proliferation compared to untreated Ti (p=0.003). However, there were no differences in proliferation between c-RGD and l-RGD (p=0.126) or c-RGD and silanised titanium (p=0.196). After 3 d, proliferation on c-RGD surfaces outranged significantly untreated titanium (p=0.004), silanised (p=0.001) and l-RGD surfaces (p=0.023), whereas no significant difference could be found between untreated Ti and l-RGD surfaces (p=0.54). According to these results, the biomimetic coating of c-RGD peptides on conventional titanium surfaces showed a positive effect on EC cell coverage and proliferation. We were able to show that modifications of titanium surfaces with c-RGD are a promising approach in promoting endothelial cell growth.

Geranylgeraniol - a new potential therapeutic approach to bisphosphonate associated osteonecrosis of the jaw.

Bisphosphonate associated osteonecrosis of the jaw (BP-ONJ) is one of the main side effects of bisphosphonate therapy (BPT). To date, there is no effective therapy of the BP-ONJ. Nitrogen-containing bisphosphonates (N-BPs) are particularly able to inhibit pyrophosphate synthase (FPPS) in the mevalonate pathway (MVP). Consequent of decreased synthesis of the metabolite Geranylgeraniol (GGOH) is believed to largely account for the development of BP-ONJ. Negative effect of N-BPs could be shown, resulting in decreased viability and migration capacity of different cell types of hard and soft tissues such as osteoblasts, fibroblast und endothelial cells. Aim of our in vitro study was to demonstrate that the mevalonate pathway metabolite GGOH could reverse the negative biological effect of N-BPs. Biological effect of GGOH on bisphosphonate-treated human umbilicord vein endothelial cells (HUVEC), fibroblast and osteogenic cells was analyzed by a viability test and measuring the migration capacity in a scratch wound assay as well as a migration assay using Boyden chambers. The morphological cell architecture of the treated cells was analyzed by phallacidin staining. GGOH cell-treatment can rescue the negative effect of bisphosphonates. These results underline the hypothesis that systemic or local treatment with GGOH could lead to new therapeutic strategies for BP-ONJ.

Modulation of platelet activation and initial cytokine release by alloplastic bone substitute materials.

OBJECTIVES: Platelet-derived cytokines play a crucial role in tissue regeneration. In regenerative dental medicine, bone substitute materials (BSM) are widely used. However, initial interactions of BSM and platelets are still unknown. The aim of this study was to evaluate the potential of platelet activation and subsequent initial cytokine release by different commercial alloplastic BSM. MATERIAL AND METHODS: Eight commercial BSM of different origins and chemical compositions (tricalcium phosphate, hydroxyapatite, bioactive glass: SiO(2) and mixtures) were incubated with a platelet concentrate (platelet-rich plasma, PRP) of three healthy volunteers at room temperature for 15 min. Platelet count, aggregation, degranulation (activated surface receptor CD62p) and cytokine release (Platelet-derived growth factor, Vascular endothelial growth factor) into the supernatant were quantified. Highly thrombogenic collagen served as a reference. RESULTS: The investigated PRP samples revealed different activation patterns when incubated with different BSM. In general, SiO(2)-containing BSM resulted in high platelet activation and cytokine release. In detail, pure bioactive glass promoted platelet activation most significantly, followed by hybrid BSM containing lower ratios of SiO(2). Additionally, we found indications of cytokine retention by BSM of large specific surfaces. CONCLUSIONS: Platelet activation as well as consecutive storage and slow release of platelet-derived cytokines are desirable attributes of modern BSM. Within the limits of the study, SiO(2)-containing BSM were identified as promising biomaterials. Further investigations on cytokine adsorption and cytokine release kinetics by the respective BSM have to be conducted.

Influence of bisphosphonates on endothelial cells, fibroblasts, and osteogenic cells.

Bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ) is a side effect primarily in patients receiving highly potent nitrogen-containing bisphosphonates. The exact etiopathology is unknown. In addition to reduced bone remodeling, there may also be an impact on soft tissues. The impact of nitrogen- (ibandronate, pamidronate, zoledronate) and non-nitrogen-containing bisphosphonates (clodronate) on human umbilicord vein endothelial cells (HUVEC), fibroblasts and osteogenic cells was analyzed employing cell viability testing and a scratch wound assay. The impact on the cell morphology of vital-stained osteogenic cells was investigated by cell visualization (confocal laser scanning microscopy). Pamidronate and zoledronate had the greatest negative impact on all cell lines, whereas the impact of ibandronate and clodronate was less distinct. The effect of clodronate on HUVEC and fibroblasts was particularly marginal. BP-ONJ could be a multifactorial event with multicellular impairments. This might result in altered wound healing. The increased impact of the highly potent bisphosphonates, particularly on non-bone cells, may explain the higher occurrence of BP-ONJ.

Functional rehabilitation of mandibular continuity defects using autologous bone and dental implants - prognostic value of bone origin, radiation therapy and implant dimensions.

AIM: The aim of this retrospective study was to investigate prognostic parameters for the rehabilitation of mandibular continuity defects with free autologous bone and dental implants for patients after intraoral squamous cell carcinoma. METHODS: Following potential prognostic factors for implant survival were analyzed: bony bed (local bone versus augmented iliac crest bone), radiation dose (no radiation, <50 Gy, >or=50 Gy) and implant dimensions. Kaplan-Meier survival estimates of the inserted implants were performed. RESULTS: After 5 years, the cumulative survival rate of all investigated implants was 82.6%. Dental implantation into augmented bone resulted in a significantly lower survival rate (78.4%), compared to original local bone (92.8%). Modifications of implant dimensions as well as radiation therapy showed no significant impact on implant survival. CONCLUSION: For the investigated compromised collective, our results reveal a satisfactory long-term survival rate of dental implants even in augmented bone and underline the value of dental implantation for the functional rehabilitation of cancer patients.

Misleading initial histological diagnosis of a polymorphous low-grade adenocarcinoma in situ ex pleomorphic adenoma-a case report.

INTRODUCTION: Polymorphous low-grade adenocarcinoma (PLGA) are frequent tumours of palatinal minor salivary glands. They appear clinically as solid mass located beneath intact surface epithelium, thus quite similar with benign neoplasm. PLGA displays a low tendency of aggressive behaviour. The correct aetiology of this disorder is still unknown. CASE REPORT: In this contribution, a PLGA is reported which was located in a pleomorphic adenoma (PA). Out of an initially incisional biopsy, only the benign part of the lesion was diagnosed. Definitive histological examination of the whole tumour revealed a small malignant fraction of the specimen besides a major part of benign tissue formations (PA). CONCLUSION: This case shows the uncertain confidence of incisional biopsy, the variably biologic behaviour of PA, providing hints for consideration of the PLGA aetiology and highlights both the necessity to remove whole PA-like lesions as well as to perform systematically histological examination of whole specimens.

Ultrasound transmission velocity for noninvasive evaluation of jaw bone quality in vivo before dental implantation.

For the insertion of dental implants, mechanical bone properties at the implantation site have great impact both for therapeutic regimes as well as for the overall long-term success, making a reliable method for the preoperative assessment of the bone quality desirable. Ultrasound transmission velocity (UTV) has been introduced as a noninvasive method to analyze mechanical properties of bone. The aim of this study was the first intra-oral in vivo assessment of alveolar crest UTV values of edentulous jaws. Partly or fully edentulous patients (n = 108) were enrolled in this study, taking into account possible influence factors that affect bone quality (osteoporosis, radiation therapy). Six intra-oral measurement points were used: left side region, right side region and frontal region, for upper and lower jaw, respectively. Ultrasound transmission velocity values were measured bicortically (in bucco-oral direction) and correlated to sex, age, measurement site and history of osteoporosis or radiation therapy. We found a minimum mouth opening of 30 mm, as well as a residual alveolar ridge height of 8 mm as thresholds for a reliable intra-oral placement of the device. Xerostomia was no contraindication. Assessment of intra-oral UTV showed significantly higher values both for mandibular side regions (female 1713 +/- 153 m/s, male 1734 +/- 221 m/s) and the maxillary frontal region (female 1665 +/- 189 m/s, male 1648 +/- 82 m/s) than for maxillary side regions (female 1538 +/- 177 m/s, male 1583 +/- 90 m/s). These data were even more clarified by intra-individual correlation of upper and lower jaw side region UTV values. We found no correlation between assessed UTV values and the variables sex, age, osteoporosis or radiation therapy. The use of a small UTV device in this study allowed the recording of intra-oral UTV values in a large and heterogeneous patient collective for the first time. Assessment of alveolar-ridge UTV might offer the possibility to identify critical bone quality before implantation or to monitor bone healing (mineralization) after augmentation procedures.

Dental implantation: ultrasound transmission velocity to evaluate critical bone quality--an animal model.

PURPOSE: In dental implantology, preoperative evaluation of bone quality is an important aspect for the long-term success of the treatment. The insertion of implants into regions with a great portion of poorly mineralised cancellous bone, in particular, increases the risk of subsequent implant failure. The measurement of Ultrasound Transmission Velocity (UTV) proved to be a non-invasive and valid method for the assessment of mechanical properties of bone. The aim of this study was to correlate conventional histomorphometric bone properties with UTV-values from mandibular and iliac crest bone specimens in an animal model. MATERIALS AND METHODS: 12 native (no sample preparation) porcine specimens from mandibular bone and 14 from iliac crest bone, respectively, were studied both by UTV measurement and by conventional histomorphometry. UTV-values were measured bicortically by three different investigators four times at each site. Bone samples from identical sites were obtained and ground down to a thickness of approx. 50 microm. Transmission light microscopy was used to assess the overall percentage of mineralised bone. Mineral bone density less than 40% was defined as "critical". RESULTS: The median bone density was 43 % for mandibular bone and 23% for iliac crest bone, respectively. The median UTV values of the mandible (1756 m/sec) were significantly higher than those of the iliac crest specimens (1613 m/sec). Intra-individual correlation testing illustrates a positive, statistically significant correlation between presurgical UTV measurement and the grade of mineralisation (r=0.54). ROC analysis defined a UTV breakpoint of 1767 m/sec to identify critical bone with a sensitivity of 75%. CONCLUSION: In this ex-vivo model, UTV measurements have proven to be a reliable method for identifying critical bone quality prior to implantation.