The purpose of this study was to ascertain whether simplifying mandibular overdenture treatment utilising single stage surgery and immediate prosthetic loading of a single implant, will achieve similar implant success rates and functional improvement to that expected using conventional techniques. As part of this study, the Mk III Brånemark implant with an oxidised surface (TiUnite™ Nobel Biocare AB, Göteborg, Sweden) was compared to the classical machined Mk III Brånemark fixture.Materials and Methods: 35 patients with a mean age of 68 years and problematic mandibular dentures were treated. The primary complaints among the patients referred to the clinic for treatment related to poor retention of the mandibular denture, instability, denture sores and phonetic problems. Patients were initially placed randomly into the “machined surface” or “oxidised surface” group. A single implant was placed into the mandibular midline with high initial stability. A ball attachment was placed and the retentive cap incorporated into the existing denture. Reviews took place at 3,12 6 6 and 36 months. Clinical assessments, radiographs made with custom film holders, and stability measurements by both manual and resonance frequency analysis methods were recorded. All complications, failures, maintenance and reasons for dropout were noted. Visual analogue scale questionnaires were utilised to record patient satisfaction. (ANOVA p<.05) Results: Three out of 8 machined surface implants failed, representing an unacceptably high failure rate (37.5%). The machined surface was therefore discontinued for this study. Three oxidised surface implants did not achieve sufficient primary stability to be immediately loaded, so were treated with a two stage delayed loading protocol. The 25 immediately loaded oxidised surface implants were all classified as surviving at the 36-month recall. Patient satisfaction was very high with a significant increase in all comfort and functional parameters. Conclusions: Within the limitations of this study and research design, it appears that the immediately loaded single implant retained mandibular overdenture, using an oxidised implant surface in a small group of maladaptive patients, can provide a beneficial treatment outcome over a three year observation period. If insufficient stability at insertion is not achieved for immediate loading, then a delayed loading protocol should be utilised.

The general aim of this thesis was to broaden our knowledge of the signs and symptoms, genetics, and outcomes of dental implant treatment in individuals with oligodontia or ectodermal dysplasia. Article I is a population-based study in three Swedish counties of 162 individuals with oligodontia, which was a prevalence of 0.09%. The intent was to explore ways for dentists to assess symptoms from other ectodermal structures than teeth through a clinical interview and chair-side analyses. Thirty per cent had low salivary secretion rates while only 11% with no known syndrome reported symptoms from hair, nails, or sweat glands. These are, together with teeth, the ectodermal structures on which it is proposed that a clinical diagnosis of ectodermal dysplasia (ED) be based. Article II screened 93 probands with oligodontia for mutations in six genes known to cause oligodontia and hypohidrotic ED. Sequence alterations predicted to be damaging or potentially damaging were revealed in the AXIN2, MSX1, PAX9, and EDARADD genes in 14 (15%) of the probands. All mutations but one were novel. For the first time, EDARADD mutations were shown to cause isolated oligodontia. No individual who had reported ectodermal symptoms from hair, nails, or sweat glands had a mutation. Article III assessed orofacial function in individuals with different types of EDs using the Nordic Orofacial Test-Screening (NOT-S) protocol. Individuals with ED scored significantly higher in orofacial dysfunction than a healthy reference sample, especially in the Chewing and swallowing, Dryness of the mouth, and Speech domains. Article IV surveyed treatment outcome of dental implants in Swedish children up to age 16 years. In a 20-year period, only 26 patients were treated, 5 of whom had hypohidrotic ED and anodontia of the mandible. Individuals with ED had 64% failed implants compared to 6% among subjects with teeth missing due to trauma or agenesis. The main conclusions of this thesis were that (i) a check of whether one or more permanent incisors are missing will identify 65% of individuals with oligodontia and 84% of individuals missing nine teeth or more, (ii) evaluation of salivary secretion is indicated in children with oligodontia, (iii) a majority of individuals with oligodontia did not report other abnormal ectodermal organ function besides teeth, (iv) no clinical indicator discriminated between individuals with and without mutations in the tested genes, and more unidentified genes are involved in tooth morphogenesis, (v) EDARADD mutations are associated with isolated oligodontia, (vi) evaluation of orofacial function is indicated in individuals with ED, and many individuals with ED would benefit from orofacial skills training, (vii) dental implant placement is a rare treatment modality in children, (viii) individuals with hypohidrotic ED seem to present special challenges due to structural as well as direct effects of the mutations on bone, which seem to compromise osseointegration, (ix) central registers on signs and symptoms in individuals with rare disorders would help establish prevalences of various diagnoses and define treatment needs, and (x) quality registers for monitoring treatment outcomes of dental implants would promote early detection of risks and side-effects in individuals with rare disorders.

Die vorliegende Arbeit untersucht neuartige Zirkonoxid-Implantatoberflächen hinsichtlich ihrer Auswirkung auf die Proliferation und Apoptose humaner Knochenzellen, die in einer Knochenzellkultur angezüchtet wurden. Weiterhin erfolgte die Messung der auf den jeweiligen Probekörperoberflächen sezernierten Knochenproteine Bone Sialo Protein, Osteonectin, Osteocalcin und des Wachstumsfaktors TGF-ß. Die Messungen geschahen am dritten, fünften, siebenten und zehnten Versuchstag. Die neuartigen Probekörper ZrO_19 und ZrO_20 haben einen Titangrundkörper und wurden im PVD-Verfahren mit Zirkoniumdioxid beschichtet. Sie mussten sich dem Vergleich mit dem Positivstandard Ticer und dem Negativstandard Titan unterziehen. Weiterhin fanden ein Probekörper aus reiner Zirkoniumdioxidkeramik (Cercon) und eine SLA-ähnliche geätzte Titanschicht Verwendung. Am meisten Knochenzellen proliferierten auf Ticer. Die kleinsten Messwerte wurden auf der Ätzschicht gemessen. Die Werte von ZrO_19, ZrO_20 und von Cercon ähnelten sich stark und siedelten sich zwischen denen von Ticer und denen der Ätzschicht an. Die größten Expressionen der Knochenproteine wurden auf Cercon und Ticer nachgewiesen. Die neuartigen Zirkoniumdioxid-Oberflächen begünstigten die Proliferation und Expression von Knochenproteinen in vitro nicht in dem Maße, wie es der Positivstandard Ticer vermochte. Möglicherweise könnten jedoch Variationen der Oberflächen-zusammensetzung die biologischen Eigenschaften verbessern. Für Cercon kann eine gute biologische Eignung vermutet werden.

An understanding of the interactions between orthopaedic and dental implant surfaces with the surrounding host tissue is critical in the design of next generation implants to improve osseointegration and clinical success rates. Critical to the process of osseointegration is the rapid establishment of a patent neovasculature in the peri-implant space to allow for the delivery of oxygen, nutrients, and progenitor cells. The central aim of this thesis is to understand how biomaterials regulate cellular and host tissue response to elicit a pro-angiogenic microenvironment at the implant/tissue interface. To address this question, the studies performed in this thesis aim to 1) determine whether biomaterial surface properties can modulate the production and secretion of pro-angiogenic growth factors by cells, 2) determine the role of integrin and VEGF-A signaling in the angiogenic response of cells to implant surface features, and 3) to determine whether neovascularization in response to an implanted biomaterial can be modulated in vivo. The results demonstrate that biomaterial surface microtopography and surface energy can increase the production of pro-angiogenic growth factors by osteoblasts and that these growth factors stimulate the differentiation of endothelial cells in a paracrine manner and the results suggest that signaling through specific integrin receptors affects the production of angiogenic growth factors by osteoblast-like cells. Further, using a novel in vivo model, the results demonstrate that a combination of a rough surface microtopography and high surface energy can improve bone-to-implant contact and neovascularization. The results of these studies also suggest that VEGF-A produced by osteoblast-like cells has both an autocrine and paracrine effect. VEGF-A silenced cells exhibited reduced production of both pro-angiogenic and osteogenic growth factors in response to surface microtopgraphy and surface energy, and conditioned media from VEGF-A silenced osteoblast-like cell cultures failed to stimulate endothelial cell differentiation in an in vitro model. Finally, the results show that by combining angiogenic and osteogenic biomaterials, new bone formation and neovascularization can be enhanced. Taken together, this research helps to provide a better understanding of the role of material properties in cell and host tissue response and will aid in the improvement of the design of new implants.

Die vorliegende Arbeit untersuchte Unterschiede im Proliferationsverhalten von vier verschiedenen humanen Knochenzellproben auf kommerziell reinem Titan mit maschinell bearbeiteter, glatter Oberfläche. Es handelte sich um frisch entnommene, nicht pathologische, humane Knochenzellen vom Oberkiefer und Unterkiefer, welche im Block entnommen und in Fragmente zerkleinert wurden. Im Anschluss kultivierten und subkultivierten wir die Knochenzellen. Einen Teil dieser Knochenzellkulturen froren wir zwischenzeitlich für 48 Stunden ein. Anschließend pipettierten wir von jeder Knochen-zellkultur jeweils 1000 Zellen der 2. Subkultur in sogenannte Chamber Slides und führten jeweils am 5., 10., 15., 20. und 25. Versuchstag in vitro Zellzählungen sowie immunhistochemisch gestützte, fluoreszenzoptische Messungen in 200facher Vergrö-ßerung von den frischen und gefrorenen Oberkieferknochenzellkulturen und den frischen und gefrorenen Unterkieferknochenzellkulturen durch. Die fluoreszenz-optischen Markierungen dienten der Visualisierung der Zellkerne, welche wir mit DAPI gegenfärbten, ebenso des Bone Sialoproteins (BSP), einem nicht-kollagenen Knochenmatrixprotein, und wurden in Form von Grauwerten erfasst. In den frischen und gefrorenen Unterkieferknochenzellkulturen konnte eine signifikant höhere Proliferations-rate der Knochenzellen im Vergleich zu den frischen und gefrorenen Oberkiefer-knochenzellkulturen nachgewiesen werden. Die höchste Proliferationsrate war dabei in den frischen Unterkieferknochenzellkulturen über den gesamten Versuchsverlauf zu verzeichnen. Interessanterweise war kein signifikantes Korrelat zwischen der Expression von BSP und der Knochenzellproliferation zwischen den einzelnen Knochenzellproben nachweisbar.

Dental caries and periodontal disease are the major causes for tooth loss. While dental caries commonly involve the posterior teeth in both jaws, the teeth most commonly lost due to periodontal problems are the first and second molars in the maxilla. As a consequence, the upper posterior jaw is frequently edentulous. Implant therapy today is a predictable treatment modality for prosthetic reconstruction of edentulous patient. Insufficient amounts of bone, due to atrophy following loss of teeth or due to the presence of the maxillary sinus, can make it impossible to insert implants in the posterior maxilla. During the 1970s and 1980s, Tatum, Boyne and James and Wood and Moore first described maxillary sinus floor augmentation whereby, after the creation of a lateral access point, autologous bone grafts are inserted to increase crestal bone height and to create the necessary conditions for the insertion of implants. This surgical procedure requires a two-stage approach and a double surgical site: first, bone is harvested from a donor site and transplanted to the recipient site; then, after a proper healing period of between 4 to 6 months, the implants are inserted. This kind of bone reconstruction, even if well documented, has its limitations, not least in the creation of two different surgical sites and the consequent increased risk of morbidity. In 2004, Lundgren et al. described a new, simplified technique for the elevation of the sinus floor. The authors showed that by lifting the sinus membrane an empty space was created in which blood clot formations resulted in the establishment of new bone. The implants were placed simultaneously to function as “tent poles”, thus maintaining the sinus membrane in a raised position during the subsequent healing period. An essential prerequisite of this technique is to obtain optimal primary implant stability from the residual bone in the sinus floor. An extremely resorbed maxillary sinus floor, with, for example, less than 2-3 mm of poor quality residual bone, could impair implant insertion. The aims of the present research project were (i) to evaluate the donor site morbidity and the acceptance level of patients when a bone graft is harvested from the anterior iliac crest, (ii) to evaluate implant stability, new bone formation inside the maxillary sinus and marginal bone resorption around the implants in long term follow up when maxillary sinus floor augmentation is performed through sinus membrane elevation and without the addition of any grafting material, (iii) to investigate new bone formation inside the maxillary sinus, in experimental design, using a resorbable space-maker device in order to maintain elevation of the sinus membrane where there is too little bone to insert implants with good primary stability. In Paper I, 70 consecutively treated patients were retrospectively evaluated in terms of postoperative donor site morbidity and donor site complications. With regard to donor site morbidity, 74% of patients were free of pain within 3 weeks, whereas 26% had a prolonged period of pain lasting from a few weeks to several months. For 11% of patients there was still some pain or discomfort 2 years after the grafting surgery. Nevertheless, patients acceptance was high and treatment significantly improved oral function, facial appearance, and recreation/social activities and resulted in an overall improvement in the quality of life of formerly edentulous patients. In Paper I and III, some differently shaped space-making devices were tested on primates (tufted capuchin - Cebus apella) in two experimental models aimed at evaluating whether a two-stage procedure for sinus floor augmentation could benefit from the use of a space-making device to increase the bone volume and enable later implant installation with good primary stability, without the use of any grafting material. An histological examination of the specimens showed that it is possible to obtain bone formation in contact with both the Schneiderian membrane and the device. In most cases the device was displaced. The process of bone formation indicated that this technique is potentially useful for two-stage sinus floor augmentation. The lack of device stability within the sinus requires further improvement in space-makers if predictable bone augmentation is to be achieved. In Paper IV, a total of 84 patients were subjected to 96 membrane elevation procedures and the simultaneous placement of 239 implants. Changes of intra-sinus and marginal bone height in relation to the implants were measured in intraoral radiographs carried out during insertion after 6 months of healing, after 6 months of loading and then annually. Computerised tomography was performed pre-surgically and 6 months post-surgically. Resonance frequency analysis measurements were performed at the time of implant placement, at abutment connection and after 6 months of loading. The implant follow-up period ranged from a minimum of one to a maximum of 6 years after implant loading. All implants were stable after 6 months of healing. A total of three implants were lost during the follow-up period giving a survival rate of 98.7%. Radiography demonstrated an average of 5.3 ± 2.1 mm of intra-sinus new bone formation after 6 months of healing. RFA measurements showed adequate primary stability (implant stability quotient 67.4 ± 6.1) and small changes over time. In conclusion, harvesting bone from the iliac crest could result in temporary donor site morbidity, but in 11% of patients pain or discomfort was still present up to 2 years after surgery. However, patient satisfaction was good despite this slow or incomplete recovery, as showed by the quality of life questionnaire. Maxillary sinus membrane elevation without the use of bone grafts or bone substitutes results in predictable bone formation both in animal design, where the sinus membrane is supported by a resorbable device, and in clinical conditions, where the membrane is kept in the upper position by dental implants. This new bone formation is accompanied by a high implant survival rate of 98.7% over a follow-up period of up to 6 years. Intra-sinus bone formation remained stable in the long-term follow-up. It is suggested that the secluded compartment allowed bone formation in accordance with the principle of guided tissue regeneration. This technique reduces the risks of morbidity related to bone graft harvesting and eliminates the costs of grafting materials.

Dental implants are an effective alternative for the replacement of missing teeth. The success of the implant depends on how well a bone heals around the implant, a process known as osseointegration. However, excessive heat generated during the bone drilling will cause cell death and may prevent osseointegration of the implant, resulting in early failure. There are many factors which contribute to the heat generation during drilling. Experiments were carried out to investigate the affect of variable drilling factors on heat generation during drilling operation. Natural bone is not an ideal material for such research, as it varies widely in density and other parameters of interest.. It would be desirable to have a more uniform and consistent material to use in such studies. However, such a material must be similar to bone to allow the results to be extrapolated to the clinical situation. The current study describes and validates a model for use in such studies. Polymethylmethacrylate (PMMA) is the material chosen for our studies. A theoretical model was developed to study the effect of different drilling parameters on temperature rise during drilling operations. Comparison of observed results obtained from experiments was made with the results from theoretical study. Comparison of results for PMMA and human bone are also shown explaining how PMMA material can be substituted for human bone. The results suggest that the PMMA model is an acceptable surrogate for bone in such studies.

The process of osseointegration described by Brånemark (Brånemark et al 1969, 1977) and Schroeder (Schroeder et al 1981) plays an integral role in dental rehabilitation. Since the first observation 40 years ago, osseointegrated titanium implants have been used predictably in the dental rehabilitation of fully edentulous patients. The application of dental implants has evolved, and from the 1980s dental implants have been used increasingly in the treatment of partially edentulous patients, with equal or better long-term success (Buser et al 1990, 1997, Lekholm et al 1994, Behneke et al 2000, Bornstein et al 2005). The surgical procedures for the placement of endosseous dental implants are based on the original work by Brånemark and colleagues approximately 40 years ago. The two-stage surgical procedure was originally advocated to obtain an optimal process of new bone formation and remodelling after implant placement (Brånemark et al 1977). Osseointegration and good long-term success was also found to be achievable with non-submerged implants (Buser et al 1990, 1992, 1997, Ericsson et al 1997) with the added advantage of avoiding a second surgical procedure (Buser et al 1999). Implant dentistry has evolved over the last 15 years and has benefited from significant progress made in associated treatment protocols and the development of bone augmentation procedures (guided bone regeneration (GBR) and sinus floor elevation) allowing for correction of alveolar bone deficiencies. Additionally, improved osteophilic microtextured implant surfaces have been developed to accelerate healing, significantly reducing treatment time. Research and clinical focus in dental implantology in the last two decades has primarily concentrated on the bone-to-implant interface of osseointegrated implants. The soft tissue profile and seal around implants have been investigated to a much lesser degree. This interest has been largely due to the fact that a successfully osseointegrated implant depends on anchorage in bone and requires a direct bone-to-implant interface to provide long-term support for a prosthesis. Both bone and soft tissue integration onto dental implants are wound healing processes whereby several stages of tissue formation and degradation are involved (Berglundh et al 2003, Abrahamsson et al 2004). Osseointegration is the result of the modelling and remodelling of bone tissue that occurs after implant placement whilst the wound healing that occurs following the closure of mucoperiosteal flaps during implant surgery results in the establishment of a mucosal attachment (transmucosal attachment) to the implant. The establishment of the mucosal barrier around the implant is characterised by the gradual shift from a coagulum to granulation tissue followed by the formation of a barrier epithelium and the maturation of the connective tissue (Berglundh et al 2007). Like natural teeth, osseointegrated implants are transmucosal “masticatory devices” that penetrate the oral mucosa with the periodontal and peri-implant tissues expected to perform a protective function (Weber & Cochran 1998). Background: Peri-implant tissues form a crucial but fragile seal between the oral environment, the bone and the implant surface. Enhancing the seal formed by the peri-implant soft tissues at the titanium/connective tissue interface may be an important factor in implant survival. Additionally, enhancing soft tissue adherence to the implant surface when implants are placed in dehiscence type defects may mean that simultaneous osseous grafting procedures will not always be required. Objective: The aim of this study was to investigate the effect of implant surface modification with either platelet-derived growth factor (PDGF) or enamel matrix derivative (EMD) on the connective tissue attachment to moderately roughened titanium implants. Material and Methods: 18 moderately roughened titanium implants were subcutaneously implanted into 14 rats. 6 implants each were coated with PDGF and EMD immediately prior to implantation and 6 implants were left uncoated. The implants were retrieved with a sample of surrounding tissue at 4 and 8 weeks. The specimens were resin-embedded and sections viewed under confocal microscopy for collagen autofluorescence and prepared for qualitative and histomorphometric analysis under light microscopy. ANOVA and t-tests were used to compare the thickness of fibroblast encapsulation on the implant surface and the depth of connective tissue penetration onto the implant grooves. Results: Qualitative analysis under confocal and light microscopy showed encapsulation of all implants by fibroblasts and good soft tissue integration at the end of 4 and 8 weeks. Coating of the implants with growth factors did not alter the orientation of fibroblasts and collagen fibres. Histomorphometric analysis demonstrated that the depth of connective tissue penetration into the implant grooves was significantly greater for the implants coated with PDGF at 4 weeks (ANOVA, P value 0.0014). The thickness of the fibroblast encapsulation on the implant surface was significantly less for the implants coated with PDGF at 8 weeks (ANOVA, P value 0.0012). Conclusion: Good soft tissue integration can be achieved on a moderately roughened titanium implant surface. Coating the implant surface with rhPDGF-BB could increase the speed of soft tissue healing around an implant surface but this increased rate of healing with rhPDGF-BB coating could also result in a less robust titanium/connective tissue interface. / Thesis (D.Clin.Dent.) -- University of Adelaide, School of Dentistry, 2010

Diss. (sammanfattning) Umeå : Univ., 2006. / Härtill 5 uppsatser.

Diss. (sammanfattning) Göteborg : Göteborgs universitet , 2008. / Härtill 5 uppsatser.