Jörg Handschel

Current trends and future perspectives of bone substitute materials - from space holders to innovative biomaterials.

An autologous bone graft is still the ideal material for the repair of craniofacial defects, but its availability is limited and harvesting can be associated with complications. Bone replacement materials as an alternative have a long history of success. With increasing technological advances the spectrum of grafting materials has broadened to allografts, xenografts, and synthetic materials, providing material specific advantages. A large number of bone-graft substitutes are available including allograft bone preparations such as demineralized bone matrix and calcium-based materials. More and more replacement materials consist of one or more components: an osteoconductive matrix, which supports the ingrowth of new bone; and osteoinductive proteins, which sustain mitogenesis of undifferentiated cells; and osteogenic cells (osteoblasts or osteoblast precursors), which are capable of forming bone in the proper environment. All substitutes can either replace autologous bone or expand an existing amount of autologous bone graft. Because an understanding of the properties of each material enables individual treatment concepts this review presents an overview of the principles of bone replacement, the types of graft materials available, and considers future perspectives. Bone substitutes are undergoing a change from a simple replacement material to an individually created composite biomaterial with osteoinductive properties to enable enhanced defect bridging.

Effects of dexamethasone, ascorbic acid and β-glycerophosphate on the osteogenic differentiation of stem cells in vitro

The standard procedure for the osteogenic differentiation of multipotent stem cells is treatment of a confluent monolayer with a cocktail of dexamethasone (Dex), ascorbic acid (Asc) and β-glycerophosphate (β-Gly). This review describes the effects of these substances on intracellular signaling cascades that lead to osteogenic differentiation of bone marrow stroma-derived stem cells. We conclude that Dex induces Runx2 expression by FHL2/β-catenin-mediated transcriptional activation and that Dex enhances Runx2 activity by upregulation of TAZ and MKP1. Asc leads to the increased secretion of collagen type I (Col1), which in turn leads to increased Col1/α2β1 integrin-mediated intracellular signaling. The phosphate from β-Gly serves as a source for the phosphate in hydroxylapatite and in addition influences intracellular signaling molecules. In this context we give special attention to the differences between dystrophic and bone-specific mineralization.

Osseointegration of zirconia implants compared with titanium: an in vivo study

BackgroundTitanium and titanium alloys are widely used for fabrication of dental implants. Since the material composition and the surface topography of a biomaterial play a fundamental role in osseointegration, various chemical and physical surface modifications have been developed to improve osseous healing. Zirconia-based implants were introduced into dental implantology as an altenative to titanium implants. Zirconia seems to be a suitable implant material because of its tooth-like colour, its mechanical properties and its biocompatibility. As the osseointegration of zirconia implants has not been extensively investigated, the aim of this study was to compare the osseous healing of zirconia implants with titanium implants which have a roughened surface but otherwise similar implant geometries.MethodsForty-eight zirconia and titanium implants were introduced into the tibia of 12 minipigs. After 1, 4 or 12 weeks, animals were sacrificed and specimens containing the implants were examined in terms of histological and ultrastructural techniques.ResultsHistological results showed direct bone contact on the zirconia and titanium surfaces. Bone implant contact as measured by histomorphometry was slightly better on titanium than on zirconia surfaces. However, a statistically significant difference between the two groups was not observed.ConclusionThe results demonstrated that zirconia implants with modified surfaces result in an osseointegration which is comparable with that of titanium implants.

TCP is hardly resorbed and not osteoconductive in a non-loading calvarial model

Tricalciumphosphate (TCP) has been used as a ceramic bone substitute material in the orthopedic field as well as in craniofacial surgery. Some controversies exist concerning the osteoconductive potential of this material in different implantation sites. This study was designed to evaluate the biological response of calvarial bone towards TCP granules under non-loading conditions to assess the potential of TCP as a biodegredable and osteoconductive bone substitue material for the cranial vault. Full-thickness non-critical size defects were made bilaterally in the calvaria of 21 adult Wistar rats. One side was filled by TCP granules, the contralateral side was left empty and used as a control. Animals were sacrified in defined time intervals up to 6 months. Bone regeneration was analyzed with special respect toward the micromorphological and microanalytical features of the material-bone interaction by electron microscopy and electron diffraction analysis. Histologic examination revealed no TCP degradation even after 6 months of implantation. In contrast, a nearly complete bone regeneration of control defects was found after 6 months. At all times TCP was surrounded by a thin fibrous layer without presence of osteoblasts and features of regular mineralization. As far as degradation and substitution are concerned, TCP is a less favourable material tinder conditions of non-loading.

Strain-related bone remodeling in distraction osteogenesis of the mandible.

Distraction osteogenesis has become a mainstay in craniofacial surgery. However, there are several unresolved problems concerning the biology of bone regeneration. We investigated the biomechanical effects of mandibular lengthening in 32 rabbits on a cellular and histologic level. The mandible was subjected to a corticotomy, held in a neutral position for 4 days, and then lengthened at various strain rates and frequencies for 10 days. Radiographic, histologic, and electron microscopic examinations showed a strain-related bone regeneration. Application of physiologic strain rates (2000 microstrains or 0.2 percent) led to a bridging of the artificial fracture exhibiting woven ossification, whereas at 20,000 microstrains trabecular bone formation was demonstrated. In contrast, hyperphysiologic strain magnitudes (200,000 microstrains and 300,000 microstrains) showed a fibrous tissue formation. Multiple strain applications (10 cycles/day versus 1 cycle/day) increased the width of the distraction gap without changing the stage of bone regeneration. The gradual distraction of bone in physiologic magnitudes at higher frequencies seems to be desirable for a bony differentiation and may help to improve clinical applications.

Behavior of osteoblastic cells cultured on titanium and structured zirconia surfaces

BackgroundOsseointegration is crucial for the long-term success of dental implants and depends on the tissue reaction at the tissue-implant interface. Mechanical properties and biocompatibility make zirconia a suitable material for dental implants, although surface processings are still problematic. The aim of the present study was to compare osteoblast behavior on structured zirconia and titanium surfaces under standardized conditions.MethodsThe surface characteristics were determined by scanning electron microscopy (SEM). In primary bovine osteoblasts attachment kinetics, proliferation rate and synthesis of bone-associated proteins were tested on different surfaces.ResultsThe results demonstrated that the proliferation rate of cells was significantly higher on zirconia surfaces than on titanium surfaces (p < 0.05; Students t-test). In contrast, attachment and adhesion strength of the primary cells was significant higher on titanium surfaces (p < 0.05; U test). No significant differences were found in the synthesis of bone-specific proteins. Ultrastructural analysis revealed phenotypic features of osteoblast-like cells on both zirconia and titanium surfaces.ConclusionThe study demonstrates distinct effects of the surface composition on osteoblasts in culture. Zirconia improves cell proliferation significantly during the first days of culture, but it does not improve attachment and adhesion strength. Both materials do not differ with respect to protein synthesis or ultrastructural appearance of osteoblasts. Zirconium oxide may therefore be a suitable material for dental implants.

Osseointegration of zirconia implants: an SEM observation of the bone-implant interface.

BackgroundThe successful use of zirconia ceramics in orthopedic surgery led to a demand for dental zirconium-based implant systems. Because of its excellent biomechanical characteristics, biocompatibility, and bright tooth-like color, zirconia (zirconium dioxide, ZrO2) has the potential to become a substitute for titanium as dental implant material. The present study aimed at investigating the osseointegration of zirconia implants with modified ablative surface at an ultrastructural level.MethodsA total of 24 zirconia implants with modified ablative surfaces and 24 titanium implants all of similar shape and surface structure were inserted into the tibia of 12 Göttinger minipigs. Block biopsies were harvested 1 week, 4 weeks or 12 weeks (four animals each) after surgery. Scanning electron microscopy (SEM) analysis was performed at the bone implant interface.ResultsRemarkable bone attachment was already seen after 1 week which increased further to intimate bone contact after 4 weeks, observed on both zirconia and titanium implant surfaces. After 12 weeks, osseointegration without interposition of an interfacial layer was detected. At the ultrastructural level, there was no obvious difference between the osseointegration of zirconia implants with modified ablative surfaces and titanium implants with a similar surface topography.ConclusionThe results of this study indicate similar osseointegration of zirconia and titanium implants at the ultrastructural level.

The new polyomavirus (MCPyV) does not affect the clinical course in MCCs

Since 2008, a new polyomavirus (MCPyV) in Merkel cell carcinomas (MCC) has been described, but little is known about its impact on the clinical course. The purpose of this study was to determine the presence of MCPyV in a large sample and to correlate the results with the clinical course of the disease. 59 samples from 44 patients were analysed for the presence of MCPyV using the primers LT3, VP1 and LT1. The clinical records of these patients were evaluated and correlated with the presence of MCPyV. 58% of specimens were positive for MCPyV. Of these, LT3 was positive in 53%, VP1 in 37% and LT1 in 10%. 57% of primary tumours and 53% of metastases were positive for LT3; the numbers for VP1 and LT1 were lower. There was no correlation between the detection of MCPyV in the primary tumour and the appearance of metastases. The survival time was statistically independent from the presence of MCPyV. There is a striking occurrence of MCPyV in MCC, but whether it affects the clinical course remains unclear.

Prospects of micromass culture technology in tissue engineering

Tissue engineering of bone and cartilage tissue for subsequent implantation is of growing interest in cranio- and maxillofacial surgery. Commonly it is performed by using cells coaxed with scaffolds. Recently, there is a controversy concerning the use of artificial scaffolds compared to the use of a natural matrix. Therefore, new approaches called micromass technology have been invented to overcome these problems by avoiding the need for scaffolds. Technically, cells are dissociated and the dispersed cells are then reaggregated into cellular spheres. The micromass technology approach enables investigators to follow tissue formation from single cell sources to organised spheres in a controlled environment. Thus, the inherent fundamentals of tissue engineering are better revealed. Additionally, as the newly formed tissue is devoid of an artificial material, it resembles more closely the in vivo situation. The purpose of this review is to provide an insight into the fundamentals and the technique of micromass cell culture used to study bone tissue engineering.

Comparison of various approaches for the treatment of fractures of the mandibular condylar process.

UNLABELLED Fractures of the mandibular condyle process are the most common fractures of the lower jaw. Unfortunately, the type of treatment is still a matter of debate. PURPOSE The aim of this investigation was to compare the outcome of different treatment approaches regarding function and surgical side-effects. PATIENTS AND METHODS 111 fractures of the mandibular condyle representing all types according to the classification of Spiessl and Schroll were included. Both closed reduction (CR) and open reduction with internal fixation (ORIF) including the retromandibular/transparotid, submandibular, preauricular and intraoral approach were performed. The clinical examination included functional and aesthetic aspects at least 1 year after the fracture. RESULTS The majority of fractures (45%) were classified into Type II and IV according to Spiessl and Schroll followed by fractures without any displacement or dislocation (29.7%). The submandibular approach showed the worst outcome regarding permanent palsy of the facial nerve and hypertrophic scarring. No significant differences between the various approaches were detected in the functional status in any diagnosis group. CONCLUSION Inferior condylar neck fractures benefit from ORIF by an intraoral approach whereas in high condylar neck fractures the retromandibular/transparotid approach shows the best results. Fractures of the condylar head were almost all treated by CR and our results cannot contribute to the debate of CR vs. ORIF in this type of fracture.