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Item type:Publication, Access status: with files , Osteoidosis leads to altered differentiation and function of osteoclasts(Wiley-Blackwell, 2020-04-13); ; ; ; In patients with osteomalacia, a defect in bone mineralization leads to changed characteristics of the bone surface. Considering that the properties of the surrounding matrix influence function and differentiation of cells, we aimed to investigate the effect of osteoidosis on differentiation and function of osteoclasts. Based on osteomalacic bone biopsies, a model for osteoidosis in vitro (OIV) was established. Peripheral blood mononuclear cells were differentiated to osteoclasts on mineralized surfaces (MS) as internal control and on OIV. We observed a significantly reduced number of osteoclasts and surface resorption on OIV. Atomic force microscopy revealed a significant effect of the altered degree of mineralization on surface mechanics and an unmasking of collagen fibres on the surface. Indeed, coating of MS with RGD peptides mimicked the resorption phenotype observed in OIV, suggesting that the altered differentiation of osteoclasts on OIV might be associated with an interaction of the cells with amino acid sequences of unmasked extracellular matrix proteins containing RGD sequences. Transcriptome analysis uncovered a strong significant up-regulation of transmembrane glycoprotein TROP2 in osteoclastic cultures on OIV. TROP2 expression on OIV was also confirmed on the protein level and found on the bone surface of patients with osteomalacia. Taken together, our results show a direct influence of the mineralization state of the extracellular matrix surface on differentiation and function of osteoclasts on this surface which may be important for the pathophysiology of osteomalacia and other bone disorders with changed ratio of osteoid to bone.Publicationtype: Journal ArticleScopus© Citations 6 149 160 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Developmental transformation and reduction of connective cavities within the subchondral boneIt is widely accepted that the subchondral bone (SCB) plays a crucial role in the physiopathology of osteoarthritis (OA), although its contribution is still debated. Much of the pre-clinical research on the role of SCB is concentrated on comparative evaluations of healthy vs. early OA or early OA vs. advanced OA cases, while neglecting how pure maturation could change the SCB’s microstructure. To assess the transformations of the healthy SCB from young age to early adulthood, we examined the microstructure and material composition of the medial condyle of the femur in calves (three months) and cattle (18 months) for the calcified cartilage (CC) and the subchondral bone plate (SCBP). The entire subchondral zone (SCZ) was significantly thicker in cattle compared to calves, although the proportion of the CC and SCBP thicknesses were relatively constant. The trabecular number (Tb.N.) and the connectivity density (Conn.D) were significantly higher in the deeper region of the SCZ, while the bone volume fraction (BV/TV), and the degree of anisotropy (DA) were more affected by age rather than the region. The mineralization increased within the first 250 µm of the SCZ irrespective of sample type, and became stable thereafter. Cattle exhibited higher mineralization than calves at all depths, with a mean Ca/P ratio of 1.59 and 1.64 for calves and cattle, respectively. Collectively, these results indicate that the SCZ is highly dynamic at early age, and CC is the most dynamic layer of the SCZ.Publicationtype: Journal ArticleScopus© Citations 14 512 348 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Matrix demineralisation leads to altered differentiation and function of osteoclasts(Public Library of Science (PLoS), 2015); ; ; ; Publicationtype: Journal Article4 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Three-dimensional quantification of calcium salt-composite resorption (CSC) in vitro by micro-computed tomography (Micro-CT)The commonly applied cell-based, two-dimensional (2D) in vitro resorption assays for biomaterials are limited in a variety of cases, including high initial roughness of material surface, uncontrollable solubilization (or resorption) of the entire material surface, or complex three-dimensional (3D) structure of the bioactive material itself. All these make the accurate assessment and successful selection of the optimal bone substitute material difficult. In vivo, micro-computed tomography (micro-CT) has been widely applied for the analysis of bone physiology and pathology, as well as for the 3D analysis of scaffolds for bone tissue engineering. In this study, we show that micro-CT can also be applied for the in vitro analysis of osteoclast-mediated resorption of biomaterials. For our experiments, we chose a calcium salt-composite (composite of calcium sulphate (CSC), calcium carbonate, glycerin-1,2,3-tripalmiate), which evades common 2D in vitro resorption analysis as a result of its high surface roughness and material composition. Human osteoclasts were differentiated from precursor cells on the surface of the material for 28 days. Cells were analyzed for expression of tartrate-resistant acid phosphatase 5b (TRAP5b), multinuclearity, and size. Volumetric analysis of resorption was performed by micro-CT. Multinucleated osteoclasts developed on the surface of the material. TRAP5b expression of the cells on CSC was comparable with TRAP5b expression of cells cultivated on dentin for the first 3 weeks of culture. At day 28, TRAP5b expression, cell number, and size of the TRAP+ cells were reduced on the CSC when compared with cells on dentin. Volumetric anaylsis by micro-CT showed a strong cellular effect on resorption of CSC. We consider micro-CT to be a promising technique for 3D quantification of cell-based resorption that will allow the study of cellular resorption of materials in vitro, which were up to now confined to animal experimental analysis. © 2014 The Minerals, Metals & Materials Society.Publicationtype: Journal Article3 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Mechanical properties of native and tissue-engineered cartilage depend on carrier permeability : a bioreactor study(Liebert, 2013-03-19); ; ; ; The implantation of osteochondral constructs-tissue-engineered (TE) cartilage on a bone substitute carrier-is a promising method to treat defects in articular cartilage. Currently, however, the TE cartilage's mechanical properties are clearly inferior to those of native cartilage. Their improvement has been the subject of various studies, mainly focusing on growth factors and physical loading during cultivation. With the approach of osteochondral constructs another aspect arises: the permeability of the carrier materials. The purpose of this study was to investigate whether and how the permeability of the subchondral bone influences the properties of native cartilage and whether the bone substitute carrier's permeability influences the TE cartilage of osteochondral constructs accordingly. Consequently, the influence of the subchondral bone's permeability on native cartilage was determined: Native porcine cartilage-bone cylinders were cultivated for 2 weeks in a bioreactor under mechanical loading with and without restricted permeability of the bone. For the TE cartilage these two permeability conditions were investigated using permeable and impermeable tricalciumphosphate carriers under equivalent cultivation conditions. All specimens were evaluated mechanically, biochemically, and histologically. The restriction of the bone's permeability significantly decreased the Young's modulus of native cartilage in vitro. No biochemical differences were found. This finding was confirmed for TE cartilage: While the biochemical parameters were not affected, a permeable carrier improved the cell morphology and mechanical properties in comparison to an impermeable one. In conclusion, the carrier permeability was identified as a determining factor for the mechanical properties of TE cartilage of osteochondral constructs. © 2013, Mary Ann Liebert, Inc.Publicationtype: Journal Article143 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Bioresorption and degradation of biomaterialsThe human body is a composite structure, completely constructed of biodegradable materials. This allows the cells of the body to remove and replace old or defective tissue with new material. Consequently, artificial resorbable biomaterials have been developed for application in regenerative medicine. We discuss here advantages and disadvantages of these bioresorbable materials for medical applications and give an overview of typically used metals, ceramics and polymers. Methods for the quantification of bioresorption in vitro and in vivo are described. The next challenge will be to better understand the interface between cell and material and to use this knowledge for the design of " intelligent" materials that can instruct the cells to build specific tissue geometries and degrade in the process.Publicationtype: Journal Article4 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , High amplitude direct compressive strain enhances mechanical properties of scaffold-free tissue-engineered cartilage(2011); ; ; ; Schüttler, DanielAdult cartilage has a limited healing capacity. Damages resulting from disease or injury increase over time and cause severe pain. One approach to reinstate the cartilage function is tissue engineering (TE). However, the generation of TE cartilage is time consuming and expensive and its properties are so far suboptimal. As in vivo cartilage is subject to loading, it is assumed that mechanical stimulation may enhance the quality of TE cartilage. In this study the short-term influence of variable compressive strain amplitudes on mechanical and biochemical properties of scaffold-free TE cartilage was investigated. Primary porcine chondrocytes were isolated, proliferated, redifferentiated, and transferred onto hydroxyapatite carriers, resulting in scaffold-free cartilage-carrier constructs. These constructs were placed in a custom-made bioreactor. Compression amplitudes of 5%, 10%, and 20% were applied. In each experiment four constructs were loaded with dynamic compression (3000 cycles/day, 1 Hz) for 14 days and four constructs served as unloaded control. The cartilage was evaluated biochemically, histological, and mechanically. No difference in glycosaminoglycan or collagen content between the loaded and the control groups was found. However, a positive correlation between compression amplitude and normalized Young's modulus was detected (R2=0.59, p<0.001). The highest compression amplitude of 20% had the strongest positive effect on the mechanical properties of the TE cartilage (Young's modulus increase of 241±28% compared to unloaded control). The data presented suggest that preconditioning with higher load amplitudes might be an attractive way of generating stiffer tissue and may help accelerating the cultivation of mechanically competent TE cartilage. © 2011 Mary Ann Liebert, Inc.Publicationtype: Journal Article5 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Volumetric analysis of osteoclastic bioresorption of calcium phosphate ceramics with different solubilities(Elsevier, 2010-10); ; 5 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Advances in porous biomaterials for dental and orthopaedic applications(Multidisciplinary Digital Publishing Institute (MDPI), 2010-04-28); ; ; ; The connective hard tissues bone and teeth are highly porous on a micrometer scale, but show high values of compression strength at a relatively low weight. The fabrication of porous materials has been actively researched and different processes have been developed that vary in preparation complexity and also in the type of porous material that they produce. Methodologies are available for determination of pore properties. The purpose of the paper is to give an overview of these methods, the role of porosity in natural porous materials and the effect of pore properties on the living tissues. The minimum pore size required to allow the ingrowth of mineralized tissue seems to be in the order of 50 μm: larger pore sizes seem to improve speed and depth of penetration of mineralized tissues into the biomaterial, but on the other hand impair the mechanical properties. The optimal pore size is therefore dependent on the application and the used material.Publicationtype: Review ArticleScopus© Citations 171 250 383 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Osteoclastic bioresorption of biomaterials : two- and three-dimensional imaging and quantification(Sage Publications, 2010-04); ; ; Berger, GeorgPurpose: Bioresorbable materials have been developed in the hope that the body will replace them with newly formed tissue. The first step of this remodeling process in bone is the bioresorption of the material by osteoclasts. The aim of this study was to analyze osteoclastic resorption of biomaterials in vitro using the commonly used two-dimensional methods of light-microscopy (LM) and scanning electron microscopy (SEM) in comparison with infinite focus microscopy (IFM), a recently developed imaging method allowing for three-dimensional surface analysis. Methods: Human hematopoietic stem cells were cultivated in the presence of the cytokines M-CSF and RANK-L for 4 weeks directly on dentin and a calcium phosphate cement. Osteoclast development was surveyed with standard techniques. After removal of the cells, resorption was characterized and quantified by LM, SEM and IFM. Results: Osteoclast cultures on the biomaterials presented the typical osteoclast-specific markers. On dentin samples LM, SEM as well as IFM allowed for discrimination of resorption. Quantification of the resorbed area showed a linear correlation between the results (LM vs. SEM: r=0.996, p=0.004; SEM vs. IFM: r=0.989, p=0.011; IFM vs. LM: r=0.995). It was not possible to demarcate resorption pits on GB14 using LM or SEM. With IFM, resorption on GB14 could be visualized and quantified two- and three-dimensionally. Conclusions: In this paper we introduce IFM as a technology for three-dimensional visualization and quantification of resorption of biomaterials. Better understanding of the bioresorption of biomaterials may help in the design of better materials and might therefore constitute an important step on the avenue to the development of artificial bone. © 2010 Wichtig Editore.Publicationtype: Journal Article5