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Item type:Publication, Access status: without files , Design of a flexible mechatronic system for mechanical impedance measurement of the wrist as one step towards robotic rehabilitationHome rehabilitation is a great complement to inpatient rehabilitation, because it allows for more regular training, especially in rural areas, where the access to physiotherapists is limited. However, unsupervised training carries the risk of deviation from the prescribed protocol. An obvious solution is to introduce a technical means for rehabilitation and continuous monitoring of performance. This paper presents a robotic system for rehabilitation of three degrees of freedom of the wrist independently, implemented with only one actuator, optimizing the design and size of the system. The device provides measurements of joint torque-position dependence, allowing objective assessment of mechanical impedance and range of motion to evaluate the progress of rehabilitation. Derived from research on haptic devices, a measurement method was implemented to measure hand impedance in the high frequency range between 100 and 200 Hz using a combination of exciters and accelerometers in the handles. This allows continuous monitoring of gripping forces without the need for complex contact-based force sensors. In collaboration between the authors’ technical and medical universities, a set of two-level passive and active safety measures was implemented to ensure the safety of the system’s users. Therefore, the presented system shows the potential to evaluate the mechanical impedance of the wrist at both low and high frequencies and to monitor the progress during rehabilitation. In the next step, a baseline of wrist impedance will be measured in a target group of healthy volunteers in order to prepare for studies in motion-restricted subjects.Publicationtype: Conference Paper45 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Design of a flexible mechatronic system for mechanical impedance measurement of the wrist as one step towards robotic rehabilitation(De Gruyter, 2023-09-01); ; ; Home rehabilitation is a great complement to inpatient rehabilitation, because it allows for more regular training, especially in rural areas, where the access to physiotherapists is limited. However, unsupervised training carries the risk of deviation from the prescribed protocol. An obvious solution is to introduce a technical means for rehabilitation and continuous monitoring of performance. This paper presents a robotic system for rehabilitation of three degrees of freedom of the wrist independently, implemented with only one actuator, optimizing the design and size of the system. The device provides measurements of joint torque-position dependence, allowing objective assessment of mechanical impedance and range of motion to evaluate the progress of rehabilitation. Derived from research on haptic devices, a measurement method was implemented to measure hand impedance in the high frequency range between 100 and 200 Hz using a combination of exciters and accelerometers in the handles. This allows continuous monitoring of gripping forces without the need for complex contact-based force sensors. In collaboration between the authors' technical and medical universities, a set of two-level passive and active safety measures was implemented to ensure the safety of the system's users. Therefore, the presented system shows the potential to evaluate the mechanical impedance of the wrist at both low and high frequencies and to monitor the progress during rehabilitation. In the next step, a baseline of wrist impedance will be measured in a target group of healthy volunteers in order to prepare for studies in motion-restricted subjects.Publicationtype: Journal ArticleScopus© Citations 1 46 56 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Generation and evaluation of input values for computational analysis of transport processes within tissue cultures(Wiley-VCH, 2022-11-04); ; ; ; Techniques for tissue culture have seen significant advances during the last decades and novel 3D cell culture systems have become available. To control their high complexity, experimental techniques and their Digital Twins (modelling and computational tools) are combined to link different variables to process conditions and critical process parameters. This allows a rapid evaluation of the expected product quality. However, the use of mathematical simulation and Digital Twins is critically dependent on the precise description of the problem and correct input parameters. Errors here can lead to dramatically wrong conclusions. The intention of this review is to provide an overview of the state-of-the-art and remaining challenges with respect to generating input values for computational analysis of mass and momentum transport processes within tissue cultures. It gives an overview on relevant aspects of transport processes in tissue cultures as well as modelling and computational tools to tackle these problems. Further focus is on techniques used for the determination of cell-specific parameters and characterization of culture systems, including sensors for on-line determination of relevant parameters. In conclusion, tissue culture techniques are well-established, and modelling tools are technically mature. New sensor technologies are on the way, especially for organ chips. The greatest remaining challenge seems to be the proper addressing and handling of input parameters required for mathematical models. Following Good Modelling Practice approaches when setting up and validating computational models is, therefore, essential to get to better estimations of the interesting complex processes inside organotypic tissue cultures in the future.Publicationtype: Review ArticleScopus© Citations 1 56 124 - Some of the metrics are blocked by yourconsent settings
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: with files , Biodegradable poly (lactic acid-co-glycolic acid) scaffolds as carriers for geneticallymodified fibroblasts(Public Library of Science (PLoS), 2017-04-05); ; ; ; Recent advances in gene delivery into cells allow improved therapeutic effects in gene therapy trials. To increase the bioavailability of applied cells, it is of great interest that transfected cells remain at the application site and systemic spread is minimized. In this study, we tested clinically used biodegradable poly(lactic acid-co-glycolic acid) (PLGA) scaffolds (Vicryl & Ethisorb) as transient carriers for genetically modified cells. To this aim, we used human fibroblasts and examined attachment and proliferation of untransfected cells on the scaffolds in vitro, as well as the mechanical properties of the scaffolds at four time points (1, 3, 6 and 9 days) of cultivation. Furthermore, the adherence of cells transfected with green fluorescent protein (GFP) and vascular endothelial growth factor (VEGF165) and also VEGF165 protein secretion were investigated. Our results show that human fibroblasts adhere on both types of PLGA scaffolds. However, proliferation and transgene expression capacity were higher on Ethisorb scaffolds most probably due to a different architecture of the scaffold. Additionally, cultivation of the cells on the scaffolds did not alter their biomechanical properties. The results of this investigation could be potentially exploited in therapeutic regiments with areal delivery of transiently transfected cells and may open the way for a variety of applications of cell-based gene therapy, tissue engineering and regenerative medicine.Publicationtype: Journal ArticleScopus© Citations 8 358 308 - 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: with files , The development of the collagen fibre network in tissue-engineered cartilage constructs in vivo : engineered cartilage reorganises fibre network(University of Wales, 2012-04-05); ; ; ; For long term durability of tissue-engineered cartilage implanted in vivo, the development of the collagen fibre network orientation is essential as well as the distribution of collagen, since expanded chondrocytes are known to synthesise collagen type I. Typically, these properties differ strongly between native and tissue-engineered cartilage. Nonetheless, the clinical results of a pilot study with implanted tissue-engineered cartilage in pigs were surprisingly good. The purpose of this study was therefore to analyse if the structure and composition of the artificial cartilage tissue changes in the first 52 weeks after implantation. Thus, collagen network orientation and collagen type distribution in tissue-engineered cartilage-carrier-constructs implanted in the knee joints of Göttinger minipigs for 2, 26 or 52 weeks have been further investigated by processing digitised microscopy images of histological sections. The comparison to native cartilage demonstrated that fibre orientation over the cartilage depth has a clear tendency towards native cartilage with increasing time of implantation. After 2 weeks, the collagen fibres of the superficial zone were oriented parallel to the articular surface with little anisotropy present in the middle and deep zones. Overall, fibre orientation and collagen distribution within the implants were less homogenous than in native cartilage tissue. Despite a relatively low number of specimens, the consistent observation of a continuous approximation to native tissue is very promising and suggests that it may not be necessary to engineer the perfect tissue for implantation but rather to provide an intermediate solution to help the body to heal itself.Publicationtype: Journal ArticleScopus© Citations 6 421 377