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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 47 58 - 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 56 128 - 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 6 150 162 - 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 14 513 349 - 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 8 358 310 - 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 6 422 378 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Bone fragility and decline in stem cells in prematurely aging DNA repair deficient trichothiodystrophy mice(Springer, 2011); ; ; ; Trichothiodystrophy (TTD) is a rare, autosomal recessive nucleotide excision repair (NER) disorder caused by mutations in components of the dual functional NER/basal transcription factor TFIIH. TTD mice, carrying a patient-based point mutation in the Xpd gene, strikingly resemble many features of the human syndrome and exhibit signs of premature aging. To examine to which extent TTD mice resemble the normal process of aging, we thoroughly investigated the bone phenotype. Here, we show that female TTD mice exhibit accelerated bone aging from 39 weeks onwards as well as lack of periosteal apposition leading to reduced bone strength. Before 39 weeks have passed, bones of wild-type and TTD mice are identical excluding a developmental defect. Albeit that bone formation is decreased, osteoblasts in TTD mice retain bone-forming capacity as in vivo PTH treatment leads to increased cortical thickness. In vitro bone marrow cell cultures showed that TTD osteoprogenitors retain the capacity to differentiate into osteoblasts. However, after 13 weeks of age TTD females show decreased bone nodule formation. No increase in bone resorption or the number of osteoclasts was detected. In conclusion, TTD mice show premature bone aging, which is preceded by a decrease in mesenchymal stem cells/osteoprogenitors and a change in systemic factors, identifying DNA damage and repair as key determinants for bone fragility by influencing osteogenesis and bone metabolism.Publicationtype: Journal ArticleScopus© Citations 18 210 232 - 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 171 250 385