TY - JOUR A1 - Steinert, Andre F. A1 - Rudert, Maximilian A1 - Sieker, Jakob T. T1 - "Symptomatic loosening of a total knee arthroplasty caused by a tibial chondrosarcoma – a case report" N2 - Premature implant loosening following total knee arthroplasty (TKA) can have several causes. In this article we report on a rare case of a 74 year old male patient suffering tibial component loosening 14 month after primary TKA. The patient did neither have any malignancies nor joint arthroplasty before. Upon clinical examination the range of motion in the diseased knee was painfully restricted to 80° of knee flexion, with the patient increasingly suffering sleeping and resting pain, and also at weight bearing. In standard radiographs, loosening of the TKA due to a large osteolysis at the tibial component was evident. Local computed tomography (CT) of the right knee revealed loosening of the tibial component due to a presumably malign bone tumor. For determination of the final diagnosis a representative biopsy of the tumor was taken by open surgery prior to the tumor resection. Histopathologic evaluation of the biopsy revealed a periprosthetic myxoid chondrosarcoma of the proximal tibia. Pre-operative staging examination included CT scans of lung and abdomen, as well as a bone scintigraphy which revealed no signs of tumor metastasis in the body. Surgical management comprised wide tumor resection and implantation of a hinged tumor knee arthroplasty with replacements of the distal femur and proximal tibia, as well as a patella tendon replacement using a synthetic ligament. Revision surgery was necessary twice due to impaired wound healing and critical soft tissue coverage, and treatment included a gastrocnemius muscle flap with skin mesh graft covering. Unfortunately long-term follow-up examinations could not be obtained, as the patient deceased due to an alveolitis during rehabilitation. In summary, the specifics of this rare case of aseptic TKA loosening, and the unusual circumstances of chondrosarcoma diagnosis and treatment are informative for those providing surgical treatment of similar cases. KW - Total knee arthroplasty KW - Bone tumor KW - Chondrosarcoma KW - Aseptic loosening Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110341 ER - TY - JOUR A1 - Klotz, Barbara A1 - Mentrup, Birgit A1 - Regensburger, Martina A1 - Zeck, Sabine A1 - Schneidereit, Jutta A1 - Schupp, Nicole A1 - Linden, Christian A1 - Merz, Cornelia A1 - Ebert, Regina A1 - Jakob, Franz T1 - 1,25-Dihydroxyvitamin D3 Treatment Delays Cellular Aging in Human Mesenchymal Stem Cells while Maintaining Their Multipotent Capacity JF - PLoS ONE N2 - 1,25-dihydroxyvitamin D3 (1,25D3) was reported to induce premature organismal aging in fibroblast growth factor-23 (Fgf23) and klotho deficient mice, which is of main interest as 1,25D3 supplementation of its precursor cholecalciferol is used in basic osteoporosis treatment. We wanted to know if 1,25D3 is able to modulate aging processes on a cellular level in human mesenchymal stem cells (hMSC). Effects of 100 nM 1,25D3 on hMSC were analyzed by cell proliferation and apoptosis assay, beta-galactosidase staining, VDR and surface marker immunocytochemistry, RT-PCR of 1,25D3-responsive, quiescence-and replicative senescence-associated genes. 1,25D3 treatment significantly inhibited hMSC proliferation and apoptosis after 72 h and delayed the development of replicative senescence in long-term cultures according to beta-galactosidase staining and P16 expression. Cell morphology changed from a fibroblast like appearance to broad and rounded shapes. Long term treatment did not induce lineage commitment in terms of osteogenic pathways but maintained their clonogenic capacity, their surface marker characteristics (expression of CD73, CD90, CD105) and their multipotency to develop towards the chondrogenic, adipogenic and osteogenic pathways. In conclusion, 1,25D3 delays replicative senescence in primary hMSC while the pro-aging effects seen in mouse models might mainly be due to elevated systemic phosphate levels, which propagate organismal aging. KW - perspectives KW - bone marrow KW - mutant mice KW - oxidative stress KW - transcription factors KW - vitamin-D-receptor KW - differentiation KW - tissue KW - 2',7'-dichlorofluorescin KW - homeostasis Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133392 VL - 7 IS - 1 ER - TY - JOUR A1 - Reichert, Johannes C. A1 - von Rottkay, Eberhard A1 - Roth, Franz A1 - Renz, Tim A1 - Hausmann, Johannes A1 - Kranz, Julius A1 - Rackwitz, Lars A1 - Nöth, Ulrich A1 - Rudert, Maximilian T1 - A prospective randomized comparison of the minimally invasive direct anterior and the transgluteal approach for primary total hip arthroplasty JF - BMC Musculoskeletal Disorders N2 - Background: The presented prospective randomized controlled single-centre study compares the clinical outcome up to 12 months after total hip arthroplasty using a minimally invasive single-incision direct anterior (DAA) and a direct transgluteal lateral approach. Methods: A total of 123 arthroplasties were evaluated utilizing the Harris Hip Score (HHS), the extra short musculoskeletal functional assessment questionnaire (XSFMA), the Short Form 36 (SF-36) health survey, a Stepwatch™ Activity Monitor (SAM), and a timed 25 m foot walk (T25-FW). Postoperative x-ray images after THA were reviewed to determine inclination and stem positioning. Results: At final follow-up, the XSFMA functional index scores were 10.3 (anterior) and 15.08 (lateral) while the bother index summed up to a score of 15.8 (anterior) and 21.66 (lateral) respectively, thus only differing significantly for the functional index (p = 0.040 and p = 0.056). The SF-36 physical component score (PCS) was 47.49 (anterior) and 42.91 (lateral) while the mental component score (MCS) summed up to 55.0 (anterior) and 56.23 (lateral) with a significant difference evident for the PCS (p = 0.017; p = 0.714). Patients undergoing THA through a DAA undertook a mean of 6402 cycles per day while those who had undergone THA through a transgluteal approach undertook a mean of 5340 cycles per day (p = 0.012). Furthermore, the obtained outcome for the T25-FW with 18.4 s (anterior) and 19.75 s (lateral) and the maximum walking distance (5932 m and 5125 m) differed significantly (p = 0.046 and p = 0.045). The average HHS showed no significant difference equaling 92.4 points in the anterior group and 91.43 in the lateral group (p = 0.477). The radiographic analysis revealed an average cup inclination of 38.6° (anterior) and 40.28° (lateral) without signs of migration. Conclusion: In summary, our outcomes show that after 1 year THA through the direct anterior approach results in a higher patient activity compared to THA utilizing a transgluteal lateral approach while no differences regarding hip function are evident. KW - total hip arthroplasty KW - direct anterior approach KW - minimally invasive KW - transgluteal approach KW - prospective study Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176072 VL - 19 IS - 241 ER - TY - JOUR A1 - Seefried, Lothar A1 - Mueller-Deubert, Sigrid A1 - Schwarz, Thomas A1 - Lind, Thomas A1 - Mentrup, Birgit A1 - Kober, Melanie A1 - Docheva, Denitsa A1 - Liedert, Astrid A1 - Kassem, Moustapha A1 - Ignatius, Anita A1 - Schieker, Matthias A1 - Claes, Lutz A1 - Wilke, Winfried A1 - Jakob, Franz A1 - Ebert, Regina T1 - A small scale cell culture system to analyze mechanobiology using reporter gene constructs and polyurethane dishes N2 - Mechanical forces are translated into biochemical signals and contribute to cell differentiation and phenotype maintenance. Mesenchymal stem cells and their tissuespecific offspring, as osteoblasts and chondrocytes, cells of cardiovascular tissues and lung cells are sensitive to mechanical loading but molecules and mechanisms involved have to be unraveled. It is well established that cellular mechanotransduction is mediated e.g. by activation of the transcription factor SP1 and by kinase signaling cascades resulting in the activation of the AP1 complex. To investigate cellular mechanisms involved in mechanotransduction and to analyze substances, which modulate cellular mechanosensitivity reporter gene constructs, which can be transfected into cells of interest might be helpful. Suitable small-scale bioreactor systems and mechanosensitive reporter gene constructs are lacking. To analyze the molecular mechanisms of mechanotransduction and its crosstalk with biochemically induced signal transduction, AP1 and SP1 luciferase reporter gene constructs were cloned and transfected into various cell lines and primary cells. A newly developed bioreactor and small-scale 24-well polyurethane dishes were used to apply cyclic stretching to the transfected cells. 1 Hz cyclic stretching for 30 min in this system resulted in a significant stimulation of AP1 and SP1 mediated luciferase activity compared to unstimulated cells. In summary we describe a small-scale cell culture/bioreactor system capable of analyzing subcellular crosstalk mechanisms in mechanotransduction, mechanosensitivity of primary cells and of screening the activity of putative mechanosensitizers as new targets, e.g. for the treatment of bone loss caused by both disuse and signal transduction related alterations of mechanotransduction. KW - Bioreaktor KW - Mechanical strain KW - mechanosensitive reporter KW - gene constructs KW - bioreactor Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68099 ER - TY - JOUR A1 - Nedopil, Alexander J. A1 - Dhaliwal, Anand A1 - Howell, Stephen M. A1 - Hull, Maury L. T1 - A surgeon that switched to unrestricted kinematic alignment with manual instruments has a short learning curve and comparable resection accuracy and outcomes to those of an experienced surgeon JF - Journal of Personalized Medicine N2 - After starting an orthopedic practice, a surgeon with a fellowship in mechanically aligned (MA) TKA initiated this study to characterize their learning curve after they switched to unrestricted kinematic alignment (KA) TKA using manual instruments. Accordingly, the present study determined for the inexperienced (IE) surgeon the number of cases required to achieve consistent femoral resections and operating times, and whether the femoral resection accuracy, patient-reported outcome measures (PROMs), and component alignment were different from an experienced (E) surgeon. This prospective cohort study analyzed the IE surgeon's first 30 TKAs, all performed with KA, and 30 consecutive KA TKAs performed by an E surgeon. The resection accuracy or deviation was the calipered thickness of the distal and posterior medial and lateral femoral resections minus the planned resection thickness, which was the thickness of the corresponding condyle of the femoral component, minus 2 mm for cartilage wear, and 1 mm for the kerf of the blade. Independent observers recorded the femoral resection thickness, operative times, PROMs, and alignment. For each femoral resection, the deviation between three groups of patients containing ten consecutive KA TKAs, was either insignificant (p = 0.695 to 1.000) or within the 0.5 mm resolution of the caliper, which indicated no learning curve. More than three groups were needed to determine the learning curve for the operative time; however, the IE surgeon's procedure dropped to 77 min for the last 10 patients, which was 20 min longer than the E surgeon. The resection deviations of the IE and E surgeon were comparable, except for the posterolateral femoral resection, which the IE surgeon under-resected by a mean of −0.8 mm (p < 0.0001). At a mean follow-up of 9 and 17 months, the Forgotten Joint Score, Oxford Knee Score, KOOS, and the alignment of the components and limbs were not different between the IE and E surgeon (p ≥ 0.6994). A surgeon that switches to unrestricted KA with manual instruments can determine their learning curve by computing the deviation of the distal and posterior femoral resections from the planned resection. Based on the present study, an IE surgeon could have resection accuracy, post-operative patient outcomes, and component alignment comparable to an E surgeon. KW - total knee arthroplasty KW - kinematic alignment KW - learning curve KW - accuracy KW - efficiency Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281842 SN - 2075-4426 VL - 12 IS - 7 ER - TY - JOUR A1 - Thibaudeau, Laure A1 - Taubenberger, Anna V. A1 - Holzapfel, Boris M. A1 - Quent, Verena M. A1 - Fuehrmann, Tobias A1 - Hesami, Parisa A1 - Brown, Toby D. A1 - Dalton, Paul D. A1 - Power, Carl A. A1 - Hollier, Brett G. A1 - Hutmacher, Dietmar W. T1 - A tissue-engineered humanized xenograft model of human breast cancer metastasis to bone JF - Disease Models & Mechanisms N2 - The skeleton is a preferred homing site for breast cancer metastasis. To date, treatment options for patients with bone metastases are mostly palliative and the disease is still incurable. Indeed, key mechanisms involved in breast cancer osteotropism are still only partially understood due to the lack of suitable animal models to mimic metastasis of human tumor cells to a human bone microenvironment. In the presented study, we investigate the use of a human tissue-engineered bone construct to develop a humanized xenograft model of breast cancer-induced bone metastasis in a murine host. Primary human osteoblastic cell-seeded melt electrospun scaffolds in combination with recombinant human bone morphogenetic protein 7 were implanted subcutaneously in non-obese diabetic/severe combined immunodeficient mice. The tissue-engineered constructs led to the formation of a morphologically intact 'organ' bone incorporating a high amount of mineralized tissue, live osteocytes and bone marrow spaces. The newly formed bone was largely humanized, as indicated by the incorporation of human bone cells and human-derived matrix proteins. After intracardiac injection, the dissemination of luciferase-expressing human breast cancer cell lines to the humanized bone ossicles was detected by bioluminescent imaging. Histological analysis revealed the presence of metastases with clear osteolysis in the newly formed bone. Thus, human tissue-engineered bone constructs can be applied efficiently as a target tissue for human breast cancer cells injected into the blood circulation and replicate the osteolytic phenotype associated with breast cancer-induced bone lesions. In conclusion, we have developed an appropriate model for investigation of species-specific mechanisms of human breast cancer-related bone metastasis in vivo. KW - breast cancer KW - bone metastasis KW - humanized xenograft model KW - melt electrospinning KW - tissue engineering KW - osteotropism KW - in vivo KW - stem-cell niche KW - human prostate-cancer KW - morphogenetic protein KW - osteoprogenitor cells KW - endochondral ossification KW - mouse model KW - trabecular bone KW - calcium phosphate KW - skeletal metastases Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117466 VL - 7 IS - 2 ER - TY - JOUR A1 - Nedopil, Alexander J. A1 - Howell, Stephen M. A1 - Hull, Maury L. T1 - A TKA insert with a lateral flat articular surface maximizes external and internal tibial orientations without anterior lift-off relative to low- and ultracongruent surfaces JF - Journal of Personalized Medicine N2 - Background: In total knee arthroplasty (TKA), inserts can have different levels of medial and lateral congruency determined by the acuteness of the upslopes of the anterior and posterior articular surfaces. The present study evaluated an insert with different levels of lateral congruency and a medial ball-in-socket congruency to test the hypothesis that a lateral flat (F) insert maximizes external tibial orientation at extension and internal orientation at 90° flexion and lowers the incidence of anterior lift-off relative to low-congruent (LC) and ultracongruent (UC) lateral inserts. Methods: Two surgeons treated 23 patients with unrestricted caliper-verified kinematic alignment (KA) and posterior cruciate ligament (PCL) retention. They randomly trialed inserts with a medial radial dial that functioned as a built-in goniometer by measuring the tibial orientation relative to a sagittal line on the femoral trial component. Anterior lift-off of the insert from the baseplate indicated PCL tightness. Results: The F insert’s mean of 9° of external tibial orientation was higher than that of the LC (5°, p < 0.0001) and UC inserts (2°, p < 0.0001). The −13° of internal tibial orientation at 90° flexion was higher than that of the LC (−9°, p < 0.0001) and UC inserts (−7°, p < 0.0001). The 0% incidence of anterior lift-off was less than that of the LC (26%) and UC inserts (57%) (p < 0.0001). Conclusions: Surgeons and implant manufacturers should know that adding congruency to the lateral articular surface limits external tibial orientation in extension and internal tibial orientation at 90° flexion and overtightens the PCL. These rotational limitations and flexion space tightness can adversely affect patellofemoral tracking and knee flexion. KW - total knee arthroplasty KW - kinematic alignment KW - implant design KW - PCL retention KW - congruency Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286142 SN - 2075-4426 VL - 12 IS - 8 ER - TY - JOUR A1 - Staab, Wieland A1 - Hottowitz, Ralf A1 - Sohns, Christian A1 - Sohns, Jan Martin A1 - Gilbert, Fabian A1 - Menke, Jan A1 - Niklas, Andree A1 - Lotz, Joachim T1 - Accelerometer and Gyroscope Based Gait Analysis Using Spectral Analysis of Patients with Osteoarthritis of the Knee JF - Journal of Physical Therapy Science N2 - [Purpose] A wide variety of accelerometer tools are used to estimate human movement, but there are no adequate data relating to gait symmetry parameters in the context of knee osteoarthritis. This study's purpose was to evaluate a 3D-kinematic system using body-mounted sensors (gyroscopes and accelerometers) on the trunk and limbs. This is the first study to use spectral analysis for data post processing. [Subjects] Twelve patients with unilateral knee osteoarthritis (OA) (10 male) and seven age-matched controls (6 male) were studied. [Methods] Measurements with 3-D accelerometers and gyroscopes were compared to video analysis with marker positions tracked by a six-camera optoelectronic system (VICON 460, Oxford Metrics). Data were recorded using the 3D-kinematic system. [Results] The results of both gait analysis systems were significantly correlated. Five parameters were significantly different between the knee OA and control groups. To overcome time spent in expensive post-processing routines, spectral analysis was performed for fast differentiation between normal gait and pathological gait signals using the 3D-kinematic system. [Conclusions] The 3D-kinematic system is objective, inexpensive, accurate and portable, and allows long-term recordings in clinical, sport as well as ergonomic or functional capacity evaluation (FCE) settings. For fast post-processing, spectral analysis of the recorded data is recommended. KW - gait KW - accelerometer KW - gyroscope KW - HIP osteoarthritis KW - kinematic analysis KW - human movement KW - in-vivo KW - artifact KW - systems KW - people Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115907 VL - 26 IS - 7 ER - TY - JOUR A1 - Arnholdt, Jörg A1 - Kamawal, Yama A1 - Horas, Konstantin A1 - Holzapfel, Boris M. A1 - Gilbert, Fabian A1 - Ripp, Axel A1 - Rudert, Maximilian A1 - Steinert, Andre F. T1 - Accurate implant fit and leg alignment after cruciate-retaining patient-specific total knee arthroplasty JF - BMC Musculoskeletal Disorders N2 - Background For improved outcomes in total knee arthroplasty (TKA) correct implant fitting and positioning are crucial. In order to facilitate a best possible implant fitting and positioning patient-specific systems have been developed. However, whether or not these systems allow for better implant fitting and positioning has yet to be elucidated. For this reason, the aim was to analyse the novel patient-specific cruciate retaining knee replacement system iTotal (TM) CR G2 that utilizes custom-made implants and instruments for its ability to facilitate accurate implant fitting and positioning including correction of the hip-knee-ankle angle (HKA). Methods We assessed radiographic results of 106 patients who were treated with the second generation of a patient-specific cruciate retaining knee arthroplasty using iTotal\(^{TM}\) CR G2 (ConforMIS Inc.) for tricompartmental knee osteoarthritis (OA) using custom-made implants and instruments. The implant fit and positioning as well as the correction of the mechanical axis (hip-knee-ankle angle, HKA) and restoration of the joint line were determined using pre- and postoperative radiographic analyses. Results On average, HKA was corrected from 174.4 degrees +/- 4.6 degrees preoperatively to 178.8 degrees +/- 2.2 degrees postoperatively and the coronal femoro-tibial angle was adjusted on average 4.4 degrees. The measured preoperative tibial slope was 5.3 degrees +/- 2.2 degrees (mean +/- SD) and the average postoperative tibial slope was 4.7 degrees +/- 1.1 degrees on lateral views. The joint line was well preserved with an average modified Insall-Salvati index of 1.66 +/- 0.16 pre- and 1.67 +/- 0.16 postoperatively. The overall accuracy of fit of implant components was decent with a measured medial overhang of more than 1 mm (1.33 mm +/- 0.32 mm) in 4 cases only. Further, a lateral overhang of more than 1 mm (1.8 mm +/- 0.63) (measured in the anterior-posterior radiographs) was observed in 11 cases, with none of the 106 patients showing femoral notching. Conclusion The patient-specific iTotal\(^{TM}\) CR G2 total knee replacement system facilitated a proper fitting and positioning of the implant components. Moreover, a good restoration of the leg axis towards neutral alignment was achieved as planned. Nonetheless, further clinical follow-up studies are necessary to validate our findings and to determine the long-term impact of using this patient- specific system. KW - total knee replacement KW - knee axis KW - patient-specific knee arthroplasty KW - knee osteoarthritis KW - implant positioning Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230012 VL - 21 ER - TY - JOUR A1 - Holzapfel, Boris Michael A1 - Prodinger, Peter M. A1 - Pilge, Hakan A1 - Banke, Ingo J. A1 - Bürklein, Dominik A1 - Miethke, Thomas A1 - Gradinger, Reiner T1 - Acute Osteomyelitis of the Humerus mimicking Malignancy: Streptococcus pneumoniae as Exceptional Pathogen in an Immunocompetent Adult JF - BMC Infectious Diseases N2 - Background Chronic osteomyelitis due to direct bone trauma or vascular insufficiency is a frequent problem in orthopaedic surgery. In contrast, acute haematogenous osteomyelitis represents a rare entity that almost exclusively affects prepubescent children or immunodeficient adults. Case Presentation In this article, we report the case of acute pneumococcal osteomyelitis of the humerus in an immunocompetent and otherwise healthy 44-year-old male patient presenting with minor inflammation signs and misleading clinical features. Conclusions The diagnosis had to be confirmed by open biopsy which allowed the initiation of a targeted therapy. A case of pneumococcal osteomyelitis of a long bone, lacking predisposing factors or trauma, is unique in adults and has not been reported previously. KW - Acute osteomyelitis KW - Haematogenous KW - Long bones KW - Immunodeficiency KW - Osteomyelitis of the humerus Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-95790 ER - TY - JOUR A1 - Ebert, Regina A1 - Benisch, Peggy A1 - Krug, Melanie A1 - Zeck, Sabine A1 - Meißner-Weigl, Jutta A1 - Steinert, Andre A1 - Rauner, Martina A1 - Hofbauer, Lorenz A1 - Jakob, Franz T1 - Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells JF - Stem Cell Research N2 - The role of serum amyloid A (SAA) proteins, which are ligands for toll-like receptors, was analyzed in human bone marrow-derived mesenchymal stem cells (hMSCs) and their osteogenic offspring with a focus on senescence, differentiation andmineralization. In vitro aged hMSC developed a senescence-associated secretory phenotype (SASP), resulting in enhanced SAA1/2, TLR2/4 and proinflammatory cytokine (IL6, IL8, IL1\(\beta\), CXCL1, CXCL2) expression before entering replicative senescence. Recombinant human SAA1 (rhSAA1) induced SASP-related genes and proteins in MSC, which could be abolished by cotreatment with the TLR4-inhibitor CLI-095. The same pattern of SASP-resembling genes was stimulated upon induction of osteogenic differentiation, which is accompanied by autocrine SAA1/2 expression. In this context additional rhSAA1 enhanced the SASP-like phenotype, accelerated the proinflammatory phase of osteogenic differentiation and enhanced mineralization. Autocrine/paracrine and rhSAA1 via TLR4 stimulate a proinflammatory phenotype that is both part of the early phase of osteogenic differentiation and the development of senescence. This signaling cascade is tightly involved in bone formation and mineralization, but may also propagate pathological extraosseous calcification conditions such as calcifying inflammation and atherosclerosis. KW - human atherosclerotic lesions KW - senescence KW - expression KW - toll-like receptor KW - mineralization KW - osteogenic differentiation KW - serum amyloid A KW - inflammation KW - mesenchymal stem cells KW - WNT5A KW - model KW - lines KW - stromal cells KW - RT-PCR Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148491 VL - 15 ER - TY - JOUR A1 - Hochleitner, Gernot A1 - Jüngst, Tomasz A1 - Brown, Toby D A1 - Hahn, Kathrin A1 - Moseke, Claus A1 - Jakob, Franz A1 - Dalton, Paul D A1 - Groll, Jürgen T1 - Additive manufacturing of scaffolds with sub-micron filaments via melt electrospinning writing JF - Biofabrication N2 - The aim of this study was to explore the lower resolution limits of an electrohydrodynamic process combined with direct writing technology of polymer melts. Termed melt electrospinning writing, filaments are deposited layer-by-layer to produce discrete three-dimensional scaffolds for in vitro research. Through optimization of the parameters (flow rate, spinneret diameter, voltage, collector distance) for poly-ϵ-caprolactone, we could direct-write coherent scaffolds with ultrafine filaments, the smallest being 817 ± 165 nm. These low diameter filaments were deposited to form box-structures with a periodicity of 100.6 ± 5.1 μm and a height of 80 μm (50 stacked filaments; 100 overlap at intersections). We also observed oriented crystalline regions within such ultrafine filaments after annealing at 55 °C. The scaffolds were printed upon NCO-sP(EO-stat-PO)-coated glass slide surfaces and withstood frequent liquid exchanges with negligible scaffold detachment for at least 10 days in vitro. KW - additive manufacturing KW - 3D printing KW - biodegradable polymers KW - microstructures KW - nanostructures Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254053 VL - 7 IS - 3 ER - TY - JOUR A1 - Rudert, Maximilian A1 - Holzapfel, Boris Michael A1 - Jakubietz, Michael T1 - Adjuvant Radiotherapy JF - Deutsches Ärzteblatt International N2 - No abstract available. KW - Soft-tissue sarcoma Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133571 VL - 108 IS - 33 ER - TY - JOUR A1 - Trivanović, Drenka T1 - Adult stem cells in aging JF - Journal of Personalized Medicine N2 - No abstract available KW - adult stem cells Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275226 SN - 2075-4426 VL - 12 IS - 5 ER - TY - JOUR A1 - Holzapfel, Boris Michael A1 - Rechl, Hans A1 - Lehner, Stefan A1 - Pilge, Hakan A1 - Gollwitzer, Hans A1 - Steinhauser, Erwin T1 - Alloplastic Reconstruction of the Extensor Mechanism after Resection of Tibial Sarcoma [Research Article] N2 - Reconstruction of the extensor mechanism is essential for good extremity function after endoprosthetic knee replacement following tumor resection. Only a few biological methods have been able to reliably restore a functional extensor mechanism, but they are often associated with significant complication rates. Reattachment of the patellar tendon to the prosthesis using an alloplastic patellar ligament (Trevira cord) can be an appropriate alternative. In vivo and in vitro studies have already shown that complete fibrous ingrowth in polyethylene chords can be seen after a period of six months. However, until now, no biomechanical study has shown the efficacy of an alloplastic cord and its fixation device in providing sufficient stability and endurance in daily life-activity until newly formed scar tissue can take over this function. In a special test bench developed for this study, different loading regimes were applied to simulate loads during everyday life. Failure loads and failuremodes were evaluated. The properties of the cord were compared before and after physiological conditioning. It was shown that rubbing was the mode of failure under dynamic loading. Tensile forces up to 2558N did not result in material failure. Thus, using an artificial cord together with this fixation device, temporary sufficient stable fixation can be expected. KW - Medizin Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-69072 ER - TY - JOUR A1 - Nedopil, Alexander J. A1 - Shekhar, Adithya A1 - Howell, Stephen M. A1 - Hull, Maury L. T1 - An insert with less than spherical medial conformity causes a loss of passive internal rotation after calipered kinematically aligned TKA JF - Archives of Orthopaedic and Trauma Surgery N2 - Introduction In total knee arthroplasty (TKA), the level of conformity, a medial stabilized (MS) implant, needs to restore native (i.e., healthy) knee kinematics without over-tensioning the flexion space when the surgeon chooses to retain the posterior cruciate ligament (PCL) is unknown. Whether an insert with a medial ball-in-socket conformity and lateral flat surface like the native knee or a less than spherical medial conformity restores higher and closer to native internal tibial rotation without anterior lift-off, an over-tension indicator, when implanted with calipered kinematic alignment (KA), is unknown. Methods and Materials Two surgeons treated 21 patients with calipered KA and a PCL retaining MS implant. Validated verification checks that restore native tibial compartment forces in passive flexion without release of healthy ligaments were used to select the optimal insert thickness. A goniometer etched onto trial inserts with the ball-in-socket and the less than spherical medial conformity measured the tibial rotation relative to the femoral component at extension and 90° and 120° flexion. The surgeon recorded the incidence of anterior lift-off of the insert. Results The insert with the medial ball-in-socket and lateral flat surface restored more internal tibial rotation than the one with less than spherical medial conformity, with mean values of 19° vs. 17° from extension to 90° flexion (p < 0.01), and 23° vs. 20°-120° flexion (p < 0.002), respectively. There was no anterior lift-off of the insert at 90° and 120° flexion. Conclusion An MS insert with a medial ball-in-socket and lateral flat surface that matches the native knee's spherical conformity restores native tibial internal rotation when implanted with calipered KA and PCL retention without over-tensioning the flexion space. KW - calipered KW - medial stabilized KW - spherical KW - conforming KW - insert KW - rotation KW - total knee arthroplasty KW - total knee replacement KW - kinematic alignment Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-266710 SN - 1434-3916 VL - 141 IS - 12 ER - TY - JOUR A1 - Pereira, A. R. A1 - Trivanović, D. A1 - Herrmann, M. T1 - Approaches to mimic the complexity of the skeletal mesenchymal stem/stromal cell niche in vitro JF - European Cells and Materials N2 - Mesenchymal stem/stromal cells (MSCs) are an essential element of most modern tissue engineering and regenerative medicine approaches due to their multipotency and immunoregulatory functions. Despite the prospective value of MSCs for the clinics, the stem cells community is questioning their developmental origin, in vivo localization, identification, and regenerative potential after several years of far-reaching research in the field. Although several major progresses have been made in mimicking the complexity of the MSC niche in vitro, there is need for comprehensive studies of fundamental mechanisms triggered by microenvironmental cues before moving to regenerative medicine cell therapy applications. The present comprehensive review extensively discusses the microenvironmental cues that influence MSC phenotype and function in health and disease – including cellular, chemical and physical interactions. The most recent and relevant illustrative examples of novel bioengineering approaches to mimic biological, chemical, and mechanical microenvironmental signals present in the native MSC niche are summarized, with special emphasis on the forefront techniques to achieve bio-chemical complexity and dynamic cultures. In particular, the skeletal MSC niche and applications focusing on the bone regenerative potential of MSC are addressed. The aim of the review was to recognize the limitations of the current MSC niche in vitro models and to identify potential opportunities to fill the bridge between fundamental science and clinical application of MSCs. KW - Mesenchymal stem/stromal cells KW - skeletal progenitor cells KW - niche KW - in vitro models KW - bone KW - tissue engineering Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-268823 SN - 1473-2262 VL - 37 ER - TY - JOUR A1 - Stratos, Ioannis A1 - Scarlat, Marius M. A1 - Rudert, Maximilian T1 - Bibliometrics of orthopaedic articles published by authors of Germanophone countries JF - International Orthopaedics N2 - No abstract available. KW - scientific publications KW - orthopaedics KW - germanophone Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-266343 VL - 45 IS - 5 ER - TY - JOUR A1 - Ramírez-Rodríguez, Gloria Belén A1 - Pereira, Ana Rita A1 - Herrmann, Marietta A1 - Hansmann, Jan A1 - Delgado-López, José Manuel A1 - Sprio, Simone A1 - Tampieri, Anna A1 - Sandri, Monica T1 - Biomimetic mineralization promotes viability and differentiation of human mesenchymal stem cells in a perfusion bioreactor JF - International Journal of Molecular Sciences N2 - In bone tissue engineering, the design of 3D systems capable of recreating composition, architecture and micromechanical environment of the native extracellular matrix (ECM) is still a challenge. While perfusion bioreactors have been proposed as potential tool to apply biomechanical stimuli, its use has been limited to a low number of biomaterials. In this work, we propose the culture of human mesenchymal stem cells (hMSC) in biomimetic mineralized recombinant collagen scaffolds with a perfusion bioreactor to simultaneously provide biochemical and biophysical cues guiding stem cell fate. The scaffolds were fabricated by mineralization of recombinant collagen in the presence of magnesium (RCP.MgAp). The organic matrix was homogeneously mineralized with apatite nanocrystals, similar in composition to those found in bone. X-Ray microtomography images revealed isotropic porous structure with optimum porosity for cell ingrowth. In fact, an optimal cell repopulation through the entire scaffolds was obtained after 1 day of dynamic seeding in the bioreactor. Remarkably, RCP.MgAp scaffolds exhibited higher cell viability and a clear trend of up-regulation of osteogenic genes than control (non-mineralized) scaffolds. Results demonstrate the potential of the combination of biomimetic mineralization of recombinant collagen in presence of magnesium and dynamic culture of hMSC as a promising strategy to closely mimic bone ECM. KW - scaffold KW - perfusion bioreactor KW - collagen KW - apatite nanoparticles KW - magnesium KW - human mesenchymal stem cell KW - osteogenesis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285804 SN - 1422-0067 VL - 22 IS - 3 ER - TY - JOUR A1 - Prasse, Tobias A1 - Stratos, Ioannis A1 - Niehoff, Anja A1 - Christ, Hildegard A1 - Heck, Vincent A1 - Meyer, Carolin A1 - Mittlmeier, Thomas T1 - Bisphenol A-related effects on bone morphology and biomechanical properties in an animal model JF - Toxics N2 - Bisphenol A (BPA), which is contained in numerous plastic products, is known to act as an endocrine-disruptive, toxic, and carcinogenic chemical. This experimental series sought to determine the influence of BPA exposure on the femoral bone architecture and biomechanical properties of male and female Wistar rats. BPA was applied subcutaneously by using osmotic pumps. After 12 weeks, the bones were analyzed by micro-computed tomography (micro-CT) and a three-point bending test. Comparing the female low- and high-dose groups, a significantly greater marrow area (p = 0.047) was identified in the group exposed to a higher BPA concentration. In addition, the trabecular number tended to be higher in the female high-dose group when compared to the low-dose group (p > 0.05). The area moment of inertia also tended to be higher in the male high-dose group when compared to the male low-dose group (p > 0.05). Considering our results, BPA-related effects on the bone morphology in female Wistar rats are osteoanabolic after high-dose exposure, while, in male rats, a tendency toward negative effects on the bone morphology in terms of a reduced cross-sectional cortical area and total area could be demonstrated. KW - bisphenol A KW - endocrine disruption KW - bone morphology KW - micro-computed tomography KW - mechanical property KW - three-point bending Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262216 SN - 2305-6304 VL - 10 IS - 2 ER - TY - JOUR A1 - Seiler, Jonas A1 - Ebert, Regina A1 - Rudert, Maximilian A1 - Herrmann, Marietta A1 - Leich, Ellen A1 - Weißenberger, Manuela A1 - Horas, Konstantin T1 - Bone metastases of diverse primary origin frequently express the VDR (vitamin D receptor) and CYP24A1 JF - Journal of Clinical Medicine N2 - Active vitamin D (1,25(OH)2D3) is known to exert direct anti-cancer actions on various malignant tissues through binding to the vitamin D receptor (VDR). These effects have been demonstrated in breast, prostate, renal and thyroid cancers, which all have a high propensity to metastasise to bone. In addition, there is evidence that vitamin D catabolism via 24-hydroxylase (CYP24A1) is altered in tumour cells, thus, reducing local active vitamin D levels in cancer cells. The aim of this study was to assess VDR and CYP24A1 expression in various types of bone metastases by using immunohistochemistry. Overall, a high total VDR protein expression was detected in 59% of cases (39/66). There was a non-significant trend of high-grade tumours towards the low nuclear VDR expression (p = 0.07). Notably, patients with further distant metastases had a reduced nuclear VDR expression (p = 0.03). Furthermore, a high CYP24A1 expression was detected in 59% (39/66) of bone metastases. There was a significant positive correlation between nuclear VDR and CYP24A1 expression (p = 0.001). Collectively, the VDR and CYP24A1 were widely expressed in a multitude of bone metastases, pointing to a potential role of vitamin D signalling in cancer progression. This is of high clinical relevance, as vitamin D deficiency is frequent in patients with bone metastases. KW - vitamin D receptor KW - VDR KW - CYP24A1 KW - bone metastasis KW - vitamin D Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297377 SN - 2077-0383 VL - 11 IS - 21 ER - TY - JOUR A1 - Genest, F. A1 - Claußen, L. A1 - Rak, D. A1 - Seefried, L. T1 - Bone mineral density and fracture risk in adult patients with hypophosphatasia JF - Osteoporosis International N2 - Summary In adult hypophosphatasia (HPP) patients, elevated lumbar spine dual X-ray absorptiometry (DXA) values are associated with markers of disease severity and disease-specific fracture risk while femoral bone mineral density (BMD), being largely unaffected by the disease severity, may still be useful to monitor other causes of increased fracture risk due to low BMD. Introduction Hypophosphatasia (HPP) is a rare inherited metabolic disorder due to deficient activity of the tissue-nonspecific alkaline phosphatase (TNAP). Clinical manifestation in adult HPP patients is manifold including an increased risk for fractures, but data regarding clinical significance of DXA measurement and associations with fracture risk and disease severity is scarce. Methods Retrospective single-center analysis of DXA scans in patients with confirmed HPP (documented mutation, clinical symptoms, low alkaline phosphatase activity). Further data evaluation included disease-related fractures, laboratory results (alkaline phosphatase, pyridoxalphosphate, phosphoethanolamine), and medical history. Results Analysis included 110 patients (84 female, mean age of 46.2 years) of whom 37.3% (n = 41) were harboring two mutations. Average T-Score level at the lumbar spine was − 0.1 (SD 1.9), and mean total hip T-Score was − 1.07 (SD 0.15). Both lower ALP activity and higher substrate levels (pyridoxalphosphate and phosphoethanolamine) were significantly correlated with increased lumbar spine T-Score levels (p < 0.001) while BMD at the hip was not affected by indicators of disease severity. Increased lumbar spine BMD was significantly associated with an increased risk for HPP-related fractures, prevalent in 22 (20%) patients (p < 0.001) with 21 of them having biallelic mutations. Conclusion BMD in adult HPP patients is not systematically reduced. Conversely, increased lumbar spine BMD appears to be associated with severely compromised mineralization and increased risk for HPP-related fractures while BMD at the hip appears unaffected by indicators of disease severity, suggesting suitability of this anatomic location for assessing and discerning disorders with increased fracture risk owing to reduced BMD like osteoporosis. Trial registration number German register for clinical studies (DRKS00014022) Date of registration 02/10/2018 – retrospectively registered KW - bone mineral density KW - fracture risk KW - hypophosphatasia KW - osteoporosis KW - pseudofracture Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235793 SN - 0937-941X VL - 32 ER - TY - JOUR A1 - Seefried, L. A1 - Rak, D. A1 - Petryk, A. A1 - Genest, F. T1 - Bone turnover and mineral metabolism in adult patients with hypophosphatasia treated with asfotase alfa JF - Osteoporosis International N2 - Summary There is limited understanding of how asfotase alfa affects mineral metabolism and bone turnover in adults with pediatric-onset hypophosphatasia. This study showed that adults with hypophosphatasia treated with asfotase alfa experienced significant changes in biochemical markers of bone and mineral metabolism, possibly reflecting enhanced bone remodeling of previously osteomalacic bone. Introduction Hypophosphatasia (HPP), due to a tissue nonspecific alkaline phosphatase (TNSALP) deficiency, can cause impaired bone mineralization and turnover. Although HPP may be treated with asfotase alfa, an enzyme replacement therapy, limited data are available on how treatment with asfotase alfa affects mineral metabolism and bone turnover in adults with HPP. Methods ALP substrates, bone turnover and mineral metabolism markers, and bone mineral density (BMD) data from EmPATHY, a single-center, observational study of adults (≥ 18 years) with pediatric-onset HPP treated with asfotase alfa (NCT03418389), were collected during routine clinical care and analyzed from baseline through 24 months of treatment. Results Data from 21 patients showed significantly increased ALP activity and reduced urine phosphoethanolamine (PEA)/creatinine (Cr) ratios after baseline through 24 months of asfotase alfa treatment. There were significant transient increases in parathyroid hormone 1-84 (PTH), osteocalcin, and procollagen type 1 N-propeptide (P1NP) levels at 3 and 6 months and in tartrate-resistant acid phosphatase 5b (TRAP5b) levels at 3 months, with a significant decrease in N-terminal telopeptide of type 1 collagen (NTX) levels at 24 months. Lumbar spine BMD T scores continuously increased during treatment. Conclusion Significant changes in bone turnover and mineral metabolism markers after asfotase alfa treatment suggest that treatment-mediated mineralization may enable remodeling and bone turnover on previously unmineralized surfaces. Urine PEA/Cr ratios may be a useful parameter in monitoring treatment during routine care. KW - bone mineral density KW - bone turnover KW - hypophosphatasia KW - enzyme replacement therapy KW - alkaline phosphatase Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265310 VL - 32 IS - 12 ER - TY - JOUR A1 - Seefried, Lothar A1 - Dahir, Kathryn A1 - Petryk, Anna A1 - Högler, Wolfgang A1 - Linglart, Agnès A1 - Martos‐Moreno, Gabriel Ángel A1 - Ozono, Keiichi A1 - Fang, Shona A1 - Rockman‐Greenberg, Cheryl A1 - Kishnani, Priya S T1 - Burden of Illness in Adults With Hypophosphatasia: Data From the Global Hypophosphatasia Patient Registry JF - Journal of Bone and Mineral Research N2 - Hypophosphatasia (HPP) is a rare, inherited, metabolic disease caused by deficient tissue non‐specific alkaline phosphatase activity. This study aims to assess patient‐reported pain, disability and health‐related quality of life (HRQoL) in a real‐world cohort of adults with HPP who were not receiving asfotase alfa during the analysis. Adults (≥18 years old) with HPP (confirmed by ALPL gene mutation and/or low serum alkaline phosphatase activity for age/sex) were identified from the Global HPP Registry (NCT02306720). Demographics, clinical characteristics, and data on patient‐reported pain, disability, and HRQoL (assessed by Brief Pain Inventory Short Form [BPI‐SF], Health Assessment Questionnaire Disability Index [HAQ‐DI], and 36‐Item Short‐Form Health Survey version 2 [SF‐36v2], respectively) were stratified by pediatric‐ and adult‐onset HPP and summarized descriptively. Of the 304 adults included (median [min, max] age 48.6 [18.8, 79.8] years; 74% women), 45% had adult‐onset HPP and 33% had pediatric‐onset HPP (unknown age of onset, 22%). Of those with data, 38% had experienced ≥5 HPP manifestations and 62% had a history of ≥1 fracture/pseudofracture. Median (Q1, Q3) BPI‐SF scores were 3.5 (1.5, 5.3) for pain severity and 3.3 (0.9, 6.2) for pain interference. Median (Q1, Q3) disability on the HAQ‐DI was 0.3 (0.0, 0.7). Median (Q1, Q3) physical and mental component summary scores on the SF‐36v2 were 42.4 (32.7, 49.9) and 45.3 (36.3, 54.8), respectively. Greater numbers of HPP manifestations experienced/body systems affected correlated significantly with poorer scores on the BPI‐SF, HAQ‐DI, and SF‐36v2 (all p < 0.05). No significant differences between adults with pediatric‐ and adult‐onset HPP were observed for patient‐reported outcomes, except for disability and the BPI‐SF question “pain at its worst,” which were significantly higher among adults with pediatric‐ versus adult‐onset HPP (p = 0.03 and 0.04, respectively). These data from the Global HPP Registry show that adults with HPP have a substantial burden of illness that is associated with reduced patient‐reported HRQoL, regardless of age of disease onset. KW - assistive devices KW - bone fractures KW - pain KW - pseudofractures KW - quality of life Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-217787 VL - 35 IS - 11 SP - 2171 EP - 2178 ER - TY - JOUR A1 - Boelch, Sebastian Philipp A1 - Barthel, Thomas A1 - Goebel, Sascha A1 - Rudert, Maximilian A1 - Plumhoff, Piet T1 - Calcinosis universalis - a rare case with classical presentation JF - Case Reports in Orthopedics N2 - Juvenile Dermatomyositis (JDM) is a rare autoimmune disease in children and adolescents. In these patients calcinosis might be the most characteristic symptom. However there are only few reported cases of intramuscular calcinosis in Dermatomyositis. We report a case of calcinosis universalis (CU) of the elbow in JDM successfully treated with broaching. The patient, a 24-year-old woman, suffered from a long history of JDM. On examination she presented with a fistula lateral to the olecranon and pain of the right elbow joint. Plain X-rays displayed a diffuse pattern of multiple periarticular, subcutaneous, and intramuscular calcifications. The patient underwent surgery for histological and microbiological sampling as well as broaching. Intraoperatively sinus formation and subfascial hard calcium deposition were found. Due to the risk of collateral tissue damage, incomplete broaching was performed. A local infection with Staphylococcus was diagnosed and treated with antibiotics. On six-week and 30-month follow-up the patient was free of pain and had very good function. Calcifications on standard radiographs had almost resolved entirely. This case report gives a summary on calcinosis in Dermatomyositis and adds a new case of recalcitrant CU to the literature. Broaching surgery proved to be a reliable treatment option in symptomatic calcinosis. Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126300 VL - 2015 ER - TY - JOUR A1 - Holzapfel, Boris Michael A1 - Chhaya, Mohit Prashant A1 - Melchels, Ferry Petrus Wilhelmus A1 - Holzapfel, Nina Pauline A1 - Prodinger, Peter Michael A1 - von Eisenhart-Rothe, Rüdiger A1 - Griensven, Martijn van A1 - Schantz, Jan-Thorsten A1 - Rudert, Maximilian A1 - Hutmacher, Dietmar Werner T1 - Can Bone Tissue Engineering Contribute to Therapy Concepts after Resection of Musculoskeletal Sarcoma? JF - Sarcoma N2 - Resection of musculoskeletal sarcoma can result in large bone defects where regeneration is needed in a quantity far beyond the normal potential of self-healing. In many cases, these defects exhibit a limited intrinsic regenerative potential due to an adjuvant therapeutic regimen, seroma, or infection. Therefore, reconstruction of these defects is still one of the most demanding procedures in orthopaedic surgery. The constraints of common treatment strategies have triggered a need for new therapeutic concepts to design and engineer unparalleled structural and functioning bone grafts. To satisfy the need for long-term repair and good clinical outcome, a paradigm shift is needed from methods to replace tissues with inert medical devices to more biological approaches that focus on the repair and reconstruction of tissue structure and function. It is within this context that the field of bone tissue engineering can offer solutions to be implemented into surgical therapy concepts after resection of bone and soft tissue sarcoma. In this paper we will discuss the implementation of tissue engineering concepts into the clinical field of orthopaedic oncology. KW - musculoskeletal sarcoma Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132465 VL - 2013 IS - Article ID 153640 ER - TY - JOUR A1 - Heinz, Tizian A1 - Meller, Felix A1 - Luetkens, Karsten Sebastian A1 - Horas, Konstantin A1 - Schäfer, Thomas A1 - Rudert, Maximilian A1 - Reppenhagen, Stephan A1 - Weißenberger, Manuel T1 - Can the MRI based AMADEUS score accurately assess pre-surgery chondral defect severity according to the ICRS arthroscopic classification system? JF - Journal of Experimental Orthopaedics N2 - Purpose The AMADEUS (Area Measurement And DEpth and Underlying Structures) scoring and grading system has been proposed for the MRI based evaluation of untreated focal chondral defects around the knee. The clinical practicability, its correlation with arthroscopically assessed grading systems (ICRS – International Cartilage Repair Society) and thereby its clinical value in terms of decision making and guiding prognosis was yet to determine. Methods From 2008 to 2019 a total of 89 individuals were indicated for high tibial valgus osteotomy (HTO) due to tibial varus deformity and concomitant chondral defects of the medial compartment of the knee. All patients received a preoperative MRI (1.5 Tesla or 3.0 Tesla) and pre-osteotomy diagnostic arthroscopy. Chondral defects of the medial compartment were scored and graded with the MRI based AMADEUS by three independent raters and compared to arthroscopic defect grading by the ICRS system. Interrater and intrarater reliability as well as correlation analysis with the ICRS classification system were assessed. Results Intraclass correlation coefficients for the various subscores of the AMADEUS showed an overall good to excellent interrater agreement (min: 0.26, max: 0.80). Intrarater agreement turned out to be substantially inferior (min: 0.08, max: 0.53). Spearman correlation revealed an overall moderate correlative association of the AMADEUS subscores with the ICRS classification system, apart from the defect area subscore. Sensitivity of the AMADEUS to accurately identify defect severity according to the ICRS was 0.7 (0.69 for 3.0 Tesla MRI, 0.67 for 1.5 Tesla MRI). The mean AMADEUS grade was 2.60 ± 0.81 and the mean ICRS score 2.90 ± 0.63. Conclusions Overall, the AMADEUS with all its subscores shows moderate correlation with the arthroscopic chondral grading system according to ICRS. This suggests that chondral defect grading by means of the MRI based AMADEUS is well capable of influencing and guiding treatment decisions. Interrater reliability shows overall good agreement. KW - MRI KW - knee KW - cartilage defect KW - grading system of chondral defects KW - AMADEUS KW - ICRS Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300781 SN - 2197-1153 VL - 9 IS - 1 ER - TY - JOUR A1 - Kamawal, Yama A1 - Steinert, Andre F A1 - Holzapfel, Boris M A1 - Rudert, Maximilian A1 - Barthel, Thomas T1 - Case report - calcification of the medial collateral ligament of the knee with simultaneous calcifying tendinitis of the rotator cuff JF - BMC Muscoskeletal Disorders N2 - Calcification of the medial collateral ligament (MCL) of the knee is a very rare disease. We report on a case of a patient with a calcifying lesion within the MCL and simultaneous calcifying tendinitis of the rotator cuff in both shoulders. Case presentation: Calcification of the MCL was diagnosed both via x-ray and magnetic resonance imaging (MRI) and was successfully treated surgically. Calcifying tendinitis of the rotator cuff was successfully treated applying conservative methods. Conclusion: This is the first case report of a patient suffering from both a calcifying lesion within the medial collateral ligament and calcifying tendinitis of the rotator cuff in both shoulders. Clinical symptoms, radio-morphological characteristics and macroscopic features were very similar and therefore it can be postulated that the underlying pathophysiology is the same in both diseases. Our experience suggests that magnetic resonance imaging and x-ray are invaluable tools for the diagnosis of this inflammatory calcifying disease of the ligament, and that surgical repair provides a good outcome if conservative treatment fails. It seems that calcification of the MCL is more likely to require surgery than calcifying tendinitis of the rotator cuff. However, the exact reason for this remains unclear to date. KW - case report KW - calcification KW - medical collateral ligament KW - knee rotator cuff KW - open surgical repair Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147669 VL - 17 IS - 283 ER - TY - JOUR A1 - Jessberger, Steffen A1 - Högger, Petra A1 - Genest, Franca A1 - Salter, Donald M. A1 - Seefried, Lothar T1 - Cellular pharmacodynamic effects of Pycnogenol\(^{®}\) in patients with severe osteoarthritis: a randomized controlled pilot study JF - BMC Complementary and Alternative Medicine N2 - Background: The standardized maritime pine bark extract (Pycnogenol\(^{®}\)) has previously shown symptom alleviating effects in patients suffering from moderate forms of knee osteoarthritis (OA). The cellular mechanisms for this positive impact are so far unknown. The purpose of the present randomized pilot controlled study was to span the knowledge gap between the reported clinical effects of Pycnogenol\(^{®}\) and its in vivo mechanism of action in OA patients. Methods: Thirty three patients with severe OA scheduled for a knee arthroplasty either received 100 mg of Pycnogenol\(^{®}\) twice daily or no treatment (control group) three weeks before surgery. Cartilage, synovial fluid and serum samples were collected during surgical intervention. Relative gene expression of cartilage homeostasis markers were analyzed in the patients' chondrocytes. Inflammatory and cartilage metabolism mediators were investigated in serum and synovial fluid samples. Results: The oral intake of Pycnogenol\(^{®}\) downregulated the gene expression of various cartilage degradation markers in the patients' chondrocytes, the decrease of MMP3, MMP13 and the pro-inflammatory cytokine IL1B were statistically significant (p ≤ 0.05). Additionally, protein concentrations of ADAMTS-5 in serum were reduced significantly (p ≤ 0.05) after three weeks intake of the pine bark extract. Conclusions: This is the first report about positive cellular effects of a dietary supplement on key catabolic and inflammatory markers in patients with severe OA. The results provide a rational basis for understanding previously reported clinical effects of Pycnogenol\(^{®}\) on symptom scores of patients suffering from OA. KW - maritime pine bark extract KW - qPCR KW - ADAMTS KW - cartilage KW - clinical study KW - osteoarthritis KW - Pycnogenol KW - serum KW - synovial fluid Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159532 VL - 17 IS - 537 ER - TY - JOUR A1 - Fuchs, Konrad F. A1 - Heilig, Philipp A1 - McDonogh, Miriam A1 - Boelch, Sebastian A1 - Gbureck, Uwe A1 - Meffert, Rainer H. A1 - Hoelscher-Doht, Stefanie A1 - Jordan, Martin C. T1 - Cement-augmented screw fixation for calcaneal fracture treatment: a biomechanical study comparing two injectable bone substitutes JF - Journal of Orthopaedic Surgery and Research N2 - Background The role of cement-augmented screw fixation for calcaneal fracture treatment remains unclear. Therefore, this study was performed to biomechanically analyze screw osteosynthesis by reinforcement with either a calcium phosphate (CP)-based or polymethylmethacrylate (PMMA)-based injectable bone cement. Methods A calcaneal fracture (Sanders type IIA) including a central cancellous bone defect was generated in 27 synthetic bones, and the specimens were assigned to 3 groups. The first group was fixed with four screws (3.5 mm and 6.5 mm), the second group with screws and CP-based cement (Graftys (R) QuickSet; Graftys, Aix-en-Provence, France), and the third group with screws and PMMA-based cement (Traumacem (TM) V+; DePuy Synthes, Warsaw, IN, USA). Biomechanical testing was conducted to analyze peak-to-peak displacement, total displacement, and stiffness in following a standardized protocol. Results The peak-to-peak displacement under a 200-N load was not significantly different among the groups; however, peak-to-peak displacement under a 600- and 1000-N load as well as total displacement exhibited better stability in PMMA-augmented screw osteosynthesis compared to screw fixation without augmentation. The stiffness of the construct was increased by both CP- and PMMA-based cements. Conclusion Addition of an injectable bone cement to screw osteosynthesis is able to increase fixation strength in a biomechanical calcaneal fracture model with synthetic bones. In such cases, PMMA-based cements are more effective than CP-based cements because of their inherently higher compressive strength. However, whether this high strength is required in the clinical setting for early weight-bearing remains controversial, and the non-degradable properties of PMMA might cause difficulties during subsequent interventions in younger patients. KW - arthritis KW - bone KW - calcaneus KW - cement KW - fracture KW - fixation KW - osteoporosis KW - sanders KW - screw Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230336 VL - 15 ER - TY - JOUR A1 - Steinert, Andre F. A1 - Kunz, Manuela A1 - Prager, Patrick A1 - Göbel, Sascha A1 - Klein-Hitpass, Ludger A1 - Ebert, Regina A1 - Nöth, Ulrich A1 - Jakob, Franz A1 - Gohlke, Frank T1 - Characterization of bursa subacromialis-derived mesenchymal stem cells JF - Stem Cell Research & Therapy N2 - Introduction The bursa subacromialis (BS) provides the gliding mechanism of the shoulder and regenerates itself after surgical removal. Therefore, we explored the presence of mesenchymal stem cells (MSCs) within the human adult BS tissue and characterized the BS cells compared to MSCs from bone marrow (BMSCs) on a molecular level. Methods BS cells were isolated by collagenase digest from BS tissues derived from patients with degenerative rotator cuff tears, and BMSCs were recovered by adherent culture from bone-marrow of patients with osteoarthritis of the hip. BS cells and BMSCs were compared upon their potential to proliferate and differentiate along chondrogenic, osteogenic and adipogenic lineages under specific culture conditions. Expression profiles of markers associated with mesenchymal phenotypes were comparatively evaluated by flow cytometry, immunohistochemistry, and whole genome array analyses. Results BS cells and BMSCs appeared mainly fibroblastic and revealed almost similar surface antigen expression profiles, which was \(CD44^+, CD73^+, CD90^+, CD105^+, CD106^+\),\(STRO-1^+, CD14^−, CD31^−, CD34^− , CD45^−, CD144^−\). Array analyses revealed 1969 genes upregulated and 1184 genes downregulated in BS cells vs. BMSCs, indicating a high level of transcriptome similarity. After 3 weeks of differentiation culture, BS cells and BMSCs showed a similar strong chondrogenic, adipogenic and osteogenic potential, as shown by histological, immunohistochemical and RT-PCR analyses in contrast to the respective negative controls. Conclusions Our in vitro characterizations show that BS cells fulfill all characteristics of mesenchymal stem cells, and therefore merit further attention for the development of improved therapies for various shoulder pathologies. Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126446 VL - 6 IS - 114 ER - TY - THES A1 - Altmann, Stephan T1 - Characterization of Metabolic Glycoengineering in Mesenchymal Stromal Cells for its Application in thermoresponsive Bioinks T1 - Charakterisierung von Metabolic Glycoengineering in mesenchymalen Stromazellen für die Anwendung in thermoresponsiven Biotinten N2 - This work developed during the first funding period of the subproject B05 in the framework of the interdisciplinary research consortium TRR 225 ‘From the Fundamentals of Biofabrication toward functional Tissue Models’ and was part of a cooperation between the Orthopedic Department represented by Prof. Dr. Regina Ebert and the Institute of Organic Chemistry represented by Prof. Dr. Jürgen Seibel. This project dealed with cellular behavior during the bioprinting process and how to influence it by modifying the cell glycocalyx with functional target molecules. The focus was on the impact of potential shear stress, that cells experience when they get processed in thermoresponsive bioinks, and a way to increase the cell stiffness via metabolic glycoengineering to attenuate shear forces. For the characterization of the metabolic glycoengineering, four different peracetylated and four non-acetylated modified monosaccharides (two mannose and two sialic acid sugars) were tested in primary human mesenchymal stromal cells (hMSC) and telomerase-immortalized hMSC (hMSC-TERT). Viability results demonstrated a dose-dependent correlation for all sugars, at which hMSC-TERT seemed to be more susceptible leading to lower viability rates. The assessment of the incorporation efficiencies was performed by click chemistry using fluorescent dyes and revealed also a dose-dependent correlation for all mannose and sialic acid sugars, while glucose and galactose variants were not detected in the glycocalyx. However, incorporation efficiencies were highest when using mannose sugars in the primary hMSC. A subsequent analysis of the temporal retention of the incorporated monosaccharides showed a constant declining fluorescence signal up to 6 d for azido mannose in hMSC-TERT, whereas no signal could be detected for alkyne mannose after 2 d. Investigation of the differentiation potential and expression of different target genes revealed no impairment after incubation with mannose sugars, indicating a normal phenotype for hMSC-TERT. Following the successful establishment of the method, either a coumarin derivative or an artificial galectin 1 ligand were incorporated into the cell glycocalyx of hMSC-TERT as functional target molecule. The biophysical analysis via shear flow deformation cytometry revealed a slightly increased cell stiffness and lowered fluidity for both molecules. A further part of this project aimed to control lectin-mediated cell adhesion by artificial galectin 1 ligands. As that hypothesis was settled in the work group of Prof. Dr. Jürgen Seibel, this work supported with an initial characterization of galectin 1 as part of the hMSC biology. A stable galectin 1 expression at gene and protein level in both hMSC and hMSC-TERT could be confirmed, at which immunocytochemical stainings could detect the protein only in the glycocalyx. The treatment of hMSC-TERT with a galectin 1 ligand in different concentrations did not show an altered gene expression of galectin 1. However, these first data in addition to the investigation of stiffness confirmed the applicability of specific and artificial IV galectin 1 ligands in biofabrication approaches to alter cell properties of hMSC. To conclude, metabolic glycoengineering has been successfully implemented in hMSC and hMSC-TERT to introduce glycocalyx modifications which reside there for several days. A proof of concept was carried out by the increase of cell stiffness and fluidity by the incorporation of a coumarin derivative or an artificial galectin 1 ligand. For the characterization of shear stress impact on cells after printing in thermoresponsive bioinks, the processing of hMSC-TERT (mixing or additionally printing) with Pluronic F127 or Polyoxazoline-Polyoxazine (POx-POzi) polymer solution was investigated. While there were no changes in viability when using POx-POzi bioink, processing with Pluronic F127 indicated slightly lower viability and increased apoptosis activity. Assessment of cellular responses to potential shear stress showed no reorganization of the cytoskeleton independent of the bioink, but highly increased expression of the mechanoresponsive proto-oncogene c Fos which was more pronounced when using Pluronic F127 and just mixed with the bioinks. Interestingly, processing of the mechanoresponsive reporter cell line hMSC-TERT-AP1 revealed slightly elevated mechanotransduction activity when using POx-POzi polymer and just mixed with the bioinks as well. In conclusion, hMSC-TERT embedded in thermoresponsive bioinks might shortly experience shear stress during the printing process, but that did not lead to remarkable cell damage likely due to the rheological properties of the bioinks. Furthermore, the printing experiments also suggested that cells do not sense more shear stress when additionally printed. N2 - Diese Arbeit entstand aus dem Projekt B05 während der ersten Förderperiode im Rahmen des interdisziplinären Sonderforschungsbereiches TRR 225 „Von den Grundlagen der Biofabrikation zu funktionalen Gewebemodellen“ und beinhaltete eine Kooperation zwischen dem Lehrstuhl für Orthopädie repräsentiert durch Prof. Dr. Regina Ebert und dem Institut für Organische Chemie repräsentiert durch Prof. Dr. Jürgen Seibel. Das Projekt beschäftigte sich mit den Auswirkungen des 3D Drucks auf Zellen während und nach dem Druck mit thermoresponsiven Biotinten. Hierbei lag der Fokus auf Scherkräften, die Zellen während des Drucks erfahren, und der Möglichkeit, deren nachteilige Auswirkungen durch gezielte Erhöhung der Zellsteifigkeit via Metabolic Glycoengineering zu minimieren. Zur Etablierung dieser Methode wurden vier azetylierte sowie vier nicht-azetylierte modifizierte Einfachzucker (zwei Mannosen und zwei Sialinsäuren) hinsichtlich ihrer Zellkompatibilität und Einbaurate in primären humanen mesenchymalen Stromazellen (hMSC) und Telomerase-immortalisierten hMSC (hMSC-TERT) charakterisiert. Bei der Viabilität zeigte sich für alle untersuchten Zucker ein konzentrationsabhängiges Verhalten, wobei die hMSC-TERT generell empfindlicher reagierten. Eine Untersuchung von verschiedenen Zielgenen nach Zuckerinkubation gab keine Hinweise auf biologisch veränderte Expressionsmuster und auch das phänotypische Differenzierungspotenzial (adipogen und osteogen) blieb erhalten. Der Einbau der modifizierten Zucker in Proteoglykane sowie Glykoproteine der Glykokalyx wurde mikroskopisch mittels Fluoreszenzfarbstoffen charakterisiert. Dabei zeigte sich ebenfalls ein konzentrationsabhängiges Verhalten für alle Mannosen und Sialinsäuren, wohingegen die Glukose- und Galaktosevarianten nicht nachgewiesen werden konnten. Die Mannosezucker zeigten die höchsten Einbauraten, welche in primären hMSC noch stärker ausfielen als in hMSC-TERT. Ein Langzeitversuch zur Beurteilung der zeitlichen Stabilität der Glykokalyxmodifikation konnte für die azetylierte Azidomannose ein abnehmendes Fluoreszenzsignal bis zum sechsten Tag nach der Klickreaktion ermitteln. Im Gegensatz dazu konnte die azetylierte Alkinmannose bereits ab dem zweiten Tag nicht mehr nachgewiesen werden. Nach der erfolgreichen Optimierung der Methodik wurde der Effekt eines Kumarinderivates oder eines künstlichen Galektin 1 Liganden auf die Zellsteifigkeit sowie die -fluidität mit Hilfe der Deformationszytometrie untersucht. Die Modifikation der Glykokalyx mit beiden untersuchten Molekülen führte zu einer leichten Erhöhung der Steifigkeit in Kombination mit einer leicht erniedrigten Fluidität. In einem weiteren Teil des Projekts sollte die Lektin-vermittelte Adhäsion von Zellen an Polymerstränge initiiert werden, indem sie mit künstlichen Galektin 1 Liganden modifiziert werden. Da diese Hypothese in der Forschungsgruppe von Prof. Dr. Jürgen Seibel bearbeitet wurde, unterstützte diese Arbeit mit einer anfänglichen Charakterisierung von Galektin 1 als Teil der hMSC Zellbiologie. In hMSC und hMSC-TERT konnte eine VI stabile Expression auf Gen- und Proteinebene nachwiesen werden, wobei das Lektin in der Glykokalyx lokalisiert war. Ein Inkubationsversuch mit einem spezifischen Liganden zeigte in hMSC-TERT unabhängig von der Konzentration keine veränderte Galektin 1 Genexpression. In Verbindung mit den Steifigkeitsuntersuchungen bestätigt diese anfängliche Charakterisierung die Anwendbarkeit von künstlichen Galektin 1 Liganden in der Biofabrikation um hMSC zu modifizieren. Somit konnte gezeigt werden, dass Metabolic Glycoengineering sich für die gezielte Einbringung von Molekülen in die Zellglykokalyx von primären hMSC sowie der entsprechenden TERT-Zelllinie zur mittelfristigen Modifikation eignet. Dies wurde durch einen funktionellen Ansatz bestätigt, indem die Zellsteifigkeit und -fluidität durch den Einsatz zwei verschiedener Moleküle erwartungsgemäß beeinflusst wurden. Für die Charakterisierung der Scherstressauswirkungen auf Zellen nach 3D Druck in thermoresponsiven Biotinten wurden hMSC und hMSC-TERT in Pluronic F127 oder Polyoxazolin-Polyoxazin (POx-POzi) Polymerlösung prozessiert (gemischt oder zusätzlich verdruckt) und direkt danach analysiert. Während letztere die Viabilität nicht verschlechterte, zeigten hMSC-TERT nach Verarbeitung in Pluronic F127 eine leicht erniedrigte Viabilität sowie leicht erhöhte Apoptoseraten. Im Zuge von Analysen der Mechanotransduktion und deren Auswirkungen konnte unabhängig von der Biotinte sowie der Behandlung kein Umbau des Zytoskeletts immunzytochemisch nachgewiesen werden. Im Gegensatz dazu zeigten Genexpressionsanalysen eine starke Hochregulierung des mechanoresponsiven Proto-Onkogens c Fos unter allen Bedingungen, wobei diese stärker ausfiel bei Verwendung der Pluronic F127 Biotinte und nur nach Mischen (gilt für beide Biotinten). Um den Scherstress quantitativ zu beurteilen, wurde die Reporterzelllinie hMSC-TERT-AP1 verwendet, welche das Auslesen der Mechanotransduktion durch eine gekoppelte Luziferase-Proteinexpression ermöglicht. Interessanterweise zeigte sich eine leicht erhöhte Luziferaseaktivität nur nach Verarbeitung mit der POx-POzi Polymerlösung, welche stärker ausfiel wenn die Zellen mit der Biotinte lediglich gemischt wurden. Zusammengenommen bestätigten die Ergebnisse die zelluläre Wahrnehmung von Scherstress in thermoresponsiven Biotinten, allerdings scheint dieser nur schwache Auswirkungen auf die Zellen zu haben, was auf die rheologischen Eigenschaften beider untersuchten Biotinten zurückgeführt werden kann. Die Druckergebnisse legten außerdem nahe, dass die Zellen nicht mehr Scherstress erfahren, wenn sie zusätzlich verdruckt wurden. KW - Glykobiologie KW - Glykokalyx KW - Tissue Engineering KW - Galectine KW - Metabolic Glycoengineering KW - Biofabrication KW - Galectin 1 KW - Glycocalyx KW - Shear Stress KW - Scherstress Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-291003 ER - TY - JOUR A1 - Konrads, Christian A1 - Barthel, Thomas T1 - Children and Adolescents with Knee Pain Need Diagnostics for Osteochondritis Dissecans JF - Journal of Pain Management & Medicine N2 - No abstract available. KW - Knieschmerzen Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146531 VL - 2 IS - 1 ER - TY - THES A1 - Heymer, Andrea T1 - Chondrogenic differentiation of human mesenchymal stem cells and articular cartilage reconstruction T1 - Chondrogene Differenzierung humaner mesenchymaler Stammzellen und Gelenkknorpelrekonstruktion N2 - Articular cartilage defects are still one of the major challenges in orthopedic and trauma surgery. Today, autologous chondrocyte transplantation (ACT), as a cell-based therapy, is an established procedure. However, one major limitation of this technique is the loss of the chondrogenic phenotype during expansion. Human mesenchymal stem cells (hMSCs) have an extensive proliferation potential and the capacity to differentiate into chondrocytes when maintained under specific conditions. They are therefore considered as candidate cells for tissue engineering approaches of functional cartilage tissue substitutes. First in this study, hMSCs were embedded in a collagen type I hydrogel to evaluate the cartilaginous construct in vitro. HMSC collagen hydrogels cultivated in different culture media showed always a marked contraction, most pronounced in chondrogenic differentiation medium supplemented with TGF-ß1. After stimulation with chondrogenic factors (dexamethasone and TGF-ß1) hMSCs were able to undergo chondrogenesis when embedded in the collagen type I hydrogel, as evaluated by the temporal induction of cartilage-specific gene expression. Furthermore, the cells showed a chondrocyte-like appearance and were homogeneously distributed within a proteoglycan- and collagen type II-rich extracellular matrix, except a small area in the center of the constructs. In this study, chondrogenic differentiation could not be realized with every hMSC preparation. With the improvement of the culture conditions, e.g. the use of a different FBS lot in the gel fabrication process, a higher amount of cartilage-specific matrix deposition could be achieved. Nevertheless, the large variations in the differentiation capacity display the high donor-to-donor variability influencing the development of a cartilaginous construct. Taken together, the results demonstrate that the collagen type I hydrogel is a suitable carrier matrix for hMSC-based cartilage regeneration therapies which present a promising future alternative to ACT. Second, to further improve the quality of tissue-engineered cartilaginous constructs, mechanical stimulation in specific bioreactor systems are often employed. In this study, the effects of mechanical loading on hMSC differentiation have been examined. HMSC collagen hydrogels were cultured in a defined chondrogenic differentiation medium without TGF-ß1 and subjected to a combined mechanical stimulation protocol, consisting of perfusion and cyclic uniaxial compression. Bioreactor cultivation neither affected overall cell viability nor the cell number in collagen hydrogels. Compared with non-loaded controls, mechanical loading promoted the gene expression of COMP and biglycan and induced an up-regulation of matrix metalloproteinase 3. These results circumstantiate that hMSCs are sensitive to mechanical forces, but their differentiation to chondrocytes could not be induced. Further studies are needed to identify the specific metabolic pathways which are altered by mechanical stimulation. Third, for the development of new cell-based therapies for articular cartilage repair, a reliable cell monitoring technique is required to track the cells in vivo non-invasively and repeatedly. This study aimed at analyzing systematically the performance and biological impact of a simple and efficient labeling protocol for hMSCs. Very small superparamagnetic iron oxide particles (VSOPs) were used as magnetic resonance (MR) contrast agent. Iron uptake was confirmed histologically with prussian blue staining and quantified by mass spectrometry. Compared with unlabeled cells, VSOP-labeling did neither influence significantly the viability nor the proliferation potential of hMSCs. Furthermore, iron incorporation did not affect the differentiation capacity of hMSCs. The efficiency of the labeling protocol was assessed with high resolution MR imaging at 11.7 Tesla. VSOP-labeled hMSCs were visualized in a collagen type I hydrogel indicated by distinct hypointense spots in the MR images, resulting from an iron specific loss of signal intensity. This was confirmed by prussian blue staining. In summary, this labeling technique has great potential to visualize hMSCs and track their migration after transplantation for articular cartilage repair with MR imaging. N2 - Gelenkknorpeldefekte stellen immer noch eine der großen Herausforderungen in der Orthopädie und Unfallchirurgie dar. Als zellbasiertes Verfahren ist die Autologe Chondrozytentransplantation (ACT) heute in der klinischen Routine etabliert. Ein großer Nachteil dieser Methode ist jedoch der Verlust des chondrozytären Phänotyps während der Expansion der Zellen. Humane mesenchymale Stammzellen (hMSZ) verfügen über ein ausgeprägtes Proliferationspotential und besitzen die Fähigkeit, unter spezifischen Bedingungen zu Knorpelzellen zu differenzieren. Sie werden daher als alternative Zellen für das Tissue Engineering von funktionellem Knorpelersatzgewebe in Betracht gezogen. In der vorliegenden Arbeit wurden erstens hMSZ in ein Kollagen Typ I Hydrogel eingebracht und zunächst der Grad der chondrogenen Zelldifferenzierung im Konstrukt evaluiert. HMSZ-Kollagenhydrogele zeigten in allen Kultivierungsmedien eine deutliche Kontraktion, welche am stärksten im chondrogenen Differenzierungsmedium unter Zugabe von TGF-ß1 ausgeprägt war. Nach Stimulation mit chondrogenen Faktoren (Dexamethason und TGF-ß1) differenzierten hMSZ zu Knorpelzellen, nachgewiesen durch die Induktion von knorpelspezifischer Genexpression. Die Zellen wiesen eine Chondrozyten-ähnliche Morphologie auf und waren bis auf einen kleinen Bereich in der Mitte des Konstrukts homogen in einer Proteoglykan- und Kollagen Typ II-haltigen extrazellulären Matrix verteilt. Eine chondrogene Differenzierung konnte in der vorliegenden Arbeit jedoch nicht mit jeder hMSZ-Präparation realisiert werden. Durch die Verbesserung der Kulturbedingungen, z.B. durch die Verwendung einer anderen Serumcharge im Gelherstellungsprozess, konnte eine Steigerung der knorpelspezifischen Matrixsynthese erzielt werden. Nichtsdestotrotz spiegeln die großen Schwankungen in der Differenzierungskapazität die hohe Variabilität zwischen verschiedenen Spendern wider, welche die Entwicklung eines knorpelartigen Gewebes beeinflussen. Zusammengefasst zeigen die Ergebnisse, dass das Kollagen Typ I Hydrogel eine geeignete Trägermatrix für hMSZ darstellt, um in Stammzell-basierten Knorpelregenerationstherapien zukünftig als vielversprechende Alternative zur ACT eingesetzt zu werden. Um die Qualität eines in vitro generierten knorpelartigen Gewebes weiter zu verbessern, wird häufig eine mechanische Stimulation in spezifischen Bioreaktorsystemen durchgeführt. In der vorliegenden Arbeit wurden daher zweitens die Effekte von mechanischer Belastung auf die Differenzierung von hMSZ untersucht. HMSZ-Kollagenhydrogele wurden im chondrogenen Differenzierungsmedium ohne TGF-ß1 kultiviert und einem kombinierten mechanischen Stimulationsprotokoll, bestehend aus Perfusion und zyklischer uniaxialer Kompression, ausgesetzt. Die Kultivierung im Bioreaktor hatte weder einen Einfluss auf die Zellvitalität noch auf die Anzahl der Zellen im Kollagen Typ I Hydrogel. Die mechanische Beeinflussung steigerte im Vergleich mit den unbelasteten Kontrollgelen die Genexpression von COMP und Biglykan und führte zu einer Hochregulation von Matrix Metalloproteinase 3. Diese Ergebnisse belegen, dass hMSZ mechanosensitiv sind, jedoch konnte keine Differenzierung zu Knorpelzellen induziert werden. Hierfür sind weitere Studien notwendig, um spezifische Stoffwechselwege zu identifizieren, welche durch die mechanische Stimulation beeinflusst werden. Drittens, für die Entwicklung von neuen zellbasierten Therapien für die Gelenkknorpelrekonstruktion ist eine zuverlässige Bildgebung auf zellulärer Ebene erforderlich, um die Zellen in vivo wiederholt nicht invasiv zu detektieren. Die vorliegende Arbeit hatte zum Ziel, systematisch die Effizienz und die biologischen Auswirkungen einer einfachen und dauerhaften Markierung für hMSZ zu untersuchen. Superparamagnetische Eisenoxidnanopartikel (VSOPs), ein Magnetresonanz (MR)-Kontrastmittel, wurden für die Markierung eingesetzt. Die Aufnahme der Eisenoxidnanopartikel wurde histologisch mittels eisenspezifischer Berliner-Blau-Färbung nachgewiesen und durch Massenspektroskopie quantifiziert. Im Vergleich zu unmarkierten Zellen beeinträchtigte die VSOP-Markierung weder die Vitalität noch das Proliferationspotential der hMSZ. Weiterhin war durch die Aufnahme der Eisenoxidnanopartikel keine Beeinflussung der Differenzierungskapazität der hMSZ zu verzeichnen. Die Effizienz der Zellmarkierung wurde mittels hochauflösender MR-Bildgebung bei 11,7 Tesla beurteilt. VSOP-markierte hMSZ im Kollagen Typ I Hydrogel erschienen als hypointense Punkte in den MR-Bildern, hervorgerufen durch die typische, VSOP-bedingte Signalauslöschung. Histologische Untersuchungen dieser Konstrukte bestätigten die MR-Ergebnisse. Zusammenfassend lässt sich festhalten, dass diese Zellmarkierungsmethode in Verbindung mit der MR-Bildgebung über das Potential verfügt, nach einer Gelenkknorpelrekonstruktion Aufschluss über die Lokalisation und Migration der transplantierten hMSZ zu liefern. KW - Gelenkknorpel KW - Tissue Engineering KW - Chondrogenese KW - Hydrogel KW - Biomechanik KW - NMR-Bildgebung KW - mesenchymale Stammzellen KW - Kollagen-Hydrogel KW - mechanische Stimulation KW - Zellmarkierung KW - superparamagnetische Eisenoxidnanopartikel KW - mesenchymal stem cells KW - collagen hydrogel KW - mechanical stimulation KW - cell labeling KW - superparamagnetic iron oxide particles Y1 - 2008 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-29448 ER - TY - JOUR A1 - Hörterer, Hubert A1 - Baumbach, Sebastian Felix A1 - Lemperle, Stefan A1 - Altenberger, Sebastian A1 - Gottschalk, Oliver A1 - Mehlhorn, Alexander Tobias A1 - Röser, Anke A1 - Walther, Markus T1 - Clinical outcome and concomitant injuries in operatively treated fractures of the lateral process of the talus JF - BMC Musculoskeletal Disorders N2 - Background The aim of this study was to review the patient rated outcome (PROM) of surgically treated fractures to the lateral process of the talus (LPTF) and identify factors influencing the outcome. Methods Retrospective study with a current follow-up. Eligible were all patients treated surgically for a LPTF (n = 23) with a minimum follow-up of one year. Demographics, medical history, trauma mechanism, fracture characteristics, concomitant injuries, treatment details, complications, return to work and sports were assessed retrospectively. The current follow-up included the VAS FA, Karlsson Score, and SF-12. The primary outcome was the VAS FA. Secondary aim was the identification of parameters influencing the PROMs. Results 22 patients (96% follow-up) with a mean age of 32 ± 9 (18 to 49) years were included. 73% suffered a Hawkins Type 1, 23% a Type 2, and one patient a Type 3 fracture. 82% suffered concomitant injuries. 9% suffered minor surgical side infections, 50% developed symptomatic subtalar osteoarthritis. At final follow-up (44 ± 2 (12 to 97) months), the mean VAS FA Overall was 77 ± 21 (20 to 100), the Karlsson Score 72 ± 21 (34 to 97), and for the SF 12 the PCS 53 ± 8 (36 to 64) and the MCS 53 ± 7 (32 to 63). 50% of patients returned to their previous level of sports. Hawkins Type 1 fractures resulted in better VAS FA Overall score than Type 2 fractures. Posttraumatic subtalar osteoarthritis was the independent factor associated to a poor patient rated outcome (VAS FA, Karlsson Score). Conclusion After a follow-up of over 3.5 years, surgically treated LPTF resulted in only moderate results. 50% suffered posttraumatic symptomatic subtalar osteoarthritis, which was the primary independent parameter for a poor outcome following LPTF. Level of evidence Level III. KW - fracture KW - snowboarder's ankle KW - snowboarder's fracture KW - lateral process of the talus Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-321207 VL - 20 ER - TY - JOUR A1 - Achenbach, Leonard A1 - Klein, Christian A1 - Luig, Patrick A1 - Bloch, Hendrik A1 - Schneider, Dominik A1 - Fehske, Kai T1 - Collision with opponents - but not foul play - dominates injury mechanism in professional men's basketball JF - BMC Sports Science Medicine and Rehabilitation N2 - Background To identify injury patterns and mechanisms in professional men’s basketball by means of video match analysis. Methods In Germany, injuries are registered with the statutory accident insurance for professional athletes (VBG) by clubs or club physicians as part of occupational accident reporting. Moderate and severe injuries (absence of > 7 days) sustained during basketball competition in one of four seasons (2014–2017 and 2018–2019) in the first or second national men’s league in Germany were prospectively analyzed using a newly developed standardized observation form. Season 2017–2018 was excluded because of missing video material. Results Video analysis included 175 (53%) of 329 moderate and severe match injuries. Contact patterns categorized according to the different body sites yielded eight groups of typical injury patterns: one each for the head, shoulders, and ankles, two for the thighs, and three for the knees. Injuries to the head (92%), ankles (76%), shoulders (70%), knees (47%), and thighs (32%) were mainly caused by direct contact. The injury proportion of foul play was 19%. Most injuries (61%) occurred in the central zone below the basket. More injuries occurred during the second (OR 1.8, p = 0.018) and fourth quarter (OR 1.8, p = 0.022) than during the first and third quarter of the match. Conclusion The eight identified injury patterns differed substantially in their mechanisms. Moderate and severe match injuries to the head, shoulders, knees, and ankles were mainly caused by collision with opponents and teammates. Thus, stricter rule enforcement is unlikely to facilitate safer match play. KW - epidemiology KW - mechanism KW - contact KW - non-contact´ KW - injury prevention KW - match load Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261765 VL - 13 ER - TY - JOUR A1 - Wagenbrenner, Mike A1 - Mayer-Wagner, Susanne A1 - Rudert, Maximilian A1 - Holzapfel, Boris Michael A1 - Weissenberger, Manuel T1 - Combinations of hydrogels and mesenchymal stromal cells (MSCs) for cartilage tissue engineering — a review of the literature JF - Gels N2 - Cartilage offers limited regenerative capacity. Cell-based approaches have emerged as a promising alternative in the treatment of cartilage defects and osteoarthritis. Due to their easy accessibility, abundancy, and chondrogenic potential mesenchymal stromal cells (MSCs) offer an attractive cell source. MSCs are often combined with natural or synthetic hydrogels providing tunable biocompatibility, biodegradability, and enhanced cell functionality. In this review, we focused on the different advantages and disadvantages of various natural, synthetic, and modified hydrogels. We examined the different combinations of MSC-subpopulations and hydrogels used for cartilage engineering in preclinical and clinical studies and reviewed the effects of added growth factors or gene transfer on chondrogenesis in MSC-laden hydrogels. The aim of this review is to add to the understanding of the disadvantages and advantages of various combinations of MSC-subpopulations, growth factors, gene transfers, and hydrogels in cartilage engineering. KW - hydrogels KW - osteoarthritis KW - cartilage defects KW - MSCs KW - cartilage regeneration KW - tissue engineering Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250177 SN - 2310-2861 VL - 7 IS - 4 ER - TY - JOUR A1 - Weißenberger, Manuel A1 - Wagenbrenner, Mike A1 - Nickel, Joachim A1 - Ahlbrecht, Rasmus A1 - Blunk, Torsten A1 - Steinert, Andre F. A1 - Gilbert, Fabian T1 - Comparative in vitro treatment of mesenchymal stromal cells with GDF-5 and R57A induces chondrogenic differentiation while limiting chondrogenic hypertrophy JF - Journal of Experimental Orthopaedics N2 - Purpose Hypertrophic cartilage is an important characteristic of osteoarthritis and can often be found in patients suffering from osteoarthritis. Although the exact pathomechanism remains poorly understood, hypertrophic de-differentiation of chondrocytes also poses a major challenge in the cell-based repair of hyaline cartilage using mesenchymal stromal cells (MSCs). While different members of the transforming growth factor beta (TGF-β) family have been shown to promote chondrogenesis in MSCs, the transition into a hypertrophic phenotype remains a problem. To further examine this topic we compared the effects of the transcription growth and differentiation factor 5 (GDF-5) and the mutant R57A on in vitro chondrogenesis in MSCs. Methods Bone marrow-derived MSCs (BMSCs) were placed in pellet culture and in-cubated in chondrogenic differentiation medium containing R57A, GDF-5 and TGF-ß1 for 21 days. Chondrogenesis was examined histologically, immunohistochemically, through biochemical assays and by RT-qPCR regarding the expression of chondrogenic marker genes. Results Treatment of BMSCs with R57A led to a dose dependent induction of chondrogenesis in BMSCs. Biochemical assays also showed an elevated glycosaminoglycan (GAG) content and expression of chondrogenic marker genes in corresponding pellets. While treatment with R57A led to superior chondrogenic differentiation compared to treatment with the GDF-5 wild type and similar levels compared to incubation with TGF-ß1, levels of chondrogenic hypertrophy were lower after induction with R57A and the GDF-5 wild type. Conclusions R57A is a stronger inducer of chondrogenesis in BMSCs than the GDF-5 wild type while leading to lower levels of chondrogenic hypertrophy in comparison with TGF-ß1. KW - bone marrow KW - cartilage KW - chondrogenesis KW - chondrogenic hypertrophy KW - mesenchymal stromal cell KW - GDF-5 KW - R57A Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357770 VL - 10 ER - TY - JOUR A1 - Boelch, Sebastian P. A1 - Rueckl, Kilian A1 - Fuchs, Clara A1 - Jordan, Martin A1 - Knauer, Markus A1 - Steinert, Andre A1 - Rudert, Maximilian A1 - Luedemann, Martin T1 - Comparison of elution characteristics and compressive strength of biantibiotic-loaded PMMA bone cement for spacers: Copal\(^®\) spacem with gentamicin and vancomycin versus Palacos\(^®\) R+G with vancomycin JF - BioMed Research International N2 - Purpose. Copal\(^®\) spacem is a new PMMA bone cement for fabricating spacers. This study compares elution of gentamicin, elution of vancomycin, and compressive strength of Copal\(^®\) spacem and of Palacos\(^®\) R+G at different vancomycin loadings in the powder of the cements. We hypothesized that antibiotic elution of Copal\(^®\) spacem is superior at comparable compressive strength. Methods. Compression test specimens were fabricated using Copal\(^®\) spacem manually loaded with 0.5 g gentamicin and additionally 2 g, 4 g, and 6 g of vancomycin per 40 g of cement powder (COP specimens) and using 0.5 g gentamicin premixed Palacos\(^®\) R+G manually loaded with 2 g, 4 g, and 6 g of vancomycin per 40 g of cement powder (PAL specimens). These specimens were used for determination of gentamicin and vancomycin elution (in fetal calf serum, at 22°C) and for determination of compressive strength both prior and following the elution tests. Results. Cumulative gentamicin concentrations (p < 0.005) and gentamicin concentration after 28 days (p ≤ 0.043) were significantly lower for COP specimens compared to PAL specimens. Cumulative vancomycin concentrations were significantly higher (p ≤ 0.043) for COP specimens after the second day. Vancomycin concentrations after 28 days were not significantly higher for the Copal specimens loaded with 2 g and 4 g of vancomycin. Compressive strength was not significantly different between COP specimens and PAL specimens before elution tests. Compressive strength after the elution tests was significantly lower (p = 0.005) for COP specimens loaded with 2 g of vancomycin. Conclusion. We could not demonstrate consistent superior antibiotic elution from Copal\(^®\) spacem compared to Palacos\(^®\) R+G for fabricating gentamicin and vancomycin loaded spacers. The results do not favor Copal\(^®\) spacem over Palacos\(^®\) R+G for the use as a gentamicin and vancomycin biantibiotic-loaded spacer. KW - Copal\(^®\) spacem KW - PMMA bone cement KW - elution KW - compressive strength Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177435 VL - 2018 IS - 4323518 ER - TY - JOUR A1 - Dotterweich, Julia A1 - Schlegelmilch, Katrin A1 - Keller, Alexander A1 - Geyer, Beate A1 - Schneider, Doris A1 - Zeck, Sabine A1 - Tower, Robert J. J. A1 - Ebert, Regina A1 - Jakob, Franz A1 - Schütze, Norbert T1 - Contact of myeloma cells induces a characteristic transcriptome signature in skeletal precursor cells-implications for myeloma bone disease JF - Bone N2 - Physical interaction of skeletal precursors with multiple myeloma cells has been shown to suppress their osteogenic potential while favoring their tumor-promoting features. Although several transcriptome analyses of myeloma patient-derived mesenchymal stem cells have displayed differences compared to their healthy counterparts, these analyses insufficiently reflect the signatures mediated by tumor cell contact, vary due to different methodologies, and lack results in lineage-committed precursors. To determine tumor cell contact-mediated changes on skeletal precursors, we performed transcriptome analyses of mesenchymal stem cells and osteogenic precursor cells cultured in contact with the myeloma cell line INA-6. Comparative analyses confirmed dysregulation of genes which code for known disease-relevant factors and additionally revealed upregulation of genes that are associated with plasma cell homing, adhesion, osteoclastogenesis, and angiogenesis. Osteoclast-derived coupling factors, a dysregulated adipogenic potential, and an imbalance in favor of anti-anabolic factors may play a role in the hampered osteoblast differentiation potential of mesenchymal stem cells. Angiopoietin-Like 4 (ANGPTL4) was selected from a list of differentially expressed genes as a myeloma cell contact-dependent target in skeletal precursor cells which warranted further functional analyses. Adhesion assays with full-length ANGPTL4-coated plates revealed a potential role of this protein in INA6 cell attachment. This study expands knowledge of the myeloma cell contact-induced signature in the stromal compartment of myelomatous bones and thus offers potential targets that may allow detection and treatment of myeloma bone disease at an early stage. KW - marrow stromal cells KW - Endothelial growth-factor KW - precedes multiple-myeloma KW - monoclonial gammopathy KW - in-vitro KW - mesenchymal stem-cells KW - undetermined significance KW - angiogenic cytokines KW - peripheral-blood KW - gene-expression KW - Multiple myeloma KW - Bone disease KW - Angiopoietin-like 4 KW - Gene expression profiling KW - Mesenchymal stem cells KW - Osteogenic precursor cells Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186688 VL - 93 ER - TY - JOUR A1 - Meyer, Till Jasper A1 - Stöth, Manuel A1 - Moratin, Helena A1 - Ickrath, Pascal A1 - Herrmann, Marietta A1 - Kleinsasser, Norbert A1 - Hagen, Rudolf A1 - Hackenberg, Stephan A1 - Scherzad, Agmal T1 - Cultivation of head and neck squamous cell carcinoma cells with wound fluid leads to cisplatin resistance via epithelial-mesenchymal transition induction JF - International Journal of Molecular Sciences N2 - Locoregional recurrence is a major reason for therapy failure after surgical resection of head and neck squamous cell carcinoma (HNSCC). The physiological process of postoperative wound healing could potentially support the proliferation of remaining tumor cells. The aim of this study was to evaluate the influence of wound fluid (WF) on the cell cycle distribution and a potential induction of epithelial-mesenchymal transition (EMT). To verify this hypothesis, we incubated FaDu and HLaC78 cells with postoperative WF from patients after neck dissection. Cell viability in dependence of WF concentration and cisplatin was measured by flow cytometry. Cell cycle analysis was performed by flow cytometry and EMT-marker expression by rtPCR. WF showed high concentrations of interleukin (IL)-6, IL-8, IL-10, CCL2, MCP-1, EGF, angiogenin, and leptin. The cultivation of tumor cells with WF resulted in a significant increase in cell proliferation without affecting the cell cycle. In addition, there was a significant enhancement of the mesenchymal markers Snail 2 and vimentin, while the expression of the epithelial marker E-cadherin was significantly decreased. After cisplatin treatment, tumor cells incubated with WF showed a significantly higher resistance compared with the control group. The effect of cisplatin-resistance was dependent on the WF concentration. In summary, proinflammatory cytokines are predominantly found in WF. Furthermore, the results suggest that EMT can be induced by WF, which could be a possible mechanism for cisplatin resistance. KW - cell proliferation KW - wound fluid KW - epithelial-mesenchymal transition KW - cisplatin resistance KW - Interleukin KW - head and neck squamous cell carcinoma Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258722 SN - 1422-0067 VL - 22 IS - 9 ER - TY - JOUR A1 - von Hertzberg-Boelch, Sebastian Philipp A1 - Wagenbrenner, Mike A1 - Arnholdt, Jörg A1 - Frenzel, Stephan A1 - Holzapfel, Boris Michael A1 - Rudert, Maximilian T1 - Custom Made Monoflange Acetabular Components for the Treatment of Paprosky Type III Defects JF - Journal of Personalized Medicine N2 - Purpose: Patient-specific, flanged acetabular components are used for the treatment of Paprosky type III defects during revision total hip arthroplasty (THA). This monocentric retrospective cohort study analyzes the outcome of patients treated with custom made monoflanged acetabular components (CMACs) with intra- and extramedullary iliac fixation. Methods: 14 patients were included who underwent revision THA with CMACs for the treatment of Paprosky type III defects. Mechanism of THA failure was infection in 4 and aseptic loosening in 10 patients. Seven patients underwent no previous revision, the other seven patients underwent three or more previous revisions. Results: At a mean follow-up of 35.4 months (14–94), the revision rate of the implant was 28.3%. Additionally, one perioperative dislocation and one superficial wound infection occurred. At one year postoperatively, we found a significant improvement of the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score (p = 0.015). Postoperative radiographic analysis revealed good hip joint reconstruction with a mean leg length discrepancy of 3 mm (−8–20), a mean lateralization of the horizontal hip center of rotation of 8 mm (−8–35), and a mean proximalization of the vertical hip center of rotation of 6 mm (13–26). Radiolucency lines were present in 30%. Conclusion: CMACs can be considered an option for the treatment of acetabular bone loss in revision THA. Iliac intra- and extramedullary fixation allows soft tissue-adjusted hip joint reconstruction and improves hip function. However, failure rates are high, with periprosthetic infection being the main threat to successful outcome. KW - patient specific implant KW - custom made implant KW - revision hip KW - Paprosky KW - pelvic discontinuity Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236513 SN - 2075-4426 VL - 11 IS - 4 ER - TY - JOUR A1 - Streck, Laura Elisa A1 - Gaal, Chiara A1 - Forster, Johannes A1 - Konrads, Christian A1 - Hertzberg-Boelch, Sebastian Philipp von A1 - Rueckl, Kilian T1 - Defining a synovial fluid white blood cell count threshold to predict periprosthetic infection after shoulder arthroplasty JF - Journal of Clinical Medicine N2 - Background: The diagnosis of periprosthetic shoulder infection (PSI) requires a thorough diagnostic workup. Synovial fluid aspiration has been proven to be a reliable tool in the diagnosis of joint infections of the lower extremity, but shoulder specific data is limited. This study defines a threshold for synovial fluid white blood cell count (WBC) and assesses the reliability of microbiological cultures. Methods: Retrospective study of preoperative and intraoperative fluid aspiration of 31 patients who underwent a revision of a shoulder arthroplasty (15 with PSI defined by IDSA criteria, 16 without infection). The threshold for WBC was calculated by ROC/AUC analysis. Results: WBC was significantly higher in patients with PSI than in other patients. A threshold of 2800 leucocytes/mm\(^3\) showed a sensitivity of 87% and a specificity of 88% (AUROC 0.92). Microbiological cultures showed a sensitivity of 76% and a specificity of 100%. Conclusions: A threshold of 2800 leucocytes/mm\(^3\) in synovial fluid can be recommended to predict PSI. Microbiological culture has an excellent specificity and allows for targeted antibiotic therapy. Joint aspiration presents an important pillar to diagnose PSI. KW - upper extremity KW - joint infection KW - joint aspiration KW - leucocyte count KW - cutibacteria KW - ICM KW - MSIS KW - IDSA KW - WBC Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252275 SN - 2077-0383 VL - 11 IS - 1 ER - TY - JOUR A1 - Eidmann, Annette A1 - Kamawal, Yama A1 - Luedemann, Martin A1 - Raab, Peter A1 - Rudert, Maximilian A1 - Stratos, Ioannis T1 - Demographics and etiology for lower extremity amputations — experiences of an university orthopaedic center in Germany JF - Medicina N2 - Background and Objectives: Currently, the worldwide incidence of major amputations in the general population is decreasing whereas the incidence of minor amputations is increasing. The purpose of our study was to analyze whether this trend is reflected among orthopaedic patients treated with lower extremity amputation in our orthopaedic university institution. Materials and Methods: We conducted a single-center retrospective study and included patients referred to our orthopaedic department for lower extremity amputation (LEA) between January 2007 and December 2019. Acquired data were the year of amputation, age, sex, level of amputation and cause of amputation. T test and Chi² test were performed to compare age and amputation rates between males and females; significance was defined as p < 0.05. Linear regression and multivariate logistic regression models were used to test time trends and to calculate probabilities for LEA. Results: A total of 114 amputations of the lower extremity were performed, of which 60.5% were major amputations. The number of major amputations increased over time with a rate of 0.6 amputation/year. Men were significantly more often affected by LEA than women. Age of LEA for men was significantly below the age of LEA for women (men: 54.8 ± 2.8 years, women: 64.9 ± 3.2 years, p = 0.021). Main causes leading to LEA were tumors (28.9%) and implant-associated complications (25.4%). Implant-associated complications and age raised the probability for major amputation, whereas malformation, angiopathies and infections were more likely to cause a minor amputation. Conclusions: Among patients in our orthopaedic institution, etiology of amputations of the lower extremity is multifactorial and differs from other surgical specialties. The number of major amputations has increased continuously over the past years. Age and sex, as well as diagnosis, influence the type and level of amputation. KW - lower extremity amputation KW - major amputation KW - minor amputation KW - orthopaedic surgery Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304856 SN - 1648-9144 VL - 59 IS - 2 ER - TY - JOUR A1 - Heinz, Tizian A1 - Eidmann, Annette A1 - Jakuscheit, Axel A1 - Laux, Tino A1 - Rudert, Maximilian A1 - Stratos, Ioannis T1 - Demographics and trends for inbound medical tourism in Germany for orthopedic patients before and during the COVID-19 pandemic JF - International Journal of Environmental Research and Public Health N2 - Medical tourism is a rapidly growing sector of economic growth and diversification. However, data on the demographics and characteristics of the traveling patients are sparse. In this study, we analyzed the common demographic properties and characteristics of the inbound medical tourists seeking orthopedic medical care in Germany for the years 2010 to 2019 compared to a domestic group. At the same time, we examined how the COVID-19 pandemic outbreak of 2020 changed the field of medical tourism in Germany. Calculations were performed using administrative hospital data provided by the Federal Statistical Department of Germany. Data were analyzed from the years 2010 to 2020. A total of six elective orthopedic surgery codes (bone biopsy, knee arthroplasty, foot surgery, osteotomy, hardware removal, and arthrodesis) were identified as key service indicators for medical tourism and further analyzed. Factors including residence, sex, year, and type of elective surgery were modeled using linear regression analysis. Age and sex distributions were compared between patients living inside Germany (DE) or outside Germany (non-DE). Between 2010 and 2020, 6,261,801 orthopedic procedures were coded for the DE group and 27,420 key procedures were identified for the non-DE group. Medical tourists were predominantly male and significantly younger than the domestic population. The linear regression analysis of the OPS codes over the past years showed a significantly different slope between the DE and non-DE groups only for the OPS code “hardware removal”. With the COVID-19 pandemic, an overall decline in performed orthopedic procedures was observed for the non-DE and the DE group. A significant reduction below the 95% prediction bands for the year 2020 could be shown for hardware removal and foot surgery (for DE), and for hardware removal, knee arthroplasty, foot surgery, and osteotomy (for non-DE). This study is the first to quantify inbound medical tourism in elective orthopedic surgery in Germany. The COVID-19 pandemic negatively affected many — but not all — areas of orthopedic surgery. It has to be seen how this negative trend will develop in the future. KW - inbound medical tourism KW - orthopedic surgery KW - Germany KW - COVID-19 KW - pandemic Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304955 SN - 1660-4601 VL - 20 IS - 2 ER - TY - JOUR A1 - Nedopil, Alexander A1 - Raab, Peter A1 - Rudert, Maximilian T1 - Desmoplastic Fibroma: A Case Report with Three Years of Clinical and Radiographic Observation and Review of the Literature JF - Open Orthopaedics Journal N2 - Background: Desmoplastic fibroma (DF) is an extremely rare locally aggressive bone tumor with an incidence of 0.11% of all primary bone tumors. The typical clinical presentation is pain and swelling above the affected area. The most common sites of involvement are the mandible and the metaphysis of long bones. Histologically and biologically, desmoplastic fibroma mimics extra-abdominal desmoid tumor of soft tissue. Case Presentation and Literature Review: A case of a 27-year old man with DF in the ilium, including the clinical, radiological and histological findings over a 4-year period is presented here. CT scans performed in 3-year intervals prior to surgical intervention were compared with respect to tumor extension and cortical breakthrough. The patient was treated with curettage and grafting based on anatomical considerations. Follow-up CT scans over 18-months are also documented here. Additionally, a review and analysis of 271 cases including the presented case with particular emphasis on imaging patterns in MRI and CT as well as treatment modalities and outcomes are presented. Conclusion: In patients with desmoplastic fibroma, CT is the preferred imaging technique for both the diagnosis of intraosseus tumor extension and assessment of cortical involvement, whereas MRI is favored for the assessment of extraosseus tumor growth and preoperative planning. While tumor resection remains the preferred treatment for DF, curettage and grafting prove to be an acceptable alternative treatment modality with close follow-up when resection is not possible. Curettage and grafting have been shown to provide good clinical results and are associated with long recurrence free intervals. KW - Desmoplastic fibroma KW - rare bone tumor KW - benign bone tumor KW - curettage KW - autograft Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96123 ER - TY - THES A1 - Haddad-Weber, Meike T1 - Development of stem cell-based ACL- and tendon reconstruction T1 - Entwicklung Stammzell-basierter Konstrukte für den Kreuzband- und Sehnenersatz N2 - Ruptures of the anterior cruciate ligament (ACL) and defects of the rotator cuff represent the most common ligament and tendon injuries in knee and shoulder. Both injuries represent significant implications for the patients. After an injury, the ACL and the rotator cuff both exhibit poor intrinsic healing capacities. In order to prevent further defects such as arthritis of the knee and fatty infiltration of the rotator cuff, surgical interaction is essential. In both cases, the currently used surgical techniques are far from optimal because even after the therapy many patients report problems ranging from pain and reduced mobility to complete dysfunction of the involved joint and muscles. Tissue engineering may be a possible solution. It is a promising field of regenerative medicine and might be an advantageous alternative for the treatment of musculoskeletal injuries and diseases in the near future. In this thesis, different tissue engineering based approaches were investigated. For the reconstruction of damaged or diseased ligaments and tendons, the use of MSCs and gene therapy with growth factors is especially suitable and possesses a great therapeutic potential. Therefore, the first method studied and tested in this thesis was the development of a biomaterial based construct for the repair of a ruptured ACL. The second approach represents a cell based strategy for the treatment of the fatty infiltration in the rotator cuff. The third approach was a combined cell, biomaterial, and growth factor based strategy for ACL ruptures. Biomaterial based ACL construct The implant is currently tested in a preclinical in vivo study in mini pigs. This proof-of-principle study is performed to validate the functional capability of the collagen fiber based implant under load in vivo and its population with fibroblasts which produce a ligamentogenic matrix. Cell based treatment of the fatty infiltration in the rotator cuff Regarding the treatment of the fatty infiltration of the rotator cuff in a rabbit model, the in vivo results are also promising. The group treated with autologous MSCs (+MSC group) showed a lower fat content than the untreated group (–MSC group) 6 weeks after the treatment. Furthermore, the SSP muscle of the MSC-treated animals revealed macroscopically and microscopically only few differences compared to the healthy control group. The exact underlying mechanisms leading to the positive results of the treatment are not yet fully understood and have therefore to be further investigated in the future. Cell, biomaterial, and growth factor based treatment of ACL ruptures Studies described in current literature show that collagen hydrogel scaffolds are not ideal for a complete ligament or tendon reconstruction, because of their insufficient mechanical stability. Introduced as an alternative and superior therapy, the combined strategy used in this thesis proves that the cultivation of BMP-12, -13, and IGF-1 transduced MSCs and ACL fibroblasts in a collagen hydrogel is successful. The results of the performed in vitro study reveal that the cells exhibit a fibroblastic appearance and produce a ligamentogenic matrix after 3 weeks. Furthermore, the adenoviral transduction of MSCs and ACL fibroblasts showed no negative effects on proliferation or viability of the cells nor was apoptosis caused. Therefore, the application of these cells represents a possible future therapy for a partial ligament and tendon rupture where the mechanical stability of the remaining ligament or tendon is sufficient and the healing can be improved substantially by this therapy. In general, prospective randomized clinical trials still have to prove the postulated positive effect of MSCs for the treatment of various musculoskeletal diseases, but the results obtained here are already very promising. Ideally, the treatment with MSCs is superior compared to the standard surgical procedures. Because of current safety issues the use of genetically modified cells cannot be expected to be applied clinically in the near future. In summary, the different tissue engineering approaches for novel therapies for musculoskeletal injuries and diseases invested in this thesis showed very promising results and will be further developed and tested in preclinical and clinical trials. N2 - 7.2 Zusammenfassung Kreuzbandrupturen und Defekte im Bereich der Rotatorenmanschette stellen die häufigsten Band- und Sehnenverletzungen im Kniegelenk bzw. in der Schulter dar. Beide Verletzungen haben erhebliche Auswirkungen für den Patienten. Sowohl das Kreuzband als auch die Rotatorenmanschette weisen ein sehr schlechtes Heilungspotential nach einer Verletzung auf. Um weiteren Schäden wie einer Kniegelenksarthrose oder einer Verfettung der Rotatorenmanschette vorzubeugen, ist ein operativer Eingriff erforderlich. In beiden Fällen sind die zurzeit verwendeten Behandlungsstandards nicht optimal, da auch nach einer Therapie viele Patienten über Beschwerden klagen, die von Schmerzen und einer eingeschränkten Mobilität bis hin zu einer kompletten Dysfunktion des betroffenen Gelenks und Muskels reichen. Tissue Engineering ist ein zukunftsträchtiges Feld der Regenerativen Medizin und kann ein möglicher Lösungsansatz sein. Vor allem bei der Behandlung von muskuloskelettalen Verletzungen und Erkrankungen kann es zukünftig eine vorteilhafte Behandlungsalternative darstellen. In dieser Doktorarbeit wurden verschiedene Tissue Engineering-basierte Lösungsansätze untersucht. Zur Rekonstruktion von defektem Band- und Sehnengewebe sind sowohl der Einsatz von mesenchymalen Stammzellen (MSZ) als auch die Gentherapie mit Wachstumsfaktoren besonders geeignet und weisen ein großes therapeutisches Potential auf. Deswegen wurde in der vorliegenden Doktorarbeit als erster innovativer Therapieansatz ein Biomaterial-basiertes Konstrukt für den Ersatz eines gerissenen Kreuzbandes entwickelt und getestet. Der zweite Lösungsansatz stellt eine Zell-basierte Therapie zur Behandlung einer fettigen Atrophie der Rotatorenmanschette dar. Die dritte Methode kombiniert Zellen, Biomaterialien und Wachstumsfaktoren zur Therapie von Kreuzbandrupturen. Biomaterial-basiertes Kreuzbandkonstrukt Das Implantat wird zurzeit in einer präklinischen in vivo Studie am Mini Pig getestet. Diese Proof-of-Principle Studie wird durchgeführt, um die Funktionsfähigkeit der Kollagenfaser-basierten Implantate unter Belastung in vivo zu validieren und ihre Besiedelung mit Fibroblasten, die eine ligamentäre Matrix ausbilden, zu beobachten. Zell-basierte Behandlung der fettig-infiltrieten Rotatorenmanschette Auch bei der Behandlung der fettigen Infiltration der Rotatorenmanschette im Kaninchenmodel, wurden in vivo sehr viel versprechende Ergebnisse erzielt. Die mit autologen MSZ (+MSZ-Gruppe) behandelte Gruppe zeigte nach 6 Wochen einen deutlich geringeren Fettanteil als die unbehandelte Gruppe (-MSZ-Gruppe). Des Weiteren wies der SSP-Muskel aller MSZ-behandelten Tiere sowohl makroskopisch als auch mikroskopisch nur geringe Unterschiede im Vergleich zur gesunden Kontrollgruppe auf. Der genaue zugrunde liegende Mechanismus dieser erfolgreichen Behandlung konnte bisher noch nicht genau geklärt werden und muss in zukünftigen Studien weiter untersucht werden. Zell-, Biomaterial- und Wachstumsfaktor-basierte Behandlung von Kreuzbandrupturen In der aktuellen Literatur beschriebenen Studien zeigen, dass Kollagenhydrogel-konstrukte aufgrund der fehlenden biomechanischen Stabilität nicht geeignet sind für den kompletten Band- bzw. Sehnenersatz. Als vorteilhafte Behandlungsalternative wurde in der vorliegenden Arbeit eine kombinierte Strategie entwickelt und erfolgreich in vitro getestet: Die Kultivierung von BMP-12-, -13- bzw. IGF-1-transduzierten MSZ und Kreuzbandfibroblasten in einem Kollagenhydrogel verlief sehr viel versprechend und ergab, dass die Zellen nach 3 Wochen im Kollagenhydrogel eine fibroblastäre Morphologie aufweisen und eine ligamentäre Matrix ausbilden. Des Weiteren führte die adenovirale Transduktion der Zellen weder zu negativen Auswirkungen auf das Proliferationsverhalten noch auf die Vitalität der Zellen und löste auch keine Apoptose bei den transduzierten Zellen aus. Zukünftig kann der Einsatz dieser Zellen deswegen ein möglicher Ansatz zur Behandlung von Teilrupturen bei Bändern und Sehnen darstellen, bei denen die biomechanische Stabilität ausreichend ist und die Heilung durch die Therapie wesentlich verbessert wird. Im Allgemeinen müssen prospektive randomisierte klinische Studien zeigen, ob sich der positive Effekt der MSZ bei der Behandlung von Erkrankungen des muskuloskelettalen Systems in der Orthopädie und Unfallchirurgie bewährt, wobei die in der vorliegenden Arbeit erzielten Ergebnisse sehr Erfolg versprechend sind. Idealerweise erweist sich die Behandlung mit MSZ als deutlich vorteilhaft gegenüber den bisher etablierten chirurgischen Standardverfahren. Aufgrund der bestehenden Sicherheitsrichtlinien für den Einsatz von gentherapeutischen modifizierten Zellen ist mit deren Verwendung zur Behandlung von Band- und Sehnenerkrankungen in naher Zukunft nicht zu rechnen. Zusammenfassend führte die Untersuchung der unterschiedlichen Tissue Engineering Ansätze, die in dieser Doktorarbeit als neue Therapien zur Behandlung von muskuloskelettalen Verletzungen und Erkrankungen evaluiert wurden, zu sehr viel versprechende Ergebnisse. Diese Therapieansätze sollen weiterentwickelt und in präklinischen und klinischen Studien getestet werden. KW - Kreuzband KW - Sehne KW - Tissue Engineering KW - Mesenchymale Stammzellen KW - Gentherpie KW - Zell-basierte Therapie KW - ACL KW - tendon KW - MSC KW - genetherapy KW - cell-based therapy Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-66796 ER - TY - JOUR A1 - Kroner-Weigl, Niklas A1 - Chu, Jin A1 - Rudert, Maximilian A1 - Alt, Volker A1 - Shukunami, Chisa A1 - Docheva, Denitsa T1 - Dexamethasone is not sufficient to facilitate tenogenic differentiation of dermal fibroblasts in a 3D organoid model JF - Biomedicines N2 - Self-assembling three-dimensional organoids that do not rely on an exogenous scaffold but maintain their native cell-to-cell and cell-to-matrix interactions represent a promising model in the field of tendon tissue engineering. We have identified dermal fibroblasts (DFs) as a potential cell type for generating functional tendon-like tissue. The glucocorticoid dexamethasone (DEX) has been shown to regulate cell proliferation and facilitate differentiation towards other mesenchymal lineages. Therefore, we hypothesized that the administration of DEX could reduce excessive DF proliferation and thus, facilitate the tenogenic differentiation of DFs using a previously established 3D organoid model combined with dose-dependent application of DEX. Interestingly, the results demonstrated that DEX, in all tested concentrations, was not sufficient to notably induce the tenogenic differentiation of human DFs and DEX-treated organoids did not have clear advantages over untreated control organoids. Moreover, high concentrations of DEX exerted a negative impact on the organoid phenotype. Nevertheless, the expression profile of tendon-related genes of untreated and 10 nM DEX-treated DF organoids was largely comparable to organoids formed by tendon-derived cells, which is encouraging for further investigations on utilizing DFs for tendon tissue engineering. KW - 3D organoids KW - dermal fibroblasts KW - dexamethasone KW - scaffold-free KW - tenogenic differentiation KW - tendon tissue engineering Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311234 SN - 2227-9059 VL - 11 IS - 3 ER - TY - JOUR A1 - Boelch, Sebastian Philipp A1 - Rüeckl, Kilian A1 - Streck, Laura Elisa A1 - Szewczykowski, Viktoria A1 - Weißenberger, Manuel A1 - Jakuscheit, Axel A1 - Rudert, Maximilian T1 - Diagnosis of chronic infection at total hip arthroplasty revision is a question of definition JF - Biomed Research International N2 - Purpose. Contradicting definitions of periprosthetic joint infection (PJI) are in use. Joint aspiration is performed before total hip arthroplasty (THA) revision. This study investigated the influence of PJI definition on PJI prevalence at THA revision. Test quality of prerevision aspiration was evaluated for the different PJI definitions. Methods. 256 THA revisions were retrospectively classified to be infected or not infected. Classification was performed according to the 4 different definitions proposed by the Musculoskeletal Infection Society (MSIS), the Infectious Diseases Society of America (IDSA), the International Consensus Meeting (ICM), and the European Bone and Joint Infection Society (EBJIS). Only chronic PJIs were included. Results. PJI prevalence at revision significantly correlated with the applied PJI definition (p=0.01, Cramer's V=0.093). PJI prevalence was 20.7% for the MSIS, 25.4% for the ICM, 28.1% for the IDSA, and 32.0% for the EBJIS definition. For synovial fluid white blood cell count, the best ROC-AUC for predicting PJI was 0.953 in combination with the MSIS definition. Conclusion. PJI definition significantly influences the rate of diagnosed PJIs at THA revision. Synovial fluid white blood cell count is a reliable means to rule out PJI. In cases with a borderline high synovial white blood cell count before THA revision as the only sign of chronic PJI, an extended diagnostic work-up should be considered. KW - periprosthetic joint infection KW - algorithm KW - consensus Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265762 VL - 2021 ER - TY - JOUR A1 - Weissenberger, Manuel A1 - Weissenberger, Manuela H. A1 - Wagenbrenner, Mike A1 - Heinz, Tizian A1 - Reboredo, Jenny A1 - Holzapfel, Boris M. A1 - Rudert, Maximilian A1 - Groll, Jürgen A1 - Evans, Christopher H. A1 - Steinert, Andre F. T1 - Different types of cartilage neotissue fabricated from collagen hydrogels and mesenchymal stromal cells via SOX9, TGFB1 or BMP2 gene transfer JF - PLoS One N2 - Objective As native cartilage consists of different phenotypical zones, this study aims to fabricate different types of neocartilage constructs from collagen hydrogels and human mesenchymal stromal cells (MSCs) genetically modified to express different chondrogenic factors. Design Human MSCs derived from bone-marrow of osteoarthritis (OA) hips were genetically modified using adenoviral vectors encoding sex-determining region Y-type high-mobility-group-box (SOX)9,transforming growth factor beta (TGFB) 1or bone morphogenetic protein (BMP) 2cDNA, placed in type I collagen hydrogels and maintained in serum-free chondrogenic media for three weeks. Control constructs contained unmodified MSCs or MSCs expressing GFP. The respective constructs were analyzed histologically, immunohistochemically, biochemically, and by qRT-PCR for chondrogenesis and hypertrophy. Results Chondrogenesis in MSCs was consistently and strongly induced in collagen I hydrogels by the transgenesSOX9,TGFB1andBMP2as evidenced by positive staining for proteoglycans, chondroitin-4-sulfate (CS4) and collagen (COL) type II, increased levels of glycosaminoglycan (GAG) synthesis, and expression of mRNAs associated with chondrogenesis. The control groups were entirely non-chondrogenic. The levels of hypertrophy, as judged by expression of alkaline phosphatase (ALP) and COL X on both the protein and mRNA levels revealed different stages of hypertrophy within the chondrogenic groups (BMP2>TGFB1>SOX9). Conclusions Different types of neocartilage with varying levels of hypertrophy could be generated from human MSCs in collagen hydrogels by transfer of genes encoding the chondrogenic factorsSOX9,TGFB1andBMP2. This technology may be harnessed for regeneration of specific zones of native cartilage upon damage. KW - stem cells KW - in vitro KW - chondrogenic differentiation KW - repair KW - chondrocytes KW - transplantation KW - stimulation KW - scaffolds KW - defects KW - therapy Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230494 VL - 15 IS - 8 ER -