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 - 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 - 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 - THES A1 - Kramer, Lisa Sophie T1 - Charakterisierung des Einflusses von Estrogenrezeptoren auf mechanoresponsive Reporter T1 - Characterization of the influence of estrogen receptors according to mechanoresponsive reporter N2 - Osteoporose wird definiert als erworbene, generalisierte Skeletterkrankung, die durch eine verminderte Knochenfestigkeit und einen pathologischen Knochenverlust charakterisiert wird. Durch die Störung der Mikroarchitektur kommt es zu strukturellen und funktionellen Defiziten im Sinne von Fragilitätsfrakturen. Mechanische Stimulation erhält die Gewebemasse und stimuliert deren kontinuierliche Anpassung. Östrogene spielen bei der Entwicklung, dem Wachstum und der Regeneration des Knochens eine bedeutende Rolle und wirken über Bindung an die Östrogenrezeptoren ER und ER in bestimmten Zielgeweben. Östrogenrezeptoren sind unverändert sehr geeignete Targets für die Entwicklung von Medikamenten im Rahmen der Osteoporosetherapie wie z.B. die selektiven Östrogen-Rezeptor-Modulatoren (SERMs). Die molekulare Klärung der Einflüsse von ER und ER ist unverändert von großer klinischer Bedeutung. Die Herstellung stabiler Zelllinien mit Überexpression von Reportergenkonstrukten und Rezeptoren kann dabei hilfreich sein. In dieser Arbeit wurde eine stabile Zelllinie mit Überexpression von ERβ etabliert, die unterschiedliche Wirkung von ER und ER wurden analysiert und die Effekte von zyklischer Dehnung auf Reportergenexpression unter der Kontrolle von mechanosensitiven responsiven Elementen wurden charakterisiert. N2 - Osteoporosis is defined as an acquired, generalized skeletal disorder which is characterized by reduced bone stability and pathological bone loss. A disorder of the microarchitecture leads to structural and functional deficiencies in the form of fragility fractures. Mechanical strain sustains tissue and stimulates its continuous adaptation. Estrogen plays an important role in the development, growth and regeneration of bones and works by binding to the estrogen receptors ERα und ERβ in certain target tissues. Estrogen receptors continue to be significant targets in the development of pharmaceuticals for osteoporosis therapy as for example selective estrogen receptor modulators (SERMs). The clarification of the influence of ERα and ERβ on a molecular level continue to be of great clinical significance. The creation of stable cell lines with overexpression of reporter gene constructs and receptors can be helpful in this. In this thesis a stable cell line with overexpression of ERβ was established, different effects of ERα und ERβ were analyzed and the effects of mechanical strain on reporter gene constructs under controlled mechanosensitive response elements were characterized. KW - Östrogene KW - Mechanorezeptor KW - Osteoporose KW - Östrogenrezeptor KW - osteoporosis KW - Mechanotransduktion KW - mechanoresponsive Elemente KW - estrogen receptor KW - mechanotransduction KW - mechanoresponsive elements Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222709 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 - 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 -