@article{HeinzMellerLuetkensetal.2023, author = {Heinz, Tizian and Meller, Felix and Luetkens, Karsten Sebastian and Anderson, Philip Mark and Stratos, Ioannis and Horas, Konstantin and Rudert, Maximilian and Reppenhagen, Stephan and Weißenberger, Manuel}, title = {The AMADEUS score is not a sufficient predictor for functional outcome after high tibial osteotomy}, series = {Journal of Experimental Orthopaedics}, volume = {10}, journal = {Journal of Experimental Orthopaedics}, doi = {10.1186/s40634-023-00575-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357765}, year = {2023}, abstract = {Purpose The Area Measurement And Depth Underlying Structures (AMADEUS) classification system has been proposed as a valuable tool for magnetic resonance (MR)-based grading of preoperatively encountered chondral defects of the knee joint. However, the potential relationship of this novel score with clinical data was yet to determine. It was the primary intention of this study to assess the correlative relationship of the AMADEUS with patient reported outcome scores in patients undergoing medial open-wedge high tibial valgus osteotomy (HTO). Furthermore, the arthroscopic ICRS (International Cartilage Repair Society) grade evaluation was tested for correlation with the AMADEUS classification system. Methods This retrospective, monocentric study found a total of 70 individuals that were indicated for HTO due to degenerative chondral defects of the medial compartment between 2008 and 2019. A preoperative MR image as well as a pre-osteotomy diagnostic arthroscopy for ICRS grade evaluation was mandatory for all patients. The Knee Osteoarthritis Outcome Score (KOOS) including its five subscale scores (KOOS-ADL, KOOS-QOL, KOOS-Sports, KOOS-Pain, KOOS-Symptoms) was obtained preoperatively and at a mean follow-up of 41.2 ± 26.3 months. Preoperative chondral defects were evaluated using the AMADEUS classification system and the final AMADEUS scores were correlated with the pre- and postoperative KOOS subscale sores. Furthermore, arthroscopic ICRS defect severity was correlated with the AMADEUS classification system. Results There was a statistically significant correlation between the AMADEUS BME (bone marrow edema) subscore and the KOOS Symptoms subscore at the preoperative visit (r = 0.25, p = 0.04). No statistically significant monotonic association between the AMADEUS total score and the AMADEUS grade with pre- and postoperative KOOS subscale scores were found. Intraoperatively obtained ICRS grade did reveal a moderate correlative relation with the AMADEUS total score and the AMADEUS grade (r = 0.28, p = 0.02). Conclusions The novel AMADEUS classification system largely lacks correlative capacity with patient reported outcome measures in patients undergoing HTO. The MR tomographic appearance of bone marrow edema is the only parameter predictive of the clinical outcome at the preoperative visit.}, language = {en} } @article{WeberBeckKlugetal.2023, author = {Weber, Patrick and Beck, Melina and Klug, Michael and Klug, Andreas and Klug, Alexander and Glowalla, Claudio and Gollwitzer, Hans}, title = {Survival of patient-specific unicondylar knee replacement}, series = {Journal of Personalized Medicine}, volume = {13}, journal = {Journal of Personalized Medicine}, number = {4}, issn = {2075-4426}, doi = {10.3390/jpm13040665}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313650}, year = {2023}, abstract = {Unicompartmental knee arthroplasty (UKA) in isolated medial or lateral osteoarthritis leads to good clinical results. However, revision rates are higher in comparison to total knee arthroplasty (TKA). One reason is suboptimal fitting of conventional off-the-shelf prostheses, and major overhang of the tibial component over the bone has been reported in up to 20\% of cases. In this retrospective study, a total of 537 patient-specific UKAs (507 medial prostheses and 30 lateral prostheses) that had been implanted in 3 centers over a period of 10 years were analyzed for survival, with a minimal follow-up of 1 year (range 12 to 129 months). Furthermore, fitting of the UKAs was analyzed on postoperative X-rays, and tibial overhang was quantified. A total of 512 prostheses were available for follow-up (95.3\%). Overall survival rate (medial and lateral) of the prostheses after 5 years was 96\%. The 30 lateral UKAs showed a survival rate of 100\% at 5 years. The tibial overhang of the prosthesis was smaller than 1 mm in 99\% of cases. In comparison to the reported results in the literature, our data suggest that the patient-specific implant design used in this study is associated with an excellent midterm survival rate, particularly in the lateral knee compartment, and confirms excellent fitting.}, language = {en} } @article{WagenbrennerPokerHeinzetal.2022, author = {Wagenbrenner, Mike and Poker, Konrad and Heinz, Tizian and Herrmann, Marietta and Horas, Konstantin and Ebert, Regina and Mayer-Wagner, Susanne and Holzapfel, Boris M. and Rudert, Maximilian and Steinert, Andre F. and Weißenberger, Manuel}, title = {Mesenchymal stromal cells (MSCs) isolated from various tissues of the human arthritic knee joint possess similar multipotent differentiation potential}, series = {Applied Sciences}, volume = {12}, journal = {Applied Sciences}, number = {4}, issn = {2076-3417}, doi = {10.3390/app12042239}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262334}, year = {2022}, abstract = {(1) Background: The mesenchymal stromal cells (MSCs) of different tissue origins are applied in cell-based chondrogenic regeneration. However, there is a lack of comparability determining the most suitable cell source for the tissue engineering (TE) of cartilage. The purpose of this study was to compare the in vitro chondrogenic potential of MSC-like cells from different tissue sources (bone marrow, meniscus, anterior cruciate ligament, synovial membrane, and the infrapatellar fat pad removed during total knee arthroplasty (TKA)) and define which cell source is best suited for cartilage regeneration. (2) Methods: MSC-like cells were isolated from five donors and expanded using adherent monolayer cultures. Differentiation was induced by culture media containing specific growth factors. Transforming growth factor (TGF)-ß1 was used as the growth factor for chondrogenic differentiation. Osteogenesis and adipogenesis were induced in monolayer cultures for 27 days, while pellet cell cultures were used for chondrogenesis for 21 days. Control cultures were maintained under the same conditions. After, the differentiation period samples were analyzed, using histological and immunohistochemical staining, as well as molecularbiological analysis by RT-PCR, to assess the expression of specific marker genes. (3) Results: Plastic-adherent growth and in vitro trilineage differentiation capacity of all isolated cells were proven. Flow cytometry revealed the clear co-expression of surface markers CD44, CD73, CD90, and CD105 on all isolated cells. Adipogenesis was validated through the formation of lipid droplets, while osteogenesis was proven by the formation of calcium deposits within differentiated cell cultures. The formation of proteoglycans was observed during chondrogenesis in pellet cultures, with immunohistochemical staining revealing an increased relative gene expression of collagen type II. RT-PCR proved an elevated expression of specific marker genes after successful differentiation, with no significant differences regarding different cell source of native tissue. (4) Conclusions: Irrespective of the cell source of native tissue, all MSC-like cells showed multipotent differentiation potential in vitro. The multipotent differentiation capacity did not differ significantly, and chondrogenic differentiation was proven in all pellet cultures. Therefore, cell suitability for cell-based cartilage therapies and tissue engineering is given for various tissue origins that are routinely removed during total knee arthroplasty (TKA). This study might provide essential information for the clinical tool of cell harvesting, leading to more flexibility in cell availability.}, language = {en} } @article{WeissenbergerWagenbrennerSchoteetal.2022, author = {Weißenberger, Manuel and Wagenbrenner, Mike and Schote, Fritz and Horas, Konstantin and Sch{\"a}fer, Thomas and Rudert, Maximilian and Barthel, Thomas and Heinz, Tizian and Reppenhagen, Stephan}, title = {The 3-triangle method preserves the posterior tibial slope during high tibial valgus osteotomy: first preliminary data using a mathematical model}, series = {Journal of Experimental Orthopaedics}, volume = {9}, journal = {Journal of Experimental Orthopaedics}, issn = {2197-1153}, doi = {10.1186/s40634-022-00466-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300806}, year = {2022}, abstract = {Purpose Despite much improved preoperative planning techniques accurate intraoperative assessment of the high tibial valgus osteotomy (HTO) remains challenging and often results in coronal over- and under-corrections as well as unintended changes of the posterior tibial slope. Noyes et al. reported a novel method for accurate intraoperative coronal and sagittal alignment correction based on a three-dimensional mathematical model. This is the first study examining preliminary data via the proposed Noyes approach for accurate intraoperative coronal and sagittal alignment correction during HTO. Methods From 2016 to 2020 a total of 24 patients (27 knees) underwent HTO applying the proposed Noyes method (Noyes-Group). Radiographic data was analyzed retrospectively and matched to patients that underwent HTO using the conventional method, i.e., gradual medial opening using a bone spreader under fluoroscopic control (Conventional-Group). All operative procedures were performed by an experienced surgeon at a single orthopaedic university center. Results From the preoperative to the postoperative visit no statistically significant changes of the posterior tibial slope were noted in the Noyes-Group compared to a significant increase in the Conventional-Group (p = 0.01). Regarding the axial alignment no significant differences between both groups were observed pre- and postoperatively. The number of over- and under-corrections did not differ significantly between both groups. Linear regression analysis showed a significant correlation of the postoperative medial proximal tibial angle (MPTA) with the position of the weightbearing line on the tibial plateau. Conclusion The 3-triangle method by Noyes seems to be a promising approach for preservation of the posterior tibial slope during HTO.}, language = {en} } @article{WagenbrennerMayerWagnerRudertetal.2021, author = {Wagenbrenner, Mike and Mayer-Wagner, Susanne and Rudert, Maximilian and Holzapfel, Boris Michael and Weissenberger, Manuel}, title = {Combinations of hydrogels and mesenchymal stromal cells (MSCs) for cartilage tissue engineering — a review of the literature}, series = {Gels}, volume = {7}, journal = {Gels}, number = {4}, issn = {2310-2861}, doi = {10.3390/gels7040217}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250177}, year = {2021}, abstract = {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.}, language = {en} } @article{WagenbrennerHeinzHorasetal.2020, author = {Wagenbrenner, Mike and Heinz, Tizian and Horas, Konstantin and Jakuscheit, Axel and Arnholdt, Joerg and Mayer-Wagner, Susanne and Rudert, Maximilian and Holzapfel, Boris M. and Weißenberger, Manuel}, title = {Impact of Tranexamic Acid on Chondrocytes and Osteogenically Differentiated Human Mesenchymal Stromal Cells (hMSCs) In Vitro}, series = {Journal of Clinical Medicine}, volume = {9}, journal = {Journal of Clinical Medicine}, number = {12}, issn = {2077-0383}, doi = {10.3390/jcm9123880}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219410}, year = {2020}, abstract = {The topical application of tranexamic acid (TXA) helps to prevent post-operative blood loss in total joint replacements. Despite these findings, the effects on articular and periarticular tissues remain unclear. Therefore, this in vitro study examined the effects of varying exposure times and concentrations of TXA on proliferation rates, gene expression and differentiation capacity of chondrocytes and human mesenchymal stromal cells (hMSCs), which underwent osteogenic differentiation. Chondrocytes and hMSCs were isolated and multiplied in monolayer cell cultures. Osteogenic differentiation of hMSCs was induced for 21 days using a differentiation medium containing specific growth factors. Cell proliferation was analyzed using ATP assays. Effects of TXA on cell morphology were examined via light microscopy and histological staining, while expression levels of tissue-specific genes were measured using semiquantitative RT-PCR. After treatment with 50 mg/mL of TXA, a decrease in cell proliferation rates was observed. Furthermore, treatment with concentrations of 20 mg/mL of TXA for at least 48 h led to a visible detachment of chondrocytes. TXA treatment with 50 mg/mL for at least 24 h led to a decrease in the expression of specific marker genes in chondrocytes and osteogenically differentiated hMSCs. No significant effects were observed for concentrations beyond 20 mg/mL of TXA combined with exposure times of less than 24 h. This might therefore represent a safe limit for topical application in vivo. Further research regarding in vivo conditions and effects on hMSC functionality are necessary to fully determine the effects of TXA on articular and periarticular tissues.}, language = {en} } @article{JessbergerHoeggerGenestetal.2017, author = {Jessberger, Steffen and H{\"o}gger, Petra and Genest, Franca and Salter, Donald M. and Seefried, Lothar}, title = {Cellular pharmacodynamic effects of Pycnogenol\(^{®}\) in patients with severe osteoarthritis: a randomized controlled pilot study}, series = {BMC Complementary and Alternative Medicine}, volume = {17}, journal = {BMC Complementary and Alternative Medicine}, number = {537}, doi = {10.1186/s12906-017-2044-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159532}, year = {2017}, abstract = {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.}, language = {en} }