@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{vonHertzbergBoelchWagenbrennerArnholdtetal.2021,
  author    = {von Hertzberg-Boelch, Sebastian Philipp and Wagenbrenner, Mike and Arnholdt, J{\"o}rg and Frenzel, Stephan and Holzapfel, Boris Michael and Rudert, Maximilian},
  title     = {Custom Made Monoflange Acetabular Components for the Treatment of Paprosky Type III Defects},
  series = {Journal of Personalized Medicine},
  volume    = {11},
  journal   = {Journal of Personalized Medicine},
  number    = {4},
  issn      = {2075-4426},
  doi       = {10.3390/jpm11040283},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236513},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}
@article{StratosScarlatRudert2021,
  author    = {Stratos, Ioannis and Scarlat, Marius M. and Rudert, Maximilian},
  title     = {Bibliometrics of orthopaedic articles published by authors of Germanophone countries},
  series = {International Orthopaedics},
  volume    = {45},
  journal   = {International Orthopaedics},
  number    = {5},
  doi       = {10.1007/s00264-021-05052-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266343},
  pages     = {1121-1124},
  year      = {2021},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{PereiraLipphausErginetal.2021,
  author    = {Pereira, Ana Rita and Lipphaus, Andreas and Ergin, Mert and Salehi, Sahar and Gehweiler, Dominic and Rudert, Maximilian and Hansmann, Jan and Herrmann, Marietta},
  title     = {Modeling of the Human Bone Environment: Mechanical Stimuli Guide Mesenchymal Stem Cell-Extracellular Matrix Interactions},
  series = {Materials},
  volume    = {14},
  journal   = {Materials},
  number    = {16},
  issn      = {1996-1944},
  doi       = {10.3390/ma14164431},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245012},
  year      = {2021},
  abstract  = {In bone tissue engineering, the design of in vitro models able to recreate both the chemical composition, the structural architecture, and the overall mechanical environment of the native tissue is still often neglected. In this study, we apply a bioreactor system where human bone-marrow hMSCs are seeded in human femoral head-derived decellularized bone scaffolds and subjected to dynamic culture, i.e., shear stress induced by continuous cell culture medium perfusion at 1.7 mL/min flow rate and compressive stress by 10\% uniaxial load at 1 Hz for 1 h per day. In silico modeling revealed that continuous medium flow generates a mean shear stress of 8.5 mPa sensed by hMSCs seeded on 3D bone scaffolds. Experimentally, both dynamic conditions improved cell repopulation within the scaffold and boosted ECM production compared with static controls. Early response of hMSCs to mechanical stimuli comprises evident cell shape changes and stronger integrin-mediated adhesion to the matrix. Stress-induced Col6 and SPP1 gene expression suggests an early hMSC commitment towards osteogenic lineage independent of Runx2 signaling. This study provides a foundation for exploring the early effects of external mechanical stimuli on hMSC behavior in a biologically meaningful in vitro environment, opening new opportunities to study bone development, remodeling, and pathologies.},
  language  = {en}
}
@article{LuedemannJakuscheitEwaldetal.2021,
  author    = {L{\"u}demann, Martin and Jakuscheit, Axel and Ewald, Andrea and Fr{\"u}hmann, Leena and H{\"o}lscher-Doht, Stefanie and Rudert, Maximilian and von Hertzberg-Boelch, Sebastian Philipp},
  title     = {Influence of Tranexamic Acid on Elution Characteristics and Compressive Strength of Antibiotic-Loaded PMMA-Bone Cement with Gentamicin},
  series = {Materials},
  volume    = {14},
  journal   = {Materials},
  number    = {19},
  issn      = {1996-1944},
  doi       = {10.3390/ma14195639},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246236},
  year      = {2021},
  abstract  = {Purpose: The topical application of tranexamic acid (TXA) into the joint space during total joint arthroplasty (TJA) with no increase of complications, has been widely reported. We investigated the influence of TXA on antibiotic release, activity of the released antibiotic against a clinical isolate of S. aureus, and compressive strength of a widely used commercially prepared gentamicin-loaded cement brand (PALACOS R + G). Method: 12 bone cement cylinders (diameter and height = 6 and 12 mm, respectively) were molded. After curing in air for at least 1 h, six of the cylinders were completely immersed in 5 mL of fetal calf serum (FCS) and the other six were completely immersed in a solution consisting of 4.9 mL of FCS and 0.1 mL (10 mg) of TXA. Gentamicin elution tests were performed over 7 d. Four hundred µL of the gentamicin eluate were taken every 24 h for the first 7 d without renewing the immersion fluid. The gentamicin concentration was determined in a clinical analyzer using a homogeny enzyme immuno-assay. The antimicrobial activity of the eluate, obtained after day 7, was tested. An agar diffusion test regime was used with Staphylococcus aureus. Bacteria were grown in a LB medium and plated on LB agar plates to get a bacterial lawn. Fifty µL of each eluate were pipetted on 12-mm diameter filter discs, which were placed in the middle of the agar gel. After 24 h of cultivation at 37 °C, the zone of inhibition (ZOI) for each specimen was measured. The compressive strength of the cements was determined per ISO 5833. Results: At each time point in the gentamicin release test, the difference in gentamicin concentration, obtained from specimens immersed in the FCS solution only and those immersed in the FCS + TXA solution was not significant (p = 0.055-0.522). The same trend was seen in each of the following parameters, after 7 d of immersion: (1) Cumulative gentamicin concentration (p < 0.297); (2) gentamicin activity against S. aureus (strongly visible); (3) ZOI size (mostly > 20 mm) (p = 0.631); and (4) compressive strength (p = 0.262). Conclusions: For the PALACOS R + G specimens, the addition of TXA to FCS does not produce significant decreases in gentamicin concentration, in the activity of the gentamicin eluate against a clinical isolate of S. aureus, the zone of inhibition of S. aureus, and in the compressive strength of the cement, after 7 d of immersion in the test solution.},
  language  = {en}
}
@article{JakuscheitSchaeferRoedigetal.2021,
  author    = {Jakuscheit, Axel and Schaefer, Nina and Roedig, Johannes and Luedemann, Martin and Hertzberg-Boelch, Sebastian Philipp von and Weissenberger, Manuel and Schmidt, Karsten and Holzapfel, Boris Michael and Rudert, Maximilian},
  title     = {Modifiable individual risks of perioperative blood transfusions and acute postoperative complications in total hip and knee arthroplasty},
  series = {Journal of Personalized Medicine},
  volume    = {11},
  journal   = {Journal of Personalized Medicine},
  number    = {11},
  issn      = {2075-4426},
  doi       = {10.3390/jpm11111223},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250290},
  year      = {2021},
  abstract  = {Background: The primary aim of this study was to identify modifiable patient-related predictors of blood transfusions and perioperative complications in total hip and knee arthroplasty. Individual predictor-adjusted risks can be used to define preoperative treatment thresholds. Methods: We performed this retrospective monocentric study in orthopaedic patients who underwent primary total knee or hip arthroplasty. Multivariate logistic regression models were used to assess the predictive value of patient-related characteristics. Predictor-adjusted individual risks of blood transfusions and the occurrence of any perioperative adverse event were calculated for potentially modifiable risk factors. Results: 3754 patients were included in this study. The overall blood transfusion and complication rates were 4.8\% and 6.4\%, respectively. Haemoglobin concentration (Hb, p < 0.001), low body mass index (BMI, p < 0.001) and estimated glomerular filtration rate (eGFR, p = 0.004) were the strongest potentially modifiable predictors of a blood transfusion. EGFR (p = 0.001) was the strongest potentially modifiable predictor of a complication. Predictor-adjusted risks of blood transfusions and acute postoperative complications were calculated for Hb and eGFR. Hb = 12.5 g/dL, BMI = 17.6 kg/m\(^2\), and eGFR = 54 min/mL were associated, respectively, with a 10\% risk of a blood transfusion, eGFR = 59 mL/min was associated with a 10\% risk of a complication. Conclusion: The individual risks for blood transfusions and acute postoperative complications are strongly increased in patients with a low preoperative Hb, low BMI or low eGFR. We recommend aiming at a preoperative Hb ≥ 13g/dL, an eGFR ≥ 60 mL/min and to avoid a low BMI. Future studies must show if a preoperative increase of eGFR and BMI is feasible and truly beneficial.},
  language  = {en}
}
@article{EidmannEwaldBoelchetal.2021,
  author    = {Eidmann, Annette and Ewald, Andrea and Boelch, Sebastian P. and Rudert, Maximilian and Holzapfel, Boris M. and Stratos, Ioannis},
  title     = {In vitro evaluation of antibacterial efficacy of vancomycin-loaded suture tapes and cerclage wires},
  series = {Journal of Materials Science: Materials in Medicine},
  volume    = {32},
  journal   = {Journal of Materials Science: Materials in Medicine},
  number    = {4},
  doi       = {10.1007/s10856-021-06513-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260089},
  pages     = {42},
  year      = {2021},
  abstract  = {Usage of implants containing antibiotic agents has been a common strategy to prevent implant related infections in orthopedic surgery. Unfortunately, most implants with microbial repellent properties are characterized by accessibility limitations during daily clinical practice. Aim of this in vitro study was to investigate whether suture tapes and cerclage wires, which were treated with vancomycin, show a sustainable antibacterial activity. For this purpose, we used 24 stainless steel wire cerclages and 24 ultra-high molecular weight polyethylene and polyester suture tape test bodies. The test bodies were incubated for 30 min. in 100 mg/ml vancomycin solution or equivalent volumes of 0.9\% NaCl. After measuring the initial solution uptake of the test bodies, antibacterial efficacy via agar diffusion test with Staphylococcus aureus and vancomycin elution tests were performed 1, 2, 3, and 6 days after incubation. Vancomycin-loaded tapes as well as vancomycin-loaded cerclage wires demonstrated increased bacterial growth inhibition when compared to NaCl-treated controls. Vancomycin-loaded tapes showed an additional twofold and eightfold increase of bacterial growth inhibition compared to vancomycin-loaded wires at day 1 and 2, respectively. Elution tests at day 1 revealed high levels of vancomycin concentration in vancomycin loaded tapes and wires. Additionally, the concentration in vancomycin loaded tapes was 14-fold higher when compared to vancomycin loaded wires. Incubating suture tapes and cerclage wires in vancomycin solution showed a good short-term antibacterial activity compared to controls. Considering the ease of vancomycin application on suture tapes or wires, our method could represent an attractive therapeutic strategy in biofilm prevention in orthopedic surgery.},
  language  = {en}
}
@article{BoelchRueecklStrecketal.2021,
  author    = {Boelch, Sebastian Philipp and R{\"u}eckl, Kilian and Streck, Laura Elisa and Szewczykowski, Viktoria and Weißenberger, Manuel and Jakuscheit, Axel and Rudert, Maximilian},
  title     = {Diagnosis of chronic infection at total hip arthroplasty revision is a question of definition},
  series = {Biomed Research International},
  volume    = {2021},
  journal   = {Biomed Research International},
  doi       = {10.1155/2021/8442435},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265762},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}
@article{BoelchGurokGilbertetal.2021,
  author    = {Boelch, Sebastian P. and Gurok, Anna and Gilbert, Fabian and Weißenberger, Manuel and Rudert, Maximilian and Barthel, Thomas and Reppenhagen, Stephan},
  title     = {Why compromise the patella? Five-year follow-up results of medial patellofemoral ligament reconstruction with soft tissue patellar fixation},
  series = {International Orthopaedics},
  volume    = {45},
  journal   = {International Orthopaedics},
  issn      = {0341-2695},
  doi       = {10.1007/s00264-020-04922-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235751},
  pages     = {1493-1500},
  year      = {2021},
  abstract  = {Purpose This study investigates the redislocation rate and functional outcome at a minimum follow-up of five years after medial patellofemoral ligament (MPFL) reconstruction with soft tissue patellar fixation for patella instability. Methods Patients were retrospectively identified and knees were evaluated for trochlea dysplasia according to Dejour, for presence of patella alta and for presence of cartilage lesion at surgery. At a minimum follow-up of five years, information about an incident of redislocation was obtained. Kujala, Lysholm, and Tegner questionnaires as well as range of motion were used to measure functional outcome. Results Eighty-nine knees were included. Follow-up rate for redislocation was 79.8\% and for functional outcome 58.4\%. After a mean follow-up of 5.8 years, the redislocation rate was 5.6\%. There was significant improvement of the Kujala score (68.8 to 88.2, p = 0.000) and of the Lysholm score (71.3 to 88.4, p = 0.000). Range of motion at follow-up was 149.0° (115-165). 77.5\% of the knees had patella alta and 52.9\% trochlear dysplasia types B, C, or D. Patellar cartilage legions were present in 54.2\%. Redislocations occurred in knees with trochlear dysplasia type C in combination with patella alta. Conclusion MPFL reconstruction with soft tissue patellar fixation leads to significant improvement of knee function and low midterm redislocation rate. Patients with high-grade trochlear dysplasia should be considered for additional osseous correction.},
  language  = {en}
}
@article{AltmannMutWolfetal.2021,
  author    = {Altmann, Stephan and Mut, J{\"u}rgen and Wolf, Natalia and Meißner-Weigl, Jutta and Rudert, Maximilian and Jakob, Franz and Gutmann, Marcus and L{\"u}hmann, Tessa and Seibel, J{\"u}rgen and Ebert, Regina},
  title     = {Metabolic glycoengineering in hMSC-TERT as a model for skeletal precursors by using modified azide/alkyne monosaccharides},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {6},
  issn      = {1422-0067},
  doi       = {10.3390/ijms22062820},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259247},
  year      = {2021},
  abstract  = {Metabolic glycoengineering enables a directed modification of cell surfaces by introducing target molecules to surface proteins displaying new features. Biochemical pathways involving glycans differ in dependence on the cell type; therefore, this technique should be tailored for the best results. We characterized metabolic glycoengineering in telomerase-immortalized human mesenchymal stromal cells (hMSC-TERT) as a model for primary hMSC, to investigate its applicability in TERT-modified cell lines. The metabolic incorporation of N-azidoacetylmannosamine (Ac\(_4\)ManNAz) and N-alkyneacetylmannosamine (Ac\(_4\)ManNAl) into the glycocalyx as a first step in the glycoengineering process revealed no adverse effects on cell viability or gene expression, and the in vitro multipotency (osteogenic and adipogenic differentiation potential) was maintained under these adapted culture conditions. In the second step, glycoengineered cells were modified with fluorescent dyes using Cu-mediated click chemistry. In these analyses, the two mannose derivatives showed superior incorporation efficiencies compared to glucose and galactose isomers. In time-dependent experiments, the incorporation of Ac\(_4\)ManNAz was detectable for up to six days while Ac\(_4\)ManNAl-derived metabolites were absent after two days. Taken together, these findings demonstrate the successful metabolic glycoengineering of immortalized hMSC resulting in transient cell surface modifications, and thus present a useful model to address different scientific questions regarding glycosylation processes in skeletal precursors.},
  language  = {en}
}