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 - 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 - TY - JOUR A1 - Wagenbrenner, Mike A1 - Heinz, Tizian A1 - Horas, Konstantin A1 - Jakuscheit, Axel A1 - Arnholdt, Jörg A1 - Hermann, Marietta A1 - Rudert, Maximilian A1 - Holzapfel, Boris M. A1 - Steinert, Andre F. A1 - Weißenberger, Manuel T1 - The human arthritic hip joint is a source of mesenchymal stromal cells (MSCs) with extensive multipotent differentiation potential JF - BMC Musculoskeletal Disorders N2 - Background While multiple in vitro studies examined mesenchymal stromal cells (MSCs) derived from bone marrow or hyaline cartilage, there is little to no data about the presence of MSCs in the joint capsule or the ligamentum capitis femoris (LCF) of the hip joint. Therefore, this in vitro study examined the presence and differentiation potential of MSCs isolated from the bone marrow, arthritic hyaline cartilage, the LCF and full-thickness samples of the anterior joint capsule of the hip joint. Methods MSCs were isolated and multiplied in adherent monolayer cell cultures. Osteogenesis and adipogenesis were induced in monolayer cell cultures for 21 days using a differentiation medium containing specific growth factors, while chondrogenesis in the presence of TGF-ss1 was performed using pellet-culture for 27 days. Control cultures were maintained for comparison over the same duration of time. The differentiation process was analyzed using histological and immunohistochemical stainings as well as semiquantitative RT-PCR for measuring the mean expression levels of tissue-specific genes. Results This in vitro research showed that the isolated cells from all four donor tissues grew plastic-adherent and showed similar adipogenic and osteogenic differentiation capacity as proven by the histological detection of lipid droplets or deposits of extracellular calcium and collagen type I. After 27 days of chondrogenesis proteoglycans accumulated in the differentiated MSC-pellets from all donor tissues. Immunohistochemical staining revealed vast amounts of collagen type II in all differentiated MSC-pellets, except for those from the LCF. Interestingly, all differentiated MSCs still showed a clear increase in mean expression of adipogenic, osteogenic and chondrogenic marker genes. In addition, the examination of an exemplary selected donor sample revealed that cells from all four donor tissues were clearly positive for the surface markers CD44, CD73, CD90 and CD105 by flow cytometric analysis. Conclusions This study proved the presence of MSC-like cells in all four examined donor tissues of the hip joint. No significant differences were observed during osteogenic or adipogenic differentiation depending on the source of MSCs used. Further research is necessary to fully determine the tripotent differentiation potential of cells isolated from the LCF and capsule tissue of the hip joint. KW - Hip joint KW - Osteoarthritis KW - MSCs KW - Cartilage regeneration KW - Tissue engineering KW - Ligamentum capitis femoris KW - Joint capsule KW - Bone marrow Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229497 VL - 21 IS - 1 ER -