Impact of femoro-tibial size combinations and TKA design on kinematics.

INTRODUCTION: The variability in patients' femoral and tibial anatomy requires to use different tibia component sizes with the same femoral component size. These size combinations are allowed by manufacturers, but the clinical impact remains unclear. Therefore, the goals of our study were to investigate whether combining different sizes has an impact on the kinematics for two well-established knee systems and to compare these systems' kinematics to the native kinematics. MATERIALS AND METHODS: Six fresh frozen knee specimens were tested in a force controlled knee rig before and after implantation of a cruciate retaining (CR) and a posterior-stabilized (PS) implant. Femoro-tibial kinematics were recorded using a ultrasonic-based motion analysis system while performing a loaded squat from 30° to 130°. In each knee, the original best fit inlay was then replaced by different inlays simulating a smaller or bigger tibia component. The kinematics obtained with the simulated sizes were compared to the original inlay kinematics using descriptive statistics. RESULTS: For all size combinations, the difference to the original kinematics reached an average of 1.3 ± 3.3 mm in translation and - 0.1 ± 1.2° in rotation with the CR implant. With the PS implant, the average differences reached 0.4 ± 2.7 mm and  - 0.2 ± 0.8°. Among all knees, no size combination consistently resulted in significantly different kinematics. Each knee showed a singular kinematic pattern. For both knee systems, the rotation was smaller than in the native knee, but the direction of the rotation was preserved. The PS showed more rollback and the CR less rollback than the native knee. CONCLUSION: TKA systems designed with a constant tibio-femoral congruency among size combinations should enable to combine different sizes without having substantial impact on the kinematics. The rotational pattern was preserved by both TKA systems, while the rollback could only be maintained by the PS design.

Third-generation autologous chondrocyte implantation after failed bone marrow stimulation leads to inferior clinical results.

PURPOSE: Third-generation autologous chondrocyte implantation (ACI) is an established and frequently used method and successful method for the treatment of full-thickness cartilage defects in the knee. There are also an increasing number of patients with autologous chondrocyte implantation as a second-line therapy that is used after failed bone marrow stimulation in the patient's history. The purpose of this study is to investigate the effect of previous bone marrow stimulation on subsequent autologous chondrocyte implantation therapy. In this study, the clinical results after the matrix-based autologous chondrocyte implantation in the knee in a follow-up over 3 years postoperatively were analysed. METHODS: Forty patients were included in this study. A total of 20 patients with cartilage defects of the knee were treated with third-generation autologous chondrocyte implantation (Novocart® 3D) as first-line therapy. The mean defect size was 5.4 cm2 (SD 2.6). IKDC subjective score and VAS were used for clinical evaluation after 6, 12, 24 and 36 months postoperatively. The results of these patients were compared with 20 matched patients with autologous chondrocyte implantation as second-line therapy. Matched pair analysis was performed by numbers of treated defects, defect location, defect size, gender, age and BMI. RESULTS: Both the first-line (Group I) and second-line group (Group II) showed significantly better clinical results in IKDC score and VAS score in the follow-up over 3 years compared with the preoperative findings. In addition, Group I showed significantly better results in the IKDC and VAS during the whole postoperative follow-up after 6, 12, 24 and 36 months compared to Group II with second-line autologous chondrocyte implantation (IKDC 6 months p = 0.015, 1 year p = 0.001, 2 years p = 0.001, 3 years p = 0.011). Additionally, we found a lower failure rate in Group I. No revision surgery was performed in Group I. The failure rate in the second-line Group II was 30%. CONCLUSION: This study showed that third-generation autologous chondrocyte implantation is a suitable method for the treatment of full-thickness cartilage defects. Both, Group I and Group II showed significant improvement in our follow-up. However, in comparing the results of the two groups, autologous chondrocyte implantation after failed bone marrow stimulation leads to worse clinical results. LEVEL OF EVIDENCE: III.

Simulated microgravity affects chondrogenesis and hypertrophy of human mesenchymal stem cells.

PURPOSE: During in vitro chondrogenesis of human mesenchymal stem cells (hMSCs) hypertrophy is an inadvertent event associated with cell differentiation toward the osteogenic lineage. Up to now, there is no stringent experimental control mechanism to prevent hypertrophy of MSCs. Microgravity is known to have an impact on osteogenesis. In this study, the influence of simulated microgravity (SMG) on both chondrogenesis and hypertrophy of hMSCs was evaluated. METHODS: A bioreactor using a rotating wall vessel was constructed to simulate microgravity. Pellet cultures formed from hMSCs (P5) were supplemented with human transforming growth factor-ß3 (TGF-ß3). The hMSC pellet cultures treated with TGF-ß3 were either kept in SMG or in a control system. After three weeks of culture, the chondrogenic differentiation status and level of hypertrophy were examined by safranin-O staining, immunohistochemistry and quantitative real-time PCR. RESULTS: SMG reduced the staining for safranin-O and collagen type II. The expression of collagen type X α1 chain (COL10A1) and collagen type II α1 chain (COL2A1) were both significantly reduced. There was a higher decrease in COL2A1 than in COL10A1 expression, resulting in a low COL2A1/COL10A1 ratio. CONCLUSIONS: SMG reduced hypertrophy of hMSCs during chondrogenic differentiation. However, the expression of COL2A1 was likewise reduced. Even more, the COL2A1/COL10A1 ratio decreased under SMG conditions. We therefore assume that SMG has a significant impact on the chondrogenic differentiation of hMSCs. However, due to the high COL2A1 suppression under SMG, this culture system does not yet seem to be suitable for a potential application in cartilage repair.

Effects of single and combined low frequency electromagnetic fields and simulated microgravity on gene expression of human mesenchymal stem cells during chondrogenesis.

INTRODUCTION: Low frequency electromagnetic fields (LF-EMF) and simulated microgravity (SMG) have been observed to affect chondrogenesis. A controlled bioreactor system was developed to apply LF-EMF and SMG singly or combined during chondrogenic differentiation of human mesenchymal stem cells (hMSCs) in 3D culture. MATERIAL AND METHODS: An external motor gear SMG bioreactor was combined with magnetic Helmholtz coils for EMF (5 mT; 15 Hz). Pellets of hMSCs (±TGF-ß3) were cultured (P5) under SMG, LF-EMF, LF-EMF/SMG and control (1 g) conditions for 3 weeks. Sections were stained with safranin-O and collagen type II. Gene expression was evaluated by microarray and real-time polymerase chain reaction analysis. RESULTS: Simulated microgravity application significantly changed gene expression; specifically, COLXA1 but also COL2A1, which represents the chondrogenic potential, were reduced (p < 0.05). Low frequency electromagnetic fields application showed no gene expression changes on a microarray basis. LF-EMF/SMG application obtained significant different expression values from cultures obtained under SMG conditions with a re-increase of COL2A1, therefore rescuing the chondrogenic potential, which had been lowered by SMG. CONCLUSIONS: Simulated microgravity lowered hypertrophy but also the chondrogenic potential of hMSCs. Combined LF-EMF/SMG provided a rescue effect of the chondrogenic potential of hMSCs although no LF-EMF effect was observed under optimal conditions. The study provides new insights into how LF-EMF and SMG affect chondrogenesis of hMSCs and how they generate interdependent effects.

Incomplete defect filling after third generation autologous chondrocyte implantation.

INTRODUCTION: Third generation autologous chondrocyte implantation (ACI) is a suitable method for the treatment of cartilage defects in the knee joint. However, knowledge about the development of graft thickness and the clinical relevance of incomplete defect filling in the postoperative course is low. This prospective study analyses the graft integration into the surrounding cartilage, with special consideration of the graft thickness. MATERIAL AND METHODS: A total of 71 consecutive patients with 79 cartilage defects were treated with third generation autologous chondrocyte implantation (NOVOCART 3D) in the knee. Follow-up magnetic resonance imaging (MRI) was performed at 0.25, 0.5, 1 and 2 years. Graft thickness was measured compared to the surrounding healthy cartilage. The International Knee Documentation Committee (IKDC) scoring system and the visual analogue scale (VAS) were used for clinical evaluation. Cartilage defect filling was classified as the percentage of the surrounding cartilage. RESULTS: The average graft thickness showed a significant increase between 3 and 6 months after autologous chondrocyte implantation. Incomplete defect filling occurred in 44 (55.7%) cases. Of these, 33 cases showed incomplete defect filling grade I (> 75%), 10 cases were grade II (> 50%) and one case grade III (> 25%). Incomplete defect filling grade IV (< 25%) was not observed. Incomplete defect filling occurred significantly more often in women (p = 0.021), without worse clinical results. CONCLUSIONS: Graft thickness after third generation autologous chondrocyte implantation shows increasing graft thickness over the period of 2 years postoperatively. A high rate of incomplete defect filling in the surrounding cartilage was observed, without worse clinical results.