The aim of this study was to investigate the biomechanical effect of the anterolateral ligament (ALL), anterior cruciate ligament (ACL), or both ALL and ACL on kinematics under dynamic loading conditions using dynamic simulation subject-specific knee models. Five subject-specific musculoskeletal models were validated with computationally predicted muscle activation, electromyography data, and previous experimental data to analyze effects of the ALL and ACL on knee kinematics under gait and squat loading conditions.Objectives
Methods
The aim of the current study was to analyse the effects of posterior cruciate ligament (PCL) deficiency on forces of the posterolateral corner structure and on tibiofemoral (TF) and patellofemoral (PF) contact force under dynamic-loading conditions. A subject-specific knee model was validated using a passive flexion experiment, electromyography data, muscle activation, and previous experimental studies. The simulation was performed on the musculoskeletal models with and without PCL deficiency using a novel force-dependent kinematics method under gait- and squat-loading conditions, followed by probabilistic analysis for material uncertain to be considered.Objectives
Methods
Mesenchymal stem cells (MSC) are promising for the treatment of articular cartilage defects; however, common protocols for in vitro chondrogenesis induce typical features of hypertrophic chondrocytes reminiscent of endochondral bone formation. This may implicate a risk for graft stability. We here analysed the early healing response in experimental full-thickness cartilage defects, asking whether and how MSC can differentiate to chondrocytes in an orthotopic environment. Cartilage defects in knees of minipigs were covered with a collagen-type I/III membrane, and half of them received transplantation of expanded autologous MSC. Integration into surrounding cartilage tissue was poor to moderate after 1 and 3 weeks and no sign of cartilaginous matrix production as indicated by negative safranin-O staining was visible for both groups. At 8 weeks regenerative tissue was integrated into the surrounding tissue and a safranin-O positively stained neocartilage was detectable in 4 tissue regenerates out of 6 in the MSC group compared to 2 out of 6 in the MSC-free group. At 1 and 3 weeks after surgery only marginal Col2A1 and no AGC expression were detectable in both groups. At 8 weeks Col2A1 and AGC levels had significantly increased. Hypertrophic maker induction (Col10A1 and MMP13) was similar in both groups 8 weeks after surgery. Immunostaining for collagen type X, however, was restricted to the regenerative tissue close to the subchondral bone in both groups, while collagen type II staining was detected from below the superficial to the deep zone. Our data provide molecular evidence for spontaneous differentiation of MSC in cartilage and the development of a collagen type II positive, collagen type X negative neocartilage. Whether by remodelling of defect filling tissue collagen type X positive areas will further diminish or even disappear from repair cartilage at later stages has to be evaluated in a longer follow-up study.
This study evaluated the effect of a collagen type I /hyaluronate (c/h) implant combined with recombinant human growth and differentiation factor-5 (rhGDF-5) in osteochondral cartilage defects of Göttinger minipigs. In 20 Göttinger minipigs, critical size defects (6.2mm wide and 10mm deep) were created in the medial condyle of both femora. Defects were treated on one side either with the c/h implant alone (n=10) or the c/h implant + rhGDF-5 (n=10), whereas the other side was left empty as an intra-individual control. After 3 and 12 months, 5 animals from each treatment group were killed. The evaluation included macroscopic investigation, biomechanical exploration by relaxation test and semi-quantitative histological scoring using the O’Driscoll score. No macroscopic differences were found between the two treatment groups, neither could any differences be found in semi-quantitative histological scoring. Biomechanical measurement after 12 months showed a significant increase in peak stress in the c/h group compared to empty defects, however, rhGDF-5 supplementation was not found to influence the biomechanical properties compared to controls. Bony cysts were seen throughout the three treatment groups, indicating insufficient bone regeneration. In two animals treated with rhGDF-5, pronounced ossifications within the joint capsule were observed. In contrast, no ossifications were detected in the knees with empty defects or single treatment with c/h implant. In conclusion, the combination of a c/h implant plus rhGDF-5 did not result in better defect regeneration compared to c/h implants alone or even to empty defects in our minipig model. One major problem seems to be the incomplete regeneration of the bony defect when using this device. In further studies, bilayer matrices should be used to address this problem. Due to the small number of specimens in this study, it cannot be resolved whether the ossifications seen in two knees were due to the usage of rhGDF-5 or can be regarded as an independent event. Further data about growth factor interaction should be acquired in animal studies before clinical introduction can be considered.
