Common cell based strategies for treating bone defects require time-consuming and expensive isolation and expansion of autologous cells. We developed a novel expedited technology creating gene activated muscle grafts. We hypothesized that BMP-2 activated muscle grafts provide healing capabilities comparable to autologous bone grafting, the clinical gold standard. Two male, syngeneic Fischer 344 rats served as tissue donors. Muscle tissue was harvested from hind limbs and incubated with an adenoviral vector carrying the cDNA encoding BMP-2. Bone tissue was harvested from the iliac crest. Segmental bone defects were created in the right femora of 12 rats and were filled with either BMP-2 activated muscle tissue or bone grafts. After 8 weeks, femora were evaluated by radiographs, microCT, and biomechanical tests. BMP-2 activated muscle grafts and autologous bone grafts resulted in complete mineralization and healing, as documented by radiographs and microCT. Bone volume in the muscle graft defects (33+/-12mm3) was similar to autologous bone graft defects (39+/-5mm3). Torque at failure of the two groups was statistically indistinguishable (240+/-115 Nmm vs. 232+/-108Nmm). In previous experiments we demonstrated that the large segmental defect model in this study will not heal with either empty defects or non-activated muscle grafts. Our findings therefore demonstrate that BMP-2 gene activation of muscle tissue effectively stimulates defect healing similar to autologous bone grafts.
Periprosthetic osteolysis depends on the biological activity of wear particles, but there is little known about the distribution of polyethylene wear particles (PE) in the surrounding joint tissue. The purpose of this study was to examine the localisation of wear particles of six different PEs, including four crosslinked polyethylenes (XPE), as well as their biological activity in the murine knee. Wear particles of 4 XPE- and 2 UHMWPE-inserts were isolated (knee joint simulator). For all groups the particles were similar in size and shape (mean diameter 0.3–05μm; 20nm-nucleopore-filter; ISO; n = 100.000).56 female Balb/c mice were randomly assigned to six treatment groups and one control group: control (PBS), XPE1 (3×30 kGy Gamma, annealed/sequential irradiated), XPE2 (95 kGy E-beam, remelted), XPE3 (65 kGy E-beam, remelted), XPE 4 (50 kGy Gamma, remelted), UHMWPE 1, UHMWPE 2. 50 μl of each particle suspension [(0.1% vol/vol (particle volume/PBS volume) after removal of endotoxin] were injected into the left knee joint. After 1 week the mice were killed and a histological and immunhistochemical analysis of the knee joints was done (IL-1, TNF-, ICAM-1). For the immunhistochemistry the articular cartilage, the bone marrow and the synovial membrane were evaluated semiquantitatively (Kruskal-Wallis test; all pairwise multiple comparison procedure; Bonferoni correction; significance level: p<0.05). All groups showed a thickened synovial layer with an increased cellular infiltration. The particles of XPE 1 and 2 were localised in the bone marrow as well as in the joint space. In contrast, the particles of XPE 3 and 4 were distributed in the synovial layer and in the bone marrow as well, but not in the joint space. The UHMWPE1 particles were mainly located in the bone marrow and joint space while the UHMWPE2 particles were mainly found in the bone marrow and the synovial layer. For all PE groups there was a higher cytokine expression compaired to control (p<0.0024) without any differences between the groups (bone marrow/synovial layer). The chondrocytes in the groups with XPE 1- and XPE 2-particles expressed more TNF- than in the control group and the other treatment groups (p = 0.000).Material and Methods
Results
Minimally invasive implanted unicompartmental knee arthroplasty (UKA) leads to excellent functional results. Due to the reduced intraoperative visibility it is difficult to remove extruded bone cement particles, as well as bone particles generated through the sawing. These loose third body particles are frequently found in minimally invasive implanted UKA. The aim of this study was to analyse the influence of bone and cement particles on the wear rate of unicompartmental knee prostheses in vitro. Fixed- bearing unicompartmental knee prostheses (n = 3; Univation F®, Aesculap, Tuttlingen) were tested with a customized four-station servo-hydraulic knee wear simulator (EndoLab GmbH, Thansau, Germany) reproducing exactly the walking cycle as specified in ISO 14243-1:2002. After 5.0 million cycles crushed cortical bone chips were added to the test fluid for 1.5 million cycles to simulate bone particles, followed by 1.5 million cycles blended with PMMA- particles (concentration of the third-body particles: 5g/l; particle diameter: 0.5- 0.7 mm). Every 500 000 cycles the volumetric wear rate was measured (ISO 14243-2) and the knee kinematics were recorded. For the interpretation of the test results we considered four different phases: breaking in- (during the first 2.0 million cycles), the steady state- (from 2.0 million to 5 million cycles), bone particle- and cement particle phase. Finally, a statistical analysis was carried out to verify the normal distribution (Kolmogorov-Smirnov test), followed by direct comparisons to differentiate the volumetric wear amount between the gliding surfaces (paired Student's t-test, p<0.05).Introduction
Material & Methods
Unicompartmental knee arthroplasty (UKA) in patients with isolated medial osteoarthritis of the knee is nowadays a standard procedure with good results, especially with the minimally-invasive approach. However, the survival rate of the unicompartmental knee prostheses is inferior to that of total knee prostheses. Therefore, further studying of UKA is still necessary. In most mobile bearing designs the femoral component has a spherical surface and therefore its positioning is not crucial. The role of the tibial slope in UKA has not been investigated so far. The manufacturers recommend tibial slopes with values between 10° positive slope and 5° negative slope. Most surgeons try to reconstruct the anatomical slope with a high failure by measuring the slope on x-rays. The aim of this study was to investigate the influence of the tibial slope on the wear rate of a medial UKA. In vitro wear simulation of medial mobile bearing unicompartmental knee prosthesis with a spherical femoral surface (Univation ®) was performed with a customized four-station servo-hydraulic knee wear simulator (EndoLab GmbH, Thansau, Germany) reproducing exactly the walking cycle as specified in ISO 14243–1:2002(E). The tibial tray was inserted with 2 different medial tibial slopes: 0°, 8° (n=3 for each group). The lateral tibial slope of the space-holder was not changed (0° for every group). We performed a total of 5 million cycles for every different slope, the gravimetric wear rate was determined gravimetrically using an analytical balance every 500 000 cycles according to the ISO 14243–2.Introduction
Materials and methods
