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Case A 49-year-old woman injured her anterior cruciate ligament (ACL) as a high-school student. Double-bundle ACL reconstruction (DBACLR) using hamstring tendon grafts was performed because of recurrent instability. Eleven years after DBACLR, total knee arthroplasty was performed because of osteoarthritis progression. Histologic analysis was completed to observe the osteointegration of the tendon in the obtained proximal tibia. The tibial tunnel showed Sharpey-like fibers anteriorly, connecting the tendon graft and lamellar bone, whereas the intraarticular exit revealed well-aligned chondrocytes posteriorly, indicating chondral metaplasia of the tendon graft. Conclusion Tendon-bone healing can regenerate both fibrous insertion and chondral metaplasia in DBACLR.

The purpose of this study was to investigate the incidence of cyclops lesions and its relationship with the cross-sectional area of the intercondylar notch.For this study, 55 patients (24 male and 31 female) underwent follow-up arthroscopy after bi-socket anterior cruciate ligament reconstruction with hamstring tendon grafts were included. All patients underwent magnetic resonance imaging measurements of intercondylar notch dimensions. We compared the femoral intercondylar notch sizes and bone tunnel sizes between knees with cyclops lesions (cyclops group) and those without cyclops lesions (no-cyclops group). The mean percentage of the tunnel size to the cross-sectional area of the femoral intercondylar notch was also compared between the groups. The median follow-up duration was 3.8 years.Cyclops lesions were found in 15 of the 55 knees (27.3 %) on second-look arthroscopy (cyclops group). Only 6 of the 55 knees (10.9 %) had extension loss (cyclops syndrome). The cyclops group included 3 men and 12 women. The two groups showed a statistical difference in sex variation (P = 0.04). No significant differences were found in the femoral and tibial tunnel sizes between the two groups. The cross-sectional area of the femoral intercondylar notch was significantly smaller in the cyclops group (251.7 ± 63.2 mm(2)) than in the no-cyclops group (335.6 ± 77.6 mm(2)) (P 0.001). The percentage of the total femoral tunnel size to the cross-sectional area of the femoral intercondylar notch was significantly higher in the cyclops group (18.6 ± 5.3 %) than in the no-cyclops group (13.2 ± 3.6 %) (P = 0.02).A smaller intercondylar notch size may be a potential risk factor for cyclops lesion formation.Case-control study, Level IV.

The meniscus is a fibrocartilaginous tissue that plays an important role in controlling complex biomechanics of the knee. A perimeniscal capillary plexus supplies the outer meniscus, whereas the inner meniscus is composed of avascular tissue. Anti-angiogenic molecules, such as chondromodulin-I (ChM-I) and endostatin, have pivotal roles in preserving the avascularity of cartilage. However, the anti-angiogenic role of ChM-I is unclear in the meniscus. We hypothesized that the inner meniscus might maintain its avascular feature by expressing ChM-I. Immunohistochemical analyses revealed that ChM-I was mainly detected in the inner and superficial zones of the meniscus. On the other hand, endostatin distribution was similar between the inner and outer meniscus. In Western blot, ChM-I was detected only in the inner meniscus, whereas endostatin was equally observed in both inner and outer menisci. In addition, ChM-I concentration of the inner meniscus-derived conditioned medium was higher than that of the outer meniscus-derived medium. ChM-I removal from the inner meniscus-derived medium and functional blocking of ChM-I significantly increased endothelial cell proliferation. In this study, we demonstrated that the inner meniscus contained larger amounts of ChM-I, and that the inner meniscus-derived ChM-I inhibited endothelial cell proliferation. Our results suggest that ChM-I may be a key anti-angiogenic factor for maintaining the avascularity of the inner meniscus.

Biomechanical stimuli have fundamental roles in the maintenance and remodeling of ligaments including collagen gene expressions. Mechanical stretching signals are mainly transduced by cell adhesion molecules such as integrins. However, the relationships between stress-induced collagen expressions and integrin-mediated cellular behaviors are still unclear in anterior cruciate ligament cells. Here, we focused on the stretch-related responses of different cells derived from the ligament-to-bone interface and midsubstance regions of human anterior cruciate ligaments. Chondroblastic interface cells easily lost their potential to produce collagen genes in non-stretched conditions, rather than fibroblastic midsubstance cells. Uni-axial mechanical stretches increased the type I collagen gene expression of interface and midsubstance cells up to 14- and 6-fold levels of each non-stretched control, respectively. Mechanical stretches also activated the stress fiber formation by shifting the distribution of integrin alphaVbeta3 to the peripheral edges in both interface and midsubstance cells. In addition, integrin alphaVbeta3 colocalized with phosphorylated focal adhesion kinase in stretched cells. Functional blocking analyses using anti-integrin antibodies revealed that the stretch-activated collagen gene expressions on fibronectin were dependent on integrin alphaVbeta3-mediated cellular adhesions in the interface and midsubstance cells. These findings suggest that the integrin alphaVbeta3-mediated stretch signal transduction might have a key role to stimulate collagen gene expression in human anterior cruciate ligament, especially in the ligament-to-bone interface.

Tool interference causes serious damage to surrounding soft tissue in minimally invasive orthopedic surgery with a milling robot. The objective of this study is to avoid the collision of cutting tool with complicated shapes, and a novel approach of interference-free toolpath generation in a short intraoperative time is proposed. In order to resolve this issue, we propose the following two methods: intraoperative modeling of soft tissues as an interference area and interference-free toolpath generation based on the model. A model is constructed to represent the opening area and the internal tissues by using a 3-dimensional optical position sensor to measure them. Based on the constructed model, interference-free toolpath is immediately determined by the preliminary definition of evacuating direction. The effectiveness of the proposed method is evaluated with artificial models on the system that the authors have developed so far. A tool contact force against the model was measured by a force sensor mounted on the cutting tool. The result revealed that the tool interference was greatly reduced by implementing the proposed method.

We prospectively evaluated the disease-specific features of the early postoperative plasma D: -dimer value and the relationship with deep venous thrombosis and/or pulmonary thromboembolism (DVT/PE) in 95 patients following total knee arthroplasty. Patients in whom DVT/PE was highly suspected were diagnosed by high-resolution multi-detector row computed tomography scanning (MDCT). Forty-nine knees in 46 patients with rheumatoid arthritis (RA, 24 knees) or osteoarthritis (OA, 25 knees) were finally recruited. DVT/PE was detected in 28 (57.1%) of the 49 cases examined by diagnostic MDCT: 12 (50.0%) of the 24 cases of RA, and 16 (64.0%) of the 25 cases of OA. Of these, PE was found in 11 cases (39.2%), but none of them showed clinical symptomatic signs of dyspnea or chest pain. In both RA and OA cases, there were statistically significant differences in the D: -dimer value on postoperative day 3 (P = 0.027) and after day 28 (P = 0.037) between the groups with and without DVT/PE. In OA cases, there were significant differences between the two groups on postoperative days 1 (P = 0.034), 3 (P = 0.020), 5 (P = 0.005), and 7 (P = 0.045), respectively. At the baseline, perioperative D: -dimer levels in the RA group without DVT/PE were higher than in the OA group. However, multivariate logistic regression analysis showed that RA was not a significant risk factor of DVT/PE in comparison with OA. In conclusion, individual evaluation of the D: -dimer level between RA and OA should provide a more precise predictive indicator of early postoperative DVT/PE.

To differentiate benign from malignant bone tumors by analyzing the vascular distribution within bone tumors with dynamic contrast-enhanced MRI.We studied dynamic contrast-enhanced MRI for 49 bone tumors (22 malignant and 27 benign tumors). Seven small regions of interest (ROI) were set inside the largest portion of each tumor. Four ROI were placed evenly on the periphery and three ROI were placed evenly on the line of the longest breadth within the tumor. The slope of the curve (%Slope) was calculated on the time-intensity curves of the whole tumor and of each ROI. The variance values for the %Slope of the ROI were calculated to assess the dispersion of the intensity change at each ROI within the tumor.Mean value of the %Slopes of whole tumor regions for malignant bone tumors (70.4 +/- 60.3%) was significantly higher than that for benign bone tumors (37.6 +/- 52.9%) (P = 0.015), although giant cell tumor (GCT), a locally aggressive tumor, had a relatively higher %Slope. Mean value of the variance of %Slopes for malignant bone tumors (3485.9 +/- 5942.5) was significantly higher than that for all benign tumors (470.4 +/- 583.9) (P = 0.012), indicating that the %Slope values of seven ROI within malignant bone tumors varied more widely compared with the ROI inside benign bone tumors. GCT also demonstrated a lower value.Our method of analyzing the signal intensity change at seven separate regions that evaluates the vascular distribution within a tumor could be a useful tool for differentiating between benign and malignant bone tumors.

In successful knee arthroplasty, the femur and the tibia must be shaped to fit an artificial joint. The recent trend towards MIS (Minimally Invasive Surgery) to decrease the length of the required incision in the skin has increased surgical difficulty, since the open access area is small. The developed system consists of (1) a preplanning system providing a CAD function, (2) a multi-axis CAM system which avoids cutting the skin and the ligament, and keeps the cutting time within acceptable limits, and (3) a 7-axis machine tool that assures the safety of the patient and the surgeon, and enables MIS.

Bone cutting experiments were conducted on a cadaver using a newly developed machine tool. The effectiveness of the system was evaluated by comparing the planned shape for the mating surface between the femur and an artificial joint with the cutting result. It is desirable to know the machining phenomena and characteristics at the microscale because the material and the tissue structure are anisotropic in both cortical and cancellous bones. In the paper, the influence of the material characteristics on machining is discussed for cortical bone. Pig cortical bone was used in the experiment for visualizing 2-dimensional micro-cutting.

We measured the cross-sectional area (CSA) of the semitendinosus tendon (SMT) in 79 anterior cruciate ligament (ACL)-injured patients using magnetic resonance imaging (MRI) to scrutinize their appropriateness for ACL grafts. Measurements of the CSAs of the SMT with MRI were closely correlated with intraoperative direct measurement (y = 0.697). The mean CSAs of the SMT measured with MRI ranged from 6.3 to 15.0 mm2 with a mean of 10.1+/-2.1 mm2. The CSA of the SMT measured with MRI proved to be a useful indicator to determine preoperatively whether the SMT graft would be of adequate dimensions (7 mm or more in diameter, 60 mm or more in length) for ACL reconstruction. If the CSA of the SMT was more than 11 mm2, a sufficiently thick and long graft could be prepared with a tripled or quadrupled SMT in 89% of cases. We conclude that tissue CSA measurements using MRI could potentially be implemented as a useful tool for determining the most appropriate donor autograft tissue preoperatively, thus minimizing harvest-site morbidity.

Clinical and radiographic studies were performed on 228 hips of 145 patients with avascular necrosis of the femoral head (ANFH). The patients were divided into three groups: group A consisted of 33 patients with systemic lupus erythematosus (SLE) who had been treated with systemic corticosteroids (59 hips); group B consisted of 41 patients with a history of corticosteroid treatment, excluding patients with SLE (69 hips); and group C consisted of 71 patients with no history of corticosteroid use (100 hips). Of the 228 hips, 80 hips at an early stage of the necrosis, but not showing collapse, were selected and classified by the criteria of the Japanese Investigation Committee (JIC) to define the natural history of the disease. In the SLE patients (group A), there was a predisposition to bilateral involvement and multiple sites of bone necrosis. Eighty percent of the femoral heads followed at an early stage had collapsed at the end of the follow-up, the incidence of collapse in group A being higher than that in the other groups. The collapses in group A were predominantly types 1C, 2, and 3B according to the JIC criteria. The incidence of collapse was significantly lower in type 1A and type 3A than in the other types. The classification proposed by the JIC, in terms of types with regard to size and location of the necrotic area on antero-posterior radiographs, was very useful for evaluation of the risk of collapse as well as for selecting appropriate treatment modalities, either conservative or surgical, during the early stages of ANFH.

Type IX collagen is a newly discovered collagen molecule that is associated with Type II-containing collagen fibrils in cartilage, vitreous and embryonic cornea. It consists of three distinct chains: alpha 1(IX), alpha 2(IX) and alpha 3(IX). The alpha 1(IX) chain has been to be synthesized in two different forms, which are generated by alternative transcription and splicing. In this manuscript we describe the isolation and sequencing of a cDNA coding for the entire coding region of the long form of mouse alpha 1(IX) chain. Nucleotide sequence analysis of this cDNA determined for the first time the primary structure of the entire long form of the mouse alpha 1(IX) chain. RT-PCR was used to examine collagen gene expression during limb development from day 10 to 18 in mouse embryos. Collagen I and II mRNA levels gradually increased all through the developmental stages. Collagen X expression increased further after day 16 in limb development, whereas the alpha 1(IX)mRNA level dropped at this time. This could be due to active bone formation relative to cartilage synthesis in the embryonic limb bud around day 16 in mouse development.

Loose fragments in spontaneous osteonecrosis of the knee (SONK) are usually removed by surgical treatment. However, the healing potential of osteonecrotic loose fragments and their clinical availability, for example as a cell source for cartilage repair and tissue engineering, have not been investigated. The objective of this study was to evaluate the cellular proliferation and redifferentiation ability of loose fragment chondrocytes for the treatment of SONK.Cells were obtained from the remaining cartilage of chondral loose fragments or fibrocartilaginous tissue under the affected femoral condyle in SONK. The proliferation activity of loose fragment-derived chondrocytes and condyle-derived fibrochondrocytes was evaluated. In-vitro differentiation ability was assessed by PCR and histological analysis.The deposition of proteoglycans and type II collagen were maintained in loose fragments. However, loose fragment-derived chondrocytes had lower proliferating activity than condyle-derived fibrochondrocytes. Chondrogenic redifferentiation ability was lower in loose fragment chondrocytes than in condyle fibrochondrocytes. Differentiation towards adipogenic and osteogenic lineages was not observed in loose fragment chondrocytes. On the other hand, lipid vacuoles were detected in fibrochondrocytes after adipogenic treatment.This study demonstrated that loose fragment-derived chondrocytes in SONK had lower potential than fibrochondrocytes in cellular proliferation and redifferentiation. Our experimental results suggest that osteonecrotic loose fragments might have restricted cellular properties in the healing of SONK-related osteochondral defects.

For the total knee arthroplasty, we developed the robotic system, such as the cutting feed rate is controlled depending on the hardness of the bone tissue predicted on the basis of the medical image. Since the cutting force is reduced by this system, the displacement of the bone is minimized during the bone cutting process. Therefore it makes a possibility to fix the target bone using “safer” and less-invasive fixation technique.

Minimally invasive surgery in orthopedic field is considered to be a challenging problem with a milling robot. One objective of this study is to minimize collision of the cutting tool with soft tissue. The authors have developed a robot with redundant axis to avoid the collision so far. Some important components are modeled based on physical requirements, and a geometric optimization approach based on the model has been also proposed to improve performance. In this paper, a protective mechanism to cover the non-working part of the cutting edge is proposed to avoid soft tissue damage. Hardware and software have been developed for this application and the effectiveness of this technique was evaluated with urethane bone.

Many of the robots developed so far, including our multi-axis bone cutting robot, use an end mill as the cutting tool, and some problems should be solved to apply them to the minimally invasive orthopedic surgery. Minimally invasive surgery makes the incisions smaller, reduces pain and trauma to the body, and enables faster recovery. The smaller incision means a small and narrow opening area. This means the robot attitude for the bone resection is restricted, and it can result in the collision of the tool with the surrounding tissue, the existence of an untouched area and the degradation of the joint position accuracy. This paper proposes a robot mechanism and a toolpath generation technique specialized for bone cutting is expected to resolve these issues.

Summary Objective To investigate the effect of the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), on joint inflammation and cartilage degeneration in a collagen antibody-induced arthritis (CAIA) mouse model. Methods CAIA mice were given daily subcutaneous injections of various concentrations of TSA (0, 0.5, 1.0, and 2.0 mg/kg) and various parameters were monitored for 14 days. On Day 15, the hind paws were examined histologically. To investigate the effects of TSA on the expressions of matrix metalloproteinase (MMP)-3, MMP-13, tissue inhibitor of MMP-1 (TIMP-1), and acetyl-H4 by chondrocytes, another group of mice was sacrificed on Day 6. In vitro direct effect of TSA was examined by real-time PCR for mRNA of type II collagen, aggrecan, MMP-3, and MMP-13 in murine chondrogenic ATDC5 cells after pro-inflammatory cytokine stimulation. Results In the TSA-treated group, clinical arthritis was significantly ameliorated in a dose-dependent manner. The severity of synovial inflammation and the cartilage destruction score were significantly lower in the TSA 2.0 mg/kg group compared to the other TSA-treated groups. On immunohistochemistry, the number of MMP-3 and MMP-13-positive chondrocytes was significantly lower in the TSA 2.0 mg/kg group than in the control group. In contrast, the number of TIMP-1-positive cells and acetyl-histone H4-positive cells was significantly higher in the TSA 2.0 mg/kg group than in the control group. TSA suppressed interleukin 1-β and tumor necrosis factor-α-stimulated up-regulation of MMP-3, but not MMP-13 mRNA expression by ATDC5. Conclusion The systemic administration of TSA ameliorated synovial inflammation in CAIA mice. Subsequently cartilage destruction was also suppressed by TSA, at least in part, by modulating chondrocyte gene expression.

Recent clinical studies have investigated postural sway characteristics in anterior cruciate ligament (ACL)-deficient knees, but the relative contributions of vision and ACL remain unclear. In the current study, we measured and compared postural sway during one-leg standing with eyes open and closed to assess the difference between legs with and without ACL injury, and we discuss the contribution of the ligament relative to vision and to postural sway in patients. We examined 32 patients (17 males, 15 females) with ACL injury before surgery from March 2001 through January 2004. None presented obvious dysfunction in the lower limbs or central nervous system. Using a gravicorder, we measured locus length per time (LG) and environmental area (AR) as the factors of postural sway during two-leg and one-leg standing with eyes open or closed. In the ACL-injured knee, the amount of postural sway increased significantly during injured leg standing with eyes closed (LG, P < 0.0001; AR, P < 0.0001), but it did not increase significantly with eyes open. There were no significant differences with respect to sex or general joint laxity. There was no correlation between postural sway and the anterior translation of the tibia measured by arthrometer KT2000 or between the muscle strength around the knee. We concluded that the amount of postural sway in the ACL-injured knee increased significantly on injured leg standing with eyes closed, and that vision appears to be dominant in compensating for the decreased contribution of the injured ACL.

Ninety-four patients with osteoarthritis (OA) and 180 with rheumatoid arthritis (RA) undergoing unilateral total knee arthroplasty (TKA) were analyzed to clarify the necessity for preoperative autogenous blood deposition or homologous blood transfusion. Two hundred and twenty-four and 50 patients underwent TKA with cement and without cement, respectively. The difference in average blood loss in patients between with (372 ml) and without cementation (449 ml) was significant. In the OA group the average blood loss significantly decreased after cementation but not in the RA group. Although the rate of avoiding transfusion in the OA group did not significantly decrease with the use of cement (92.4% vs. 93.3%), that in the RA group did (80% to 57.1%). Eight of 159 patients with hemoglobin level (Hb) of 11.0 g/dl or higher received homologous blood transfusion. Of these eight patients five had associated disorders. Only one patient with Hb of 12.0 g/dl or higher underwent homologous blood transfusion. Patients with Hb of 12.0 g/dl or higher are not indicated for preoperative autologous blood deposition. In patients with Hb between 11.0 and 12.0 g/dl preoperative blood deposition may be planned after consideration of general condition and complication. Patients with Hb lower than 11.0 g/dl should undergo preoperative blood deposition.

We examined the differential expressions of collagen types IV, III and I in the developing feto-maternal placental tissue of pregnant rats by a combination of in situ hybridization and immunohistochemistry. At day 9.5 of gestation, polygonal invasive cytotrophoblasts from the ectoplacental cone, which was modifying the maternal central artery, revealed intensely expressed alpha 1 (IV) and alpha 1 (III) collagen mRNAs. The localization patterns of these translated products, collagen type IV and procollagen type III, were slightly different in the invasive cytotrophoblasts. Collagen type IV densely deposited intracellularly and intercellularly in the maternal central artery and in the thickened basement membranes of the cytotrophoblasts. However, expression of alpha 1 (I) collagen mRnA and procollagen type I was hardly detectable in the cytotrophoblasts. At day 13 of gestation, a high level of alpha 1 (IV) collagen mRNA was expressed in the cytotrophoblastic cell layer (trophospongium) and in the invasive large cytotrophoblasts. A moderate level of alpha 1 (III) collagen mRNA was also expressed mainly in the cytotrophoblasts, while alpha 1 (I) collagen mRNA was expressed at very low levels. Interestingly, procollagen type III failed to show linear immunoreactivity in the subepithelial extracellular matrix beneath the maternal artery with the invasive cytotrophoblasts. Additional quantitative analyses of these type IV, III, and I collagen mRNA levels in in situ hybridization experiments between several cell types also revealed significant differences individually. Electron-microscopic study detected no cross-striated collagen fibers in the thickened basement membrane-like structures adjacent to the invasive cytotrophoblasts. Fibrillar and basement membrane collagen gene expressions, their protein syntheses, and the processing of these procollagens seems to be developmentally regulated in the invasive cytotrophoblasts during the organization of feto-maternal placental tissue. The remodeling of the maternal central artery by the invasive cytotrophoblasts is important for ensuring the adequate blood supply to the developing placenta and fetus.

1) The amplitude of the b-wave of the ERG in rabbits was found to increase following optic nerve section orr compression. 2) After section of the optic nerve, either intracranial or intraorbital, the b-wave amplitude rose rapidly, up to the peak of 300-330% of the original amplitude, but hence decreased to 200-250% in 12 hours after the lesion of the optic nerve. 3) After compression of the optic nerve, the rise of the b-wave amplitudc was slower. The peak value did not exceed the range of 180-250%, the subsequent drop being also less marked. 4) The results showed no obvious difference whether the site of lesion orr the optic nerve was intracranial or intraorbital. 5) The results of the present experiments are in line with those by Jacobsor et al., but not enough to justify their hypothesis.

Tissue engineering has been increasingly applied to treat diseases of the joints that adversely affect components such as cartilage and ligaments. These components do not contain blood vessels and nerves; the risk of rejection during tissue transplantation is therefore less than that for other organs. Treatment of cartilage and ligaments requires highly skilled surgeons, however, and it is necessary to establish a quantitative evaluation method. It is difficult to measure the mechanical properties of cartilage because of its viscoelasticity. Sensing technology that enables uniform qualitative evaluation is therefore desired. In this study, a portable diagnostic probe was developed and the viscoelasticity of cartilage was measured quantitatively over a short period of time. The probe was designed based on the Voigt model and comprises a piezoelectric actuator, a force sensor, and a contact probe. Stiffness and viscosity coefficients of various samples such as silicone rubber and the bovine meniscus were measured, and the accuracy of the developed probe was evaluated. Finally, the mechanical properties of human articular cartilage were measured using the diagnostic probe.