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Skeletal muscle injuries often leave lasting functional damage or pain. Muscle injuries are routinely treated conservatively, but the most effective treatment to promote the repair of injured muscles has not yet been established. Our previous report demonstrated that human peripheral blood-derived CD133(+) cell transplantation to rat skeletal muscle injury models inhibited fibrosis and enhanced myogenesis after injury. However, the acquisition of a sufficient number of cells remains the limitation for clinical application, as the CD133(+) population is rare in human blood. In this study, we applied a magnetic cell targeting system to accumulate transplanted cells in the muscle injury site and to enhance the regenerative effects of CD133(+) cell transplantation, focusing on the fact that CD133(+) cells are labeled with a magnetic bead for isolation. For the magnetic cell targeting, the magnet field generator was set up to adjust the peak of the magnetic gradient to the injury site of the tibialis anterior muscle, and 1×10(4) human peripheral blood CD133(+) cells were locally injected into the injury site. This cell number is 10% of that used in the previous study. In another group, the same number of CD133(+) cells was injected without magnetic force. The CD133(+) cells transplanted with the magnetic force were more accumulated in the muscle injury site compared with the CD133(+) cells transplanted without the magnetic force. In addition, the transplantation of CD133(+) cells under the magnetic control inhibited fibrous scar formation and promoted angiogenesis and myogenesis, and also upregulated the mRNA expression of myogenic transcription factors, including Pax7, MyoD1 and Myogenin. However, the transplantation of CD133(+) cells without the magnetic force failed to demonstrate these effects. Thus, our magnetic cell targeting system enables transplantation of a limited number of CD133(+) cells to promote the repair of skeletal muscle injury.

Objectives: MicroRNAs, a class of noncoding RNAs, play roles in human diseases. MicroRNA-223 (miR-223) is reported to play critical roles in osteoclastogenesis. The purpose of this study was to analyze the expression pattern of miR-223 in rheumatoid arthritis (RA) synovium and examine the suppression of osteoclastogenesis from human peripheral blood mononuclear cells (PBMC) by overexpression of miR-223., Methods: Expression of miR-223 in synovium from RA patients was analyzed by quantitative reverse transcription polymerase chain reaction (RT-PCR) and section in situ hybridization. MiR-223 was overexpressed in an osteoclastogenesis coculture system with PBMC and RA synovial fibroblast. At 3 weeks after transfection of double-stranded miR-223, the formation of tartrate-resistant acid phosphatase (TRAP)-stained multinucleated cells was analyzed to evaluate the inhibitory effect of miR-223 on osteoclastogenesis., Results: MiR-223 was more highly expressed in RA synovium than in osteoarthritis (OA) synovium due to the increased number of miR-223-positive cells in RA synovium. MiR-223 was expressed in the superficial and sublining layers, and macrophages, monocytes, and CD4 T cells also expressed miR-223. The number of TRAP-positive multinucleated cells was significantly decreased by overexpression of miR-223 in a dose-dependent manner. The expression of osteoclastogenesis marker genes was significantly down-regulated by miR-223 overexpression., Conclusion: MiR-223 is intensely expressed in RA synovium, and overexpression of miR-223 suppresses osteoclastogenesis in vitro. This study demonstrates the possibility of gene therapy with miR-223 to treat bone destruction in RA patients.

Background: Cell therapies are hampered by the difficulty of delivering cells to and retaining them in target tissues long enough to repair or regenerate local tissues., Hypothesis: Magnetic-assisted delivery of magnetically labeled mesenchymal stem cells (m-MSCs) would be rapid, allowing for chondrogenic differentiation and functional joint repair without replacement., Study Design: Controlled laboratory study., Methods: Sixteen mini-pigs aged 6 to 7 months were used. A full-thickness cartilage defect was created in the center of the patella with a cylindrical punch (diameter, 6 mm). At 4 weeks after creation of the cartilage defects, the animals were divided into 3 treatment groups: In the M group, m-MSCs (5 × 10(6) cells) were injected and accumulated to the cartilage defect using an external magnetic force (1.5 T) for 10 minutes; in the G group, the patella was faced upward, filled with MSCs (5 × 10(6) cells), and held for 10 minutes; and in the C group, only phosphate-buffered saline was injected. The regenerated cartilage was evaluated in 5 knees in each of the 3 groups by arthroscopic surgery at 6 and 12 weeks and histological and ultrasound evaluation at 12 and 24 weeks., Results: The mean arthroscopic scores at 6 weeks were 10.4 ± 1.10 in the M group, 8.8 ± 0.84 in the G group, and 7.4 ± 0.89 in the C group. There was a statistically significant difference between the M group and the other 2 groups. The mean arthroscopic scores at 12 weeks were 12.8 ± 1.30 (M group), 10.5 ± 1.30 (G group), and 9.5 ± 0.58 (C group), with a statistically significant difference between the M and C groups. The mean histological scores using the Wakitani scoring system at 12 weeks were 2.8 ± 0.96 (M group), 5.4 ± 0.55 (G group), and 6.0 ± 2.20 (C group), and the mean histological scores at 24 weeks were 2.4 ± 1.50 (M group), 3.5 ± 0.56 (G group), and 5.3 ± 1.50 (C group). The mean histological scores at 12 weeks were significantly better in the M group than in the other groups, and the M group maintained a significantly better histological score than did the C group at 24 weeks., Conclusion: The m-MSCs had no adverse effect on chondrogenic differentiation, and m-MSCs delivered by magnetic field application repaired cartilage defects., Clinical Relevance: The clinical application of this novel stem cell delivery system is a potential therapeutic option for treating cartilage defects and may be more applicable throughout the body than traditional methods.

Background: It is difficult for an articular cartilage injury to repair spontaneously. There are many procedures for treating cartilage injury, however there is no standard procedure for middle-aged patients who have diffuse knee osteoarthritis, especially of the lateral compartment. Therefore, Ochi developed a new distraction device that uses magnetic power to enlarge a joint space and promote cartilage regeneration with microfracture. The purpose of this study is to evaluate this new distraction arthroplasty system by using the cadaveric knee., Methods: This study used ten knees from six cadavers that were embalmed by Thiel's methods. The medial and lateral joint space was measured by AP radiographic view before and after distraction, and after weight-bearing to evaluate the joint distraction. The contact pressure of the medial and lateral compartments at the knee extension position by using a prescale film system was measured before and after weight-bearing with a 15 or 30-kg weight-bearing load to evaluate the effectiveness of this device., Findings: The lateral joint space significantly increased from the pre-distraction to the post-distraction; however, it did not change significantly between post-distraction and post-weight-bearing. With a 15 or 30-kg weight-bearing load, the contact pressure of the lateral compartment significantly decreased from the pre-distraction to the post-distraction., Interpretation: The most important advantage of this device is that it maintains a continuous distraction tension and enables almost the full range of motion of the knee. We believe that joint distraction by using magnetic force can be a promising option for cartilage injury in middle-aged patients., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The impact of aging on joints can have a profound effect on an individual's functioning. Our objectives were to assess the histological and mechanical properties of the knee joint capsule and articular cartilage with aging, and to examine the effects of exercise on age-related changes in the knee joint. 2-year-old Wistar rats were divided into a sedentary control group and an exercise-trained group. 10-week-old animals were used to investigate the changes with aging. The joint capsule and cartilage were evaluated with histological, histomorphometric, immunohistochemical, and mechanical analyses. Severe degenerative changes in articular cartilage were observed with aging, whereas exercise apparently did not have a significant effect. The articular cartilage of aged rats was characterized by damage to the cartilage surface, cell clustering, and an abnormal cartilage matrix. Histomorphometric analysis further revealed changes in cartilage thickness as well as a decreased number of chondrocytes. Aging led to stiffness of the articular cartilage and reduced the ability to dissipate the load and distribute the strain generated within the joint. Joint stiffness with aging was independent of capsular stiffness and synovitis was not a characteristic feature of the aging joint. This study confirms that aging alone eventually leads to joint degeneration in a rat model. The lack of recovery in aging joint changes may be due to several factors, such as the duration of the intervention and the regeneration ability of the cartilage.

Background: Autologous chondrocyte implantation (ACI) is an important procedure when repairing cartilage defects of the knee. We previously reported several basic studies on tissue-engineered cartilage, and conducted a multicenter clinical study in 2009. In this clinical study, we evaluated the patients' clinical scores and MRI findings before and after tissue-engineered cartilage implantation, and compared the data obtained at 1 year and approximately 6 years post-implantation., Methods: Fourteen patients who underwent implantation of tissue-engineered cartilage to repair cartilage defects of the knee were evaluated. Tissue-engineered cartilage was produced by culturing autologous chondrocytes three dimensionally in atelocollagen gel. The patients were evaluated clinically using the Lysholm score, and the original knee-function score at pre-implantation and at 1 year and approximately 6 years post-implantation. MRI scans were obtained at the same observation periods. A modified magnetic resonance observation of cartilage repair tissue (MOCART) system was used to quantify clinical efficacy based on the MRI findings., Results: In approximately 6 years of follow-up, none of the 14 patients reported any subjective symptoms of concern. The mean Lysholm score and the original knee-function score (63.0 ± 10.1, 59.9 ± 5.7) significantly improved at 1 year after implantation (86.4 ± 11.8, 94.1 ± 9.2), and were maintained until 6 years after implantation (89.8 ± 6.2, 89.9 ± 11.2), although some patients showed deterioration of Lysholm and original knee scores between 1 year post-implantation and the final follow-up. The mean MOCART score was 13.2 ± 12.0 pre-implantation, and 62.5 ± 24.7 at 1 year and 70.7 ± 22.7 at approximately 6 years post-implantation. The MOCART scores at 1 year and 6 years were significantly higher than the pre-implantation score, but there was no significant difference between the scores at 1 and 6 years, indicating that the MRI results at 1 year after implantation were maintained for the next 5 years., Conclusions: The clinical scores and MRI findings after implantation of tissue-engineered cartilage were improved at 1 year after implantation and were maintained until 6 years after implantation.

MicroRNAs (miRNAs) are a family of non-coding RNAs that play an important role in human diseases, including osteoarthritis (OA). The objective of this study was to investigate the expression patterns of miRNAs in the peripheral blood mononuclear cells (PBMCs) of OA patients. PBMCs were isolated from 36 patients with OA, 6 RA patients, and 36 healthy controls. The expression patterns of miR-146a, 155, 181a, and 223 in PBMCs were analyzed using quantitative reverse transcription-polymerase chain reaction (qPCR). We investigated the expression patterns of the miRNAs in OA progression, and their relationships with the parameters of age, body mass index (BMI), the femorotibial angle (FTA), and serum keratan sulfate (KS). The relative expression levels of miR-146a, 155, 181a, and 223 in the OA patients were significantly higher than those found in healthy controls. In the early stages of OA, miR-146a and 223 expressions were significantly higher than they were at later stages. There was a significant correlation between the expression of miR-223 and KS. This study demonstrated that high expression levels of miR-146a, 155, 181a, and 223 in the PBMCs of OA patients might be related to the pathogenesis of OA. This evidence could lead to the elucidation of the mechanism underlying OA pathogenesis and hence to a novel therapeutic strategy for OA.

Purpose: The purpose of this study was to compare the clinical results of the transtibial and far anteromedial portal techniques for posterolateral (PL) femoral tunnel drilling in double-bundle anterior cruciate ligament reconstruction., Methods: This study involved 50 patients who underwent double-bundle anterior cruciate ligament reconstruction and were followed up for more than 2 years. The anteromedial bundle was reconstructed with the far anteromedial portal technique in all patients. However, the PL bundle was reconstructed with the transtibial and far anteromedial portal techniques in 22 patients (group T) and 28 patients (group F), respectively. The follow-up visits included evaluation of Lysholm knee scores, KT-2000 measurement of anterior knee laxity (MEDmetric, San Diego, CA), the pivot-shift test, and radiography., Results: The length of the PL femoral tunnel in group F (32.2 mm) was significantly shorter than that in group T (39.0 mm). Lateral knee radiographs showed that the positions of the EndoButtons (Smith & Nephew Endoscopy, Andover, MA) for the PL bundles were significantly more posterior (12.8 mm) and distal (3.1 mm) in group F than in group T. The mean KT-2000 side-to-side difference in group T (0.9 mm) and group F (0.7 mm) did not significantly differ. In addition, no significant difference was noted between the groups with respect to Lysholm knee scores and the pivot-shift test results., Conclusions: This study showed that the far anteromedial portal technique is as effective as the transtibial technique and results in good restoration of joint stability and knee scores despite shorter femoral tunnel length and inferoposterior position of the EndoButton., Level of Evidence: Level III, retrospective comparative study., (Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose: Recently, a computer-assisted navigation system has been used for the quantitative evaluation not only of anterior-posterior (AP) laxity but also rotational laxity of the tibia intraoperatively. The purpose of this study was to investigate how intraoperative AP or rotational laxities measured by the navigation system could correlate with postoperative AP and rotational laxities of the patients., Methods: 125 patients who underwent primary isolated anatomical single- or double-bundle ACL reconstruction or augmentation using multistranded autologous hamstring tendons were included in the study after a minimum of 2-year follow-up. Clinically, absolute value and side-to-side difference (SSD) of AP translation of the tibia were measured by KT-2000 preoperatively and postoperatively. Intraoperative measurement of AP translation of the tibia and total range of tibial rotation of the ACL-injured knee were carried out using the computer-assisted navigation system. We have investigated the relationship between intraoperative measurements using the navigation system and AP laxity measurements using the KT-2000 knee arthrometer as well as rotational laxity measurements using the manual pivot shift test., Results: There was a positive correlation between the SSD of preoperative AP translation of the tibia measured by KT-2000 arthrometer and the reduction in AP laxity following ACL reconstruction measured by the navigation system. However, we found no significant correlation between the reduction in AP laxity measured by the navigation system and the SSD of AP translation of the tibia measured by the KT-2000 arthrometer at final follow-up. Postoperatively, eight patients had a positive pivot shift test. Using the navigation system pre- and post-ACL reconstruction, these patients could not be identified by high absolute values for AP laxity nor rotational laxity., Conclusion: Although AP and rotational laxities vary largely among the patients, and AP and rotational stabilization are successfully achieved immediately after ACL reconstruction, intraoperative AP and rotational laxity measured by the navigation system did not influence the postoperative AP and rotational laxities after ACL reconstruction., Level of Evidence: III.

Background: There are various indirect signs of a discoid lateral meniscus in radiographs, for example lateral joint space widening, hypoplasia of the LFC, etc. There has, however, been no previous report of the characteristic shape of the lateral femoral condyle (LFC) in patients with osteochondritis dissecans (OCD) accompanied by a discoid lateral meniscus. The purpose of this study was to evaluate the characteristic shape of the LFC in patients with OCD accompanied by a discoid lateral meniscus, and sex differences associated with the shape of the LFC in those patients., Methods: This study included 29 males (31 knees) and 29 females (32 knees) of average age 17.7 years. There were 15 knees in 15 patients that were accompanied by OCD of the LFC (9 males, 9 knees; 6 females, 6 knees; average age 14.9 years; OCD group). There were 48 knees in 43 patients that were not accompanied by OCD of the LFC (20 males, 22 knees; 23 females, 26 knees; average age 17.6 years; non-OCD group). Standardized Rosenberg view radiographs of the knee were obtained for all patients. We evaluated the shape of LFC using the Rosenberg view and measured the condylar prominence ratio of the medial and lateral condyles adjacent to the intercondylar notch, in accordance with Ha's procedure., Results: The OCD group had a significantly larger prominence ratio than the non-OCD group. The prominence ratio for males was significantly larger than that for females., Conclusion: We clearly demonstrated that the prominence ratio in the OCD group was significantly larger than that in the non-OCD group, indicating that the shape of the LFC and OCD in the LFC may be associated with the development of these lesions.

Background: It is desirable to maintain the morphology of the semitendinosus muscle-tendon complex after tendon harvesting for anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to evaluate the effect of knee immobilization on morphological changes in the semitendinosus muscle-tendon complex., Methods: In total, 39 patients who underwent ACL reconstruction with autologous semitendinosus tendons were included in this study. After surgery, the knee was immobilized for 3 days in 1 group of patients (group 1; 24 patients; control group) and for a longer period (10-14 days) in the other group (group 2; 15 patients). Three-dimensional computed tomography (3D CT) examination was performed at 6 and/or 12 months after the surgery for all patients. Morphological changes in the semitendinosus muscle-tendon complex (proximal shift of the semitendinosus muscle-tendon junction, width of the regenerated semitendinosus tendons, re-insertion sites of the regenerated tendons, and rate of semitendinosus tendon regeneration) were evaluated., Results: Successful regeneration of the semitendinosus tendon was confirmed in all patients in group 2. In group 1, 3D CT showed that regeneration of the semitendinosus tendon was unsuccessful in 1 of the 24 patients. The average length of the proximal shift of the semitendinosus muscle-tendon junction was 7.3 ± 2.5 cm in group 1 and 7.2 ± 1.9 cm in group 2. There were no significant differences between the 2 groups with regard to the morphological changes in the semitendinosus muscle-tendon complex., Conclusions: This study showed that the structure of regenerated tendons could be clearly identified in 38 of 39 cases (97.4%) after ACL reconstruction. However, prolonged knee immobilization (10-14 days) could not prevent morphological changes in the semitendinosus muscle-tendon complex.

Purpose: The objective of this study was to determine the safe penetration depth of the FasT-Fix meniscal suture repair system during all-inside repair of the posterior part of the lateral meniscus., Methods: Thirty-one knees from 17 embalmed and formalin-fixed cadavers (11 women, 6 men) were used. In each case, the circumference of the cadaver knee was measured before dissection. After dissection, 41 Fast-Fix meniscal repair devices were used in different predetermined penetration depths ranging from 8 to 16 mm. In this study, non-involvement of the popliteal neurovascular bundle, common peroneal nerve or the inferior lateral genicular vessels by either needle penetration or affixment by the suture bar anchors was considered to be a safe trial., Results: Out of the 41 FasT-Fix devices used in this study, only one device bent during introduction and was excluded from the study. For the remaining 40 trials, 27 of them were considered safe, while 13 trials were considered unsafe. The ratio of the average penetration depth to the average circumference of the cadaver knee was found to be >0.05 for the unsafe penetrations, and this was statistically significant P < 0.05. Additionally, for the first point, which is more central, there was a trend for the straight needles through the direct lateral approach to be less safe, and this was found to be statistically significant P < 0.05., Conclusions: Correlating the needle-penetration depth to the measured circumference of the cadaver knee may be an important clinical predictor of safety whereby a ratio of less than 0.05 might be useful as a guide to determine the safe penetration depth of the FasT-Fix suture repair needle during repair of the posterior horn lateral meniscus. Also, it is better to avoid using straight needles through the direct lateral approach during repair of the more central portion of the posterior horn lateral meniscus.

Background: Osteoarthritis affects the whole body, thus biomechanical effects on other joints should be considered. Unloading knee braces could be effective for knee osteoarthritis, but their effects on the contralateral knee and bilateral hip joints remain unknown. This study investigated the effects of bracing on the kinematics and kinetics of involved and contralateral joints during gait., Methods: Nineteen patients with medial compartment knee osteoarthritis were analysed. Kinematics and kinetics of the knee and hip joints in frontal and sagittal planes were measured during walking without and with bracing on the more symptomatic knee., Findings: The ipsilateral hip in the braced condition showed a lower adduction angle by an average of 2.58° (range, 1.05°-4.16°) during 1%-49% of the stance phase, and a lower abduction moment at the second peak during the stance phase than the hip in the unbraced condition (P<0.05 and P<0.005, respectively). With bracing, the contralateral hip showed a more marked peak extension moment and lower abduction moment at the first peak (P<0.05), and the contralateral knee adduction angle increased by an average of 0.32° (range, 0.21°-0.45°) during 46%-55% of the stance phase (P<0.05), compared to no bracing., Interpretation: Unloading bracing modified the contralateral knee adduction angle pattern at a specific time point during gait. It also affected the frontal plane on the ipsilateral hip and the frontal and sagittal planes on the contralateral hip joint. Consideration should be provided to other joints when treating knee osteoarthritis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The purpose of this study was to investigate the chondrogenic potential of magnetically labeled synovium-derived cells (M-SDCs) and examine whether M-SDCs could repair the articular cartilage using an intra-articular magnet after delivery to the lesion. Synovium-derived cells (SDCs) were cultured from the synovium of a rat knee, and were magnetically labeled with ferumoxides. M-SDCs were examined with a transmission electron microscope. A pellet culture system was used to evaluate the chondrogenic potential of M-SDCs in a magnetic field. In a rat model, allogeneic M-SDCs were injected into the knee after we made an osteochondral defect on the patellar groove and implanted an intra-articular magnet at the bottom of the defect. We histologically examined the defects at 48 h, 4 weeks, 8 weeks, and 12 weeks after treatment. Electron microscopy showed the transfection of ferumoxides into SDCs. The pellet cultures revealed the chondrogenic potential of M-SDCs in a magnetic field. M-SDCs accumulated in the osteochondral defect at 48 h after treatment, and we confirmed the regeneration of the articular cartilage at 4 weeks, 8 weeks, and 12 weeks after treatment using an intra-articular magnet. We demonstrated that articular cartilage defects could be repaired using an intra-articular magnet and M-SDCs. We believe that this system will be useful to repair human articular cartilage defects., (Copyright © 2010 Orthopaedic Research Society.)

Background: The medial patellofemoral ligament (MPFL) is the most important factor for stabilizing the patella and preventing lateral patellar dislocation. Medial patellofemoral ligament reconstruction is an accepted surgical technique to restore patellofemoral stability after lateral patellar dislocation. The authors recently developed a new anatomical MPFL reconstruction method using a cylindrical bone plug and grafted semitendinosus tendon at the anatomical femoral attachment site to mimic the native MPFL. This study evaluated the new technique for stabilizing recurrent patellar dislocation., Hypothesis: This new MPFL reconstruction technique will improve knee symptoms and function with excellent clinical results., Study Design: Case series; Level of evidence, 4., Method: Thirty-one knees were evaluated from 29 cases of recurrent patellar dislocation that were surgically treated using the anatomical MPFL reconstruction technique. The average patient age was 22.2 years (range, 12-34 years); postsurgery follow-up was 2 to 5 years (average, 3.2 years). The patients were clinically evaluated based on the Kujala score, range of motion, and signs of apprehension. The Merchant view was used to measure congruence and tilting angles., Results: Of the 31 knees, 30 showed good clinical results after surgery, while 1 patient showed remaining signs of apprehension. The Kujala score improved from an average of 64 points (range, 35-70) initially to an average of 94.5 points (range, 79-100) at the final follow-up. Range of motion improved for all patients, with an average knee extension of 0° ± 2° and knee flexion of 145° ± 3° at final follow-up. No patellar redislocation was reported. Radiological assessment indicated significant improvement to the congruence angle from 13° ± 4° before surgery to -5° ± 5° at the final follow-up, while the tilting angle went from 8° ± 7° before surgery to 7° ± 4° at the final follow-up., Conclusion: This study demonstrated excellent results using the new procedure for recurrent dislocation of the patella, with instability in only 1 of 31 knees (3.2%).

The objective of this study was to investigate the effect of microRNA-21 (miR-21) on the proliferation and matrix synthesis of chondrocytes embedded in atelocollagen gel. Articular cartilage was harvested aseptically from the knee and hip joints of rats. In the experimental group, double-stranded miR-21 was transfected into the chondrocytes, and in the control group, scrambled siRNA was used. After that, chondrocytes were cultured in atelocollagen gel for 3 weeks. At 1, 2, and 3 weeks after transfection, the cell numbers were counted, and the expression levels of Col2a1 and aggrecan were measured by real-time PCR. Histological analysis by toluidine blue staining was performed at 3 weeks. The cell number in the experimental group rapidly increased compared to the control group. The expression levels of Col2a1 and aggrecan in the experimental group were higher than in the control. Histological analysis revealed that many more cells with a metachromatic stain were present in the experimental group than in the control. This study demonstrated that miR-21 promotes high proliferation and matrix synthesis of chondrocytes embedded in atelocollagen gel.

Purpose: This study aimed to evaluate the biomechanical function of anterior cruciate ligament (ACL) remnants in anteroposterior and rotational knee stability in patients with a complete ACL injury., Methods: ACL remnants were classified into 5 morphologic patterns: group 1, bridging between the posterior cruciate ligament and tibia; group 2, bridging between the intercondylar notch and tibia; group 3, partial rupture of the posterolateral bundle; group 4, partial rupture of the anteromedial bundle; and group 5, no substantial ACL remnants. The decision of whether the remaining bundle represented partial or complete rupture of the ACL was made based on physical, magnetic resonance imaging, and arthroscopic findings in a comprehensive manner. Patients in groups 1 (n = 18) and 2 (n = 12) underwent intraoperative arthrometry with a navigation system before and immediately after resection of the ACL remnant. The effects of chronicity (duration between injury and surgery) and ACL remnant pattern on changes in knee laxity after debridement of the ACL remnant were investigated., Results: Chronicity had a significant effect on changes in anteroposterior knee laxity evaluated at 30° of knee flexion after resection of the ACL remnant (change in laxity of 2.22 mm for chronicity ≤1 year and 0.17 mm for chronicity >1 year). Chronicity did not influence changes in rotational knee stability after resection of the remnant. There were no significant differences between groups 1 and 2 with regard to any of the evaluated changes in knee stability., Conclusions: In groups 1 and 2 ACL remnants contributed to anteroposterior knee stability evaluated at 30° of knee flexion for up to 1 year after injury, beyond which this biomechanical function was lost. Chronicity and remnant pattern did not influence changes in rotational knee stability after resection of the remnant., Level of Evidence: Level III, diagnostic study of nonconsecutive patients., (Copyright © 2010 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

The biological reconstruction of a large osteochondral defect in the weight-bearing area of the knee joint has long been a challenge to orthopedic surgeons. We present a case of a large posttraumatic defect in the weight-bearing area of knee joint treated with a novel distraction arthroplasty device after reconstruction of the joint surface using combined autologous and artificial bone graft.

We evaluated the efficacy of transforming growth factor (TGF)-beta-immobilized magnetic beads for chondrogenesis in vitro using a mesenchymal stem cell (MSC) delivery system and an external magnetic force (EMF). MSCs isolated from the bone marrow of Sprague Dawley rats were mixed with carboxyl group-combined magnetic beads (Ferri Sphere 100C) coated with anti-rat CD44 mouse monoclonal antibodies. TGF-beta3 (10 and 1 ng/mL) was attached magnetically to such other Ferri Sphere 100C beads via an amide bond formed between a primary amino group on the TGF-beta3 and the carboxyl groups on the surface of the beads. MSC-magnetic bead complexes were centrifuged to form a pellet and cultured in chondrogenic differentiation medium (CDM) supplemented with either 10 or 1 ng/mL TGF-beta-immobilized magnetic beads (10 or 1 ng/mL TGF-beta-immobilized magnetic bead groups) or in CDM supplemented with 1 or 10 ng/mL TGF-beta (1 or 10 ng/mL TGF-beta group). TGF-beta-immobilized magnetic beads were gathered effectively under an EMF. Chondrogenesis was achieved from the MSC-magnetic bead complexes in the presence of 1 ng/mL TGF-beta-immobilized magnetic beads.

Purpose: The purpose of this study was to investigate whether it is possible to regenerate degenerated human cartilage in vitro by use of magnetically labeled mesenchymal stem cells (MSCs) and an external magnetic device., Methods: MSCs from human bone marrow were cultured and magnetically labeled. Degenerated human cartilage was obtained during total knee arthroplasty. The osteochondral fragments were attached to the sidewall of tissue culture flasks, and magnetically labeled MSCs were injected into the flasks. By use of an external magnetic device, a magnetic force was applied for 6 hours to the direction of the cartilage, and then the degenerated cartilage was cultured in chondrogenic differentiation medium for 3 weeks. In the control group a magnetic force was not applied. The specimens were evaluated histologically., Results: A cell layer was formed on the degenerated cartilage as shown by H&E staining. The cell layer was also stained in toluidine blue and safranin O and with anti-collagen type II immunostaining, indicating that the cell layer contained an extracellular matrix. In the control group a cell layer was not observed on the cartilage., Conclusions: We were able to show that our system could deliver MSCs onto degenerated human cartilage and then form an extracellular matrix on the degenerated cartilage in vitro., Clinical Relevance: Our novel cell delivery system using magnetic force may lead toward a new treatment option for osteoarthritis.

Purpose: The purpose of this study was to estimate the potential risks when drilling femoral tunnels through the far anteromedial portal in double-bundle anterior cruciate ligament reconstruction in cadaveric knees., Methods: Ten cadaveric knees were used. We drilled the anteromedial bundle (AMB) and posterolateral bundle (PLB) through the far anteromedial portal at 3 different knee flexion angles: 70 degrees, 90 degrees, and 110 degrees. We measured the shortest distance to the common peroneal nerve and the posterior articular cartilage of the lateral femoral condyle and the femoral tunnel length., Results: At 70 degrees, the distance to the nerve was less than 10 mm in 7 AMB cases and in 9 PLB cases, and the distance to the cartilage was less than 10 mm in all the AMB and PLB cases. At 90 degrees, the distance to the nerve was less than 10 mm in 1 AMB and 5 PLBs, and the distance to the cartilage was less than 10 mm in 2 AMBs and all the PLBs. On the other hand, at 110 degrees , the distance to the nerve was greater than 10 mm in all the AMBs and PLBs, and the distance to the cartilage did not exceed 10 mm in just 2 of the PLBs., Conclusions: In our cadaveric study we found that the low knee flexion angles when drilling femoral tunnels through the far anteromedial portal might have the potential risks of damage to the common peroneal nerve and the posterior articular cartilage, and the risks would be decreased at higher degrees of knee flexion. However, we found there was a 20% risk of damage to the cartilage while drilling the PLB at 110 degrees., Clinical Relevance: High knee flexion angles are recommended to avoid damage to the nerve and the cartilage when drilling femoral tunnels through the far anteromedial portal in double-bundle anterior cruciate ligament reconstruction.

Objective: A role of microRNA, which are approximately 22-nucleotide noncoding RNAs, has recently been recognized in human diseases. The objective of this study was to identify the expression pattern of microRNA-146a (miR-146a) in cartilage from patients with osteoarthritis (OA)., Methods: The expression of miR-146a in cartilage from 15 patients with OA was analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and by in situ hybridization. Induction of the expression of miR-146a by cultures of normal human articular chondrocytes following stimulation with interleukin-1beta (IL-1beta) was examined by quantitative RT-PCR., Results: All cartilage samples were divided into 3 groups according to a modification of the Mankin score (grade I = mild OA scored 0-5, grade II = moderate OA scored 6-10, and grade III = severe OA scored 11-14). In grade I OA cartilage samples, the expression of miR-146a and COL2A1 was significantly higher than that in the other groups (P < 0.05). In grades II and III OA cartilage, the expression of miR-146a and COL2A1 was decreased, whereas the expression of matrix metalloproteinase 13 (MMP-13) was elevated in grade II OA cartilage. These data showed that miR-146a is expressed intensely in cartilage with a low Mankin grade and that miR-146a expression decreases in parallel with the level of MMP-13 expression. Tissue section in situ hybridization of primary miR-146a (pri-miR-146a) revealed that pri-miR-146a was expressed in chondrocytes residing in all tissue layers, especially in the superficial layer, where it was intensely expressed. The expression of miR-146 was markedly elevated by IL-1beta stimulation in human chondrocytes in vitro., Conclusion: This study shows that miR-146 is intensely expressed in low-grade OA cartilage and that its expression is induced by stimulation of IL-1beta. Thus, miR-146 might play a role in OA cartilage pathogenesis.

Muscle injuries in sport activities can pose challenging problems in traumatology and sports medicine. The best treatment for muscle injury has not been clearly established except for the conservative treatment that is routinely performed. We investigated the potential of human adult CD133+ cells to contribute to skeletal muscle regeneration in an athymic rat model. We tested whether CD133+ cells locally transplanted to the skeletal muscle lacerated models could (a) induce vasculogenesis/angiogenesis, (b) differentiate into endothelial and myogenic lineages, and (c) finally promote histological and functional skeletal myogenesis. Granulocyte colony stimulating factor-mobilized peripheral blood (PB) CD133+ cells, PB mononuclear cells, or phosphate-buffered saline was locally injected after creating a muscle laceration in the tibialis anterior muscle in athymic rats. After treatment, histological and functional skeletal myogenesis was observed significantly in the CD133+ group. The injected CD133+ cells differentiated into endothelial and myogenic lineages. Using real-time polymerase chain reaction analysis, we found that the gene expressions related to microenvironment conduction for host angiogenesis, fibrosis, and myogenesis were ideally up/downregulated. Our results show that CD133+ cells have the potential to enhance the histological and functional recovery from skeletal muscle injury rather via indirect contribution to environment conduction for muscular regeneration. It would be relatively easy to purify this cell fraction from PB, which could be a feasible and attractive autologous candidate for skeletal muscle injuries in a clinical setting. These advantages could accelerate the progression of cell-based therapies for skeletal muscle injuries from laboratory to clinical implementation.

Purpose: The purpose of this study was to investigate the 2-year follow-up clinical results of 45 patients who had undergone our anterior cruciate ligament (ACL) augmentation procedure using an autogenous semitendinosus tendon and the EndoButton CL (Smith & Nephew, Andover, MA)., Methods: We followed up 45 patients for more than 2 years after their ACL augmentations. Of these, 37 were anteromedial (AM) bundle reconstructions and 8 were posterolateral (PL) bundle reconstructions. They were assessed using a KT-2000 knee arthrometer (MEDmetric, San Diego, CA) at 30 lb by joint position sense, Lysholm knee score, and magnetic resonance imaging (MRI)., Results: The mean side-to-side difference of anterior displacement measured by the KT-2000 knee arthrometer at 30 degrees of knee flexion preoperatively was 3.3 +/- 2.4 mm, significantly improving to a mean of 0.5 +/- 2.7 mm 2 years after surgery. The preoperative joint position sense inaccuracy was 1.6 degrees +/- 1.8 degrees , which improved significantly to 0.3 degrees +/- 2.0 degrees after surgery. The median Lysholm knee score significantly improved from 74 (range, 44 to 95) to 100 points (range, 81 to 100) after surgery. In 20 of 29 patients who had the postoperative MRI examination, the augmented ACL resembled 1 bundle on the sagittal planes of the postoperative MRI., Conclusions: Selective AM or PL bundle reconstruction showed improved joint stability, joint position sense, and Lysholm scores postoperatively. This procedure can be a treatment option for patients whose ACL remnants are left in certain conditions.

Purpose: The purpose of this study was to evaluate the functional and radiographic outcome of retroarticular drilling for patients with juvenile osteochondritis dissecans after 6 months of unsuccessful nonoperative treatment., Methods: A total of 20 osteochondritis dissecans lesions in 12 skeletally immature patients were treated with retroarticular drilling without bone grafting. There were 10 boys and 2 girls with a mean age of 12.0 years (range, 9 to 15 years). The functional outcomes were evaluated by use of the Lysholm score at a mean follow-up of 2.7 years after drilling, and healing of the lesions was confirmed by use of plain radiographs and magnetic resonance imaging., Results: The mean Lysholm score significantly improved postoperatively (from 72.3 to 95.8). All lesions except 1 healed after retroarticular drilling. Healing was achieved at a mean of 4.4 months on plain radiographs and 7.6 months on magnetic resonance imaging., Conclusions: This study shows that retroarticular drilling without bone grafting leads to improved clinical outcomes and high healing rates. We advocate retroarticular drilling for patients with stable juvenile osteochondritis dissecans of the knee whose initial nonoperative treatment has failed.

Introduction: We previously observed medial and/or lateral expansion of the subchondral bone in the acetabulum 3 years postoperatively in two out of three cases in which rotational acetabular osteotomy (RAO) was performed. Then we performed multiple drillings at the acetabular fossa in order to induce expansion of the medial subchondral bone in the acetabulum. The purpose of this study is to evaluate the effect of multiple drillings on early joint remodeling after RAO., Patients and Methods: Twenty-one women (21 joints) who had undergone RAO with multiple drillings at acetabular fossa (group D) were included. As a control group, 12 women (14 joints) without drillings in RAO procedure were observed (group C). The center-edge angle (CE angle), acetabular roof obliquity (AC angle), head lateralization index (HLI), and the angle between medial and lateral edge of acetabular roof (LOM angle) were measured on the radiographs preoperatively, at 1 month, 2 years postoperatively, and at the last follow-up., Results: As regards the mean CE angle, AC angle, and HLI, there was no significant difference between the two groups. The mean LOM angle at 2 years and the last follow-up demonstrated significant difference between the two groups., Interpretation: Biomechanical and anatomical changes after RAO cause increasing stress to the medial side of the acetabulum. Moreover, bone marrow-stimulating procedure at acetabular fossa might be beneficial to develop early joint remodeling affected by bone marrow derived cells such as mesenchymal stem cells.

We employed a new surgical method for the treatment of spontaneous osteonecrosis of the medial femoral condyle of the knee joint. Twelve spontaneous osteonecrosis patients of Koshino's classification stage 2 or 3 underwent core decompression curettage with an artificial bone graft [hydroxyapatite ceramic with an interconnected porous structure (IP-CHA)]. The mean age at surgery was 69.6 years and the mean follow-up term was 24.6 months. All patients reported a decrease in knee pain, immediately after surgery. The Japanese Orthopaedic Association (JOA) scores of all the patients also improved post-surgery; X-ray and MR imaging indicated no worsening of the osteoarthritis, and smooth surfaces at the grafted areas of the artificial bone. No severe complications appeared in the patients. Our procedure was, therefore, less invasive and achieved results comparable to those involving traditional, more invasive methods. We recommend our novel procedure as a treatment for spontaneous osteonecrosis of the femoral condyle.

The purpose of this study was to assess transplantation of regenerated menisci using scaffolds from normal allogeneic menisci and bone-marrow-derived mesenchymal stromal cells (BM-MSCs) of rats. We reported that scaffolds derived from normal menisci seeded with BM-MSCs in vitro could form meniscal tissues within 4 weeks. Then, we hypothesized that our tissues could be more beneficial than allogeneic menisci regarding early maturation and chondroprotective effect. Bone marrow was aspirated from enhanced green fluorescent protein transgenic rats. BM-MSCs were isolated and seeded onto scaffolds which were prepared from Sprague-Dawley rat menisci. After 4 weeks in coculture, the tissues were transplanted to the defect of menisci. Repopulation of BM-MSCs and expression of extracellular matrices were observed in the transplanted tissues at 4 weeks after surgery. At 8 weeks, articular cartilage in the cell-free group was more damaged compared to that in the cell-seeded group or the meniscectomy group.

Background: The quality of tendons has considerable limitations regarding torn rotator cuff tendons. Tissue-engineering techniques using a biodegradable scaffold offer potential alternatives for recreating a valid tendon-to-bone interface., Hypothesis: A polyglycolic acid (PGA) sheet could facilitate the regeneration of the rotator cuff tendon insertion in vivo., Study Design: Controlled laboratory study., Methods: An implant consisting of a PGA sheet, a rapidly absorbable material, was used to replace a completely resected infra-spinatus tendon insertion in 33 adult Japanese white rabbits. The contralateral infraspinatus tendon was replaced by poly-L-lactate-epsilon-caprolactone (PLC), a slowly absorbable material, by the same methods based on the results of the pilot study. Histological comparisons were made at 4, 8, and 16 weeks, and mechanical evaluations were performed at 4 and 16 weeks in both groups. Unrepaired defects were created in a control group., Results: In the control group, the rotator cuff defects were covered with thin fibrous membranes with many fibroblasts arranged in an irregular pattern. In the PLC group, some chondrocytes were seen in the tendon insertion; however, these were not arranged along the long axis for a 16-week period. In the PGA group, a well-arranged fibrocartilage layer could be found in the regenerated tendon insertions; however, these tendon insertions were mainly regenerated by type III collagen. In mechanical examinations, the PGA group had significantly higher values in the maximum failure load, tensile strength, and Young's modulus for the 4-week and 16-week periods. These 3 categories statistically improved from 4 to 16 weeks postoperatively in both groups except for the Young's modulus in the PGA group (E = 5.66 at 4 weeks to 5.53 at 16 weeks)., Conclusion: The PGA sheet scaffold material allows for tendon insertion regeneration with a fibrocartilage layer but displays mechanical properties inferior to those of the normal tendon in an animal model., Clinical Relevance: The PGA sheet represent a possible alternative scaffold material for tendon regeneration in rotator cuff repair.

Bach 1 is a transcription factor that negatively regulates the transcription of heme oxygenase-1 (HO-1), a stress-responding protein. In this study, we investigated the reaction to oxidative stress in the meniscus of Bach 1 deficient mice, and the suppression of meniscal degeneration by the induction of HO-1. We carried out a comparative study between Bach 1 deficient mice and wild type mice, in which the oxidative stress reaction and age-related changes were investigated using the menisci of 6-, 12-, and 24-week-old mice. The degrees of meniscal degeneration and expression of HO-1 were evaluated using the menisci cultured under oxidative stress with cadmium chloride or interleukin-1 beta. The age-related changes in the meniscus were histologically examined. The expression of HO-1 was higher, and the degrees of histological degeneration were lower in the Bach 1 deficient mice than in wild type mice (HO-1 mRNA expression: In both the Cd group and the IL group, two-fourfold higher in the meniscus). The age-related changes were lower in the Bach 1 deficient mice than in wild type mice. In 24-week-old mice, a moderate decrease in the cell density and proteoglycan content was observed in wild type mice compared with Bach 1 deficient mice. In the menisci of Bach 1 deficient mice, the anti-oxidative stress activity was considered to be increased by abrogating the suppression of HO-1 expression, resulting in a reduction of histological degeneration. This finding showed a potential new strategy for the prevention and treatment of meniscal degeneration., ((c) 2008 Orthopaedic Research Society.)

Articular cartilage has very limited healing potential. Although there are several treatment options for cartilage defect, no treatment has been established as a gold standard procedure. Recently, a tissue-engineering technique has made great progress, and repair of cartilage has been given much attention in regenerative medicine. Since 1996, we have been performing transplantation of tissue-engineered cartilage made ex vivo for the treatment of human cartilage defect of the joint. This paper will summarize our procedure of articular cartilage repair and our novel stem cell delivery system using magnetic field.

Thirty-nine knees in 39 patients with recent anterior cruciate ligament (ACL) rupture (age 14-55 years; with a mean age of 22.8 years) were selected from our cases of ACL reconstruction from July 2005 to June 2006, to take part in a study on articular cartilage injury of the posterior lateral tibial plateau associated with acute ACL injury and on the correlation between bone bruises depicted on MRI and cartilage injury of the posterior lateral tibial plateau detected at arthroscopic ACL reconstruction. Using preoperative MRI, we evaluated whether there were bone bruises or not in the lateral compartment of the knee and divided them accordingly into two groups: the bone bruise positive group and the negative group. The differences in the proportions of the lateral meniscus (LM) tears and the cartilage injuries in the two groups were evaluated using Fisher's exact probability test. Thirty-five cases out of 39 arthroscopic ACL reconstructions (89.7%) were regarded as bone bruise positive in the lateral compartment and four cases (10.3%) were regarded as negative. At arthroscopic ACL reconstruction, 33 cases (84.6%) had tears in the LM posterior horn, 34 cases (87.2%) had articular cartilage injuries in the lateral femoral condyle and 29 cases (74.3%) had articular cartilage injuries in the posterior lateral tibial plateau. From 35 bone bruise positive cases, 32 cases (91.4%) had tears in the LM posterior horn, 33 cases (94.3%) had articular cartilage injuries in the lateral femoral condyle and 28 cases (80%) had articular cartilage injuries in the posterior lateral tibial plateau. Of four bone bruise negative cases, one case (25%) had a tear in the LM posterior horn, articular cartilage injury of the lateral femoral condyle and of the posterior lateral tibial plateau. There was a statistically significant correlation between the proportion of bone bruise and cartilage injury of the lateral femoral condyle (P = 0.004), that of the posterior lateral tibial plateau (P = 0.04) and that of tears in the LM posterior horn (P = 0.008). This current study has demonstrated that we need to pay attention to cartilage damage of the posterior lateral tibial plateau as well as to posterior horn tears in LM, when acute ACL injury is shown. We also have to ensure that we follow the long-term progress of cartilage injuries, with the aim of preventing these injuries becoming osteoarthritis after ACL reconstruction.

Purpose: The purpose of this study was to investigate whether it is possible to successfully accumulate magnetically labeled mesenchymal stem cells (MSCs), under the direction of an external magnetic force, to the desired portion of osteochondral defects of the patellae after intra-articular injection of the MSCs., Methods: MSCs were cultured from bone marrow and were labeled magnetically. Osteochondral defects were made in the center of rabbit and swine patellae, and magnetically labeled MSCs were injected into the knee joints either under the direction of an external magnetic force or with no magnetic force applied. In the rabbit model we evaluated the patellae macroscopically and histologically, and in the swine model we observed the patellae arthroscopically., Results: Accumulation of magnetically labeled MSCs to the osteochondral defect was shown macroscopically and histologically in the rabbit model and was shown by arthroscopic observation to be attached to the chondral defect in the swine model., Conclusions: We showed the ability to deliver magnetically labeled MSCs to a desired place in the knee joint., Clinical Relevance: Our novel approach is applicable for human cartilage defects and may open a new era of repairing cartilage defects caused by osteoarthritis or trauma by use of a less invasive technique.

The purpose of this study was to examine the role of the synovium in the transitional zone between the articular cartilage and the synovial membrane in cartilage repair and the relationship between the origin of the repaired cartilage and the grafted synovium. We used 8-week-old Sprague Dawley (SD) rats and green fluorescent protein (GFP) transgenic rats. In study 1, a full-thickness cartilage defect was created at the medial condyle of the femur, and the synovium 5 x 5 mm extending up to the cartilage defect was resected in the left knee (cartilage defect without synovium group) but not resected in the right knee (cartilage defect with intact synovium group). In study 2, after the creation of a full-thickness cartilage defect and resection of the synovium, the synovium of the GFP rats was transplanted into the unilateral knee (cartilage defect with transpl.synovium group). At 2, 4, 6, and 8 weeks after surgery, we evaluated the repaired tissue in cartilage defects histologically and immunohistochemically, and the expression of aggrecan and type II collagen in the repaired tissue was also investigated using reverse transcriptase-polymerase chain reactions (RT-PCR). At 6 and 8 weeks after surgery, the defect was filled with cartilage-like tissue in cartilage defect with intact synovium group and cartilage defect with transpl.synovium group, but not in cartilage defect without synovium group. GFP positive cells were observed in the repaired tissue and the expression of aggrecan and type II collagen was found in cartilage defect with transpl.synovium group. We concluded that the synovium in the transitional zone between the articular cartilage and the grafted synovial membrane invades the cartilage defects where the cells could be detected as GFP-positive cells. Those cells may take part in the repair and may induce chondrogenesis.

Purpose: The aim of this study was to evaluate the clinical results of a new distraction arthroplasty device when used in conjunction with a bone marrow-stimulating technique for the treatment of osteoarthritis of the knee., Methods: We developed a new distraction arthroplasty device that allows continuous joint movement. We compared preoperative and postoperative findings for 6 knees (6 patients; age range, 42 to 58 years). The fixation period for the distraction device ranged from 7 to 13 weeks, and the follow-up period ranged from 1 to 3.5 years., Results: The Japanese Orthopaedic Association knee score, range of motion, and joint space values were significantly improved in all cases at the latest follow-up (P < .05). Scores on a visual analog pain scale were also significantly improved (P < .05)., Conclusions: We conclude that treatment using this new arthroplasty device in combination with a bone marrow-stimulating method was effective for osteoarthritic knees in middle-aged patients., Level of Evidence: Level IV, therapeutic case series.

Purpose: The purpose of this study was to biomechanically and histologically evaluate whether intra-articularly injected mesenchymal stromal cells can accelerate the healing of a partially torn anterior cruciate ligament (ACL)., Methods: Ninety-eight 12-week-old male Sprague-Dawley rats were studied. The right ACL was partially transected, and a sham operation was performed on the left knee. Mesenchymal stromal cells obtained from bone marrow of green fluorescent protein (GFP) transgenic Sprague-Dawley rats were cultured for 2 weeks in medium. In the MSC(+) group, 1 x 10(6) cells were suspended in phosphate-buffered saline solution and were injected into the right knee with the partially transected ACL. In the MSC(-) group, only phosphate-buffered saline solution was injected. Six animals from each group were evaluated histologically at 1, 2, 3, and 4 weeks after surgery, and they were evaluated biomechanically immediately after surgery (time zero) (n = 9) and also at 2 weeks (n = 11) and 4 weeks (n = 12) after surgery in both groups. For biomechanical testing, the ultimate failure load of a prepared femur-ACL-tibia complex was measured. We then compared the transected side with the sham side in each group. GFP luminescence was observed with a fluorescence microscope to detect whether the injected cells mobilized into the covered tissue., Results: In the MSC(-) group the transected area retracted with increasing time, and the gap remained void of any tissues at all time points after surgery. In the MSC(+) group at 2 and 4 weeks after surgery, the transected area was covered with healing tissues in which GFP-positive cells were detected. Furthermore, the histologic score of the MSC(+) group was significantly better than that of the MSC(-) group. The ultimate failure load of the femur-ACL-tibia complex in the MSC(+) group was significantly higher than that in the MSC(-) group at 4 weeks after surgery., Conclusions: We conclude from our histologic and biomechanical measurements that injected mesenchymal stromal cells can accelerate the healing of partially torn ACLs., Clinical Relevance: The intra-articular injection of mesenchymal stromal cells can be a viable option for treating partially torn knee ACLs.

Purpose: The purpose of this study was to evaluate histologic changes in osteochondral loose bodies in the rabbit knee joint and histologic changes in repaired tissue after fixation of osteochondral loose bodies following isolation periods of varying length., Methods: We harvested osteochondral fragments from the patellar groove in rabbit knee joints and left them in the lateral gutters of the joints for periods of varying duration to create osteochondral loose bodies. We then evaluated histologic and immunohistochemical changes within these loose bodies. Next, we fixed osteochondral loose bodies that had been isolated for various periods within the joints to the osteochondral defect in the patellar groove. Twelve weeks after fixation, repaired tissues were evaluated histologically and immunohistochemically, and results were analyzed according to the varying isolation periods of fragments., Results: Extracellular matrix and type II collagen expression of osteochondral loose bodies deteriorated with increased duration of fragment isolation periods. A significantly negative correlation was noted between length of isolation periods and histologic grading scores. After osteochondral loose bodies had been fixed, repaired tissues deteriorated significantly in accordance with duration of fragment isolation periods. However, in some cases, even when osteochondral fragments had been isolated for 12 weeks, repaired tissues showed dense extracellular matrix stained by safranin O and abundant type II collagen expression, which indicated regeneration of the cartilage layer., Conclusions: Osteochondral loose bodies and repaired tissues deteriorated after they were fixed to osteochondral defects. Although a direct correlation was noted between isolation periods of fragments and time to their deterioration, some osteochondral loose bodies showed regeneration of cartilage after fixation., Clinical Relevance: Clinically, reduction of osteochondral loose bodies should be performed as early as possible, if these can be found. However, even if the fragment seems to be old, fragment fixation is worthy of consideration.

Background: Aggressive early rehabilitation is recommended after reconstruction of the anterior cruciate ligament (ACL) using a patellar tendon-bone graft. However, rehabilitation after reconstruction of ACL using the multistranded hamstring is controversial. In this study, we compared the clinical results of 3-day immobilization after reconstruction of ACL using the multistranded hamstring, with those of 2-week immobilization prospectively., Methods: A total of 30 consecutive patients with ruptured ACL underwent single-socket ACL reconstruction. 10 male and 5 female patients (mean age of 29.2+/-10.0 years) were prospectively randomized for a 3-day immobilization period, and 6 male and 9 female patients (mean age of 27.3+/-10.9 years) were randomized for a 2-week immobilization period. We measured the anterior laxity with a KT-2000 arthrometer, joint position sense, and thigh muscle strength at 3, 6 and 12 months after surgery., Results and Conclusions: There were no statistically significant differences between the two groups. We concluded that the post-operative 3-day immobilization period is preferable to the longer 2-week period in our rehabilitation program from the viewpoint of psychological load to the patients and the duration of hospitalization after ACL reconstruction using multistranded hamstring tendons.

The purpose of this study was to examine the long-term clinical results of meniscus transplantation for articular cartilage defects in the knee joint. The type of study was case series. From October 1990 to June 1995, eight cases underwent allogenic or autogenic meniscus transplantations for articular cartilage defects, and seven cases were available for follow-up evaluations. The age at surgery ranged from 14 to 42 years of age (average 22.5). In one case, transplantation of tissue-engineered cartilage was performed due to pain 5 years after surgery. The other six cases were followed up for 8-13 years (average 10.1). The size of the cartilage defect ranged from 1.0 to 6.3 cm2 (average 2.8 cm2). Patients were evaluated with the Lysholm score and MR images. We also performed arthroscopic examinations in three cases at the final evaluation. This study leads to the conclusion that meniscus transplantation for articular cartilage damage is not comparable to autologous chondrocyte transplantation. Two cases showed a good clinical outcome but the tissue remained as fibrocartilage tissue in the long-term.

In this study, we describe a new hamstring fixation technique with a bone graft using the Mosaicplasty system for the reconstruction of the medial collateral ligament (MCL) or posterolateral corner (PLC) of the knee. In this technique, a cylindrical bone plug (6.5 mm in diameter, 15 mm in length) is harvested from the anatomical femoral attachment of the MCL or popliteal tendon using the Mosaicplasty system. After placing the autologous semitendinosus or gracilis tendon as a graft in the created bone socket, the bone plug is replaced over the graft. The graft is secured with a spike staple after appropriate tension is applied to the graft. This fixation technique can provide rigid and less invasive fixation, because the distance between the fixation sites can be shorter than that in the Endobutton technique. Compared to fixation with only a staple with no bone graft, the bone graft may enhance tendon to bone healing.

Arthroscopic examination before anterior cruciate ligament (ACL) reconstruction sometimes reveals that there is a relatively thick ACL remnant bridging the femur and the tibia that may function to stabilize the knee, although its attachment is not the same as the anatomic site. We have established an ACL augmentation procedure that preserves the ACL remnant with the 1-incision technique using an autogenous semitendinosus tendon and EndoButton-CL (Acufex, Smith & Nephew, Mansfield, MA) instead of ACL reconstruction. When the ACL remnant was attached to the anteroinferior portion of the anatomic femoral origin and the posterolateral (PL) bundle was well preserved, the anteromedial (AM) bundle was reconstructed. When, in contrast, the ACL remnant was attached to the high-noon position with a well-preserved AM bundle, the PL bundle should be reconstructed. We have performed 13 AM bundle reconstructions and 4 PL bundle reconstructions. The merits of our ACL augmentation procedure are (1) it is performed under arthroscopy with 1 incision, (2) it avoids resection of the ACL remnant, which contributes to prevention of anterior laxity, (3) it preserves the ACL remnant's neural elements and mechanoreceptors, and (4) it provides a favorable influence on vascularity and reinnervation to the graft.

Purpose: The aim of this study was to evaluate preoperative measurement of the semitendinosus tendon (ST) by 3-dimensional computed tomography (3-D CT), before using ST as the substitute in the anterior cruciate ligament (ACL) reconstruction., Type of Study: Cross-sectional study to compare anatomic findings with clinical findings., Methods: The study involved 28 patients who underwent ACL reconstruction using autogenous ST graft. Preoperative 3-D CT images of ST were obtained with a multidetector-row CT scanner, and rendered qualitatively by the volume-rendering technique. The length and cross-sectional area of ST measured with 3-D CT were compared with the length of the harvested ST and the cross-sectional area of the grafted quadrupled tendon., Results: The total length of ST measured with 3-D CT ranged from 220.3 to 285.4 mm, with a mean (+/- SD) of 248.0 +/- 17.1 mm, and that measured at surgery ranged from 230.0 to 290.0 mm, with a mean of 257.1 +/- 16.5 mm. These 2 values showed a close positive correlation (gamma = 0.634, P = .002). The cross-sectional area of ST measured with 3-D CT ranged from 4.29 to 18.5 mm2 with a mean of 11.9 +/- 4.6 mm2, and that of the substitute measured at surgery ranged from 28.3 to 56.7 mm2 with a mean of 45.5 +/- 6.9 mm2). There was no significant correlation between the areas of ST measured by CT and the areas of ST measured during surgery., Conclusions: Preoperative 3-D CT imaging predicts the length of ST. These findings support the measurement of ST length by 3-D CT as a useful tool for planning ACL reconstructive surgery and for providing important preoperative information to patients., Level of Evidence: Level III, diagnostic study.

The purpose of this study was to examine the relationship between osteochondritis dissecans (OCD) of the lateral femoral condyle and lateral menisci. From 1993 to 2002, 38 knees (28 patients) were diagnosed with OCD of the lateral femoral condyle. OCD locations were graded by the Cahill and Berg classification. The types of lateral menisci were classified by Watanabe's classification. The relationship between OCD of the lateral femoral condyle and lateral menisci was examined. On the anterior-posterior view, 25 OCDs were located in zone 4 and 13 in zone 5. The types of lateral menisci were complete discoid in 19 knees, incomplete discoid in 15, and normal in 4. Ten of the 19 complete discoid menisci were damaged. Complete discoid menisci without tears were found in OCDs located in zone 4; incomplete discoid menisci were found in OCDs located in zone 5. The authors found a relationship between the type of OCD and the state of the lateral meniscus.

Management of osteoarthritis of the knee after meniscectomy has been challenging, especially for young patients, because articular cartilage has very poor healing capacity because of its lack of vessels, nerve supply, and isolation from systemic regulation. Osteoarthritic lesions often involve both femoral and tibial cartilage, requiring treatments for both lesions. We report the case of a 14-year-old girl with lateral compartment osteoarthritis of the knee after a total meniscectomy of the discoid meniscus, who was successfully treated by the transplantation of both tissue-engineered cartilage made ex vivo for a femoral lesion and an autologous osteochondral plug for a tibial lesion. We treated both femoral and tibial cartilage defects simultaneously with this procedure. We confirmed cartilaginous regeneration in both femoral and tibial lesions at second-look arthroscopy. This procedure is one option to prevent further development of osteoarthritis in young patients.

We evaluated the efficacy of a novel natural killer (NK) cell delivery system in vitro, and also investigated the antitumor effect of the accumulated cells on HOS osteosarcoma cells. Human peripheral blood mononuclear cells were isolated and co-cultured with inactivated K562 erythroleukaemic cells in the presence of IL-2 for 5 days. CD3- CD56+ NK cells were labeled with immunomagnetic beads and separated using a magnetic cell sorting system. Purity and cytotoxicity against K562 cells and HOS cells of the magnetically labeled NK cells were measured. To evaluate whether magnetically labeled NK cells could be accumulated in a specific area by magnetic force, the NK cells were placed in chamber slides in the presence, or not, of an external magnetic force of a neodymium magnet (diameter: 1.5 mm, height: 3 mm, total magnetic flux density: 0.282 T). Moreover, to investigate the antitumor effect on HOS cells, the magnetically labeled NK cells were added to HOS cells in chamber slides in the presence, or not, of an external magnetic force for various times. HOS cells were subsequently stained with Papanicolaou for histological examination. It was found that the magnetically labeled NK cells were highly purified and had cytotoxicity against target cells. The NK cells were accumulated effectively by the magnetic field and, when the NK cells were added to HOS cells in a chamber slide with a magnet placed beneath, a significantly larger number of HOS cells detached from the magnet zone than from other zones. Apoptosis was detected in most detached HOS cells. In conclusion, these findings indicate that magnetically accumulated NK cells efficiently induced apoptosis in HOS cells, suggesting that magnetic targeting therapy using magnetically labeled NK cells holds promise as an immunotherapy for osteosarcoma.

The purpose of this study was to regenerate a meniscus using a scaffold from a normal meniscus and mesenchymal stromal cells derived from bone marrow (BM-MSCs). Thirty Sprague-Dawley rat menisci were excised and freeze-thawed three times with liquid nitrogen to kill the original meniscal cells. Bone marrow was aspirated from enhanced green fluorescent protein transgenic Sprague-Dawley rats. BM-MSCs were isolated, cultured for 2 weeks, and 2 x 10(5) cells were then seeded onto the meniscal scaffolds. Using a fluorescent microscope and immunohistochemical staining, repopulation of enhanced green fluorescent protein positive cells was observed in the superficial zone of the scaffold after 1 week of culture, and then in the deep zone after 2 weeks. At 4 weeks, expression of extracellular matrices was detected histologically and expression of mRNA for aggrecan and type X collagen was detected. Stiffness of the cultured tissue, assessed by the indentation stiffness test, had increased significantly after 2 weeks in culture, and approximated the stiffness of a normal meniscus. From this study, we conclude that a scaffold derived from a normal meniscus seeded with BM-MSCs can form a meniscus approximating a normal meniscus., ((c) 2005 Wiley Periodicals, Inc.)

The management of patellar dislocation syndrome has traditionally been difficult. There are no golden standard methods for patellar dislocations probably due to the many etiologies. However, it is known that medial patellofemoral ligament (MPFL) is damaged when the patella is dislocated. The purpose of this study is to examine whether our method of MPFL reconstruction is useful for the treatment of dislocated patellae and unstable patellae. Forty-six knees (43 patients) of 68 knees (65 patients) that were operated on using our surgical procedure for MPFL reconstruction with the advancement of the vastus medialis or the MPFL reconstruction with Insall's procedure were followed up for at least 5 years. The patient age ranged from 6 to 43 years. These knees consisted of six habitual dislocation patellae, twenty-six recurrent dislocation patellae, ten traumatic dislocation patellae, and four unstable patellae. The patients were evaluated pre-operatively and more than three times post-operatively at 6, 12, 36, 60, or 120 months. No patient experienced patellar dislocation after surgery. Their post-operative Kujala's scores were significantly improved. On conventional X-ray and on stress X-ray evaluations, the mean values for congruence angle, tilting angle, lateral shift ratio, medial stress shift ratio, and lateral stress shift ratio at the final follow-up (60 or 120 months) were demonstrated to be within the normal range. We conclude that our MPFL reconstruction method with the advancement of the vastus medialis or with Insall's procedure might be recommended for the treatment of habitual, recurrent, and indeed any other type of patellar dislocation, as well as for unstable patellae.

We describe a 21-year-old man with a large osteochondral defect of the knee after septic arthritis, successfully treated by transplant of mesenchymal stem cells (MSC) from bone marrow and a new type of interconnected porous hydroxyapatite ceramic (IP-CHA). We confirmed successful cartilage-like tissue regeneration by a second arthroscopy. Biopsy of the repaired tissue revealed cartilage-like regeneration and bone formation. We were able to regenerate new bone and cartilage-like tissue in a one-stage operation, without sacrificing autologous bone or other tissue. This cultured MSC and IP-CHA hybrid material transplant represents a novel treatment for a severe osteochondral defect after septic arthritis.

Meniscal tears in the avascular zone have very limited potential to heal because of a poor blood supply. Although there have been many attempts to promote the healing potential of the torn meniscus, no established treatments have achieved sufficient meniscal healing. In this study, we evaluated the efficacy of mesenchymal stem cell transplantation as a cell source to promote meniscal healing, using cells from the green fluorescent protein (GFP) transgenic rat and organ culture model. Mesenchymal stem cells from bone marrow were isolated and expanded in monolayer culture. They were embedded in fibrin glue and were transplanted into the meniscal defects of Sprague-Dawley rats. In the control groups, the defects remained untreated, or only fibrin glue without cells was transplanted. The GFP-positive cells enabled us to detect the transplanted cells from recipient cells easily. As a result, transplanted mesenchymal stem cells could survive and proliferate in the meniscal defects in the organ culture model. They also could produce an abundant extracellular matrix stained by toluidine blue around the cells which contributed to meniscal healing in the avascular status. We could detect transplanted GFP cells under a fluorescent microscope until 8 weeks after transplantation. In a clinical situation, mesenchymal stem cell transplantation is a promising new clinical strategy for the treatment of meniscal tears in the avascular zone.

We evaluated the efficacy of a magnetic liposomal delivery system of transforming growth factor (TGF)-beta(1) in the treatment of articular cartilage defects in a rabbit model. Articular cartilage defects were created in the patellar groove of rabbits, and a permanent magnet or a nonmagnetic alloy was implanted in the defect site. Magnetic liposomal drugs, prepared by the conventional film method and sonication, were injected into the defect site 1 week after surgery. First, the efficacy of the magnetic liposomal delivery system was evaluated by using a model compound fluorescence-labeled dextran 40,000 (FD-40). Then, the therapeutic efficiency of magnetic liposomal TGF-beta(1) was evaluated by cartilage histological scoring at 4, 8, and 12 weeks after surgery. The injected magnetic liposomal FD-40 accumulated at the target site where a permanent magnet had been implanted. The histological score showed that the injection of magnetic liposomal TGF-beta(1) under magnetic force was significantly effective in the repair of the defect site over 12 weeks after surgery. Injection of TGF-beta(1) into the cartilage defect was effective as a magnetic liposomal preparation under magnetic force, resulting in acceleration of the cartilage repair, probably because of the desirable accumulation of TGF-beta(1) at the target site., (Copyright 2005 Wiley Periodicals, Inc.)