Tomomasa Nakamura

Arthroscopic, histological and MRI analyses of cartilage repair after a minimally invasive method of transplantation of allogeneic synovial mesenchymal stromal cells into cartilage defects in pigs

Background aims Transplantation of synovial mesenchymal stromal cells (MSCs) may induce repair of cartilage defects. We transplanted synovial MSCs into cartilage defects using a simple method and investigated its usefulness and repair process in a pig model. Methods The chondrogenic potential of the porcine MSCs was compared in vitro. Cartilage defects were created in both knees of seven pigs, and divided into MSCs treated and non-treated control knees. Synovial MSCs were injected into the defect, and the knee was kept immobilized for 10 min before wound closure. To visualize the actual delivery and adhesion of the cells, fluorescence-labeled synovial MSCs from transgenic green fluorescent protein (GFP) pig were injected into the defect in a subgroup of two pigs. In these two animals, the wounds were closed before MSCs were injected and observed for 10 min under arthroscopic control. The defects were analyzed sequentially arthroscopically, histologically and by magnetic resonance imaging (MRI) for 3 months. Results Synovial MSCs had a higher chondrogenic potential in vitro than the other MSCs examined. Arthroscopic observations showed adhesion of synovial MSCs and membrane formation on the cartilage defects before cartilage repair. Quantification analyses for arthroscopy, histology and MRI revealed a better outcome in the MSC-treated knees than in the non-treated control knees. Conclusions Leaving a synovial MSC suspension in cartilage defects for 10 min made it possible for cells to adhere in the defect in a porcine cartilage defect model. The cartilage defect was first covered with membrane, then the cartilage matrix emerged after transplantation of synovial MSCs.

Repetitive allogeneic intraarticular injections of synovial mesenchymal stem cells promote meniscus regeneration in a porcine massive meniscus defect model.

OBJECTIVE A new strategy is required in order to regenerate a meniscus for extensive defects. Synovial mesenchymal stem cells (MSCs) are an attractive cell source for meniscus regeneration due to their high proliferation and chondrogenic potential. We examined the effect of repetitive intraarticular injections of synovial MSCs on meniscus regeneration in a massive meniscal defect of pigs. We followed up the efficacy using MRI evaluation in addition to macroscopic and histological observations. DESIGN Two weeks before the injection of synovial MSCs, the anterior half of the medial menisci was resected in both knees of pigs. Fifty million allogeneic synovial MSCs were injected into the right knee at 0, 2, and 4 weeks and followed up by sequential MRI. The regenerated meniscus, adjacent articular cartilage, and subchondral bone were evaluated by MRI at 2, 4, 8, 12 and 16 weeks. They were also evaluated macroscopically and histologically at 16 weeks (n = 7). RESULTS The resected meniscus regenerated significantly better in the MSC group than in the control group based on histological and MRI analyses. Macroscopically, the meniscal defect already appeared to be filled with synovial tissue at 2 weeks. Articular cartilage and subchondral bone at the medial femoral condyle were also significantly more preserved in the MSC group based on MRI, macroscopic, and histological analyses. CONCLUSIONS Intraarticular injections of allogeneic synovial MSCs appeared to promote meniscus regeneration and provide protection at the medial femoral articular cartilage in a porcine massive meniscal defect model.

Mid- to Long-term Results of Single-Bundle Versus Double-Bundle Anterior Cruciate Ligament Reconstruction: Randomized Controlled Trial

PURPOSE To evaluate the mid-to long-term results of a randomized controlled trial of single-bundle (SB) versus double-bundle (DB) anterior cruciate ligament (ACL) reconstruction using a semitendinosus tendon. METHODS Seventy-eight patients who underwent primary ACL reconstruction with an autologous semitendinosus tendon were prospectively randomized into 2 groups: SB reconstruction (n = 39) and DB reconstruction (n = 39). In both groups, grafts were fixed at 30° of flexion with a total tension of 80 N. The following evaluation methods were used: clinical examination, KT-1000 arthrometer (MEDmetric, San Diego, CA) measurement, muscle strength, Tegner activity score, Lysholm score, subjective rating scale regarding patient satisfaction and sports performance level, graft retear, contralateral ACL tear, and additional meniscus surgery. RESULTS Fifty-three patients (25 in SB group and 28 in DB group) who were followed up for a minimum of 3 years (mean, 69 months; range, 36 to 140 months) were evaluated. Preoperatively, there were no differences between the groups. Postoperatively, the Lachman and pivot-shift test results were better in the DB group (P = .024 and P < .0001, respectively). KT measurements were better in the DB group (mean, 1.4 mm v 2.7 mm; P = .0023). The Tegner score was also better in the DB group (P = .033). There were no significant differences in range of motion, muscle strength, Lysholm score, subjective rating scale, graft retear, and secondary meniscal tear. CONCLUSIONS In ACL reconstruction using the transtibial approach, DB reconstruction was significantly better than SB reconstruction regarding anterior and rotational stability during the 3- to 12-year follow-up. The results of KT measurements and the Lachman and pivot-shift tests were significantly better in the DB group, whereas there was no difference in the anterior drawer test results. The Tegner score was also better in the DB group; however, there were no differences in the other subjective findings. LEVEL OF EVIDENCE Level II, lesser-quality prospective randomized trial.

Arthroscopic Centralization of an Extruded Lateral Meniscus

Extrusion of the lateral meniscus has been reported after posterior root tear or radial tear, partial meniscectomy, and meniscoplasty of discoid meniscus. It has also been shown to be associated with the development of osteoarthritis. This technical note describes a new arthroscopic technique to centralize and stabilize the mid body of the lateral meniscus to restore and maintain the lateral meniscus function by repairing/preventing extrusion of the meniscus. A JuggerKnot Soft Anchor (Biomet, Warsaw, IN), loaded with a MaxBraid suture (Biomet), was placed on the lateral edge of the lateral tibial plateau, just anterior to the popliteal hiatus, through a midlateral portal. A Micro Suture Lasso Small Curve with Nitinol Wire Loop (Arthrex, Naples, FL) was used to pass 2 limbs of the MaxBraid suture through the meniscus at the margin between the meniscus and the capsule. Another anchor was inserted on the lateral edge of the lateral tibial plateau, 1 cm anterior to the first anchor, and the same procedure was repeated. The sutures were then tied by use of a self-locking sliding knot, achieving centralization and secure stabilization of the lateral meniscus.

Effect of Posterolateral Bundle Graft Fixation Angles on Graft Tension Curves and Load Sharing in Double-Bundle Anterior Cruciate Ligament Reconstruction Using a Transtibial Drilling Technique

PURPOSE To evaluate the effect of posterolateral bundle (PLB) graft fixation angles on graft tension curves and load sharing between the anteromedial bundle (AMB) and the PLB in double-bundle anterior cruciate ligament (ACL) reconstruction. METHODS Twenty-four patients who underwent double-bundle ACL reconstruction were included in this study. AMB and PLB were provisionally fixed to a graft tensioning system during surgery. The graft fixation settings were as follows: (1) AMB at 20° and PLB at 0° (A20P0), (2) AMB at 20° and PLB at 20° (A20P20), and (3) AMB at 20° and PLB at 45° (A20P45). Bundle tension was recorded during knee flexion-extension and in response to anterior or rotatory loads. A pivot-shift test, as well as factors affecting the residual pivot-shift, was also evaluated. RESULTS A20P45 created reciprocal tension curves and load sharing, in which the tension in both bundles was equivalent during flexion-extension and during each loading test at 30°. In A20P0, the tension of the AMB was constantly higher than that of the PLB. Seven patients showed grade 1 pivot-shift phenomenon in A20P0, whereas no patient showed a positive pivot-shift at other settings. Larger tension reduction of the PLB between 0° and 30° and smaller load sharing of the PLB were significant factors affecting residual pivot-shift. CONCLUSIONS In double-bundle ACL reconstruction, fixation of the AMB at 20° and the PLB at 45° created reciprocal tension curves and load sharing between the bundles. Fixation of the AMB at 20° and the PLB at 0° led to insufficient tension in the PLB, resulting in a residual pivot-shift phenomenon in 7 of 24 patients. LEVEL OF EVIDENCE Level IV, therapeutic case series.

Effect of Initial Graft Tension on Knee Stability and Graft Tension Pattern in Double-Bundle Anterior Cruciate Ligament Reconstruction

PURPOSE To determine the initial minimal tension for restoring knee stability during double-bundle anterior cruciate ligament (ACL) reconstruction in vivo. METHODS Patients who underwent primary double-bundle ACL reconstruction with an autologous semitendinosus tendon during 2012 were included. The bundles were fixed to a graft-tensioning system during surgery. Initial graft tensions were set to the following tensions per 6 mm in graft diameter: (1) 30 N, (2) 25 N, and (3) 20 N. Bundle tension was recorded during knee flexion-extension and in response to anterior or rotatory loads. In addition, anterior knee laxity was measured with the KT-1000 arthrometer (MEDmetric, San Diego, CA), and the pivot-shift test was evaluated. RESULTS Sixty patients were evaluated. The tension curves of both bundles among different initial tension settings were significantly different (P < .0001), with the tension in the 30-N setting being highest and that in the 20-N setting being lowest. The tension in both bundles showed reciprocal pattern during flexion-extension (P = .019). The tension of the posterolateral bundle graft was significantly lower than that of the anteromedial bundle graft in response to the anterior load at all settings (P = .0017, P = .0019, and P = .0021 at 30° in the 30-N, 25-N, and 20-N settings, respectively, and P < .0001 at 90° at all settings), whereas the tensions in both bundles in response to rotatory loads were equivalent. Two cases showed a grade 1 pivot shift in the 20-N setting, whereas no case showed a positive pivot shift in the other settings. KT measurements in the 30-N and 25-N settings showed no difference. CONCLUSIONS In double-bundle ACL reconstruction, initial tension could be set as low as 25 N; however, initial tension of 20 N is not recommended because it might result in residual pivot shift in some cases, although the pivot-shift difference was not significant. LEVEL OF EVIDENCE Level IV, therapeutic case series.

Effect of Notchplasty in Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction

Background: The effects of notchplasty on the clinical outcome after anatomic double-bundle anterior cruciate ligament (ACL) reconstruction remain unclear. Hypothesis: Anatomic ACL reconstruction with notchplasty would result in less risk of loss of extension and would provide adequate space for better graft healing, leading to better knee stability compared with anatomic ACL reconstruction without notchplasty. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 137 patients who underwent anatomic double-bundle ACL reconstruction were included. Seventy-three patients without notchplasty were classified as the control group, and 64 patients with 2-mm notchplasty were classified as the notchplasty group. The following evaluation methods were used: loss of extension, patient’s subjective feeling of limited extension and pain at passive full extension, muscle strength, manual laxity tests, KT-1000 arthrometer measurement, patellofemoral joint findings, Tegner score, Lysholm score, subjective scores, and time to return to sports. Tearing of the reconstructed ACL and additional synovectomy were recorded. Both tibial and femoral tunnel positions were measured using 2-view radiographs: a Rosenberg and a lateral view. Results: Loss of extension was larger in the notchplasty group compared with controls (at 6 months: 0.8° vs 1.4°, P = .012; at 2 years: 0.4° vs 0.9°, P = .0053). The number of patients with a feeling of limited extension was also larger in the notchplasty group (at 6 months: 13 patients graded 1+ [somewhat limited] and 2 patients graded 2+ [very limited] vs 18 graded 1+ and 6 graded 2+, P = .015; at 2 years: 2 graded 1+ and 0 graded 2+ vs 4 graded 1+ and 5 graded 2+, P = .011). Six patients in the notchplasty group required additional synovectomy because of the prolonged loss of extension, whereas no patient in the control group required additional synovectomy. There were no differences between groups regarding muscle strength, patellofemoral findings, Lysholm score, Tegner score, subjective scores, or time to return to sports. The KT-1000 arthrometer measurement was better in the notchplasty group (1.2 vs 0.4 mm, P = .0017). However, 6 patients in the notchplasty group showed an overconstrained knee (KT-1000 measurement ≤–2 mm), compared with only 1 patient in the control group. There were no differences between groups in the other manual laxity tests or the tunnel positions. Conclusion: In anatomic double-bundle ACL reconstruction, anterior stability was improved and there were no harmful effects on patellofemoral joint findings by 2-mm notchplasty; however, notchplasty likely caused overconstrained knee, leading to a need for additional synovectomy in some patients. In contrast, anatomic double-bundle ACL reconstruction without notchplasty did not increase the incidence of loss of extension or of graft failure.

In vivo pharmacokinetics of ketoprofen after patch application in the Mexican hairless pig.

To evaluate the pharmacokinetics of topical drugs, in vitro permeation studies are performed using sacrificed pig skin or human tissues resected at surgery; however, these methods have their limitations in in vivo pharmacokinetics. This study examined the usefulness of Mexican hairless pigs for in vivo pharmacokinetic study, especially the drug concentration in the tissues. A ketoprofen patch was applied on the back of Mexican hairless pigs for 24 h, followed by sequential collection of blood specimens from 0 to 36 h (n=3). Also, the skin, subcutaneous fat, fascia and muscle from the center of the site of application were excised at 12 h after the application (n=4). Ketoprofen was first detected in the plasma at 8 h, the concentration increasing up to 24 h; the plasma concentration began to decrease after the removal of the ketoprofen patch. Ketoprofen concentrations in the tissues decreased with increasing depth of the tissues, but the values in the deep muscles, being the lowest among the tissues examined, were still higher than those in the plasma. While the data of drug concentration in human tissue are difficult to test, the Mexican hairless pig model appears to be attractive for in vivo pharmacokinetic studies of topically applied ketoprofen. Copyright

Evaluation of a behind-remnant approach for femoral tunnel creation in remnant-preserving double-bundle anterior cruciate ligament reconstruction — Comparison with a standard approach

PURPOSE To evaluate a novel approach for femoral tunnel creation, a behind-remnant approach, in remnant-preserving double-bundle anterior cruciate ligament (ACL) reconstruction through comparison with a standard approach. METHODS Sixty patients who underwent remnant-preserving double-bundle ACL reconstruction were included. Thirty patients with a standard approach were classified as the standard group, and 30 patients with a behind-remnant approach as the behind-remnant (BR) group. The anteromedial bundle (AMB) and posterolateral bundle (PLB) were provisionally fixed at 20° and 45° of flexion to a graft tensioning system during surgery. Bundle tension was recorded during knee flexion-extension and in response to anterior or rotatory loads. Femoral tunnel positions were then assessed using the quadrant method. RESULTS During flexion-extension, the BR group showed equivalent tension curves between AMB and PLB, while the standard group showed reciprocal tension curves. The tension on the PLB was lower than the AMB in response to anterior or rotatory loads in the BR group, while the AMB and PLB shared equivalent loads in the standard group. Tunnel position of the AMB in the BR group was lower and deeper, with smaller variances, than that in the standard group. Tunnel position of the PLB in the BR group was lower than that in the standard group. CONCLUSIONS In remnant-preserving double-bundle ACL reconstruction, a behind-remnant approach can be achieved without any removal of the remnant tissue, and could create a deeper and lower AMB tunnel and a lower PLB tunnel with higher reproducibility, showing equivalent tension curves between the AMB and PLB.

Effect of Posterolateral Bundle Graft Fixation Angles on Clinical Outcomes in Double-Bundle Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial

Background: In double-bundle (DB) anterior cruciate ligament (ACL) reconstruction, no consensus exists on an optimal setting for the posterolateral bundle (PLB) graft fixation angles. Hypothesis: Different PLB fixation angles would affect clinical outcomes in DB ACL reconstruction. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This study prospectively included 90 patients who underwent primary DB ACL reconstruction with an autologous semitendinosus tendon. The PLB fixation angles were randomly set as follows: 0° of flexion (P0; n = 30), 20° (P20; n = 30), and 45° (P45; n = 30). In all groups, the anteromedial bundle was fixed at 20° of flexion. The following evaluation methods were used at the preoperative period and at 3, 6, and 9 months and 1 and 2 years after the surgery: clinical examination, KT-1000 arthrometer measurement, muscle strength, Tegner score, Lysholm score, and subjective rating scale regarding patient satisfaction and sports performance levels. Graft retear, contralateral ACL tear, and additional meniscus surgery were also recorded. Results: Seventy-five patients (P0, n = 25; P20, n = 26; P45, n = 24) who were followed for 2 years were evaluated. Preoperatively, there were no differences among the groups. Postoperatively, pivot-shift test results in the P0 and P20 groups were better than those in the P45 group (P0, n = 23 graded negative and 2 graded 1+; P20, n = 23 and 2; P45, n = 15 and 7, respectively; P0 vs P45: P = .038 and P20 vs P45: P = .038). Average KT-1000 arthrometer laxity measurements were better in the P20 group than in the P45 group (P0, 0.4 mm; P20, 0.3 mm; P45, 1.3 mm; P20 vs P45: P = .048), and there were more patients with graft failure (KT-1000 measurement, ≥4 mm) in the P45 group (n = 3) than the P0 and P20 groups (each, n = 0). There were no significant differences in range of motion, other laxity tests, muscle strength, Tegner score, Lysholm score, subjective rating scale, or additional surgery. Conclusion: In DB ACL reconstruction, when the anteromedial bundle was fixed at 20° of flexion, fixation of the PLB at 45° was worse than fixation at 0° and 20° with respect to anterior and rotational stability during the 2-year follow-up. KT-1000 arthrometer measurements and pivot-shift test results were significantly worse, and there were more patients with graft failure in the P45 group. There were no differences among groups in other findings.