Kyohei Nishida

Age-Dependent Healing Potential of Anterior Cruciate Ligament Remnant-Derived Cells

Background: The anterior cruciate ligament (ACL) does not heal spontaneously after injury, and ACL patients of different ages respond differently to treatment. Although ACL-derived CD34-positive cells contribute to bone-tendon healing after ACL reconstruction, the relationship between the healing potential of ACL-derived cells and a patient’s age is unknown. Hypothesis: ACL-derived cells from young patients will have a greater effect on the maturation of bone-tendon integration in an immunodeficient rat model of ACL reconstruction compared with cells derived from older patients. Study Design: Controlled laboratory study. Methods: Sixty 10-week-old female immunodeficient rats underwent ACL reconstruction (using the autologous flexor digitorum longus tendon as a graft) followed by intracapsular administration of ACL-derived cells from patients aged 10 to 19 years (younger group) or patients aged 30 to 39 years (older group), or they were given phosphate-buffered saline (PBS; PBS group). Histologic, radiographic, and biomechanical examinations were performed 2 to 8 weeks after surgery. In addition, intrinsic and human cell–derived angiogenesis and osteogenesis were examined by immunohistochemistry. Results: In the younger group, histologic assessment demonstrated early bone-tendon healing, which induced endochondral ossification-like integration. Micro–computed tomography showed a statistically significant reduction in the area of tibial bone tunnel in the younger group (week 4, 20.0% ± 11.2% reduction; week 8, 25.7% ± 5.6% reduction) compared with the older group (week 4, 1.8% ± 3.0% reduction; week 8, 4.0% ± 5.9% reduction) and the PBS group (week 4, –0.5% ± 3.2% reduction; week 8, 3.3% ± 5.2% reduction) (week 4, P < .05; week 8, P < .01). Failure loads during tensile testing demonstrated a significantly higher ultimate load to failure in the younger group (17.52 ± 4.01 N) compared with the older (8.05 ± 2.91 N) and PBS (7.01 ± 3.16 N) groups (P < .05), and isolectin B4 and rat osteocalcin immunostaining indicated enhanced intrinsic angiogenesis and osteogenesis in the younger group. There was no statistically significant difference in the results of radiographic and biomechanical examinations between the older and PBS groups. Double immunohistochemistry for human-specific endothelial cell and osteoblast markers demonstrated a greater ability of differentiation into endothelial cells and osteoblasts in the younger group. Conclusion: ACL-derived cells from younger patients enhanced early bone-tendon healing in an immunodeficient rat model of ACL reconstruction. Clinical Relevance: Surgeons should consider a patient’s age when performing ACL reconstruction with remnant preservation or ruptured tissue incorporation, as this can predict healing ability.

Local Administration of Simvastatin Stimulates Healing of an Avascular Meniscus in a Rabbit Model of a Meniscal Defect

Background: Repair of an avascular meniscus is challenging because of its low capacity for healing. Several reports have shown that simvastatin stimulates the anabolic activity of intervertebral fibrochondrocytes, suggesting that simvastatin may be used for the treatment of meniscal defects. Purpose: To test whether the local administration of simvastatin stimulates healing of an avascular meniscus in rabbits. Study Design: Controlled laboratory study. Methods: In 30 Japanese White rabbits, a cylindrical defect (1.5-mm diameter) was introduced into the avascular zone of the anterior part of the medial meniscus in bilateral knees. Either a gelatin hydrogel (control group) or simvastatin-conjugated gelatin hydrogel (simvastatin group) was implanted into the defect. Histological assessments were performed using qualitative scoring systems, and immunohistochemical analysis was performed at 12 weeks after surgery. The occupation ratio (OR) and safranin O staining occupation ratio (SOR) were evaluated quantitatively at each time point. Stiffness of the regenerated tissue was analyzed biomechanically at 12 weeks after surgery. Rabbit meniscal cells were cultured in the presence or absence of 0.5 μM simvastatin, and then real-time polymerase chain reaction was performed to evaluate gene expression. Results: The qualitative score was significantly higher in the simvastatin group after 8 and 12 weeks (P = .031 and .035, respectively). The mean OR and SOR were also significantly higher in the simvastatin group (OR at 8 weeks: 0.396 ± 0.019 [control] vs 0.564 ± 0.123 [simvastatin], P = .008; OR at 12 weeks: 0.451 ± 0.864 [control] vs 0.864 ± 0.035 [simvastatin], P = .001; SOR at 8 weeks: 0.071 ± 0.211 [control] vs 0.487 ± 0.430 [simvastatin], P = .009; SOR at 12 weeks: 0.093 ± 0.088 [control] vs 0.821 ± 0.051 [simvastatin], P = .006). Immunohistochemical analysis showed that at 12 weeks, the reparative tissue was more strongly positive for type I collagen (COL1), type II collagen (COL2), bone morphogenetic protein 2 (BMP-2), and BMP-7 in the simvastatin group than in the control group. Biomechanical analysis showed significantly higher stiffness in the simvastatin group (2.417 ± 1.593 N/ms [control] vs 5.172 ± 1.078 N/ms [simvastatin]; P = .005). In rabbit meniscal cells, BMP-2 and BMP-7 were upregulated after 4 and 8 hours and after 7 and 14 days, whereas COL1A1 and COL2A1 were significantly upregulated by simvastatin after 7 and 14 days. Conclusion: The local administration of simvastatin promotes the regeneration of an avascular meniscus in the rabbit model of a meniscal defect. The mechanism may involve the upregulation of BMPs and the subsequent upregulation of COL1 and COL2. Clinical Relevance: This study suggests that simvastatin stimulated intrinsic healing of an avascular meniscus. The local administration of simvastatin is safe and inexpensive and seems to be a promising treatment of meniscal injuries.

The diagnostic reliability of the quantitative pivot-shift evaluation using an electromagnetic measurement system for anterior cruciate ligament deficiency was superior to those of the accelerometer and iPad image analysis

PurposeSeveral non-invasive devices have been developed to obtain quantitative assessment of the pivot-shift test in clinical setting using similar but diverse measurement parameters. However, the clinical usability of those measurements has yet to be closely investigated and compared. The purpose of this study was to compare the diagnostic accuracy of three non-invasive measurement devices for the pivot-shift test.MethodsThirty patients with unilateral anterior cruciate ligament (ACL) injury were enrolled. The pivot-shift test was performed under general anaesthesia. Three devices, an accelerometer system (KiRA), an image analysis iPad application (iPad), and electromagnetic measurement system (EMS), were used simultaneously to provide two parameters, namely tibial acceleration monitored using KiRA and EMS, and tibial translation recorded using iPad and EMS. Side-to-side differences in each parameter and correlation between the measurements were tested, and a receiver-operating characteristic (ROC) curve analysis was conducted to compare their measurement accuracy.ResultsSignificant side-to-side differences were successfully detected using any of the measurements (all p < 0.01). KiRA demonstrated moderate correlation with the EMS for tibial acceleration (r = 0.54; p < 0.01), while poor correlation was observed between iPad and the EMS for the translation (r = 0.28; p < 0.01). The ROC curve analysis demonstrated better accuracy for the detection of ACL insufficiency in the EMS than KiRA and iPad for tibial acceleration and translation, respectively.ConclusionsAlthough all three measurements were similarly capable of detecting ACL deficiency, the EMS has the advantage of comprehensive evaluation of the pivot-shift test by evaluating both tibial acceleration and translation with higher accuracy than those of KiRA and iPad. It could be suggested that any of those measurement tools might improve the clinical diagnosis of ACL insufficiency.Level of evidenceDiagnostic study of consecutive patients with a universally applied gold standard, Level Ib.

Analysis of Graft Length Change Patterns in Medial Patellofemoral Ligament Reconstruction via a Fluoroscopic Guidance Method

Background: A fluoroscopic guidance method for medial patellofemoral ligament (MPFL) reconstruction has been widely used to determine the anatomic femoral attachment site. Purpose: To examine the graft length change patterns in MPFL reconstruction with a fluoroscopic guidance method. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Forty-four knees of 42 patients who underwent MPFL reconstruction for the treatment of recurrent patellar dislocation were examined prospectively. During surgery, suture anchors were inserted into the proximal one-third and center of the patella. A guide pin for the femoral tunnel was inserted into the position reported by Schöttle et al based on the true lateral view of the knee under fluoroscopic control. Changes in graft length patterns of the proximal and center anchors were examined through 0° to 120° of knee flexion. Favorable changes in length patterns were defined as meeting 2 of 3 criteria: (1) not long during flexion (≤3 mm between 30° and 120° of flexion) and either (2) nearly isometric during flexion between 0° and 90° or (3) slightly long during maximum extension (≤3 mm). Other patterns were considered unfavorable. If the change in length pattern was unfavorable, then the pin for the femoral tunnel was moved to different positions until it was favorable. Knees were separated into the favorable group and the unfavorable group. Differences between the groups regarding radiographic parameters were assessed. Student t test or chi-square test was used for statistical analysis. Results: Of the 44 knees, 31 (70.5%) showed favorable patterns. However, 13 knees (29.5%) showed unfavorable patterns; therefore, the position of the pin was changed. The mean ± SD distance from the original position to the final position was 5.3 ± 1.1 mm distal for 7 patients and 5.2 ± 0.4 mm posterodistal for 6 patients. Technical errors, including a nontrue lateral view and the tip of the wire not being in the determined area, were found for 4 of 13 knees in the unfavorable group. There was no statistical difference in radiographic parameters between the groups. Conclusion: The graft length change pattern could be nonphysiologic at the position determined through the fluoroscopic guidance method; thus, caution may be necessary. The change in length pattern should be checked before graft fixation. If the length change pattern is unfavorable, then it is advisable to move it approximately 5 to 7 mm distally or posterodistally from the first position.

Anterolateral Capsule Injury Did Not Aggravate Rotational Laxity of the Anterior Cruciate Ligament Injured Knees Measured by Quantitative Pivot-shift Evaluation

Objectives: The anterolateral capsule (ALC) injury concomitant with the anterior cruciate ligament (ACL) injured knees has been recently focused with potential effect on the knee rotational laxity. Although some basic in-vitro studies explored the effect of the additional ALC injury, most of such studies utilized their original rotational stress test rather than the clinically-used pivot-shift test. The knee rotational instability should be examined by the clinical pivot-shift test. Some quantitative measurement devices for the pivot-shift test have been clinically available lately. The purpose of this study were to evaluate the pivot-shift test using a quantitative measurement in clinical cases and to compare them between ACL injured knees with and without the ALC injury determined by magnetic resonance imaging (MRI). Methods: Eighty-five unilateral ACL injury patients (40 male and 45 female, age 25.3±11.7 y.o.) who were scheduled to have primary ACL reconstruction were included. Just prior to the ACL reconstruction, the pivot-shift test was performed under anesthesia while making the quantitative evaluation using electromagnetic measurement system (Fig.1). The tibial acceleration (m/sec2) during the pivot-shift was calculated, and the four levels of clinical grading was also determined according to the IKDC (none, glide, clunk, and gross). The concomitant ALC injury in the ACL injured knees was diagnosed on the MRI and divided into two groups ALC injured group (ALC+) and ALC intact group (ALC-). The differences of clinical grading and quantitative measurements were tested between ALC+ and ALC- groups. P-value of <0.05 was considered as statistically significant. Results: Forty-two patients had concomitant ALC injury. 21 knees of ALC+ group were graded as glide in clinical grading, 18 knees as clunk, and 3 knees as gross in ALC+ group, meanwhile 22 knees were assessed as glide, 17 knees as clunk, and 3 knees as gross in ALC- group. There was no difference in clinical grading between ALC+ and ALC- groups (p=0.97). The tibial acceleration measurement during the pivot-shift test demonstrated no significant difference between ALC+ group (1.4±1.2 m/sec2) and ALC- group (1.6±1.3 m/sec2) (p=0.21). Conclusion: This study demonstrated that the ALC injury accompanied with the ACL injury did not have significant effect on the rotational laxity based on either clinical grading or quantitative evaluation. There was a limitation of this study that statistical power was not so strong around 0.6, but, interestingly, the rotational laxity measurements was slightly larger in the ALC intact group. The ALC injury has been advocated as a major factor to aggravate the knee rotational laxity. In this study, however, the impact of the ALC injury on the rotational laxity was not confirmed. Therefore, we should pay more attention to other common and identifiable injures such as meniscus and cartilage tear.