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Background: There is controversy regarding the efficacy of remnant tissue preservation on graft healing in anterior cruciate ligament (ACL) reconstruction., Hypothesis: The preserved remnant tissue will (1) adhere to the graft surface and undergo a remodeling process, (2) accelerate graft revascularization, (3) increase the number of graft mechanoreceptors by 4 weeks, and (4) improve anteroposterior knee laxity and structural properties of the graft by 12 weeks., Study Design: Controlled laboratory study., Methods: Forty-two sheep were randomly divided into 2 groups of 21 animals. In group I, the ACL was completely removed. In group II, the ACL was transected at the midsubstance but not debrided. ACL reconstruction was performed using a semitendinosus tendon autograft in both groups. Histological changes of the grafted tendon and the remnant tissue were evaluated at 4 and 12 weeks after surgery. Biomechanically, anterior translation and knee joint stiffness under an anterior drawer force and the structural properties of the femur-graft-tibia complex were evaluated., Results: The preserved remnant tissue was histologically distinct from the graft at 4 weeks, while the tissue partially adhered to the graft surface at 12 weeks. The ACL remnant tissue significantly accelerated revascularization in the grafted tendon at 4 weeks and significantly increased the number of mechanoreceptors at 4 and 12 weeks. In addition, remnant preservation significantly improved anterior translation (9.3 ± 2.1 mm and 5.4 ± 1.7 mm at 60° of knee flexion in groups I and II, respectively) and knee joint stiffness at 12 weeks. However, there were no significant differences in the structural properties between the 2 groups at 4 and 12 weeks after surgery., Conclusion: Preservation of the ACL remnant tissue in ACL reconstruction enhanced cell proliferation, revascularization, and regeneration of proprioceptive organs in the reconstructed ACL and reduced anterior translation. However, remnant preservation did not improve the structural properties of the graft., Clinical Relevance: These results imply that preservation of the ACL remnant tissue may improve graft healing after ACL reconstruction., (© 2016 The Author(s).)

Background: The data available from the previously reported clinical studies remains insufficient concerning the hamstring graft preparation in double-bundle anterior cruciate ligament (ACL) reconstruction., Objective: To test the hypothesis that there are no significant differences between the semitendinosus tendon alone and the semitendinosus and gracilis tendon graft fashioning techniques concerning knee stability and clinical outcome after anatomic double-bundle ACL reconstruction., Methods: A prospective study was performed on 120 patients who underwent anatomic double-bundle ACL reconstruction according to the graft fashioning technique. The authors developed the protocol to use hamstring tendon autografts. When the harvested doubled semitendinosus tendon is thicker than 6 mm, each half of the semitendinosus tendon is doubled and used for the anteromedial (AM) and posterolateral (PL) bundle grafts (Group I). On the other hand, when the harvested semitendinosus tendon is under 6 mm in thickness, the gracilis tendon is harvested additionally. The distal half of the semitendinosus and gracilis tendons are doubled and used for the AM bundle graft, and the remaining proximal half of the semitendinosus tendon is doubled and used for the PL bundle grafts (Group II). Sixty-one patients were included in Group I, and 59 patients in Group II. The two groups were compared concerning knee stability and clinical outcome 2 years after surgery., Results: The postoperative side-to-side anterior laxity averaged 1.3 mm in both groups, showing no statistical difference. There were also no significant differences between the two groups concerning the peak isokinetic torque of the quadriceps and the hamstrings, the Lysholm knee score, and the International Knee Documentation Committee evaluation., Conclusion: There were no significant differences between the two graft fashioning techniques after anatomic double-bundle ACL reconstruction concerning knee stability and postoperative outcome. The present study provided orthopedic surgeons with important information on double-bundle ACL reconstruction with hamstring tendons., Level of Evidence: Level II; prospective comparative study.

Background: Several new procedures for medial collateral ligament (MCL) reconstruction using a hamstring tendon graft have been reported in the 2000s. However, the midterm and long-term clinical outcomes of these procedures have not been reported., Hypothesis: Postoperative medial stability of the knee that underwent our MCL reconstruction may not be significantly different from that of the noninjured knee., Study Design: Case series; Level of evidence, 4., Methods: A total of 37 patients who sustained multiligamentous knee injuries underwent combined MCL and cruciate ligament reconstruction at our institution between 1994 and 2007. Thirty of the 37 patients were clinically evaluated at least 2 years after surgery. Sixteen had combined MCL and anterior cruciate ligament (ACL) reconstruction, 5 had combined MCL and posterior cruciate ligament (PCL) reconstruction, and 9 had combined MCL, ACL, and PCL reconstruction. The International Knee Documentation Committee (IKDC) evaluation form and Lysholm score were used to evaluate postoperative knee function. Anteroposterior knee laxity was examined with a KT-2000 arthrometer. To assess objective medial instability, we performed a stress radiograph examination under valgus stress with the knee at 20° of flexion., Results: At the final follow-up, 1 patient showed a loss of knee extension of more than 3°. Five patients revealed a loss of knee flexion of 6° to 15° and 2 patients of 16° to 25°. Lysholm scores averaged 94.8 points. In the IKDC evaluation, 9 patients were graded as A, 17 were graded as B, 3 were graded as C, and 1 was graded as D. In the stress radiograph examination, the mean medial joint opening was 8.5 ± 1.6 mm in the reconstructed knee and 8.0 ± 1.2 mm in the healthy opposite knee. There was no significant difference in the medial joint opening between reconstructed and intact knees., Conclusion: Medial collateral ligament reconstruction for chronic combined knee instabilities can be safely performed using hamstring tendon autografts, and the clinical outcome with a minimum 2-year follow-up was favorable with satisfactory stability.

Aim: To compare tissue concentrations of flurbiprofen resulting from topical application and oral administration according to the regulatory approved dosing guidelines., Method: Sixteen patients were included in this study. Each patient was randomly assigned to the topical application or oral administration group. In each group, a pair of tapes or a tablet, containing a total of 40 mg flurbiprofen, was administered twice at 16 and 2 h before the surgery., Results: The flurbiprofen concentration in the fat, tendon, muscle and periosteum tissues was significantly higher (P < 0.0330) after topical application (992 ng g⁻¹ [95% CI 482, 1503], 944 [95% CI 481, 1407], 492 [95% CI 248, 735], and 455 [95% CI 153, 756], respectively) than after oral administration (150 ng g⁻¹ [95% CI 84, 217], 186 [95% CI 118, 254], 82 [95% CI 49, 116],and 221 [95% CI, 135, 307], respectively)., Conclusion: Topical application is an effective method to deliver flurbiprofen to the human body, particularly to soft tissues near the body surface., (© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.)

Purpose: The aim of this study was to compare the operation time required and the clinical outcome 2 years postoperatively, after anatomic double-bundle ACL reconstructions using hamstring tendon grafts fixed with either the EndoButton-CL-BTB(®) (ECL-BTB) or the EndoButton-CL(®) (ECL)., Methods: Forty-six patients, who underwent anatomic double-bundle ACL reconstruction, were non-randomly divided into 2 groups. Patients with a combined ligament injury or complete meniscal tear were excluded from this study. In group I, an ECL was used with 23 patients. In group II, an ECL-BTB was used with the remaining 23 patients. In groups I and II, the ECL or ECL-BTB was attached to the femoral ends of the hamstring tendon autografts. In both groups, a polyester tape was connected in series with the tibial ends of the grafts. The patients were examined with standard clinical evaluations at 2 years after surgery., Results: The operation time in group II was significantly shorter than that in group I (P = 0.0459). Concerning the intra- and postoperative complications, there were no serious complications in either group. No significant differences were found between the 2 groups in terms of knee laxity measurements, the peak muscle torque of quadriceps and hamstrings, the Lysholm score and the IKDC evaluation., Conclusions: This study demonstrated that the usage of the ECL-BTB for graft preparation significantly shortens the total operation time in comparison with the ECL and that there were no significant differences in the 2-year clinical outcome and the intra- and postoperative complications between the 2 graft preparation procedures of the anatomic double-bundle ACL reconstruction. The ECL-BTB can be an alternative device for the hamstring tendon graft in double-bundle ACL reconstruction., Level of Evidence: Prospective comparative cohort study, Level II.

Background: A sheep or goat anterior cruciate ligament (ACL) reconstruction model with the semitendinosus tendon autograft has not as of yet been established., Hypothesis: The semitendinosus tendon graft may be necrotized after ACL reconstruction until 12 weeks. Structural properties of the femur-graft-tibia complex may not be restored to the normal ACL level even at 12 months after surgery., Study Design: Controlled laboratory study., Methods: Thirty-eight mature sheep were used. In each animal, the right knee underwent ACL reconstruction using the semitendinosus tendon autograft. Two of them were not tested because of pneumonia. Twenty of 36 sheep were used for biomechanical evaluations. Five randomly selected animals were sacrificed at 0, 12, 24, or 52 weeks after surgery. In each animal, both the knees were harvested, and the left knee was used to obtain the control data. The remaining 16 sheep were used for histological evaluation. Two or 3 randomly selected animals were sacrificed at 0, 2, 6, 12, 24, or 52 weeks after surgery., Results: The tendon graft was predominantly acellular at 2 weeks. Although cell infiltration increased at 6 weeks, the core portion remained necrotic even at 12 weeks. At 24 and 52 weeks, the necrotic lesion disappeared in the core portion. In each period, the anteroposterior translation of the reconstructed knee remained significantly greater than that of the control (P < .0001). At 52 weeks, the maximum load of the femur-graft-tibia complex was significantly lower than that of the femur-ACL-tibia complex (P < .0001), although there was no significant difference in the cell density, the tissue dimensions, the stiffness, and the elongation at failure between the 2 complexes., Conclusion: The sheep ACL reconstruction model showed predominant intrinsic fibroblast necrosis in the tendon autograft until 12 weeks. Although the structural properties of the femur-graft-tibia complex gradually improved, they were not completely restored to the femur-ACL-tibia complex level even at 52 weeks., Clinical Relevance: Remodeling of the semitendinosus tendon autograft after ACL reconstruction is not different from that of the bone-tendon-bone graft. This study has suggested that vigorous activity should not be permitted for patients in the early periods after ACL reconstruction using semitendinosus tendon autografts, which are necrotized and weakened after surgery.

Background: Although previous studies suggested that female patients are predisposed to increase graft laxity compared with male patients after single-bundle anterior cruciate ligament reconstruction using autogenous hamstring tendons, there have been no studies specifically examining gender-based differences in outcome after anatomic double-bundle anterior cruciate ligament reconstruction with hamstring tendon autografts., Hypotheses: (1) Female patients have significantly smaller hamstring graft diameters than do men for anatomic double-bundle anterior cruciate ligament reconstruction surgery; (2) female patients will have increased graft laxity compared with male patients after anatomic double-bundle anterior cruciate ligament reconstruction using autogenous hamstring tendons., Study Design: Cohort study; Level of evidence, 2., Methods: The consecutive 174 patients who underwent anatomic double-bundle anterior cruciate ligament reconstruction using autogenous hamstring tendons were enrolled. Of these patients, 49 women and 73 men were prospectively evaluated 2 years after surgery., Results: The diameters for anteromedial and posterolateral grafts in the female group were significantly smaller than those in the male group. On Lachman testing, 98% of the female group and 97% of the male group were rated as negative. Regarding the pivot-shift test, 80% of the female group and 85% of the male group were rated as negative. No significant differences were found between the female and male groups in these tests. The average side-to-side differences in the KT-2000 knee ligament arthrometer values were 1.3 mm in the female group and 1.4 mm in the male group; this difference between females and males was not statistically significant. The average Lysholm scores were 96.7 points in the female group and 97.2 points in the male group. Thirty-five cases (73%) in the female group and 54 cases (74%) in the male group were graded as normal on the International Knee Documentation Committee (IKDC) evaluation. There were no significant differences in Lysholm score or IKDC evaluation between the female and male groups., Conclusion: The results of assessment for ligament laxity at the 2-year postoperative evaluation in the female group were approximately identical to those of the male group after anatomic double-bundle anterior cruciate ligament reconstruction using autogenous hamstring tendons. Therefore, the present study suggests that anatomic double-bundle anterior cruciate ligament reconstruction using autogenous hamstring tendons provides satisfactory knee stability to female patients as well as male patients.

Purpose: Authors have hypothesized that the incidence and the degree of femoral tunnel enlargement after the hamstring ACL reconstruction may be significantly less in the anatomic double-bundle procedure than in single-bundle procedure. The purpose of this study is to test this hypothesis., Methods: Seventy-two patients who underwent single-bundle reconstruction (Group S) and 97 patients who underwent anatomic double-bundle reconstruction (Group D) were followed up for 2 years after surgery. The hamstring tendon grafts were used in each procedure. All of the 169 patients were examined with computed radiography, and the standard clinical evaluation methods., Results: In Group S, the incidence of femoral tunnel enlargement was 48.6 and 54.2% in the anteroposterior and lateral views. In Group D, the incidence of femoral anteromedial and posterolateral tunnel enlargement was 36.1 and 23.7%, respectively, in the anteroposterior view, and that of femoral anteromedial and posterolateral tunnel enlargement was 33.0 and 21.6%, respectively, in the lateral view. The incidence of femoral tunnel enlargement was significantly less in Group D than in Group S (P < 0.0133). Concerning the degree of the tunnel enlargement, a similar tendency with statistical significance was observed (P < 0.0001). In each group, there were no significant relationships between the degree of tunnel enlargement and each clinical measure., Conclusion: Both the incidence and the degree of femoral tunnel enlargement after anatomic double-bundle reconstruction with the hamstring tendon grafts are significantly less than those after single-bundle reconstruction with the same graft., Level of Evidence: Prospective comparative cohort study, Level II.

Purpose: The purpose of this biomechanical study was to compare the structural properties of the flexor tendon graft connected to the EndoButton CL BTB (ECL-BTB) (Smith & Nephew Endoscopy, Andover, MA), which is newly developed to fix the bone-tendon-bone graft, with those of the same graft connected to the EndoButton CL (ECL) (Smith & Nephew Endoscopy), which is commonly used as a standard fixation device., Methods: We randomly divided 40 porcine flexor digitorum profundus tendons into 4 groups. An ECL and an ECL-BTB were attached to the doubled tendon measuring 6 mm in diameter in groups I and II, respectively. An ECL and an ECL-BTB were attached to the doubled tendon measuring 7 mm in diameter in the same manner in groups III and IV, respectively. Tensile testing was performed with a tensile tester., Results: The linear stiffness of the tendon-device composite (mean +/- SD) was 131.8 +/- 18.3 N/mm, 109.7 +/- 14.9 N/mm, 132.4 +/- 20.5 N/mm, and 123.8 +/- 10.7 N/mm in groups I, II, III, and IV, respectively. The 2-way analysis of variance (ANOVA) showed a significant difference (P = .0058) between the ECL and the ECL-BTB. Concerning the maximum load and the elongation at failure of the tendon-device composite, the 2-way ANOVA showed no significant difference between the 2 fixation devices. Regarding the cross-sectional area, the 2-way ANOVA indicated no significant difference between the 2 fixation devices., Conclusions: This study has shown that the maximum load of the flexor tendon graft connected to the ECL-BTB is similar to that of the ECL whereas the stiffness of the ECL-BTB is inferior to that of the ECL., Clinical Relevance: This study has suggested that patients should not be permitted to perform vigorous activities in the early period after anterior cruciate ligament reconstruction by use of the ECL-BTB fixation technique, because of its low stiffness compared with the ECL device., (2010 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Several double-bundle anterior cruciate ligament (ACL) reconstruction procedures were reported in the 1980s and 1990s. However, no significant differences were found in the clinical results between these double-bundle procedures and single-bundle procedures because the double-bundle procedures appeared to reconstruct only the anteromedial bundle with 2 bundles. In the early 2000s, we proposed a new concept of anatomic reconstruction of the anteromedial and posterolateral bundles, in which 4 independent tunnels were created through the center of each anatomic attachment of the 2 bundles. We called it "anatomic" double-bundle ACL reconstruction. Biomechanical studies have shown that the anatomic double-bundle ACL reconstruction can restore knee stability significantly more closely to the normal level than the conventional single-bundle reconstruction. Recent intraoperative measurement studies have shown that the clinically available anatomic double-bundle procedures can reconstruct knee stability significantly better and improve knee function close to the normal level at the time immediately after surgery compared with the conventional single-bundle procedures. However, the greatest criticism of the anatomic double-bundle reconstruction is whether its clinical results are better than the results of single-bundle reconstruction. To date (January 2010), 10 prospective comparative clinical trials (Level I or II) and 1 meta-analysis have been reported comparing single-bundle and anatomic double-bundle reconstructions using hamstring tendons. In 8 of the 10 studies, the anterior and/or rotatory stability of the knee was significantly better with the anatomic double-bundle ACL reconstruction than with the conventional single-bundle reconstruction. However, 1 original trial and the meta-analysis found that there were no differences in the results between the 2 types of reconstructions. Thus the utility of the anatomic double-bundle reconstruction has not yet been established. Our review does show how much evidence exists as to the benefits of double-bundle ACL reconstruction at present.

Background: Several trials have compared the clinical results between anatomic double-bundle and single-bundle anterior cruciate ligament reconstruction procedures. However, it remains controversial whether the anatomic double-bundle procedure is superior to the single-bundle procedure., Hypothesis: The anatomic double-bundle procedure will be better than the single-bundle procedure at resisting anterior laxity, internal rotation laxity, and pivot-shift instability., Study Design: Controlled laboratory study., Methods: Eight cadaveric knees were tested in a 6 degrees of freedom rig using the following loading conditions: 90-N anterior tibialforce, 5-N.m internal and external tibial torques, and a simulated pivot-shift test. Tibiofemoral kinematics during the flexion-extension cycle were recorded with an optical tracking system for (1) intact, (2) anterior cruciate ligament-deficient knee, (3) anatomic double-bundle reconstruction, and (4) single-bundle reconstruction placed at 11 o'clock in the intercondylar notch., Results: There were significant reductions of anterior laxity of 3.5 mm at 20 degrees of flexion, internal rotational laxity of 2.5 degrees at 20 degrees of flexion, and anterior translations (2 mm) and internal rotations (5 degrees ) in the simulated pivot-shift test in the double-bundle reconstruction com-pared with the single-bundle reconstruction. There were no significant differences between the 2 procedures for external rotation laxity., Conclusion: The postoperative anterior translation and internal rotation stability after anatomic double-bundle anterior cruciate ligament reconstruction were significantly better than after single-bundle reconstruction, in both static tests and the pivot shift., Clinical Relevance: Unlike previous laboratory studies, this work used clinical arthroscopic methods for anterior cruciate ligament reconstruction, and found that the anatomic reconstruction was superior to a single graft placed at 11 o'clock.

This is the first report of an anatomic double-bundle ACL and PCL reconstruction procedure with the autogenous hamstring tendons. We prepare two pairs of the doubled tendon grafts, to which a polyester tape and an Endobutton-CL are attached using our original technique at the tibial and femoral ends, respectively. Under arthroscopic and fluoroscopic observations, two tibial tunnels for PCL reconstruction are created so that they pass through the posteromedial and anterolateral bundle attachments, respectively. Then, we create two tibial tunnels for anatomic double-bundle ACL reconstruction so that each tunnel axis is aimed at a targeted point on the femoral condyle. Using the outside-in technique, two femoral tunnels for PCL reconstruction are created so that the tunnel outlets are located at the center of the anterolateral and posteromedial bundle attachments. Then, two femoral tunnels for anatomic double-bundle ACL reconstruction are created with the trans-tibial tunnel technique. After the two grafts have been placed for PCL reconstruction, the two grafts are placed for ACL reconstruction. After all the femoral graft ends are fixed, the knee joint is reduced to the full extension position, and then, the four tibial tape portions are simultaneously fixed with the turn-buckle stapling technique.

In anterior cruciate ligament (ACL) reconstruction, slow graft maturation may result in graft failure or elongation during the postoperative rehabilitation period. Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis. The findings of recent studies suggest that VEGF application is a potential strategy to accelerate angiogenesis in the graft after ACL reconstruction. However, the biomechanical results indicate that exogenous VEGF application decreases the stiffness of the grafted tendon at least temporarily. Therefore, we should take into account this adverse effect of exogenous VEGF application on the mechanical characteristics of the grafted tendon.

The purpose of this study was to evaluate the clinical results of simultaneous arthroscopically assisted reconstruction of anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) using autogenous tendon grafts in chronic knee injuries. Nineteen patients (17 men and 2 women) with chronic multi-ligamentous injuries underwent one-stage ACL and PCL reconstruction. ACL, PCL and medial collateral ligament were reconstructed in seven knees, and ACL, PCL and posterolateral structure were reconstructed in two knees. Function of the operated knee was evaluated according to the International Knee Documentation Committee (IKDC) and Lysholm scale. Anterior and posterior knee laxity was examined with a KT-2000 arthrometer. Eighteen of 19 patients were able to return for follow-up and were evaluated objectively and subjectively. The average patient age at surgery was 30.5 years, and the average postoperative follow-up was 3.5 years. No patients showed loss of knee extension more than 5 degrees , while three patients revealed loss of knee flexion more than 16 degrees . The mean postoperative total anterior-posterior side-to-side difference was 1.9 +/- 1.5 mm at 20 degrees and 2.1 +/- 1.9 mm at 70 degrees . The average of the Lysholm score was 95.1 points at the final follow-up. At the IKDC evaluation, three patients were grade A, 11 were grade B, 3 were grade C, and 1 patient was grade D. The results showed the effectiveness and safety of one-stage reconstruction of combined ligamentous injuries of the knee that can adequately restore satisfactory stability.

The present study was conducted to test a hypothesis that the ex vivo supplementation of TGF-beta1 into medium will significantly improve the mechanical properties of the fibrous tissue regenerated in the patellar tendon defect after transplantation of cultured autologous synovium-derived fibroblasts. Thirty rabbits were divided into the following three groups. In Group A, we applied phosphate buffered saline of 0.1 ml to the defect created in the patellar tendon. In Group B, we transplanted autologous fibroblasts, which had been cultured into the tendon defect. In Group C, we transplanted autologous fibroblasts, which had been cultured with supplementation of TGF-beta1, into the tendon defect. Animals were killed at 6 weeks, and the regenerated tissue was examined for biomechanics and histology. The tangent modulus and the tensile strength of Group C were significantly higher than that of Group B, while the tensile strength of Group C was significantly lower than that of Group A. Histologically, vascular formation was abundantly found in the regenerated tissue of Groups B and C as compared to the regenerated tissues in Group A. The present study showed that transplantation of cultured autologous synovium-derived fibroblasts enhanced vascular formation in the fibrous tissue regenerated in the patellar tendon defect, while cell transplantation deteriorated the mechanical properties of the regenerated fibrous tissue. However, the ex vivo supplementation of TGF-beta1 into the medium significantly decreased mechanical deterioration of the fibrous tissue regenerated in the tendon defect after transplantation of cultured autologous synovium-derived fibroblasts.

Purpose: The purposes of this study were to determine the relation between the graft tension and the knee flexion angle in the anteromedial (AM) and posterolateral (PL) bundles of a clinically simulated anatomic double-bundle anterior cruciate ligament (ACL) reconstruction procedure and to clarify the effect of initial tension on the tension-versus-flexion curve of each graft, as well as the effect of internal rotation of the tibia on the tension of the 2 grafts., Methods: During ACL reconstruction in 30 patients, 2 suture anchors with a No. 1 polyester suture were firmly screwed into the center of the anatomic attachment of the AM and PL bundles on the femur, respectively, and each graft tension was measured with a strain gauge-type tensiometer attached at the end of the suture under 2 conditions of initial tension., Results: The averaged tension-versus-flexion curves were significantly different between the AM and PL grafts under each initial tension condition (P < .0001). The initial tension applied at 30 degrees of knee flexion significantly affected the absolute values of each graft tension at each knee flexion angle (P < .0001) but did not significantly affect the tension-versus-flexion curve pattern of each graft. The maximal internal rotation of the tibia significantly increased the tension on both the AM and PL grafts at knee flexion angles of less than 60 degrees under each initial tension condition (P < .0001)., Conclusions: The tension-versus-flexion curves of the 2 sutures, which mimicked the AM and PL grafts reconstructed clinically with the anatomic double-bundle ACL reconstruction procedure, were significantly different in the tension values. Differences in initial tension applied to the 2 grafts significantly affected the absolute values of each graft tension at each knee flexion angle but did not significantly affect the tension-versus-flexion curve pattern. The maximal internal rotation of the tibia significantly increased the tension on both the AM and PL suture grafts at knee flexion angles of less than 60 degrees ., Level of Evidence: Level I, testing of previously developed diagnostic criteria in series of consecutive patients with universally applied gold standard.

Background: After ligament reconstruction, mechanical deterioration of the grafted tendon is observed with revascularization and cellular infiltration. However, the effect of cellular infiltration on the mechanical properties of the tendon matrix has not been fully understood., Methods: Cultured fibroblasts derived from the rabbit patellar tendon were seeded around an acellular rabbit patellar tendon that had undergone freeze-thaw treatment. At time-0, 3, and 6 weeks after seeding the cells, we evaluated cellular distribution in the tendon using a confocal laser microscope and the mechanical evaluations of the tendon fascicles and the tendon bundles., Findings: The confocal laser microscopic analysis showed fibroblast infiltration ex vivo into the acellular tendon matrix. We could not find significant effects of the cellular infiltration on the tangent modulus of the tendon bundle, although the ex vivo cellular infiltration significantly reduced the modulus of the tendon fascicle. In addition, the tangent modulus of the incubated tendon without fibroblasts significantly decreased with time, particularly in the tendon bundle levels., Interpretation: The findings of this study suggested that the effects of ex vivo cellular infiltration on the mechanical properties of the tendon bundles are relatively small, compared with its striking effect on the tendon fascicles.

Background: Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis., Hypothesis: An application of VEGF may enhance angiogenesis in the grafted tendon in anterior cruciate ligament (ACL) reconstruction, and the application may affect mechanical characteristics of the ACL graft., Study Design: Controlled laboratory study., Methods: Eighteen sheep were divided into groups I and II. In group I, the harvested semitendinosus tendon was soaked in VEGF solution, and the right knee then underwent ACL reconstruction using this tendon. In group II, the right knee underwent identical procedures to those of group I except that the harvested tendon was soaked in phosphate-buffered saline. All animals were sacrificed 12 weeks after ACL reconstruction., Results: Histologic findings showed that newly formed vessels and infiltrative fibroblasts were more abundant in group I than in group II. The anterior-posterior translation of the knee during an anterior-posterior force of +/- 100 N was significantly larger in group I than in group II by 2.58 mm (95% confidence interval, -1.76 mm to 1.76 mm) (P = .002). The linear stiffness of the femur-graft-tibia complex in group I was significantly lower than that in group II by 41.5 N/mm (95% confidence interval, -32.2 N/mm to 32.2 N/mm) (P = .017)., Conclusion: This study has revealed that VEGF as administered in this study promotes angiogenesis in the ACL graft and significantly reduces the stiffness of the ACL graft with increased knee laxity at 12 weeks after ACL reconstruction., Clinical Relevance: Exogenous VEGF application for ACL reconstruction can induce an increase in knee laxity and a decrease in the stiffness of the grafted tendon at least temporarily after ACL reconstruction. These potentially negative mechanical effects need to be taken into account when considering clinical use of VEGF.

The current study was performed to understand the relationship between graft length placed within the bone tunnel and intraosseous graft healing in anterior cruciate ligament (ACL) reconstruction. Twenty-four adult beagle dogs were divided into two groups of 12 animals each. In each animal, ACL reconstruction using a 4-mm diameter autogenous flexor tendon graft was done in the left knee. In groups I and II, the graft having a length of 15 and 5 mm, respectively, was placed within the tibial tunnel. The proximal end of the graft was placed through the over-the-top route in all animals. In each group, five animals were sacrificed immediately after surgery, and the remaining seven were sacrificed at 6 weeks postoperatively. Biomechanical and histologic evaluations were performed. In pull out testing, the ultimate failure load and the linear stiffness of the graft-tibia complex harvested at 6 weeks were significantly greater than those harvested at the time-zero period. There were no significant differences in those parameters between groups I and II at 6 weeks. In each group, the perpendicular collagen fibers connecting the tendon to the bone tunnel wall were observed only in the narrow area located close to the intra-articular tunnel outlet. In conclusion, excessively long placement of the flexor graft within the bone tunnel does not result in an additional increase of anchoring strength and stiffness of the graft in ACL reconstruction.

Purpose: To compare the clinical outcome of anatomic double-bundle anterior cruciate ligament (ACL) reconstruction with that of nonanatomic single- and double-bundle reconstructions., Type of Study: Prospective comparative cohort study., Methods: Seventy-two patients with unilateral ACL-deficient knees were randomly divided into 3 groups. Concerning all background factors, there were no statistical differences among the 3 groups. In group S (n = 24), single-bundle ACL reconstruction was performed. In group N-AD (n = 24), nonanatomic double-bundle reconstruction was carried out. In group AD (n = 24), anatomic double-bundle reconstruction was performed. One surgeon performed all operations using hamstring tendon autografts. Each patient underwent clinical examinations, before surgery and at 2 years., Results: No intraoperative and postoperative complications were experienced in each group. There were no significant differences concerning the time for operation among the 3 groups. The statistical analysis showed a significant difference in the postoperative side-to-side anterior laxity among the 3 groups (P = .006). The laxity was significantly less (P = .002) in group AD (1.1 mm) than in group S (2.8 mm), while there was no significant difference (P = .072) between groups AD and N-AD. Concerning the pivot-shift test, group AD was significantly superior to group S (P = .025). There were no significant differences in the range of knee motion, the muscle torque, and the International Knee Documentation Committee evaluation., Conclusions: On the basis of the KT-2000 measurement, the side-to-side anterior laxity of our anatomic double-bundle ACL reconstruction was significantly better than that of the single-bundle reconstruction with the hamstring tendon graft, although there were no significant differences in the other clinical measures among any of the 3 procedures., Level of Evidence: Level II.

We compared the biological characteristics of extrinsic fibroblasts infiltrating the patellar tendon with those of normal, intrinsic fibroblasts in the normal tendon in vitro. Infiltrative fibroblasts were isolated from the patellar tendons of rabbits six weeks after an in situ freeze-thaw treatment which killed the intrinsic fibroblasts. These intrinsic cells were also isolated from the patellar tendons of rabbits which had not been so treated. Proliferation and invasive migration into the patellar tendon was significantly slower for infiltrative fibroblasts than for normal tendon fibroblasts. Flow-cytometric analysis indicated that expression of alpha5beta1 integrin at the cell surface was significantly lower in infiltrative fibroblasts than in normal tendon fibroblasts. The findings suggest that cellular proliferation and invasive migration of fibroblasts into the patellar tendon after necrosis are inferior to those of the normal fibroblasts. The inferior intrinsic properties of infiltrative fibroblasts may contribute to a slow remodelling process in the grafted tendon after ligament reconstruction.

Purpose: To clarify the effect of transforming growth factor (TGF)-beta1 on intraosseous healing of the flexor tendon autograft in anterior cruciate ligament (ACL) replacement., Type of Study: Randomized trial in animals., Methods: Twenty-one adult beagle dogs were divided into 3 groups of 7 animals each. The ACL was replaced with a flexor tendon autograft in the left knee. The distal end of each graft was placed in the tibial bone tunnel. In group I, no treatment was applied in the bone tunnel. In group II, 0.1 mL of fibrin sealant was applied in the tendon-bone gap. In group III, 2 ng of TGF-beta1 mixed with 0.1 mL fibrin sealant was applied in the gap. Each animal was euthanized 3 weeks after surgery., Results: In pullout testing, the ultimate load of the graft-tibia complex of group III (188.2 +/- 51.4 N) was significantly greater than that of groups I (86.7 +/- 36.5 N) and II (99.0 +/- 18.7 N) (P = .005). There were no significant differences between groups I and II. Histologically, the perpendicular collagen fibers connecting the tendon to the bone were narrowly seen in groups I and II, whereas the fibers were richly generated in group III., Conclusions: In ACL replacement using flexor tendon autograft, exogenous administration of TGF-beta1 significantly increased the bonding strength of the graft to the tunnel wall at 3 weeks, although the long-term effects are unknown., Clinical Relevance: Intraosseous healing of the flexor tendon autograft in ACL reconstruction may be enhanced by a use of some growth factors involving TGF-beta1 in the future.

Purpose: Posterior cruciate ligament (PCL) reconstruction procedures have not been thoroughly evaluated under cyclic loading conditions. We tested the hypothesis that PCL reconstruction with a quadrupled flexor-tendon graft and fixation using tapes and staples is biomechanically superior to that fixed with sutures, a button, and a post-screw, and is comparable to reconstruction with a bone--patellar tendon--bone (BPTB) graft., Study Design: In vitro biomechanical study., Methods: A total of 45 porcine knees were used. The quadrupled flexor-tendon graft was fixed using the suture/button/post-screw procedure in 15 knees, and with the tape/staples procedure in another 15 knees. The remaining 15 knees underwent reconstruction with a BPTB graft secured with screws as the standard control. In each group of 15 knees, 5 underwent tensile testing without cyclic loading, and 10 underwent the same tensile test after 5,000 cycles of load-controlled or displacement-controlled loading., Results: Each type of cyclic loading produced larger biomechanical changes in the knees fixed with the suture/button/post-screw procedure than in the knees secured using the other 2 procedures., Conclusions: In PCL reconstruction, the tape/staples procedure is biomechanically superior to the suture/button/post-screw procedure, and is comparable to the BPTB/screws procedure with regard to the ultimate failure load. Neither of the procedures using the quadrupled flexor-tendon graft was comparable to the BPTB graft in linear stiffness and the initial displacement after load-controlled cyclic testing., Clinical Relevance: The biomechanical behaviors of PCL-reconstructed knees are significantly different, depending on surgical techniques.

To test the hypothesis that stress deprivation induces over-expression of cytokines in the patellar tendon, 40 rats were divided into the following two groups. In the stress-shielded group, we slackened the patellar tendon in the right knee by drawing the patella toward the tibial tubercle with flexible wires. In the control group, we performed a sham operation on the right knee. Animals were killed at 2 or 6 weeks for immunohistological evaluation and biomechanical examination. For IL-1beta, TNF-alpha and TGF-beta, the ratio of positively stained specimens to total specimens was significantly higher in the stress-shielded tendons than in the control tendons. The elastic modulus of the stress-shielded tendon was significantly lower than that of the control tendon, while the cross-sectional area of the stress-shielded tendon was significantly greater than that of the control tendon. Therefore, the present study indicated that stress shielding induced the over-expression of IL-1beta, TNF-alpha and TGF-beta in patellar tendon fibroblasts with mechanical deterioration of the tendon. Regarding clinical relevance, the present study suggests a possible application of an anti-IL-1beta or anti-TNF-alpha strategy for reducing the mechanical deterioration of tendons and ligaments in response to stress deprivation, although this study did not directly show that over-expression of IL-1beta or TNF-alpha in response to stress deprivation was the causation of mechanical deterioration of tendons.

Purpose: To develop and evaluate an anatomic reconstruction procedure of the posterolateral and anteromedial bundles of the anterior cruciate ligament (ACL)., Type of Study: Anatomic study and case series., Methods: The femoral attachment of the anteromedial and posterolateral bundles of the ACL was anatomically analyzed with 5 cadaveric knees. Using another 3 cadaveric knees, anatomic reconstruction of the posterolateral and anteromedial bundles was performed with the transtibial technique, and tunnel positioning and graft function in a range of knee motion was observed. Based on this anatomic study, an anatomic reconstruction procedure of the anteromedial and posterolateral bundles was developed using hamstring tendon autografts. This procedure was carried out in 57 consecutive patients with an ACL-deficient knee. The patients were followed-up for a minimum of 24 months., Results: We developed the arthroscopically assisted anatomic reconstruction procedure of the posterolateral and anteromedial bundles, involving a new method of creating the tibial and femoral tunnels for the posterolateral bundle. To visualize the femoral attachment of the posterolateral bundle, the medial infrapatellar portal was more useful than the lateral portal. In clinical results, the side-to-side difference of anterior laxity averaged 1.0 mm with a standard deviation of 0.9., Conclusions: The anatomic reconstruction of the anteromedial and posterolateral bundles using hamstring tendon autografts is clinically practical in the treatment for the ACL-deficient knee., Level of Evidence: Level IV.

Manganese superoxide dismutase (Mn-SOD) is a key antioxidant enzyme that prevents reactive oxygen species (ROS) damage to biological tissues. Although Mn-SOD has been investigated for a variety of cells, little is known about its expression in the tendon, particularly in the stress-deprived condition. The present study demonstrated that Mn-SOD is excessively expressed in the cultured fibroblasts derived from the stress-deprived patellar tendon in the rat using subtractive hybridization analysis. In addition, we confirmed that the expression of Mn-SOD is up-regulated in the stress-deprived patellar tendon in vivo at both the mRNA and protein levels. These results suggest that Mn-SOD may play a role in regulating ROS and matrix degradation involving mechanical deterioration of the stress-deprived tendon tissue.

Background: No studies have dealt with the effect of growth factors on the free tendon autograft in anterior cruciate ligament reconstruction., Hypothesis: Application of exogenous transforming growth factor-beta and epidermal growth factor may affect the structural properties and histology of the bone-patellar tendon-bone autograft after anterior cruciate ligament reconstruction., Study Design: Controlled laboratory study., Methods: Twenty dogs underwent anterior cruciate ligament reconstruction with the autogenous bone-patellar tendon-bone graft in bilateral knees. In 10 animals, 12 ng transforming growth factor-beta and 300 ng epidermal growth factor mixed with fibrin sealant of 0.6 mL were applied to the left knee. In the remaining 10 dogs, fibrin sealant alone was applied to the left knee. No additional treatments were applied to the right knee., Results: The growth factor application increased the stiffness and maximum failure load of the femur-graft-tibia complex at 12 weeks (P =.016 and P =.012, respectively); the sham treatment did not significantly affect them. Histologically, most of the cells in the grafts treated with growth factors had spindle-shaped nuclei; cells in the other grafts had round-shaped nuclei., Conclusions: Application of transforming growth factor-beta and epidermal growth factor improves the structural properties of the autograft after anterior cruciate ligament reconstruction in the canine model., Clinical Relevance: Application of growth factors is a possible strategy to prevent graft deterioration in anterior cruciate ligament reconstruction.

The purpose of this study was to assess the effects of stress shielding on the microstructure and ultrastructure of the patellar tendon using 40 mature female Japanese white rabbits. The patellar tendon was completely released from stress by drawing the patella toward the tibial tubercle with a stainless steel wire installed between them. Microstructurally, stress shielding for 3 and 6 weeks increased the number of cells approximately fivefold, to that of the control tendon. Collagen bundles were less well oriented in the stress-shielded tendon than in the control. Ultrastructurally, small collagen fibrils with a diameter of less than 90 nm increased in the stress-shielded tendon. The median collagen fibril diameter in 6-week stress-shielded tendon was significantly smaller ( P << 0.05) than in the control tendon (58.8% of control). The ratio of the total area of collagen fibrils to the whole visualized area in the stress-shielded patellar tendon was significantly smaller at 3 and 6 weeks than that in the control. This study demonstrated that complete stress shielding significantly affects the microstructure and ultrastructure of the patellar tendon

Objective: To clarify the effect of complete stress deprivation on the mechanical properties of the in situ frozen-thawed semitendinosus tendon, an idealized autograft model., Design: Ninety-six rabbits were divided into three groups. In the frozen group (n=36), we applied the freeze-thaw treatment to the semitendinosus tendon to necrotize fibroblasts in the tendon. In the frozen and stress-shielded group (n=30), after we applied the same freeze-thaw treatment to the tendon, we completely released the tendon from stress. In the sham group (n=30), a sham operation was applied. In each group, 6 rabbits were sacrificed at 0 (only in the frozen group), 1, 2, 3, 6 and 12 weeks after surgery., Background: Previous studies have not clarified remodeling of the semitendinosus autograft in ligament reconstruction or its idealized model., Methods: The tendon was frozen with liquid nitrogen. The tendon was released from stress with the originally developed technique using a polyester tape. In each period, 5 out of the 6 rabbits were evaluated with tensile testing, and the remaining rabbit was histologically observed., Results: Complete stress shielding significantly increased the cross-sectional area of the frozen-thawed tendon at 1 and 2 weeks, while it significantly inhibited the increase of the area due to the freeze-thaw treatment at 3 and 6 weeks. Complete stress shielding significantly reduced material properties of the frozen-thawed tendon after 2 weeks., Conclusions: The frozen-thawed semitendinosus tendon has unique remodeling characteristics under a stress-shielded condition, which were not the same as those of the frozen-thawed patellar tendon., Relevance: Remodeling of the semitendinosus tendon autograft under stress-shielded conditions may be different from that of the patellar tendon autograft.

Background: Graft-to-tunnel healing is a significant factor in anterior cruciate ligament reconstruction, but there have been few studies on the effect of graft-tunnel diameter disparity on intraosseous healing of the flexor tendon graft., Hypothesis: Graft-tunnel diameter disparity of 2 mm has no effect on the pull-out strength of the graft from the bone tunnel., Study Design: Controlled laboratory study., Methods: Forty-two beagle dogs were divided into three groups. In each animal, reconstruction was performed in the left knee by using a 4-mm diameter autogenous flexor tendon for groups 1 and 2 and by using a 4-mm wide bone-patellar tendon-bone graft in group 3. A 4-mm diameter tunnel was drilled in the tibia of groups 1 and 3 and a 6-mm diameter tunnel, in group 2. In each group, seven animals were sacrificed at 3 and 6 weeks., Results: The perpendicular fibers connecting the graft to the bone were generated in groups 1 and 2, and the number appeared to be higher in group 2, where the space was greater. There was no significant difference in the ultimate failure load between groups 1 and 2 at each period., Conclusion: Graft-tunnel diameter disparity of up to 2 mm may not adversely affect intraosseous healing of the flexor tendon graft., Clinical Relevance: Surgeons need not be overly concerned about minor graft-tunnel diameter disparities.

Purpose: The purpose of this study was to compare intraosseous graft healing between the doubled flexor tendon (FT) graft and the bone-patellar tendon-bone (BPTB) graft in anterior cruciate ligament (ACL) reconstruction., Type of Study: Randomized trial., Methods: A biomechanical and histologic study was conducted with 24 adult beagle dogs. Bilateral ACL reconstructions were performed in each animal. Autogenous doubled FT and BPTB grafts were used for the left and right knees, respectively. Each end of the 2 grafts was tethered with a polyester suture to a screw post with a washer. The animals were then allowed unrestricted activities in their cages. Eight animals were killed at 3, 6, and 12 weeks, respectively., Results: Histologically, the FT graft was anchored to the tunnel wall with newly formed collagen fibers resembling Sharpey's fibers by 12 weeks. These fibers were more abundant in the anterior (ventral) gap than in the posterior (dorsal) gap. In the BPTB graft, the bone plug was anchored with newly formed bone at 3 weeks, although osteocytes in the plug trabeculae were necrotic for 12 weeks. Degeneration of the tendon-bone junction in the plug progressed at 6 weeks. Tensile testing showed that the weakest site was different not only between the 2 grafts but also between the observation periods. In the FT graft, the weakest site was the graft-wall interface at 3 weeks and the intraosseously grafted tendon at 6 weeks. In the BPTB graft, the weakest site was the graft-wall interface at 3 weeks and the proximal site in the bone plug at 6 weeks. The ultimate failure load of the FT graft was significantly inferior (45.8%) to that of the BPTB graft at 3 weeks (P =.021). At 6 weeks, the load of the FT graft was 85% that of the BPTB graft without a significant difference (P =.395)., Conclusions: As to the clinical relevance, the fixation device chosen for soft-tissue fixation appears to be more important than comparing it to the BPTB graft, although this has yet to be conclusively proven.

This study was performed to determine the contribution of extrinsic cell infiltration and revascularization into the patellar tendon in alteration of the mechanical properties of the patellar tendon after intrinsic fibroblast necrosis using 77 rabbits. In Group I, after the patellar tendon underwent the in situ freeze-thaw treatment, a wrapping treatment was performed to inhibit any extrinsic cell infiltration into the tendon. In Group II, the patellar tendon underwent the freeze-thaw treatment without any of the wrapping treatment. In Group III, the patellar tendon underwent the same wrapping treatment but without any freeze-thaw treatment. The cell culture study demonstrated that the in situ freeze-thaw treatment killed from 97 to 100 percent of the cells in the patellar tendon. Histologically, no cells were found in the midsubstance of the patellar tendon in Group I at 1, 3, and 6 weeks. In Group II, a number of cells and some vessels were found scattered in the tendon at 3 and 6 weeks. Mechanically, the elastic modulus and the tensile strength of the patellar tendon of Group II were significantly lower than those of Groups I and III at 3 and 6 weeks. These facts suggest that extrinsic cell infiltration and revascularization from the surrounding tissues accelerate the deterioration of the mechanical properties of the patellar tendon matrix after intrinsic fibroblast necrosis.

Objective: To biomechanically evaluate interference screw fixation of the doubled flexor tendon graft in anterior cruciate ligament reconstruction using cyclic elongation., Design: Biomechanical properties of the interference screw fixation of the flexor tendons were compared with those of three standard fixation techniques which had been commonly performed in anterior cruciate ligament reconstruction., Background: The interference screw fixation of the flexor tendon graft has attracted notice because of various possible advantages., Methods: Forty fresh frozen porcine hind limbs were divided into four groups of ten knees each. Anterior cruciate ligament reconstruction was carried out in each group using one of four different procedures. For each group, five femur-graft-tibia complexes underwent submaximal cyclic elongation of 5000 cycles after initial tension of 80 N was applied. Then, tensile testing was performed in the same manner for the complex with a tensile tester. The remaining five complexes were examined in the same tensile test without applying any cyclic elongation., Results: The initial tension was more rapidly relaxed by cyclic elongation in the flexor tendon graft fixed with interference screws than in the bone-patellar tendon-bone graft fixed with two standard techniques. After cyclic elongation, while the ultimate failure load of the former was significantly lower than the latter, the linear stiffness of the former was significantly higher than the flexor tendon graft fixed with sutures., Conclusion: The present study has clarified that the advantage of the interference fixation for the doubled flexor tendon graft is the high linear stiffness of the FGT complex, and the disadvantage of this screw is the low ultimate failure load of the FGT complex., Relevance: The present study has suggested that vigorous activities should not be permitted for the patients in the early period after anterior cruciate ligament reconstruction using this fixation technique, because of its low ultimate failure load.

An experimental study was conducted to compare the biomechanical characteristics of six currently available anterior cruciate ligament (ACL) reconstruction procedures with flexor digitorum profundus tendons. Forty porcine knees were divided into eight groups, of 5 knees each. In groups A, B, C, and D, the flexor tendon graft was fixed with sutures and an Endobutton, with 20-mm-wide polyester tapes and staples, with 10-mm-wide polyester tapes and an Endobutton, and with bone plugs and interference screws, respectively. In group E, the graft was fixed using a combined procedure of those in groups B and D. In group F, the graft was directly fixed with interference screws. In groups G and H, the bone-patellar tendon-bone graft was fixed with interference screws, and sutures, respectively. Each femur-graft-tibia complex specimen was tested with a tensile tester by anteriorly translating the tibia until failure. This study demonstrated that the biomechanical properties of the femur-graft-tibia complex reconstructed with the flexor tendon graft were significantly affected by synthetic fixation devices. Regarding the average maximal load of the groups with the flexor tendon graft, group B had the highest (893 N) and group C had the second highest (770 N). Groups E and A were in the third rank. Group F had the second lowest (312 N), and Group D had the lowest (230 N). The maximal load of group B was significantly greater (P < 0.01) than that of group G (656 N) with the bone-patellar tendon-bone grafts. As to clinical relevance, this study indicated that the flexor tendon graft can be an alternative substitute for the bone-patellar tendon-bone graft for ACL reconstruction, if we understand the biomechanical characteristics of each reconstruction procedure.

Effects of the overstressing induced by the harvest of grafts from the patellar tendon on the mechanical properties and morphometry of remaining tendon were studied using a rabbit model. The width of the patellar tendon was reduced by one-fourth or one-half equally removing the medial and lateral portions; by this surgery, the cross-sectional area was decreased by 25 or 50 percent from the original area. After all the rabbits were allowed unrestricted activities in cages for 3 to 12 weeks, their patellar tendons were harvested for mechanical and histological studies. The one-fourth removal induced no significant changes in the mechanical properties, but significantly increased the cross-sectional area. In the case of one-half removal, tensile strength and tangent modulus did not change in some tendons, although the cross-sectional area increased significantly. In the other central half tendons, mechanical strength decreased markedly, while the cross-sectional area increased; hypercellular areas and breakage of collagen bundles were observed in these tendons. These results indicate that the patellar tendon has an ability of functionally adapting to overstressing by changing the cross-sectional area, while keeping the mechanical properties unchanged, if the extent of overstressing is less than 30 percent.

Objective: The purpose of this paper is to review changes in the biomechanical properties of tendons and ligaments from joint disuse., Method: We have reviewed 37 experimental studies on joint disuse, which have been carried out with various models of disuse and with various animals., Results: Immobilization of joints has most commonly been used as a model of disuse. Immobilization of the joint deteriorates the mechanical properties of tendons and ligaments, and reduces their cross-sectional area, although there are some differences in the speed of deterioration among tissues. Remobilization returns the mechanical properties once reduced by immobilization to nearly normal quickly, although the structural properties of the bone-ligament-bone complex continue to lag behind those of the controls. Stress deprivation has been regarded as an essential causative factor in joint disuse. Even if joint motion is allowed, stress deprivation rapidly reduces the mechanical properties of the tendon and ligament tissues, and increases the cross-sectional area of them. These effects appear time- and dose-dependent. Restressing increases the mechanical properties once reduced by stress deprivation, although it takes much time to completely recover them. The reduction of the ultimate stress may be explained by the reduction of the total area of collagen fibrils in tendon cross-section and the increase of thin and immature fibrils.

The purpose of this paper is to review scientific evidence that graft tension affects remodelling of the autograft in ligament reconstruction. The in situ freezing model of the patellar tendon, an ideal patellar tendon autograft model, demonstrated that subsequent cellular proliferation following fibroblast necrosis reduces the mechanical properties of the autograft. Stress shielding enhances reduction of the strength in the once-frozen patellar tendon. The strength of the patellar tendon also changes depending on the degree of stress shielding. Transmission electron micrographs revealed that the number of small-diameter fibrils decreases in the stress-shielded tendons compared with non-stress-shielded tendons after in situ freezing. Restressing essentially restores the mechanical properties of patellar tendon autografts even if the strength has been much reduced by complete stress shielding. The effects of restressing may depend on the period of stress shielding applied before restressing. Unphysiologically high tension significantly reduces the mechanical properties of the in situ frozen anterior cruciate ligament (ACL). Therefore, not only stress-deprivation but also stress-enhancement significantly affect the mechanical properties of tendon autografts. Results of in vivo and in vitro studies suggest that cyclic tensile loading may inhibit the deterioration in mechanical strength of the transplanted tendon. Clinically, our prospective randomized study demonstrated that a relatively high initial tension reduces the postoperative anterior laxity of the knee joint after ACL reconstruction using the doubled autogenous hamstring tendons connected in series with polyester tapes, when the tension applied is less than 80 N. Our experimental and clinical results indicate that the initial tension is one of the significant factors that affect the results of ACL reconstruction, although the optimal initial tension for the other graft materials still remains unknown.

The effects of in situ freezing and the combination of in situ freezing and stress-shielding on the microstructure and ultrastructure of the patellar tendon were studied with use of 20 mature rabbits. The patellar tendon was frozen in situ with liquid nitrogen to kill fibroblasts and then was completely released from stress by chronically pulling a stainless-steel wire installed between the patella and the tibial tubercle. Microstructurally, the freezing treatment induced separation of collagen fiber bundles and fibroblast necrosis at 3 weeks, although the separation disappeared at 6 weeks. Ultrastructurally, small collagen fibrils with a diameter of less than 90 nm were predominant; at 6 weeks, the area occupied by collagen fibrils had decreased. In the frozen-shielded tendon, numerous large spaces were observed in the matrix at 3 weeks. This treatment increased the number of fibrils with a diameter greater than 360 nm and decreased the number of collagen fibrils per unit of area and the area occupied by collagen fibrils at 3 weeks. This study demonstrated that in situ freezing and the combination of in situ freezing and stress-shielding leads to a smaller volume of collagen fibrils per unit of cross section of the patellar tendon by mechanisms that remain to be defined.

We conducted a prospective, randomized, short-term study to clarify the effects of initial graft tension on clinical outcome after arthroscopically assisted anterior cruciate ligament reconstruction with autogenous doubled semitendinosus and gracilis tendons connected in series with polyester tapes. Seventy Japanese patients with chronic, "isolated" anterior cruciate ligament tears were entered in the study. The patients were randomly divided into three groups based on initial graft tension: Group 1 (20 N), Group 2 (40 N), or Group 3 (80 N). No statistical differences were noted among the three groups with regard to their background factors. The patients were observed for 2 years or more after surgery. Postoperatively, the average side-to-side difference in anterior laxity was 2.2 +/- 2.4 mm in Group 1, 1.4 +/- 1.8 mm in Group 2, and 0.6 +/- 1.7 mm in Group 3. Analysis of variance testing showed that the postoperative laxity in Group 3 was significantly less than that in Group 1. Spearman's rank-order correlation analysis also demonstrated significant correlation between the magnitude of initial graft tension and the magnitude of the postoperative laxity. This study demonstrates that relatively high initial tension (up to 80 N) reduces the postoperative anterior laxity of the knee joint after anterior cruciate ligament reconstruction using the doubled autogenous hamstring tendons connected in series with polyester tapes.

An experiment was conducted to verify if resumption of loading (restressing) on autografts after augmentation procedures can recover the mechanical properties of the grafts that were deteriorated by complete stress shielding. One hundred ten Japanese White rabbits were used. After the patellar tendon in each right knee was frozen in situ, tension applied to the tendon was released for an interval in 80 rabbits. These 80 animals were divided into four groups of 20 rabbits. The patellar tendons in these groups were completely shielded from stress for 1, 2, 3, and 6 weeks, respectively. From each group, rabbits were sacrificed immediately before restressing (N = 5), and after 3 (N = 5), 6 (N = 5), and 12 (N = 5) weeks of restressing. The remaining 30 rabbits underwent sham operations. The results showed that complete stress shielding markedly decreased tensile strength of the patellar tendon. However, if restressing was applied within 3 weeks of complete stress shielding, the once-reduced strength gradually increased to the level of the sham-operated tendons by 12 weeks after the onset of restressing. Restressing applied after 6 weeks of complete stress shielding also increased the strength of the tendon; however, it reached only 65% the strength of the sham-operated tendons at 12 weeks after restressing. The timing to apply stress to grafts should be carefully determined for optimal recovery.

A rabbit model was used to discover whether the effects of stress shielding on the mechanical properties of the patellar tendon depend on the degree of stress reduction. Ninety mature female Japanese White rabbits were divided into three groups: completely stress-shielded partially stress-shielded and sham-operation and contralateral controls. In the experimental groups, tension applied to the patellar tendon was 0%, approximately 30%, and 100% of the normal tension, respectively, with a polyester artificial ligament. Tensile tests were carried out on patella-patellar tendon-tibia complexes harvested 1, 2, 3, 6, or 12 weeks after surgery. The tensile strength decreased in comparison with the sham-operation group to 50.2, 13.5, 9.7, and 20.7% in the completely stress-shielded group and to 75.2, 57.6, 59.6, 57.3, and 72.9% in the partially stress-shielded group. The tensile strength in the completely stress-shielded group was significantly less than that in the partially stress-shielded group at 1, 2, 3, and 6 weeks. The cross-sectional area of the patellar tendon significantly increased to 132, 206, 237, and 136% in the completely stress-shielded group and to 136, 170, 175, 155, and 127% in the partially stress-shielded group compared with the sham-operation group. The cross-sectional area of the completely stress-shielded tendon was significantly larger than that of the partially stress-shielded tendon at 1, 2, and 3 weeks. This study demonstrated that effects of stress shielding on the mechanical properties of the patellar tendon were dependent on the degree of stress shielding.

We studied the effects of restressing on the mechanical properties and morphology of stress-shielded rabbit patellar tendons. After completely unloading the patellar tendon for 1 to 3 weeks, tension was again applied to the tendon for subsequent 3 to 12 weeks. Although the stress shielding markedly decreased the tangent modulus and tensile strength of the tendon, restressing significantly increased them. However, the mechanical properties of the tendon were not completely recovered even after a prolonged period of restressing. The microstructure of the tendon was also restored by restressing, although the recovery was incomplete. These results indicate that the mechanical properties and morphology of tendinous tissue change in response to mechanical demands.

To distinguish between morbidity caused by harvesting semitendinosus and gracilis tendons and morbidity associated with anterior cruciate ligament reconstruction surgery, we performed a prospective randomized study using 65 patients who underwent anterior cruciate ligament reconstruction using these tendons. The patients underwent either contralateral (N = 34) or ipsilateral (N = 31) graft harvest. For the nonoperated knees in the ipsilateral harvest group, isometric and isokinetic strength of the quadriceps and hamstring muscles increased to approximately 120% of the preoperative value at 12 months after surgery. Compared with these knees, the tendon harvest did not affect quadriceps muscle strength at all. However, harvest did decrease hamstring muscles strength for 9 months after surgery. The graft harvest in the knees with anterior cruciate ligament reconstruction also did not significantly affect quadriceps muscle strength, but it did significantly decrease hamstring muscles strength only at 1 month. Activity-related soreness at the donor site was rarely restricting and resolved by 3 months. This study demonstrated that the semitendinosus and gracilis tendon graft is a reasonable choice to minimize the donor site morbidity in ligament reconstruction using autografts.

Effects of partial and complete stress shielding on mechanical properties and histology of in situ frozen patellar tendons were studied in 120 mature female Japanese White rabbits that were divided into three groups: completely stress-shielded, partially stress-shielded, and sham-operated groups. In the former two groups, tendon tension was reduced to 0% and about 30% of normal force, respectively, with a polyester artificial ligament. Tensile tests were conducted on patella-patellar tendon-tibia complexes harvested 1, 2, 3, 6, or 12 weeks after surgery. Tensile strength significantly decreased compared with the sham group to 17% and 28% at 3 and 6 weeks, respectively, in the completely stress-shielded group, and to 54% and 63% at 3 and 12 weeks, respectively, in the partially stress-shielded group. Patellar tendon cross-sectional area significantly increased to 156% and 157% at 2 and 3 weeks, respectively, in the completely stress-shielded group and to 133% at 2 weeks in the partially stress-shielded group, compared with the sham group. Stress shielding significantly changed tensile strength, tangent modulus, and cross-sectional area of in situ frozen patellar tendon; these changes depended on degree of stress shielding. Histologic observations indicated that remodeling occurred in the patellar tendon while there were no cells in the fascicle.

The effects of freezing and stress-shielding on the mechanical properties and histology of the patellar tendon (PT) were studied with the use of 28 mature Japanese white rabbits. The PT was frozen in situ by liquid nitrogen to kill the fibroblasts and then, for stress-shielding, a stainless-steel wire, installed between the patella and the tibial tubercle, was stretched to release all tension in the PT. After being allowed unrestricted activity in their cages for 1, 2, 3, or 6 weeks, the animals were killed, and the PTs were excised for mechanical and histological study. The cross-sectional area of the frozen and stress-shielded PT started to increase significantly 1 week after the treatment and leveled off at 3 weeks. In contrast, the tensile strength and elastic modulus began to decrease significantly at 1 week, falling to 15% of the control values at 6 weeks. Histologically, cells were absent until 2 weeks after freezing and stress-shielding, although new cells appeared by 3 weeks. Splitting and fragmentation of collagen bundles were observed beginning at 2 weeks. These results indicate that complete stress-shielding led to substantial changes in the mechanical properties of the once-frozen PT, even in the absence of the tissue remodeling process by fibroblasts.

Mechanical properties of the stress-shielded patellar tendon were studied in the rabbit knee. Stress shielding was accomplished by stretching a stainless-steel wire installed between the patella and tibial tubercle and thus, releasing the tension in the patellar tendon completely. Tensile tests were carried out on the specimens obtained from the patellar tendons which were exposed to the stress shielding for 1 to 6 weeks. The stress shielding changed the mechanical properties of the patellar tendon significantly: it decreased the tangent modulus and tensile strength to 9 percent of the control values after 3 weeks. There was a 131 percent increase in the cross-sectional area and a 15 percent decrease in the tendinous length. Remarkable changes were also observed in the structural properties: for example, the maximum load of the bone-tendon complex decreased to 20 percent of the control value after 3 weeks. Histological studies showed that the stress shielding increased the number of fibroblasts and decreased the longitudinally aligned collagen bundles. These results imply that if no stress is applied to the autograft in the case of augmentative reconstruction of the knee ligament, the graft strength decreases remarkably.

The mechanical and structural properties of the patellar tendon fascicle-bone units of rabbit knees were determined by tensile tests, particularly focusing on their local differences. There were no significant differences in the strains measured by a video dimension analyzer among the proximal, middle, and distal regions of the central portion of tendon. The mechanical properties of the medial portion agreed well with those of the central portion. However, significant differences were observed in the tensile strength between the lateral and the other two portions: the tensile strength of the lateral portion was about 16 percent larger than those in the other portions.

Anterior cruciate ligament reconstruction using an autologous graft harvested from the central one-third of the patellar and quadriceps tendon was performed in 65 knees of 65 patients who were followed from 3 to 7 years. Mean anterior laxity of both knees was measured before and after surgery in each patient using the Styker Knee Laxity Tester. At 30 degrees of knee flexion, 58 patients (89%) had differences of less than 2.5 mm between the operated and unoperated knees. Quadriceps strength was measured with the Cybex II and was less than 50% of the uninjured knee at 3 months after surgery. In men, quadriceps strength returned to 78% of normal at 1 year and 85% at final followup. These values were equal to the preoperative level. In women, the quadriceps strength at final followup was 70%, significantly lower than preoperative strength. Hamstring strength recovered to equal the normal strength. Although anterior cruciate ligament reconstruction using one-third of the patellar and quadriceps tendon achieves stability, postoperative quadriceps weakness is a disadvantage. This weakness may be caused by impairment of the knee extensor mechanism resulting from harvesting the graft. We do not currently recommend this technique for anterior cruciate ligament reconstruction.

Eighty-five knees of 85 patients who underwent anterior cruciate ligament reconstruction with autologous patellar and quadriceps tendon grafts were followed for 3-7 years. Hamstrings strength improved to normal. Quadriceps strength in men returned to the preoperative level, but not to normal strength. Quadriceps strength in women, at the final follow-up, was significantly less than it had been preoperatively. This weakness may be a consequence of impairment of the knee extensor mechanism resulting from harvesting the graft. Although favorable postoperative stability of the knee was obtained, we do not recommend this technique for ACL reconstruction because of the quadriceps weakness.

Fifty-six arthroscopic observations on 53 knees at various intervals after anterior cruciate ligament (ACL) reconstruction using the autogenous quadriceps and patellar tendon were analyzed to clarify the morphological maturation process of the grafts in human patients. Arthroscopic observations of the grafts were divided into four types, except for one rerupture case. In type I, thick synovial tissue with abundant capillary blood vessels filled the intercondylar fossa. In type II, synovial tissue mass was decreased and ligamentous tissue showed through the thin synovial tissue. In type III, relatively thick synovial tissue with many folds and abundant capillary blood vessels enveloped thick ligamentous tissue. In type IV, thin synovial tissue with relatively few blood vessels enveloped thick ligamentous tissue. Correlation between these graded types and intervals after reconstruction was significant (chi-square test, p less than 0.001). These four types of arthroscopic findings are thought to represent four phases of the maturation process of autogenous grafts after ACL reconstruction in human patients.