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Effect of Early and Delayed Mechanical Loading on Tendon-to-Bone Healing After Anterior Cruciate Ligament Reconstruction
Asheesh Bedi, MD1; David Kovacevic, MD1; Alice J.S. Fox, MD1; Carl W. Imhauser, PhD1; Mark Stasiak, MSE1; Jonathan Packer, MD1; Robert H. Brophy, MD2; Xiang-Hua Deng, MD1; Scott A. Rodeo, MD1
1 Sports Medicine and Shoulder Service (A.B. and S.A.R.) and Laboratories for Soft Tissue Research (D.K., A.J.S.F., M.S., J.P., and X.-H.D.) and Biomechanics (C.W.I.), Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address for A. Bedi: bedia@hss.edu. E-mail address for S.A. Rodeo: rodeos@hss.edu
2 Washington University Orthopedics, 14532 South Outer Forty Drive, Chesterfield, MO 63017
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Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the National Institutes of Health (Grant R01 AR053689-01A1). Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity.

Investigation performed at the Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, NY

Copyright © 2010 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2010 Oct 20;92(14):2387-2401. doi: 10.2106/JBJS.I.01270
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Modulation of the mechanical environment may profoundly affect the healing tendon graft-bone interface. The purpose of this study was to determine how controlled axial loading after anterior cruciate ligament reconstruction affects tendon-to-bone healing. Our hypothesis was that controlled cyclic axial loading after a period of immobilization would improve tendon-to-bone healing compared with that associated with immediate axial loading or prolonged immobilization.


One hundred and fifty-six male Sprague-Dawley rats underwent anterior cruciate ligament reconstruction with use of a flexor digitorum longus autograft. A custom-designed fixture was used to apply an external fixator across the knee parallel to the anterior cruciate ligament graft. Animals were randomly assigned to be treated with immobilization (n = 36) or controlled knee distraction along the long axis of the graft to achieve approximately 2% axial strain beginning (1) immediately postoperatively (n = 36), (2) on postoperative day 4 ("early delayed loading," n = 42), or (3) on postoperative day 10 ("late delayed loading," n = 42). The animals were killed at fourteen or twenty-eight days postoperatively for biomechanical testing, micro-computed tomography, and histomorphometric analysis of the bone-tendon-bone complex. Data were analyzed with use of a two-way analysis of variance followed by a post hoc Tukey test with p < 0.05 defined as significant.


Delayed initiation of cyclic axial loading on postoperative day 10 resulted in a load to failure of the femur-anterior cruciate ligament-tibia complex at two weeks that was significantly greater than that resulting from immediate loading or prolonged immobilization of the knee (mean and standard deviation, 9.6 ± 3.3 N versus 4.4 ± 2.3 N and 4.4 ± 1.5 N, respectively; p < 0.01). The new-bone formation observed in the tibial tunnels of the delayed-loading groups was significantly increased compared with that in the immediate-loading and immobilization groups at both two and four weeks postoperatively (1.47 ± 0.11 mm3 [postoperative-day-10 group] versus 0.89 ± 0.30 mm3 and 0.85 ± 0.19 mm3, respectively, at two weeks; p < 0.003). There were significantly fewer ED1+ inflammatory macrophages and significantly more ED2+ resident macrophages at the healing tendon-bone interface in both delayed-loading groups compared with the counts in the immediate-loading and immobilization groups at two and four weeks (2.97 ± 0.7 [postoperative day 10] versus 1.14 ± 0.47 and 1.71 ± 1.5 ED2+ cells, respectively, per high-power field at two weeks; p < 0.02). The numbers of osteoclasts in the delayed-loading groups were significantly lower than those in the immediate-loading and immobilization groups at two and four weeks postoperatively (0.35 ± 0.15 [postoperative-day-10 group] versus 1.02 ± 0.08 and 1.44 ± 0.2 cells, respectively, per high-power field at two weeks; p < 0.01), and the delayed-loading groups also had significantly reduced interface tissue vascularity compared with the other groups (p < 0.003).


Delayed application of cyclic axial load after anterior cruciate ligament reconstruction resulted in improved mechanical and biological parameters of tendon-to-bone healing compared with those associated with immediate loading or prolonged postoperative immobilization of the knee.

Clinical Relevance: 

This study of anterior cruciate ligament reconstruction may have important implications for rehabilitation after soft-tissue reconstructive procedures in the knee. Controlled mechanical loads after a delay to allow resolution of acute postoperative inflammation may be most favorable to the healing enthesis.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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