Date of Degree

2-2016

Document Type

Dissertation

Degree Name

Ph.D.

Program

Engineering

Advisor(s)

Luis Cardoso

Scott A. Rodeo

Committee Members

Peter A. Torzilli

Mitchell B. Schaffler

Susannah P. Fritton

Subject Categories

Biomedical Devices and Instrumentation | Biomedical Engineering and Bioengineering

Keywords

tendon to bone healing, Anterior Cruciate Ligament

Abstract

Background: Exposure to tensile loading has been shown to maintain tendon/ligament homeostasis, with the tensile modulus of the tissue increasing in response to greater loading frequency, and even decreasing in the absence of load. However after injury or surgical repair the effect of tensile load is controversial, with many studies implicating mechanical loading with impaired healing. It is currently unknown when the tensile loading imparted during rehabilitation exercise, can be safely reintroduced after surgical tendon repair or ligament reconstruction, and at what time point it can most benefit the remodeling process. To investigate the effect of tensile loading protocols on tendon graft to bone tunnel healing, we developed and validated a novel device to cyclically distract the knee joint in a rat model of anterior cruciate ligament reconstruction (ACL_R), thereby imposing a controlled amount of tensile strain on the tendon graft. Using this device we tested the following hypotheses; H0 which predicts that the immediate resumption of tensile load after ACL_R surgery will impair tendon-to-bone healing compared to continuous knee immobilization. And H1 which predicts that after ACL_R surgery, insertion of a of 4 to 10 day load shielding period, prior to the resumption of tensile load, will improve tendon-to-bone healing compared with both immediate load resumption or continuous immobilization.

Methods: Male Sprague Dawley rats who had undergone ACL_R surgery via a flexor digitorum longus tendon auto-graft were randomly assigned to either; 1) a continuous-immobilization group to strain shield the graft or a cyclic knee distraction group using the device to achieve two-percent strain of the tendon graft. The animals receiving cyclic knee distraction were further subdivided into; 2) an immediate-loading group beginning on postoperative day one, 3) a four-day delayed-loading group beginning on postoperative day four, and 4) a ten-day delayed-loading group beginning on postoperative day ten. The above experiment was were repeated with the device applying ten-percent strain to additional four-and ten-day delayed-loading groups. All animals were sacrificed on either postoperative day fourteen or twenty-eight for immuno-histochemical, biomechanical, and micro-computed tomography analysis of the femur-graft-tibia complex.

Results: Immediate-loading, beginning on postoperative day one did not result in a significantly reduced load-to-failure mechanical response or bone tunnel volume, compared with continuous-immobilization. However a significantly greater number of inflammatory macrophage cells in the immediate-loading group provided partial support for hypothesis H0. The data supported hypothesis H1, with the four- and ten-day delayed-loading groups having significantly less inflammatory macrophages and more new bone volume at both two and four weeks. The failure load of the femur-graft-tibia complex was significantly greater in the ten-day delayed-loading group at two weeks, and in the four-day delayed-loading group at four weeks. Repeating the experiment with cyclic knee joint distraction increased to ten-percent of graft length did not recapitulate the significantly greater failure loads in the delayed loading groups.

Conclusion: On the basis of greatest failure load, most bone tunnel ingrowth, and lowest inflammatory cell population, the four-day delayed-loading protocol was judged most effective for tendon-to-bone healing in the rat model of ACL_R. These parameters could be extrapolated to a human clinical trial of an improved ACL rehabilitation protocol, provided a careful choice of knee exercises applying a maximum of two-percent tendon graft strain were made.

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