Compression Therapy Promotes Proliferative Repair during Rat Achilles Tendon Immobilization Nikos Schizas, 1,2 Jian Li, 1 Therese Andersson, 3 Anna Fahlgren, 3 Per Aspenberg, 3 Mahmood Ahmed, 1,4 Paul W. Ackermann 1,4 1 Orthopaedic Laboratory, Department of Molecular Medicine and Surgery, M1:02, The King ‘‘Gustav V’’ Research Building, Karolinska University Hospital 171 76 Stockholm, Sweden, 2 Orthopaedic Clinic, Akademiska University Hospital, Uppsala, Sweden, 3 Division of Orthopaedics, IKE, Faculty of health sciences, Linko ¨ ping, Sweden, 4 Department of Orthopaedics, Karolinska University Hospital, Stockholm, Sweden Received 18 August 2009; accepted 24 October 2009 Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jor.21066 ABSTRACT: Achilles tendon ruptures are treated with an initial period of immobilization, which obstructs the healing process partly by a reduction of blood circulation. Intermittent pneumatic compression (IPC) has been proposed to enhance tendon repair by stimulation of blood flow. We hypothesized that daily IPC treatment can counteract the deficits caused by 2 weeks of immobilization post tendon rupture. Forty- eight Sprague-Dawley SD) rats, all subjected to blunt Achilles tendon transection, were divided in three equal groups. Group A was allowed free cage activity, whereas groups B–C were immobilized at the operated hindleg. Group C received daily IPC treatment. Two weeks postrupture the rats were euthanatized and the tendons analyzed with tensile testing and histological assessments of collagen organization and collagen III-LI occurrence. Immobilization significantly reduced maximum force, energy uptake, stiffness, tendon length, transverse area, stress, organized collagen diameter and collagen III-LI occurrence by respectively 80, 75, 77, 22, 47, 65, 49, and 83% compared to free mobilization. IPC treatment improved maximum force 65%, energy 168%, organized collagen diameter 50%, tendon length 25%, and collagen III-LI occurrence 150% compared to immobilization only. The results confirm that immobilization impairs healing after tendon rupture and furthermore demonstrate that IPC-treatment can enhance proliferative tendon repair by counteracting biomechanical and morphological deficits caused by immobilization. ß 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res Keywords: tendon injury; immobilization; intermittent pneumatic compression devices; biomechanics; collagen type III Achilles tendon ruptures, whether operated or not, are treated with an initial period of immobilization. 1 Accumulating data demonstrate that already 2 weeks of immobilization after tendon rupture impedes the healing process, leading to downregulated production of growth factors, matrix proteins, collagens, and sub- sequently reduced biomechanical tissue properties. 2–5 Immobilization additionally inhibits blood circulation and nerve regeneration at the site of injury, which are vital for early proliferative healing. 6 In the rat, the intact tendon proper is practically devoid of nerve fibers and blood vessels, which are located in the paratenon and surrounding connective tissue. Following injury, how- ever, new blood vessels and nerve fibers grow into the tendon proper supplying growth factors and releasing different neuronal mediators vital for repair. 7,8 One way to counteract the reduction in blood flow and neurovascular supply following immobilization after injury could be the use of external compression therapy. Intermittent pneumatic compression (IPC) treatment aims at passive increase of blood flow by cycling external pressure leading to reduced venous stasis and pressure and enhanced arterial blood flow. 9 IPC is also clinically used to prevent thrombosis in immobilized patients. 10 The circulatory increase after compression treatment has also been hypothesized to benefit tissue healing. 11,12 A recent study demonstrated that daily IPC treatment in a rat model of mobilized Achilles tendon healing enhanced neurovascular ingrowth as well as fibroblast proliferation at 2 weeks postrupture. 13 However, whether IPC treatment could counteract the negative influence on healing due to immobilization has not previously been studied. Thus, in this study we examined quantitatively the biomechanical properties as well as histological healing with respect to the occurrence and organization of collagen in mobilized, immobilized, as well as immobi- lized IPC-treated fully ruptured Achilles tendons at 2 weeks postinjury, corresponding to the proliferative phase of healing. 14 MATERIALS AND METHODS The study included 48 male Sprague-Dawley rats (B&K Universal, Stockholm, Sweden; 8 weeks old, 180–200 g), housed three or four per cage at 218, 45–55% humidity, in a 12:12-h light:dark cycle with water and food pellets ad libitum. The rats were allowed 1 week of undisturbed acclimatization before initiation of the experiments. All experiments were approved by the Local Committee for Animal Research and Ethics and conducted in accordance with the Institute’s protocols. All rats were subjected to blunt complete Achilles tendon transection in the right hind leg and subsequently divided into three groups of 16 rats each. Group one (mobilized) was allowed free cage activity post surgery. Group two (immobilized) was immobilized with a synthetic cast on the operated leg. Group three (immobilized þ IPC treated) was immobilized in the same way and additionally received intermittent pneumatic com- pression (IPC) treatment. Surgery The rats were anesthetized by an injection of a mixture of one- quarter Midazolam 1 (5 mg/mL, Pharma Hameln, Germany) and one-quarter Hypnorm 1 (Janssen Pharmaceutica, Bel- gium) in sterile water (2 mL/kg body weight, s.c). The operations were performed under sterile conditions. A 1-cm longitudinal incision was made in the midline of the Achilles tendon on the right foot, exposing the Achilles and plantaris JOURNAL OF ORTHOPAEDIC RESEARCH 1 Correspondence to: Nikos Schizas (T: þ468 51776870; E-mail: nikos.schizas@ki.se) ß 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.