CORR® ORS Richard A. Brand Award for Outstanding Orthopaedic Research: Engineering Flexor Tendon Repair With Lubricant, Cells, and Cytokines in a Canine Model

Zhao, Chunfeng; Ozasa, Yasuhiro; Reisdorf, Ramona L.; Thoreson, Andrew R.; Jay, Gregory D.; An, Kai Nan; Amadio, Peter C.

doi:10.1007/s11999-014-3690-y

Cited by 43 publications

(55 citation statements)

References 37 publications

(55 reference statements)

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“…Canine, and rabbit studies have demonstrated both the intrinsic and extrinsic healing ability of flexor tendons 5,6 , the importance of early controlled passive motion in minimizing adhesion formation, relative to immobilization 7 , as well as the effects of different suture patterns on the healing process 8,9 . In addition, the canine model has been useful in testing translational tissue-engineering approaches to improve healing 10 . However, there are several important advantages in using a murine model relative to a large animal model including the relative cost, availability of murine specific reagents, and the ease of generating global knock-outs or tissue-specific deletion/overexpression constructs.…”

Section: Introductionmentioning

confidence: 99%

Murine Flexor Tendon Injury and Repair Surgery

Ackerman

Loiselle

2016

JoVE

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Tendon connects muscle and bone, facilitating movement of nearly the entire body. In the hand, flexor tendons enable flexion of the fingers and general hand function. Injuries to the flexor tendons are common, and satisfactory healing is impaired due to excess scar tissue and adhesions between the tendon and surrounding tissue. However, very little is known about the molecular and cellular components of flexor tendon repair. To that end, we have previously described a murine model of flexor tendon repair that recapitulates many aspects of healing in humans including impaired range of motion and decreased mechanical properties. Here we provide an in-depth description and demonstration of this surgical procedure to completely transect and repair the flexor digitorum longus (FDL) tendon in the hind paw of the mouse. This technique can be used to conduct lineage analysis of different cell types, assess the effects of gene gain or loss-of-function, and to test the efficacy of pharmacological interventions in the healing process. However, there are two primary limitations to this model: i) the FDL tendon in the mid-portion of the murine hind paw, where the transection and repair occur, is not surrounded by a synovial sheath. Therefore this model does not account for the potential contribution of the sheath the scar formation process. ii) To protect the integrity of the repair site, the tendon is release at the myotendinous junction, decreasing the mechanical forces of the tendon, likely contributing to increased scar formation. In addition, we demonstrate the use of the cytospin method to identify and quantify different cell populations during healing. Isolation of sufficient cells during the healing process for flow cytometric analysis has proved quite challenging; cytospin requires far fewer cells but allows for simple immunofluorescent labeling and quantification of cells or proteins of interest.

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Section: Introductionmentioning

confidence: 99%

Murine Flexor Tendon Injury and Repair Surgery

Ackerman

Loiselle

2016

JoVE

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“…72,73 The canine Zone II FDP tendon repair surgical model allows direct testing of surgical modifications and biological approaches before performing clinical trials in humans. 24,25,43,48,74–76 …”

Section: Animal Modelsmentioning

confidence: 99%

“…37,39,45,47,48,81 By introducing cells into the paucicellular intrasynovial flexor tendon milieu and inducing a developmental paradigm between the repaired tendon ends, biological approaches attempt to accelerate healing and regenerate normal tissue. Multipotent MSCs from a variety of adult tissues have an excellent capacity to differentiate into the relevant tissue-specific phenotype and to provide potent immunosuppressive and anti-inflammatory effects.…”

Section: Biologic Treatmentsmentioning

confidence: 99%

“…37,39,45–48 The goal of recent studies has been to: (1) promote matrix synthesis at the tendon repair site leading to increased biomechanical strength and stiffness and (2) suppress matrix synthesis along the tendon surface and synovial sheath preventing adhesion formation. 31,33,35,36 Biological approaches to augment repair have the potential to advance both of these goals.…”

Section: Introductionmentioning

confidence: 99%

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Cell and Biologic-Based Treatment of Flexor Tendon Injuries

Linderman

Gelberman

Thomopoulos

et al. 2016

Operative Techniques in Orthopaedics

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The two primary factors leading to poor clinical results after intrasynovial tendon repair are adhesion formation within the digital sheath and repair-site elongation and rupture. As the outcomes following modern tendon multi-strand repair and controlled rehabilitation techniques are often unsatisfactory, alternative approaches, such as the application of growth factors and mesenchymal stem cells (MSCs), have become increasingly attractive treatment options. Successful biological therapies require carefully controlled spatiotemporal delivery of cells, growth factors, and biocompatible scaffold matrices in order to simultaneously (1) promote matrix synthesis at the tendon repair site leading to increased biomechanical strength and stiffness and (2) suppress matrix synthesis along the tendon surface and synovial sheath preventing adhesion formation. This review summarizes recent cell and biologic-based experimental treatments for flexor tendon injury, with an emphasis on large animal translational studies.

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“…Zhu et al showed that, Sox9 gene was not only able to promote the healing, but also increased the biomechanical strength at tendon-bone healing interface into an established bone-tendon healing model in rabbits (the long digital extensor tendon was detached from the lateral femoral condyle, and the free end of the tendon was inserted into a tunnel drilled into the proximal tibial metaphysis) [ 56 ]. In addition the recombinant Sox9 delivered by adenoviral vector can be expressed at a high level in the damaged tissues of the bone-tendon junction, which can stimulate the production of type II collagen and improve the healing [ 55 ]. In a rabbit model, Lattermann et al designed a study by inserting fl exor digitorum longus tendon into the calcaneus and applied gene delivery to the healing tendon insertion site.…”

Section: Different Treatment Modalities In Tendon-bone Interface Healingmentioning

confidence: 99%

Updated Animal Models in Orthopaedic Research

Öztuna

2015

European Instructional Lectures

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Cionne et al. designed a study to characterize the early infl ammatory phase of fl exor tendon healing with the goal of identifying infl ammationrelated targets for future treatments. Canine fl exor tendons were transected and repaired with core and running epitenon suture. A controlled passive motion rehabilitation protocol was started on the fi rst post-operative day. The infl ammatory response was monitored for 9 days. Temporal changes in immune cell populations and gene expression of infl ammation-, matrix degradation-, and extracellular matrixrelated factors were examined. The most dramatic effect was a greater than 4,000-fold up-regulation in the expression of the proinfl ammatory factor IL-1β. While an infl ammatory response is likely necessary for healing to occur, high levels of pro-infl ammatory cytokines may result in impaired tendon healing. The tendon treatment approaches should include the modulation strategies of the infl ammatory phase of healing [ 37 ]. AbstractThere has been growing innovation in Orthopaedic basic science research over the past years. This study presents the newest knowledge about the musculoskeletal tissue healing which were investigated by animal studies and recently published in the major Orthopaedic journals. These studies demonstrate some modifi cations in methodology of animal models and a multidisciplinary approach to understanding the mechanisms underlying tissue healing and regeneration. Besides, the effects of gene therapies, different molecules, growth factors, some drugs which are widely used in daily practice and popular modalities (like ESWT and PRP) on tissue regeneration are summarized in this manuscript.

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CORR® ORS Richard A. Brand Award for Outstanding Orthopaedic Research: Engineering Flexor Tendon Repair With Lubricant, Cells, and Cytokines in a Canine Model

Cited by 43 publications

References 37 publications

Murine Flexor Tendon Injury and Repair Surgery

Murine Flexor Tendon Injury and Repair Surgery

Cell and Biologic-Based Treatment of Flexor Tendon Injuries

Updated Animal Models in Orthopaedic Research

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