Response of the Injured Tendon to Growth Factors in the Presence or Absence of the Paratenon

Background: The paratenon is important for Achilles tendon healing. There is much interest in the use of exogenous growth factors (GFs) as potential agents for accelerating the healing of damaged Achilles tendons. Purpose/Hypothesis: The present study used a rat model to study the responses of the injured Achilles tendon to GFs in the presence or absence of the paratenon. The hypothesis was that responses of the injured tendon to GFs would be lower in the absence of a paratenon. Study Design: Controlled laboratory study. Methods: A 4-mm defect was created in the right Achilles tendon of 60 skeletally mature rats, which were treated with a validated combination of GFs (bFGF, BMP-12, and TGF-β1). Animals were randomly assigned to the intact paratenon (IP) group or resected paratenon (RP) group. Healing was studied anatomically, mechanically, and histologically after 1, 2, and 4 weeks. Results: IP tendons showed improved healing compared with RP tendons. IP tendons were significantly stronger (32.2 N and 48.9 N, respectively) than RP tendons (20.1 N and 31.1 N, respectively) after 1 and 2 weeks. IP tendons did not elongate as much as RP tendons and had greater cross-sectional areas (18.0 mm2, 14.4 mm2, and 16.4 mm2, respectively) after 1, 2, and 4 weeks compared with RP tendons (10.5 mm2, 8.4 mm2, and 11.9 mm2, respectively). On histology, earlier collagen deposition and parallel orientation of fibrils were found for IP tendons. Conclusion: The paratenon is essential for efficient Achilles tendon healing. Healing with GFs in this Achilles tendon defect model was superior in the presence of the paratenon. Clinical Relevance: Biological approaches to tendon engineering using GFs are in vogue and have been shown to improve healing of the rat Achilles tendon, most likely by inducing progenitor cells located within the paratenon. Clinically, resection or incision of the paratenon has been proposed for wound closure. Our data demonstrate the fundamental importance of the paratenon, which therefore should be preserved during Achilles tendon repair, especially if augmented with products such as platelet-rich plasma or autologous conditioned serum that are rich in GFs.

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Strength of Braided Polyblend Polyethylene Sutures versus Braided Polyester Sutures in Achilles Tendon Repair

Journal of the American Podiatric Medical Association ◽

10.7547/1000185 ◽

2010 ◽

Vol 100 (3) ◽

pp. 185-188 ◽

Cited By ~ 7

Author(s):

Keith D. Cook ◽

Greg Clark ◽

Eric Lui ◽

Gaurav Vajaria ◽

George F. Wallace

Keyword(s):

Achilles Tendon ◽

Suture Material ◽

Tendon Repair ◽

Contralateral Side ◽

Suture Technique ◽

Materials Testing ◽

Suture Materials ◽

Cross Sectional ◽

The Mean ◽

The Right

Background: Various techniques may be used to repair Achilles tendon ruptures; however, we contend that using the strongest suture with the least amount of suture material is ideal. Methods: To compare the strength of 2-0 FiberLoop (Arthrex Inc, Naples, Florida) and #2 Ethibond (Ethicon Inc, Somerville, New Jersey) suture materials in Achilles tendon repairs, 12 Achilles tendons were harvested from cadavers aged 18 to 62 years (median age, 42 years). The tendons were transected and repaired using a modified Krackow suture technique. All of the right limbs were repaired with 2-0 FiberLoop, and the contralateral side was repaired with #2 Ethibond. The specimens were mounted to a materials testing system, and the repairs were pulled to failure in an anatomical direction. Results: The mean ± SD yield loads of 2-0 FiberLoop and #2 Ethibond were 233 ± 48 N and 134 ± 34 N, respectively (P = .002). The mean ± SD ultimate load of 2-0 FiberLoop was 282 ± 58 N, and that of #2 Ethibond was 135 ± 33 N (P < .001). The cross-sectional area of one pass of 2-0 FiberLoop was calculated to be 0.21 mm2, and one pass of #2 Ethibond was 0.28 mm2. Conclusions: The smaller-caliber 2-0 FiberLoop was significantly stronger than #2 Ethibond. This study suggests that there is no advantage to using the traditional larger suture material for Achilles tendon repairs; however, further clinical testing is needed to determine the optimal repair technique. (J Am Podiatr Med Assoc 100(3): 185–188, 2010)

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Comparison on effects of platelet-rich plasma versus autologous conditioned serum on Achilles tendon healing in a rat model

Acta Orthopaedica et Traumatologica Turcica ◽

10.5152/j.aott.2020.18498 ◽

2020 ◽

Vol 54 (4) ◽

pp. 438-444

Author(s):

Erdinc Genc ◽

◽

Serdar Yuksel ◽

Aysel Caglar ◽

Ozan Beytemur ◽

...

Keyword(s):

Achilles Tendon ◽

Rat Model ◽

Platelet Rich Plasma ◽

Tendon Healing ◽

Autologous Conditioned Serum

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Bevacizumab Improves Achilles Tendon Repair in a Rat Model

Cellular Physiology and Biochemistry ◽

10.1159/000489057 ◽

2018 ◽

Vol 46 (3) ◽

pp. 1148-1158 ◽

Cited By ~ 7

Author(s):

Herbert Tempfer ◽

Alexandra Kaser-Eichberger ◽

Christine Lehner ◽

Renate Gehwolf ◽

Stefanie Korntner ◽

...

Keyword(s):

Achilles Tendon ◽

Biomechanical Testing ◽

Tendon Repair ◽

Tendon Healing ◽

Control Group ◽

Polarization Microscopy ◽

Tissue Quality ◽

Cross Sectional ◽

Repair Tissue ◽

Post Surgery

Background/Aims: Effective wound-healing generally requires efficient re-vascularization after injury, ensuring sufficient supply with oxygen, nutrients, and various cell populations. While this applies to most tissues, tendons are mostly avascular in nature and harbor relatively few cells, probably contributing to their poor regenerative capacity. Considering the minimal vascularization of healthy tendons, we hypothesize that controlling angiogenesis in early tendon healing is beneficial for repair tissue quality and function. Methods: To address this hypothesis, Bevacizumab, a monoclonal antibody blocking VEGF-A signaling, was locally injected into the defect area of a complete tenotomy in rat Achilles tendon. At 28 days post-surgery, the defect region was investigated using immunohistochemistry against vascular and lymphatic epitopes. Polarization microscopy and biomechanical testing was used to determine tendon integrity and gait analysis for functional testing in treated vs non-treated animals. Results: Angiogenesis was found to be significantly reduced in the Bevacizumab treated repair tissue, accompanied by significantly reduced cross sectional area, improved matrix organization, increased stiffness and Young’s modulus, maximum load and stress. Further, we observed an improved gait pattern when compared to the vehicle injected control group. Conclusion: Based on the results of this study we propose that reducing angiogenesis after tendon injury can improve tendon repair, potentially representing a novel treatment-option.

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Experimental Morphologic and Clinical Substantiation of Autothrombocytic Growth Factors in Complex Treatment of Achilles Tendon Rupture

N.N. Priorov Journal of Traumatology and Orthopedics ◽

10.17816/vto20120432-37 ◽

2012 ◽

Vol 19 (4) ◽

pp. 32-37

Author(s):

G. A Kesyan ◽

G. N Berchenko ◽

T. G Nakhapetyan ◽

N. S Gavryushenko ◽

R. Z Uraxgil’deev ◽

...

Keyword(s):

Growth Factors ◽

Achilles Tendon ◽

Group Treatment ◽

Platelet Rich Plasma ◽

Achilles Tendon Rupture ◽

Tendon Healing ◽

Main Group ◽

Surgical Reconstruction ◽

Autologous Platelet Rich Plasma ◽

Autologous Platelet

Study of the influence of autothrombocytic growth factors upon the injured tendinous tissue was performed. Experimental results (60 Chinchilla rabbits, 3—5 kg) showed that administration of autologous platelet-rich plasma (PRP) into Achilles tendon (AT) injury zone promoted activiza- tion of reparative processes with diminution of inflammatory manifestations; increase in angio- genesis, proliferative and synthetic fibroblasts activity, fibrillogenesis processes; earlier tendon healing. Clinical study included 57 patients (33—68years) with acute (8—48 hours) and old (1—12 months) AT ruptures. After AT surgical reconstruction(Cuneo tendon sutures in acute AC ruptures and Chernavsiautoplasty in the old ones) PRP was additionally administrated to 30 patients from the main group. Treatment results were evaluated by J. Leppilahti and AOFAS scales in 4 months after surgical intervention. In no one patient from the main group AT reruptures were recorded while in control groupreruptures were recorded in 26% of patients.

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Platelet-Rich Plasma Applications for Achilles Tendon Repair: A Bridge between Biology and Surgery

International Journal of Molecular Sciences ◽

10.3390/ijms22020824 ◽

2021 ◽

Vol 22 (2) ◽

pp. 824

Author(s):

Sabino Padilla ◽

Mikel Sánchez ◽

Victor Vaquerizo ◽

Gerard A. Malanga ◽

Nicolás Fiz ◽

...

Keyword(s):

Achilles Tendon ◽

Ex Vivo ◽

Platelet Rich Plasma ◽

Achilles Tendon Rupture ◽

Tendon Repair ◽

Modern Society ◽

Preparation Methods ◽

Tendon Ruptures ◽

The Right

Achilles tendon ruptures are very common tendon ruptures and their incidence is increasing in modern society, resulting in work incapacity and months off sport, which generate a need for accelerated and successful therapeutic repair strategy. Platelet-rich plasma (PRP) is emerging as adjuvant human blood-derived constructs to assist Achilles tendon rupture treatment. However, myriad PRP preparation methods in conjunction with poor standardization in the modalities of their applications impinge on the consistent effectiveness of clinical and structural outcomes regarding their therapeutic efficacy. The purpose of this review is to provide some light on the application of PRP for Achilles tendon ruptures. PRP has many characteristics that make it an attractive treatment. Elements such as the inclusion of leukocytes and erythrocytes within PRP, the absence of activation and activation ex vivo or in vivo, the modality of application, and the adjustment of PRP pH can influence the biology of the applied product and result in misleading therapeutic conclusions. The weakest points in demonstrating their consistent effectiveness are primarily the result of myriad PRP preparation methods and the poor standardization of modalities for their application. Selecting the right biological scaffold and applying it correctly to restitutio ad integrum of ruptured Achilles tendons remains a daunting and complex task.

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Autologous Tenocyte Implantation (ATI) and the Use of Collagen Scaffolds: a Case Report of a Novel Surgical Treatment for Gluteal Tendon Repair

International Journal of Case Reports ◽

10.28933/ijcr-2020-12-2605 ◽

2021 ◽

pp. 194

Author(s):

◽

Keyword(s):

Platelet Rich Plasma ◽

Tendon Repair ◽

Tendon Healing ◽

Collagen Scaffold ◽

Gluteus Medius ◽

Normal Function ◽

Collagen Scaffolds ◽

Mri Findings ◽

Level Of Evidence ◽

Mri Scans

Background: Ortho-biological therapies such as platelet-rich plasma and autologous tenocyte implantation injections are hypothesized to introduce cellular mediators such as growth factors into tendons, promoting natural healing. Methods: This case introduces a 63-year-old female with an extensive history of lateral hip pain and treatment refractory tendinopathy with tearing. She underwent open surgery to repair the gluteus medius tendon, using supplementary autologous tenocyte implantation (ATI) in conjunction with a Celgro (Orthocell, Perth, Australia) collagen scaffold. Level of evidence: 4 Results: She had normal function in the hip at 12 months. MRI scans post-operatively at 12 months showed a marked reduction in inflammation, an intact tendon and a reduction in atrophic changes in the muscle belly. Conclusion: Surgical repair of a large degenerate tear of the gluteus medius tendon, augmented with autologous tenocyte implantation in a collagen scaffold led to an excellent patient outcome and MRI findings demonstrated tendon healing with improved tendon structure and reduced inflammation.

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Improved Healing of Transected Rabbit Achilles Tendon after a Single Injection of Cartilage-Derived Morphogenetic Protein-2

The American Journal of Sports Medicine ◽

10.1177/03635465030310041301 ◽

2003 ◽

Vol 31 (4) ◽

pp. 555-559 ◽

Cited By ~ 61

Author(s):

Carina Forslund ◽

Per Aspenberg

Keyword(s):

Achilles Tendon ◽

Single Injection ◽

Rabbit Model ◽

Tendon Healing ◽

Radiographic Examination ◽

Morphogenetic Protein ◽

Tendon Ruptures ◽

The Right ◽

Callus Size ◽

Positive Effect

Background Achilles tendon ruptures in humans might be treated more efficiently with the help of a growth factor. Cartilage-derived morphogenetic protein-2 has been shown to induce formation of tendon-like tissue. Hypothesis Cartilage-derived morphogenetic protein-2 has a positive effect on mechanical parameters for tendon healing in a rabbit model with Achilles tendon transection. Study Design Controlled laboratory study. Methods The right Achilles tendon of 40 rabbits was transected without tendon suture. Cartilage-derived morphogenetic protein-2 (10 μg) or vehicle control (acetate buffer) was injected locally 2 hours postoperatively. All tendons were tested biomechanically at 8 and 14 days, and treated tendons were histologically and radiographically evaluated at 56 days. Results At 14 days, both failure load and stiffness of treated tendons were increased by 35%. The treated tendons had significantly larger callus size at 8 and 14 days. Histologic and radiographic examination showed no signs of ossification in the treated tendons after 56 days. Conclusions A single injection of cartilage-derived morphogenetic protein-2 led to a stronger and stiffer tendon callus than that in the controls without inducing bone formation. Clinical Relevance Similar results from a larger animal model would suggest a possible future use of cartilage-derived morphogenetic protein-2 in the treatment of human Achilles tendon ruptures.

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