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

Abstract

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.

Keywords

paratenon Achilles tendon growth factors tendon healing rat

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References

Carr

Norris

. The blood supply of the calcaneal tendon. J Bone Joint Surg Br. 1989;71(1):100-101.

Darabos

Haspl

Moser

Darabos

Bartolek

Groenemeyer

. Intraarticular application of autologous conditioned serum (ACS) reduces bone tunnel widening after ACL reconstructive surgery in a randomized controlled trial. Knee Surg Sports Traumatol Arthrosc. 2011;19(suppl 1):S36-S46.

De Carli

Lanzetti

Ciompi

et al . Can platelet-rich plasma have a role in Achilles tendon surgical repair? Knee Surg Sports Traumatol Arthrosc. 2016;24(7):2231-2237.

Docheva

Muller

Majewski

Evans

. Biologics for tendon repair. Adv Drug Deliv Rev. 2015;84:222-239.

Dyment

Hagiwara

Matthews

Kalajzic

Rowe

. Lineage tracing of resident tendon progenitor cells during growth and natural healing. PLoS One. 2014;9(4):e96113.

Ebert

Wang

Smith

et al . A midterm evaluation of postoperative platelet-rich plasma injections on arthroscopic supraspinatus repair: a randomized controlled trial. Am J Sports Med. 2017;45(13):2965-2974.

Evans

. Cytokines and the role they play in the healing of ligaments and tendons. Sports Med. 1999;28(2):71-76.

Gentile

De Angelis

Agovino

et al . Use of platelet rich plasma and hyaluronic acid in the treatment of complications of Achilles tendon reconstruction. World J Plast Surg. 2016;5(2):124-132.

Heisterbach

Todorov

Fluckiger

Evans

Majewski

. Effect of BMP-12, TGF-beta1 and autologous conditioned serum on growth factor expression in Achilles tendon healing. Knee Surg Sports Traumatol Arthrosc. 2012;20(10):1907-1914.

10.

Hurley

Lim Fat

Moran

Mullett

. The efficacy of platelet-rich plasma and platelet-rich fibrin in arthroscopic rotator cuff repair: a meta-analysis of randomized controlled trials [published online February 1, 2018]. Am J Sports Med. doi:10.1177/0363546517751397

11.

Keyhani

Mardani-Kivi

Abbasian

Emami-Moghaddam Tehrani

Lahiji

. Achilles tendon repair, a modified technique. Arch Bone Jt Surg. 2013;1(2):86-89.

12.

Krapf

Kaipel

Majewski

. Structural and biomechanical characteristics after early mobilization in an Achilles tendon rupture model: operative versus nonoperative treatment. Orthopedics. 2012;35(9):e1383-e1388.

13.

Labib

Hoffler

2nd Shah

Rolf

Tingan

. The gift box open Achilles tendon repair method: a retrospective clinical series. J Foot Ankle Surg. 2016;55(1):39-44.

14.

Maffulli

Longo

Franceschi

Rabitti

Denaro

. Movin and Bonar scores assess the same characteristics of tendon histology. Clin Orthop Relat Res. 2008;466(7):1605-1611.

15.

Majewski

Heisterbach

Jaquiery

et al . Improved tendon healing using bFGF, BMP12, and TGFβ1 in a rat model. Eur Cell Mater. 2018;35:318-334.

16.

Majewski

Ochsner

Liu

Fluckiger

Evans

. Accelerated healing of the rat Achilles tendon in response to autologous conditioned serum. Am J Sports Med. 2009;37(11):2117-2125.

17.

Maquirriain

. Surgical treatment of chronic Achilles tendinopathy: long-term results of the endoscopic technique. J Foot Ankle Surg. 2013;52(4):451-455.

18.

Molloy

Wang

Murrell

. The roles of growth factors in tendon and ligament healing. Sports Med. 2003;33(5):381-394.

19.

Müller

Dürselen

Heisterbach

Evans

Majewski

. Effect of a simple collagen type I sponge for Achilles tendon repair in a rat model. Am J Sports Med. 2016;44(8):1998-2004.

20.

Müller

Evans

Heisterbach

Majewski

. The role of the paratenon in Achilles tendon healing: a study in rats. Am J Sports Med. 2018;46(5):1214-1219.

21.

Müller

Todorov

Heisterbach

Martin

Majewski

. Tendon healing: an overview of physiology, biology, and pathology of tendon healing and systematic review of state of the art in tendon bioengineering. Knee Surg Sports Traumatol Arthrosc. 2015;23(7):2097-2105.

22.

Naidu

Abbassian

Nielsen

Uppalapati

Shetty

. Minimally invasive paratenon release for non-insertional Achilles tendinopathy. Foot Ankle Int. 2009;30(7):680-685.

23.

Saper

Lybrand

Creevy

. Using a posterior compartment fasciotomy and paratenon closure in acute Achilles tendon repair. Orthopedics. 2016;39(4):e790-e793.

24.

Saxena

Hong

Hofer

. Peritenolysis and debridement for main body (mid-portion) Achilles tendinopathy in athletic patients: results of 107 procedures. J Foot Ankle Surg. 2017;56(5):922-928.

25.

Sharma

Maffulli

. Biology of tendon injury: healing, modeling and remodeling. J Musculoskelet Neuronal Interact. 2006;6(2):181-190.

26.

Wieloch

Buchmann

Roth

Rickert

. A cryo-jaw designed for in vitro tensile testing of the healing Achilles tendons in rats. J Biomech. 2004;37(11):1719-1722.

27.

Wurgler-Hauri

Dourte

Baradet

Williams

Soslowsky

. Temporal expression of 8 growth factors in tendon-to-bone healing in a rat supraspinatus model. J Shoulder Elbow Surg. 2007;16(suppl 5):S198-S203.

28.

Yang

Rothrauff

Tuan

. Tendon and ligament regeneration and repair: clinical relevance and developmental paradigm. Birth Defects Res C Embryo Today. 2013;99(3):203-222.

29.

Yodlowski

Scheller

Jr Minos

. Surgical treatment of Achilles tendinitis by decompression of the retrocalcaneal bursa and the superior calcaneal tuberosity. Am J Sports Med. 2002;30(3):318-321.

30.

Zantop

Tillmann

Petersen

. Quantitative assessment of blood vessels of the human Achilles tendon: an immunohistochemical cadaver study. Arch Orthop Trauma Surg. 2003;123(9):501-504.

31.

Zou

Shi

et al . A prospective study of platelet-rich plasma as biological augmentation for acute Achilles tendon rupture repair. Biomed Res Int. 2016;2016:9364170.