Quynhhoa T Nguyen1, Jolanta B Norelli2,3, Adam Graver4, Charles Ekstein4, Johnathan Schwartz2, Farzana Chowdhury1, Mark C Drakos4,5, Daniel A Grande2,3,4, Nadeen O Chahine1,3. 1. Bioengineering-Biomechanics Laboratory, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, USA. 2. Orthopaedic Research Laboratory, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, USA. 3. Hofstra Northwell School of Medicine, Hofstra University, Hempstead, New York, USA. 4. Department of Orthopaedic Surgery, Long Island Jewish Medical Center, New Hyde Park, New York, USA. 5. Hospital for Special Surgery, New York, New York, USA.
Abstract
BACKGROUND: Achilles tendon tears are devastating injuries, especially to athletes. Elevated matrix metalloproteinase (MMP) activity after a tendon injury has been associated with deterioration of the collagen network and can be inhibited with doxycycline (Doxy). HYPOTHESIS: Daily oral administration of Doxy will enhance the histological, molecular, and biomechanical quality of transected Achilles tendons. Additionally, suture repair will further enhance the quality of repaired tendons. STUDY DESIGN: Controlled laboratory study. METHODS: Randomized unilateral Achilles tendon transection was performed in 288 adult male Sprague-Dawley rats. The injured tendons were either unrepaired (groups 1 and 2) or surgically repaired (groups 3 and 4). Animals from groups 2 and 4 received Doxy daily through oral gavage, and animals from groups 1 and 3 served as controls (no Doxy). Tendons were harvested at 1.5, 3, 6, and 9 weeks after the injury (n = 18 per group and time point). The quality of tendon repair was evaluated based on the histological grading score, collagen fiber orientation, gene expression, and biomechanical properties. RESULTS: In surgically repaired samples, Doxy enhanced the quality of tendon repair compared with no Doxy ( P = .0014). Doxy had a significant effect on collagen fiber dispersion, but not principal fiber angle. There was a significant effect of time on the gene expression of MMP-3, MMP-9 and TIMP1, and Doxy significantly decreased MMP-3 expression at 9 weeks. Doxy treatment with surgical repair increased the dynamic modulus at 6 weeks but not at 9 weeks after the injury ( P < .001). Doxy also increased the equilibrium modulus and decreased creep strain irrespective of the repair group. Doxy did not have a significant effect on the histology or biomechanics of unrepaired tendons. CONCLUSION: The findings indicate that daily oral administration of Doxy accelerated matrix remodeling and the dynamic and equilibrium biomechanics of surgically repaired Achilles tendons, although such enhancements were most evident at the 3- to 6-week time points. CLINICAL RELEVANCE: The inhibition of MMPs at the optimal stage of the repair process may accelerate Achilles tendon repair and improve biomechanical properties, especially when paired with surgical management.
BACKGROUND: Achilles tendon tears are devastating injuries, especially to athletes. Elevated matrix metalloproteinase (MMP) activity after a tendon injury has been associated with deterioration of the collagen network and can be inhibited with doxycycline (Doxy). HYPOTHESIS: Daily oral administration of Doxy will enhance the histological, molecular, and biomechanical quality of transected Achilles tendons. Additionally, suture repair will further enhance the quality of repaired tendons. STUDY DESIGN: Controlled laboratory study. METHODS: Randomized unilateral Achilles tendon transection was performed in 288 adult male Sprague-Dawley rats. The injured tendons were either unrepaired (groups 1 and 2) or surgically repaired (groups 3 and 4). Animals from groups 2 and 4 received Doxy daily through oral gavage, and animals from groups 1 and 3 served as controls (no Doxy). Tendons were harvested at 1.5, 3, 6, and 9 weeks after the injury (n = 18 per group and time point). The quality of tendon repair was evaluated based on the histological grading score, collagen fiber orientation, gene expression, and biomechanical properties. RESULTS: In surgically repaired samples, Doxy enhanced the quality of tendon repair compared with no Doxy ( P = .0014). Doxy had a significant effect on collagen fiber dispersion, but not principal fiber angle. There was a significant effect of time on the gene expression of MMP-3, MMP-9 and TIMP1, and Doxy significantly decreased MMP-3 expression at 9 weeks. Doxy treatment with surgical repair increased the dynamic modulus at 6 weeks but not at 9 weeks after the injury ( P < .001). Doxy also increased the equilibrium modulus and decreased creep strain irrespective of the repair group. Doxy did not have a significant effect on the histology or biomechanics of unrepaired tendons. CONCLUSION: The findings indicate that daily oral administration of Doxy accelerated matrix remodeling and the dynamic and equilibrium biomechanics of surgically repaired Achilles tendons, although such enhancements were most evident at the 3- to 6-week time points. CLINICAL RELEVANCE: The inhibition of MMPs at the optimal stage of the repair process may accelerate Achilles tendon repair and improve biomechanical properties, especially when paired with surgical management.
Authors: Sarah Ilkhanipour Rooney; Daniel J Torino; Rachel Baskin; Rameen P Vafa; Pooja S Khandekar; Andrew F Kuntz; Louis J Soslowsky Journal: J Biomech Date: 2018-09-05 Impact factor: 2.712
Authors: Jolanta B Norelli; Dawid P Plaza; Drew N Stal; Anish M Varghese; Haixiang Liang; Daniel A Grande Journal: J Tissue Eng Date: 2018-11-12 Impact factor: 7.813