Nguyen Quynhhoa T, Norelli Jolanta B, Graver Adam, Ekstein Charles, Schwartz Johnathan, Chowdhury Farzana, Drakos Mark C, Grande Daniel A, Chahine Nadeen O
Bioengineering-Biomechanics Laboratory, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, USA.
Orthopaedic Research Laboratory, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, New York, USA.
Am J Sports Med. 2017 Oct;45(12):2872-2881. doi: 10.1177/0363546517716637. Epub 2017 Jul 31.
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).
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.
Controlled laboratory study.
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.
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.
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.
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.
跟腱断裂是一种严重的损伤，对运动员来说尤其如此。肌腱损伤后基质金属蛋白酶（MMP）活性升高与胶原网络的退化有关，强力霉素（Doxy）可抑制这种活性。
每日口服强力霉素将提高横断跟腱的组织学、分子和生物力学质量。此外，缝合修复将进一步提高修复肌腱的质量。
对照实验室研究。
对288只成年雄性Sprague-Dawley大鼠进行随机单侧跟腱横断。受伤的肌腱要么不进行修复（第1组和第2组），要么进行手术修复（第3组和第4组）。第2组和第4组的动物通过口服灌胃每日接受强力霉素，第1组和第3组的动物作为对照（不接受强力霉素）。在损伤后1.5、3、6和9周采集肌腱（每组和每个时间点n = 18）。根据组织学分级评分、胶原纤维取向、基因表达和生物力学特性评估肌腱修复质量。
在手术修复的样本中，与不使用强力霉素相比，强力霉素提高了肌腱修复质量（P = .0014）。强力霉素对胶原纤维分散有显著影响，但对主纤维角度没有影响。时间对MMP-3、MMP-9和TIMP1的基因表达有显著影响，强力霉素在9周时显著降低了MMP-3的表达。手术修复并使用强力霉素治疗在损伤后6周增加了动态模量，但在9周时没有增加（P < .001）。无论修复组如何，强力霉素还增加了平衡模量并降低了蠕变应变。强力霉素对未修复肌腱的组织学或生物力学没有显著影响。
研究结果表明，每日口服强力霉素可加速手术修复的跟腱的基质重塑以及动态和平衡生物力学，尽管这种增强在3至6周时间点最为明显。
在修复过程的最佳阶段抑制MMPs可能会加速跟腱修复并改善生物力学特性，特别是与手术治疗相结合时。
