SLR - July 2014 - Alysha Patel

Augmentation of Tendon Healing with an Injectable Tendon Hydrogel in a Rat Achilles Tendon Model

Reference: Kim MY, Farnebo S, Woon CY, Schmitt T, Pham H, Chang J. Plastic and Reconstructive Surgery. Volume 133(5), May 2014, p645e-653e.

Reviewed By: Alysha Patel, DPM
Residency Program: Forest Hills Hospital, NY.

Podiatric Relevance: As the prevalence of poor healing tendon injuries have been increasing, products to augment or improve tendon healing have been increasing in kind.  Current methods include injections of platelet-rich plasma, whole blood, growth hormones and even stem cells. Previous literature has shown that tendon healing can be accelerated by direct delivery of a three-dimensional biodegradable scaffold to the injured site. The efficacy of extracellular matrix hydrogels derived from the tissue targeted for treatment or replacement has also been widely researched. Based upon the aforementioned literature, the authors hypothesize that tendon healing may be augmented by the introduction of a tendon-derived hydrogel into the injury site.
 
Methods: A human-tendon derived extracellular matrix hydrogel was first fabricated utilizing a technique the authors had previously developed (the author’s extracellular matrix gel contains not only matrix material but also their associated proteins and biological cues.)  Thirty-six Wistar rats were used for this study. A slightly curved 1cm incision was made lateral to the Achilles tendon to ensure the Achilles tendon defect would not be directly underneath the incision. Full-thickness Achilles tendon defects were created in each rat bilaterally utilizing two no. 15 blades which were bonded together. This was used to make a parallel incision in the Achilles tendon 0.5mm apart and 5mm long, spanning from the tendon-bone insertion at the calcaneus to the midtendon. Microscissors were then used to remove the scored sections such that a full-thickness defect was created mid substance. Then 0.05ml of tendon derived hydrogel was injected into the wound space on one leg while the other leg received 0.05ml of a phosphate-buffered saline. The wound was then sutured close. The tendons were harvested at two, four, and eight weeks. At each interval, 10 specimens were killed for biomechanical testing and two specimens were killed for histological evaluation. Biomechanical testing was performed utilizing a Mini Bionix testing system to measure ultimate failure load, ultimate tensile stress and ultimate tensile stiffness.
 
Results: Biomechanical Results – At two weeks, the majority of ruptures occurred in the tendon. At four and eight weeks, ruptures were more common at the tendon-bone insertion. No statistical difference was noted in ultimate tensile stress or stiffness and ultimate failure load at two and eight weeks between the hydrogel and the saline treatments. However, at four weeks, tendons treated with hydrogel has an ultimate failure load that was 28 percent stronger on average than the saline treated tendons. There was no statistical difference in the ultimate tensile stress or stiffness. Histological Results – Cross-sections showed similar injury morphologies at two and four weeks. By week eight, the wound space was indiscernible from healing tendon tissue. In week two and four, the hydrogel specimens showed a stronger presence of collagen I in the wound trough of the tendons compared to those of the saline specimens.

Conclusion: The results of the study support the hypothesis that tendon-derived extracellular matrix hydrogel augments healing when applied to a tendon injury site. The higher collagen I content may explain the difference in the ultimate failure load noted at the four-week period. In a clinical setting, application of the gel could improve the healing process, allowing for more rapid mobilization of the injured tendon.

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