Study Evaluates Injectable Treatment for Tendon Injuries

Research shows a new treatment modality for tendon injuries could improve healing time in horses and help prevent reinjury. Tom Hedman, PhD, a research associate professor at the University of Kentucky's Center for Biomedical Engineering Coldstream Research Campus' Soft-Tissue Matrix Modification Research Laboratory, introduced to the audience an injectable, nonbiologic treatment approach called NEXT developed to improve the function of mechanically deficient tissues in horses.

During the May 8 Veterinary Science Seminar "ECM2: Introduction to an Injectable Treatment for Mechanically Dysfunctional Tissues with Initial Results from Equine SDFT Testing," Hedman explained that he originally developed the injectable treatment method for use in humans with degenerative disc disease. But upon moving to Lexington, commonly known as "The Horse Capital of the World," Hedman saw potential for the reagent's use in horses.

What Is It?

NEXT (nonsurgical exogenous crosslink therapy, sometimes called ECM2 or exogenous crosslink modification of the extracellular matrix) involves chemical modification--using the plant-derived reagent genipin, which Hedman noted the FDA classifies as nontoxic--of connective tissue to improve mechanical and nutritional properties. Although it sounds complicated, the theory behind NEXT is relatively simple, he said.

Essentially, when tissue is injured (specifically tendons, which are Hedman's current research focus) a veterinarian can hypothetically inject genipin into the lesion. The reagent is designed to provide internal bracing to collagen tissues (the main substance of which tendon is comprised) while increasing nutrient flow into the tissue. Genipin's protein crosslinking activity confers a high tensile strength when injected into collagen.

Hedman relayed that researchers have seen this combination of factors in both healthy and pathologic human and animal tissues help adhere adjacent tissues, increase tear resistance, reduce joint instability, maintain range of motion, and increase tissue durability, among other benefits.

He also noted that NEXT is long-lasting, fast-acting, and low cost compared to other treatment options in human healthcare.

NEXT for Tendon Injuries in Horses

Hedman then discussed NEXT's potential use in treating very common superficial digital flexor tendon (SDFT) injuries in horses. In recent in vitro (in the lab) testing, Hedman said NEXT increased equine tendon strength following a simulated core tendon-lesion. In fact, the damaged tendon post-treatment exhibited greater strength than the normal, intact tendon.

Most recently, Hedman and a team of veterinarians conducted an in vivo (in the live horse) safety study, which he described to the audience.

In the safety study the team used three yearling Thoroughbreds with healthy SDFTs. He said the horses served as their own controls: The researchers injected the animals' right front SDFTs with 2 mL of buffered genipin, and they injected the left front SDFTs with the buffer only. The horses received no follow-up treatment.

They designed the study as a "worst-case" safety study, Hedman said. With no tendon lesion to receive this relatively large amount of injected fluid, the team expected the reagent to backflow out of the tendon to the surrounding tissues, he explained.

The team members evaluated the horses several times throughout the 30-day study. They used ultrasonography to evaluate SDFT area and tissue patterns, a telemetered motion measurement system (Equinosis Lameness Locator) for an objective assessment of soundness, and visual examinations to identify swelling at or around the injection site.

The team then injected another 2 mL of genipin at a second site on the horses' SDFTs of at Day 37, at which point the animals received local anti-inflammatory and anti-bacterial agents to simulate the routine aftercare used for other injectable procedures such as stem cell injections.

The study results were as follows:

  • The researchers noticed some swelling at the injection sites on NEXT-treated legs over the first three days;
  • The leg circumference increased post-injection but returned to baseline within a few days;
  • On visual assessment, lameness was greatest 24 hours post-injection, but subsided and was gone by day 14;
  • The lameness locator detected gait abnormalities up until day 30 in one of the horses;
  • The routine aftercare following the second injection reduced the negative reactions substantially;
  • At necropsy, the team observed moderate to substantial backflow of the reagent to the surrounding tissues in five of six injections, but no associated tissue damage; and
  • The tendon tissue pattern was "substantially straighter" in two of the three horses, but otherwise healthy and normal.

These results suggest that even in a worst-case scenario exposing the surrounding tissues to a large amount of the reagent, no lasting adverse effects were evident, and proper routine aftercare could effectively minimize negative effects, Hedman said. A larger scale study to further evaluate NEXT in vivo is currently in the works, he added.

Hedman concluded that these initial experimental results demonstrated a potential for veterinarians to use NEXT injections in the future to stabilize and strengthen injured tendons, shorten healing periods, and prevent tendon reinjury.

Disclaimer: Seek the advice of a qualified veterinarian before proceeding with any diagnosis, treatment, or therapy.

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