Stimulation of Tendon Healing with Delayed Dexamethasone Treatment Is Modified by the Microbiome

SLR - December 2018 - Bryan M. Duffin

Reference: Dietrich-Zagonel, F., Hammerman, M., Tätting, L., Dietrich, F., Kozak Ljunggren, M., Blomgran, P., Aspenberg, P. Stimulation of Tendon Healing with Delayed Dexamethasone Treatment Is Modified by the Microbiome. The American Journal of Sports Medicine, 46(13), 3281–3288.

Scientific Literature Review

Reviewed By: Bryan M. Duffin, DPM
Residency Program: Hunt Regional Medical Center, Greenville, TX

Podiatric Relevance: Tendon ruptures are a common injury seen by foot and ankle surgeons and can be treated with both conservative and surgical intervention. There are many physiological pathways involved with healing that influence the ability to restore strength to an injured tendon and allow patients to return to normal activity. Little is known about how the immune system affects the healing process of tendons. The purpose of this study was to explore the effects of delayed dexamethasone treatment and the microbiota (or more specifically, the immune system) on tendon healing.

Methods: This was a controlled laboratory study. Eighty-two specific opportunists and pathogen-free (SOPF) rats were divided equally into two groups. One group was cohoused with specific pathogen-free rats who had been raised in a microbial-rich environment. After six weeks, this group remained healthy but upon testing, the bacterial flora in their gut had been contaminated with higher levels of Staphylococcus aureus. Both the clean and contaminated rats then underwent Achilles tendon transection. Eight days after surgery, 12 rats (clean and contaminated) were sacrificed and the healing tendons were collected for T-cell characterization by flow cytometry. The remaining 60 rats were used for mechanical evaluation and were randomized to receive either dexamethasone or saline injections on days five through nine after Achilles transection. All rats were sacrificed 12 days postoperatively, and the healing tendons were evaluated by tensional mechanical testing until failure.

Results: While dexamethasone roughly doubled peak stress to failure in both groups, a larger increase in peak stress was noted among the contaminated group, 105 percent compared to 53 percent in the clean group. Dexamethasone was also noted to decrease the transverse area of the tendon callus. In regard to T-cell characterization of contaminated rats, there was a double in the ratio of CD45 to CD3/CD4 cells noted when compared to the clean group.

Conclusions: Dexamethasone has a positive effect on tendon healing in rats when administered after the initial inflammatory phase of healing. This is likely due to its ability to down regulate the inflammatory response, which allows for the tendon to enter earlier into the remodeling phase. The authors also concluded that changes in mircobiome influenced tendon healing and enhanced the positive effects of dexamethasone in this study.