The effects of 5-fluorouracil on flexor tendon healing by using a biodegradable gelatin, slow releasing system: experimental study in a hen model

Abstract

This study investigated the effects of 5-fluorouracil in a slow-release biodegradable gelatin system on tendon healing. Gelatin blocks prepared in a size of 10 × 20 × 1 mm were loaded with 10, 20, and 30 mg of 5-fluorouracil, and 30 adult white Leghorn chickens were used. The tendons to the third and fourth toes were severed and repaired. The extremities were casted for three weeks. After sacrifice, the tendons were examined histologically and biomechanically for adhesion formation. The 10 mg-loaded gelatin group showed a decrease in adhesion formation when compared with the operative control group; the 20 and 30 mg groups showed signs of severe inflammation. Low doses of 5-fluorouracil applied via a slow-release gelatin system reduced adhesion formation in flexor tendon healing.

The use of 5‐fluorouracil in the prevention of tendon adhesions: A systematic review

“…The dosage used ranged from 1 mg/mL to 50 mg/mL of 5FU topically to repaired tendons. Nearly all studies used 5 minute exposures expect for Karaaltin et al 11 who wrapped slow‐releasing biodegradable gelatin infused‐5‐FU blocks to the repaired tendons. The details of these articles have been summarized in Table 3.…”

“…This suggests that similar outcomes would be able to be replicated with similar ease. Of note Karaaltin et al 11 in their 2013 study involving 5FU gelatin‐infused blocks reported significantly higher inflammation at the higher dosing levels of 20 and 30 mg/mL. Of importance however is that this study was the one to use 5FU gelatin‐infused blocks rather than the 5‐minute “single touch” technique adopted by the other nine studies.…”

“…The focus on 5FU in these studies reflects the desire to modify the activity of fibroblasts, which play a vital role in the formation of adhesions. As an antimetabolite it modifies adhesion formation by inhibiting the proliferation of inflammatory cells and inhibits the invasion of fibroblasts from outside of the tendon, extrinsic fibroblasts 2,11,13 . Despite the initial necessity of the formation of scar tissue for the physical joining of the injured tendon, the studies in this review did not report that the use of 5FU resulted in a weaker tendon.…”

Biomechanical and Macroscopic Evaluations of the Effects of 5-Fluorouracil on Partially Divided Flexor Tendon Injuries in Rabbits

“…Our results generally agree with those of the biomechanical studies conducted by Karaaltin et al . [ 29 ]…”

Battling adhesions: from understanding to prevention

“…Further strategies are based on the use of agents that limit cellular proliferation by preventing DNA replication, thus preventing fibroblasts from expanding and forming adhesions. Agents that present these characteristics include mitomycin-C, which has been demonstrated to reduce adhesions in a rabbit pericardial model [111], or 5-fluoroacil, which also reduced adhesions in the flexor tendon in chickens [112]. However, the side effects of these drugs still represent a crucial limitation for their use as antiadhesive agents.…”