An in vitro collagen gel contraction assay to assess the relaxing effect of potential pharmacological alternatives to oxytetracycline on foals’ tendons

Oxytetracycline has been successfully used to treat flexural limb deformities in foals. However, its antimicrobial properties and potential adverse side effects warrant the investigation of alternatives. Inhibition of matrix metalloproteinases (MMPs) or collagen cross-linking have been suggested as possible mechanisms of action. This study assessed the influence of potential alternative substances lacking antimicrobial properties on collagen gel contraction by juvenile equine myofibroblasts in vitro. Myofibroblasts were isolated from forelimb SDFTs and inferior check ligaments from foals euthanised for reasons unrelated to this study, and seeded in collagen gels containing oxytetracycline, MMP-inhibitors incyclinide, ilomastat, aprotinin, and pentoxifylline, β-aminopropionitrile fumarate (BAPN), and control medium. The gels were measured in photographs up to 96 h after release, and differences in contraction were evaluated. Compared to control, BAPN and incyclinide induced significant inhibition (p < 0.05) of collagen gel contraction by myofibroblasts at all time points, and the inhibition was more potent than that observed with oxytetracycline. Consequently, the inhibitory capacity of BAPN and incyclinide on myofibroblast-mediated collagen gel contraction, which demonstrates their effect on tractional structuring of collagen, makes them promising candidates as potential substitutes for oxytetracycline. Further investigations into their side effects, pharmacodynamics, pharmacokinetics, and application methods in juvenile equine patients are needed.