Examination of toxicity and collagen linearity after the administration of the protein cross-linker genipin in equine tendon and dermis: a pilot study.

Abstract

OBJECTIVE: Collagen cross-linking is an attractive therapeutic route aimed at supplementing natural collagen stabilisation. In this study the toxicity of the cross-linker genipin (GP) was examined in avascular (tendon) and vascular (dermis) tissue. METHODS: High doses of GP were injected intratendinously into three yearling horses and evaluated at various time points up to 30 days. A second group of three yearlings were injected into the dermis and evaluated at various time points up to 1 year. Metrics used included lameness, circumferential swelling, ultrasound evaluation, microscopic morphology, collagen production and systemic effect on blood parameters. RESULTS: The tendon injection sites exhibited mild lameness and swelling with no apparent systemic toxicity or stabilisation defects. Treated tendons exhibited increased linear collagen microscopically. Dermal injections showed similar results, with mild swelling at the injection site. Microscopic morphology resulted in a decrease in dermal collagen at 30 days post-injection. Dermis injected at the high dose of 355 mmol/L examined 1 year post-treatment appeared similar to the untreated biopsies; however, there was an increase in mature collagen. CONCLUSION: GP injection appeared to be well tolerated, with transient lameness and mild circumferential swelling when injected into the tendon and local tissue swelling when injected into the dermis. No systemic hypersensitivities or toxicities were observed. Microscopically, GP resulted in increased linear collagen in tendons at 30 days post-injection and overall increased collagen in dermal tissue when evaluated 1 year post-injection.