Examination of toxicity and collagen linearity after the administration of the protein cross-linker genipin in equine tendon and dermis: a pilot study.
Abstract: 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. Conclusions: 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.
© 2017 Australian Veterinary Association.
Publication Date: 2017-04-27 PubMed ID: 28444753DOI: 10.1111/avj.12583Google Scholar: Lookup
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- Journal Article
Summary
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The research article describes a pilot study examining the toxicity and collagen linearity following the administration of genipin, a protein cross-linker, in equine (horse) tendon and dermis tissue. The findings suggest that genipin is well-tolerated as a therapeutic agent for collagen stabilization, without showing any systemic toxicity or hypersensitivity.
Methods
- The researchers injected high doses of a cross-linker called genipin (GP) directly into the tendons and dermis of yearling horses.
- For the tendon experiment, the horses were evaluated at various times up to 30 days post-injection, while for the dermis experiment, evaluations were conducted up to 1 year after treatment.
- The health impacts and potential toxicity were measured through numerous metrics such as lameness, swelling, ultrasound evaluation, blood parameters, and microscopic morphologies of collagen production.
Results
- Post injection, mild lameness and swelling were observed in the tendons. However, there was no systemic toxicity, meaning no harmful effects on the animal’s whole biological system, and no collagen stabilization defects.
- Microscopic evaluation showed an increase in linear collagen in treated tendons, suggesting that the genipin injection successfully enhances collagen stabilization in tendon tissues.
- Similar mild swelling occurred in the dermis at the injection site. There was a temporary decrease in dermal collagen 30 days post-injection, but after 1 year, the high-dose injection site showed an increase in mature collagen, similar to untreated sites. This might mean that the GP has a long-term beneficial effect on collagen formation in the dermis.
Conclusions
- The results suggest that GP injections are well-tolerated in equine tendon and dermis tissue. No systemic hypersensitivity or toxicities were observed in the subjects, implying that GP is not harmful on a biological level.
- From a microscopic perspective, the GP injections resulted in increased linear collagen in tendons at 30 days post-injection, and an overall increase in collagen in dermal tissue when evaluated 1 year post-injection.
- As such, the results of this study suggest that genipin could potentially be used as a safe and effective therapeutic agent for collagen stabilization in equine medicine.
Cite This Article
APA
Bellefeuille M, Peters DF, Nolin M, Slusarewicz P, Telgenhoff D.
(2017).
Examination of toxicity and collagen linearity after the administration of the protein cross-linker genipin in equine tendon and dermis: a pilot study.
Aust Vet J, 95(5), 167-173.
https://doi.org/10.1111/avj.12583 Publication
Researcher Affiliations
- Equine Sports Medicine & Surgery, Weatherford, Texas, USA.
- College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
- Equinext LLC, Lexington, Kentucky, USA.
- Equinext LLC, Lexington, Kentucky, USA.
- Medical Laboratory Science Department, Tarleton State University, 1501 Enderly Place, Fort Worth, Texas 76104, USA.
MeSH Terms
- Animals
- Collagen / drug effects
- Dermis / drug effects
- Dermis / pathology
- Horses / injuries
- Injections, Intradermal / veterinary
- Iridoids / metabolism
- Iridoids / toxicity
- Lameness, Animal / chemically induced
- Male
- Pilot Projects
- Tendon Injuries / drug therapy
- Tendon Injuries / veterinary
- Tendons / drug effects
- Wound Healing
Citations
This article has been cited 6 times.- Utami Nike D, Md Fadilah NI, Sallehuddin N, Nor Azlan AYH, Imran FH, Maarof M, Fauzi MB. Genipin-Crosslinking Effects on Biomatrix Development for Cutaneous Wound Healing: A Concise Review. Front Bioeng Biotechnol 2022;10:865014.
- Nike DU, Katas H, Mohd NF, Hiraoka Y, Tabata Y, Idrus RBH, Fauzi MB. Characterisation of Rapid In Situ Forming Gelipin Hydrogel for Future Use in Irregular Deep Cutaneous Wound Healing. Polymers (Basel) 2021 Sep 17;13(18).
- Wang Z, Liu H, Luo W, Cai T, Li Z, Liu Y, Gao W, Wan Q, Wang X, Wang J, Wang Y, Yang X. Regeneration of skeletal system with genipin crosslinked biomaterials. J Tissue Eng 2020 Jan-Dec;11:2041731420974861.
- Tondelli T, Götschi T, Camenzind RS, Snedeker JG. Assessing the effects of intratendinous genipin injections: Mechanical augmentation and spatial distribution in an ex vivo degenerative tendon model. PLoS One 2020;15(4):e0231619.
- Camenzind RS, Tondelli TO, Götschi T, Holenstein C, Snedeker JG. Can Genipin-coated Sutures Deliver a Collagen Crosslinking Agent to Improve Suture Pullout in Degenerated Tendon? An Ex Vivo Animal Study. Clin Orthop Relat Res 2018 May;476(5):1104-1113.
- Luss AL, Bobrova MM, Kulikov PP, Keskinov AA. Collagen-Based Scaffolds for Volumetric Muscle Loss Regeneration. Polymers (Basel) 2024 Dec 6;16(23).
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