Effects of avotermin (transforming growth factor β3) in a clinically relevant pig model of long, full-thickness incisional wounds.

Abstract

BACKGROUND:

The pig is an accepted species for evaluating the safety of molecules in dermal wound healing indications; however, the sizes of wounds assessed have not always been comparable to large incisions encountered clinically.

OBJECTIVE:

To develop a clinically relevant model of incisional wounding in the Göttingen minipig for assessing the safety and tolerance of compounds in development to improve scarring.

METHODS:

Intradermal avotermin (recombinant transforming growth factor β3 [TGFβ3]) up to 6,000 ng/100μL was administered twice to 20 cm full-thickness incisions.

RESULTS:

Incisions were well tolerated in the minipig. Avotermin treatment was not associated with adverse changes in a range of clinical parameters, including wound healing and strength. Plasma TGFβ3 levels were transient with ≈0.1% bioavailability.

CONCLUSION:

A clinically relevant model of long, full-thickness, sutured surgical incisions in the minipig is achievable. Avotermin is well tolerated in this model and does not adversely affect normal wound healing at levels that significantly exceed those doses to be used clinically in humans.

• Authors: Hugh G Laverty, Nick L Occleston, Mark Johnson, John Little, Richard Jones, David Fairlamb, Mark W J Ferguson, Sharon O'Kane
• Journal: Journal of cutaneous medicine and surgery (J Cutan Med Surg) 2010 Sep-Oct Vol. 14 Issue 5 Pg. 223-32 ISSN: 1203-4754 [Print] United States
• PMID: 20868619 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Proteins
• Transforming Growth Factor beta3

Topics

• Animals
• Cicatrix (prevention & control)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Female
• Male
• Recombinant Proteins (administration & dosage, therapeutic use)
• Swine
• Transforming Growth Factor beta3 (administration & dosage, pharmacology)
• Wound Healing (drug effects)