A Brief Summary of the Science

by Dr. Tracey Sturgill, DVM, University of Georgia

The majority of wound healing research has been performed for human medicine. Additional research in veterinary species,1-3 including the horse,4 indicates that mammalian species heal in a similar fashion. Normal healing requires a balancing act between the removal of dead tissue and the construction of new tissue. This involves a precise interaction between numerous cell types, as well as growth factors, enzymes and cytokines for normal healing to proceed.4,5 The normal healing process should proceed as in the diagram below.

chartChronic wounds are due to an imbalance in the healing process. Matrix metalloproteinases (MMP) and their inhibitors, (tissue inhibitors of metalloproteinases (TIMPs)) are key for this process to occur in the horse6 as well as the human.5 In the normally healing wound, various MMPs are expressed throughout the healing process7. In chronic wounds, MMP/TIMP imbalances decrease healing. Naturally occurring cations, such as Potassium, Rubidium, Calcium, and Zinc, have been shown to alter the expression of over 10,000 genes, regulate protease imbalances, down-regulate the production of reactive oxygen species (ROS) which can damage other molecules and the cell structures of which they are a part, and stimulate re-epithelialization.8,9


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1. Madlener M. Differential expression of matrix metalloproteinases and their physiological inhibitors in acute murine skin wounds. Arch Dermatol Res 1998;Jul:S24-29.
2. Corr DT. Biomechanical behavior of scar tissue and uninjured skin in a porcine model. Wound Repair and Regeneration 2009;17:250-259.
3. Vu TH, Werb Z. Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev 2000;14:2123-2133.
4. Theoret CL. Update on Wound Repair. Clinical Techniques in Equine Practice 2004;3:110-122.
5. Martin P. Wound healing–aiming for perfect skin regeneration. Science 1997;276:75-81.
6. Cochrane CA. Models of in vivo wound healing in the horse and the role of growth factors. Veterinary Dermatology 1997;8:259-272.
7. Clutterbuck AL, Harris P, Allaway D, et al. Matrix metalloproteinases in inflammatory pathologies of the horse. Vet J;183:27-38.
8. A.J.J. van den Berg I. A novel formulation of metal ions and citric acid reduces reactive oxygen species in vitro Journal of Wound Care 2003;12.
9. Hoekstra MJ. Polyhydrated ionogens regulate matrix metalloproteinase expression and reactive oxygen species production in recalcitrant wounds. Wound Repair and Regeneration;77.