Animal Models of Wound Healing
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For more than 20 years I have had the opportunity to work closely with many companies in the development of their products using animal models. Together with wound healing model pioneers William H. Eaglstein, MD and Prof. Patricia M. Mertz, we have evaluated numerous dressings, devices, and topical agents on healing1–11 and studied their effects on bacteria.12–18 Our objectives have been to develop both in-vitro and in-vivo models that can be used as a springboard to assess potential therapeutics prior to their clinical application. However, transitional research from the laboratory to the clinic is not always straightforward. Addressing complex issues in the clinic takes a team approach with both basic and clinical scientists. Most patients have multiple problems that may affect the healing course and preclinical evaluations can help focus on specific therapies or treatment regimens.
I always tell companies that negative results are just as important as positive results. When first developing a product for commercial use it is very unlikely that the optimal delivery system, dose, or treatment regimen has been established. A product that may be effective in vitro may take 1000x the concentration to work in vivo. It is always prudent to include a dose response study during preclinical evaluations to determine optimal concentrations before proceeding to the clinical trials. The number of applications, which are needed to achieve optimal efficacy, should also be evaluated (eg, twice daily application may be necessary for optimal healing and/or antimicrobial activity). Translational research needs to be taken in stepwise manner. These steps included in-vitro experiments, animal studies, and clinical evaluations, respectively.
It is my pleasure to be the editor of this WOUNDS section on Animal Models of Wound Healing. I have been able to gather some of the leading experts in the field who will illustrate the many ways in which animal models can be used in studying wound healing and infection. First, my colleague Roberto Perez and I discuss the general importance of preclinical models and the benefits and disadvantages of each. Myers and Gould discuss the use of ischemic models to evaluate the importance of oxygen in the wound environment. Scherer and colleagues review the use of diabetic models to allow a better understanding of the pathophysiology of wound healing and assess a variety of therapeutic modalities.
There is no doubt of the importance of pre-clinical testing and the immense contribution that animal models have had to our comprehension of the wound healing and infection process. The animal model is an essential tool in evaluating therapeutic agents that might eventually be used at the bedside to close wounds and/or treat infection.
1. Eaglstein WH, Davis SC, Mehle AL, Mertz PM. Optimal use of an occlusive dressing to enhance healing. Arch Dermatol. 1988;124(3):392–395.
2. Davis SC, Mertz PM, Eaglstein WH. Second-degree burn healing: the effect of occlusive dressings and a cream. J Surg Res. 1990;48(3):245–248.
3. Mertz PM, Davis SC, Brewer LD, Franzén L. Can antimicrobials be effective without impairing wound healing? The evaluation of a cadexomer iodine ointment. WOUNDS. 1994;6(6):184–193.
4. Davis SC, Eaglstein WH, Cazzaniga AL, Mertz PM. An octyl-2-cyanoacrylate formulation speeds healing of partial-thickness wounds. Dermatol Surg. 2001;27(9):783–788.
5. Mertz PM, Davis SC, Franzén L, et al. Effects of an arginine-glycine-aspartic acid peptide-containing artificial matrix on epithelial migration in vitro and experimental second-degree burn wound healing in vivo. J Burn Care Rehabil. 1996;17(3):199–206.
6. Davis SC, Mertz PM, Bilevich ED, Cazzaniga AL, Eaglstein WH. Early debridement of second-degree burn wounds enhances the rate of epithelization—an animal model to evaluate burn wound therapies. J Burn Care Rehabil. 1996;17(6 Pt 1):558–561.
7. Davis SC, Mertz PM, Cazzaniga AL, Serralta V, Orr R, Eaglstein WH. The use of new antimicrobial gauze dressings: effects on the rate of epithelialization of partial-thickness wounds. WOUNDS. 2002;14(7);252–256.
8. Davis SC, Badiavas E, Rendon-Pellerano MI, Pardo RJ. Histological comparison of postoperative wound care regimens for laser resurfacing in a porcine model. Dermatol Surg. 1999;25(5);387–393.
9. Mertz PM, Davis SC, Cazzaniga AL, Cheng K, Reich JD, Eaglstein WH. Electrical stimulation: acceleration of soft tissue repair by varying polarity. WOUNDS. 1993;5(3):153–159.
10. Kaiser MR, Davis SC, Mertz PM. The effect of ultraviolet irradiation-induced inflammation on epidermal wound healing. Wound Repair Regen. 1995;3(3):311–315.
11. Sauder DN, Kilian PL, McLane JA, et al. Interleukin-1 enhances epidermal wound healing. Lymphokine Res. 1990;9(4):465–473.
12. Oliveria-Gandia MF, Davis SC, Mertz PM. Can occlusive dressing composition influence proliferation of bacterial wound pathogens? WOUNDS. 1998;10(1):4–11.
13. Mertz PM, Oliveria-Gandia MF, Davis SC. The evaluation of a cadexomer iodine wound dressing on methicillin resistant staphylococcus aureus (MRSA) in acute wounds. Dermatol Surg. 1999;25(2):89–93.
14. Serralta VW, Harrison-Balestra C, Cazzaniga AL, Davis SC, Mertz PM. Lifestyles of bacteria in wounds: presence of biofilms? WOUNDS. 2001;13(1):29–34.
15. Cazzaniga A, Serralta V, Davis SC, Orr R, Eaglstein W, Mertz P. The effect of an antimicrobial gauze dressing impregnated with 0.2% polyhexamethylene biguanide as a barrier to prevent Pseudomonas aeruginosa wound invasion. WOUNDS. 2002;14(5):169–176.
16. Mertz PM, Davis SC, Cazzaniga A, Drosou A, Eaglstein WH. Barrier and antibacterial properties of 2-octyl cyanoacrylate-derived wound treatment films. J Cutan Med Surg. 2003;7(1):1–6.
17. Davis SC, Cazzaniga AL, Eaglstein WH, Mertz PM. Over-the-counter topical antimicrobial: effective treatments? Arch Dermatol Res. 2005;297(5):190–195.
18. Martineau L, Davis SC. Controlling methicillin resistant Staphylococcus aureus and Pseudomonas aeruginosa wound infections with a novel biomaterial. J Invest Surg. 2007;20(4):217–227.