Wound Healing

Discover how Melior’s unique phenotypic screening platforms can uncover the untapped value of your candidate therapeutic

Impaired wound healing is responsible for significant morbidity and mortality worldwide.  The process of wound healing is complex, involving a number of biological pathways that become activated after tissue injury.  This process can become impaired under a number of conditions, such as in diabetic subjects, leading to complications such as higher susceptibility to infection and / or amputation.  Agents that promote epithelialization, cellular proliferation or angiogenesis may improve the wound healing process.

Mice represent an ideal preclinical model, as they are economical and amenable to genetic manipulation, which allows for mechanistic investigation. While requiring consistency and care, this model does not involve complicated surgical techniques and allows for the relatively robust testing of promising agents that may, for example, promote angiogenesis or inhibit inflammation.

The most common and simple way of studying wound healing in rodents involves creating a standardized wound with a skin biopsy punch.  The model can be setup in way such that each animal serves as its own control by applying two wounds to either side of the animal—one treated and one untreated or vehicle-treated.  Evaluation of wound diameter over time as well as time to wound closure is a simple, cost-effective way of measuring the healing process.  Melior also routinely includes histological evaluations in our wound healing studies.

The study illustrated below shows the effect of a test article compared to vehicle over the course of the wound healing process.

Male C57BL/6 mice were anesthetized with ketamine/xylazine and the caudal half of their back shaved with a clipper to remove excess hair. This is done carefully to avoid cuts in skin. Depilatory cream (Nair) was used to remove all remaining hair. Mice received a full thickness 8-mm skin punch biopsy in the center of the shaved area. Wounds were dressed after the first measurement with a Bioclusive transparent oxygen permeable wound dressing (Johnson & Johnson). This dressing was removed for pictures and measurements on day 2 and was not be reapplied for the remainder of the study.

Wound sizes in diameter were measured with a digital caliper (mm), and representative pictures typically were also taken on days 0, 2, 4, 7, 9, 11, 14, and 16.  Mice were anesthetized to allow pictures and measurements to be taken.

Data are mean ±SEM analyzed using a t-test. (N=8) **p<0.01

This is a sub-chronic model evaluating effects of test articles (typically with multiple administrations).  Group sizes of 8 to 10 are conventional. It works well in both rats and mice. It also works in specialty model such as diabetes models such a STZ-insulin-depleted rat model.