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Toxicologic Pathology
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Article

Differential Evaluation of Excisional Non-occluded Wound Healing in db/db Mice

Vanesa Ivetic Tkalcevic*, Snjezana Cuzic, Michael J. Parnham, Ivanka Pasalic, and Karmen Brajsa

GSK Research Centre in Zagreb, Ltd.

* To whom correspondence should be addressed. E-mail: vanesa.it{at}gmail.com; vanesa.i.ivetic-tkalcevic@gsk.com.


   Abstract

The full-thickness wound in the genetically diabetic (db/db) mouse is a commonly used model of impaired wound healing. We investigated delayed healing of non-occluded, excisional, full-thickness, dermal wounds in db/db mice in comparison to their normal littermate controls and refined methods for monitoring skin wound re-epithelialization, contraction, granulation tissue formation, and inflammation. We have confirmed with a computer-assisted planimetry method the results of previous studies showing that healing of non-occluded full excision wounds in db/db mice does not occur by contraction as much as in healthy mice. In addition, we have developed separate histological methods for the assessment of re-epithelialization, contraction, granulation tissue (mature, immature, fibrosis), and inflammation (lipogranulomas, secondary, nonspecific). Using a new approach to histological assessment, we have shown that wound closure in db/db mice is delayed owing to: (1) delayed granulation tissue maturation; (2) "laced," widely distributed granulation tissue around fat lobules; and (3) obstruction by lipogranulomas, whereas the rate of re-epithelialization seems to be the same as in C57Bl/6 mice. This methodology should permit a more precise differentiation of effects of novel therapeutic agents on the wound healing process in db/db mice.

First published on January 30, 2009, doi:10.1177/0192623308329280

Toxicologic Pathology 2009;37:183.

A more recent version of this article appeared on February 1, 2009
This version was published on February 2, 2009


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