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Toxicologic Pathology
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Articles

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

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

GSK Research Centre Zagreb Ltd., Zagreb, Croatia

Correspondence: Vanesa Ivetic Tkalcevic, GSK Research Centre Zagreb Ltd., Prilaz baruna Filipovica 29, 10000 Zagreb, Croatia; e-mail:vane-sa.i.ivetic-tkalcevic{at}gsk.com.

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.

Key Words: diabetes • histopathology • planimetry • wound healing

Abbreviations: db/db mice, genetically diabetic female C57BL/KsJ db+/db+ mice • FGF, fibroblast growth factor • HoxD3, homeobox D3 • MCP-1/CCL2, macrophage chemoattractant protein 1 • MIP-2, macrophage inflammatory protein 2 • PDGF, platelet-derived growth factor • VEGF, vascular endothelial growth factor

This version was published on February 1, 2009

Toxicologic Pathology, Vol. 37, No. 2, 183-192 (2009)
DOI: 10.1177/0192623308329280
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