The future of wound healing: Pursuing surgical models in transgenic and knockout mice

BACKGROUND: Transgenic and knockout technologies have made determination of the molecular basis of wound healing possible. But there is no comprehensive or standardized approach to the investigation of wound healing in the mouse. A convention is proposed for assessing the multiple dimensions of wound healing. An approach to phenotyping a transgenic or knockout animal in a reproducible fashion is presented using this convention. STUDY DESIGN: Age- and gender-matched wildtype and knockout mice were characterized using six parameters of wound healing: epithelialization, granulation tissue formation, contraction, tensile strength, angiogenesis, and response to ischemia. Six surgical (four standard and two impaired) models were designed and used to quantitate these parameters. These models can be combined to efficiently maximize the data from any given subject. RESULTS: Each model leads to a rapid yield of results, with an average turnover of 4.9 days (range 3 to 7 days), and morbidity and mortality were minimal. A combinatorial approach elucidates the precise wound repair deficit of any subject. A case example is presented. CONCLUSIONS: Six surgical models investigating pertinent wound healing parameters are available. A factorial approach of quantitative wound healing assays maximizes data gathered from any one animal, minimizing,the number of transgenic and knockout subjects needed; finely dissects molecular pathways of wound healing; and rapidly phenotypes a particular genetically altered mouse. We propose a standardized approach to wound healing assays that will elucidate critical cellular and molecular mechanisms and potential therapies. (C) 2004 by the American College of Surgeons.