1. ¹Institute of Cell Biology, Eidgenössische Technische Hochschule Zürich, Hönggerberg, Zürich, Switzerland
2. ²Department of Dermatology, University of Cologne, Cologne, Germany

Correspondence: Dr Hans Smola, Paul Hartmann AG, PO Box 1420, Heidenheim D-89504, Germany. Email: hans.smola@hartmann.info

³Current address: Paul Hartmann AG, PO Box 1420, Heidenheim 89504, Germany.

Received 25 October 2006; Revised 8 December 2006; Accepted 14 December 2006.

Abstract

Cutaneous tissue repair aims at restoring the barrier function of the skin. To achieve this, defects need to be replaced by granulation tissue to form new connective tissue, and epithelial wound closure is required to restore the physical barrier. Different wound-healing phases are recognized, starting with an inflammation-dominated early phase giving way to granulation tissue build-up and scar remodeling after epithelial wound closure has been achieved. In the granulation tissue, mesenchymal cells are maximally activated, cells proliferate, and synthesize huge amounts of extracellular matrix. Epithelial cells also proliferate and migrate over the provisional matrix of the underlying granulation tissue, eventually closing the defect. This review focuses on the role of keratinocyte–fibroblast interactions in the wound-healing process. There is ample evidence that keratinocytes stimulate fibroblasts to synthesize growth factors, which in turn will stimulate keratinocyte proliferation in a double paracrine manner. Moreover, fibroblasts can acquire a myofibroblast phenotype under the control of keratinocytes. This depends on a finely tuned balance between a proinflammatory or a transforming growth factor (TGF)--dominated environment. As the phenotype of fibroblasts from different tissues or body sites becomes better defined, we may understand their individual contribution in wound healing in more detail and possibly explain different clinical outcomes.