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BioMed Research International
Volume 2015, Article ID 712546, 10 pages
Research Article

Cooperative Regulation of Substrate Stiffness and Extracellular Matrix Proteins in Skin Wound Healing of Axolotls

1Liver Disease Prevention and Treatment Research Foundation, Taipei 10002, Taiwan
2Institute of Biotechnology, College of Bioresources and Agriculture, National Taiwan University, Taipei 10617, Taiwan
3Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan
4Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, Taiwan

Received 9 December 2014; Revised 22 February 2015; Accepted 24 February 2015

Academic Editor: Paul J. Higgins

Copyright © 2015 Ting-Yu Huang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Urodele amphibians (Ambystoma mexicanum), unique among vertebrates, can regenerate appendages and other body parts entirely and functionally through a scar-free healing process. The wound epithelium covering the amputated or damaged site forms early and is essential for initiating the subsequent regenerative steps. However, the molecular mechanism through which the wound reepithelializes during regeneration remains unclear. In this study, we developed an in vitro culture system that mimics an in vivo wound healing process; the biomechanical properties in the system were precisely defined and manipulated. Skin explants that were cultured on 2 to 50 kPa collagen-coated substrates rapidly reepithelialized within 10 to 15 h; however, in harder (1 GPa) and other extracellular matrices (tenascin-, fibronectin-, and laminin-coated environments), the wound epithelium moved slowly. Furthermore, the reepithelialization rate of skin explants from metamorphic axolotls cultured on a polystyrene plate (1 GPa) increased substantially. These findings afford new insights and can facilitate investigating wound epithelium formation during early regeneration using biochemical and mechanical techniques.