Scarless healing of oral mucosa is characterized by faster resolution of inflammation and control of myofibroblast action compared to skin wounds in the red Duroc pig model

Mak, Karen; Manji, Aleem; Gallant-Behm, Corrie; Wiebe, Colin; Hart, David A.; Larjava, Hannu; Häkkinen, Lari

doi:10.1016/j.jdermsci.2009.09.005

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Scarless healing of oral mucosa is characterized by faster resolution of inflammation and control of myofibroblast action compared to skin wounds in the red Duroc pig model

Karen Mak
- Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada
Aleem Manji
- Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada
- Schulich School of Dentistry, University of Western Ontario, London, ON, Canada
Corrie Gallant-Behm
- Department of Surgery, McCaig Institute of Bone and Joint Health, University of Calgary, Calgary, AB, Canada
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Colin Wiebe
- Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada
David A. Hart
- Department of Surgery, McCaig Institute of Bone and Joint Health, University of Calgary, Calgary, AB, Canada
Hannu Larjava
- Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada
Lari Häkkinen
- Faculty of Dentistry, University of British Columbia, Vancouver, BC, Canada
- Corresponding author at: Faculty of Dentistry, University of British Columbia, Department of Oral Biological and Medical Sciences, Laboratory of Periodontal Biology, 2199 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3. Tel.: +1 604 822 0096; fax: +1 604 822 3562.

Received 8 April 2009; received in revised form 21 July 2009; accepted 11 September 2009. published online 12 July 2010.
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Abstract

Background

Scar formation following skin trauma can have devastating consequences causing physiological and psychosocial concerns. Currently, there are no accepted predictable treatments to prevent scarring which emphasizes a need for a better understanding of the wound healing and scar formation process.

Objectives

Previously it was shown that healing of small experimental wounds in the oral mucosa of red Duroc pigs results in significantly reduced scar formation as compared with equivalent full-thickness skin wounds. In the present study, scar formation was assessed in 17 times larger experimental wounds in both oral mucosa and skin of the red Duroc pigs.

Methods

Equivalent experimental wounds were created in the oral mucosa and dorsal skin of red Duroc pigs, and scar formation, localization and abundance of key wound healing cells, transforming growth factor-β (TGF-β) and phosphorylated Smad3 (pSmad3) were assessed.

Results

Oral mucosal wounds displayed significantly less clinical and histological scar formation than did the corresponding skin wounds. The number of macrophages, mast cells, TGF-β and pSmad3 immunopositive cells was significantly reduced in the oral mucosal wounds as compared with skin wounds during the maturation stage of the healing process. Although the number of myofibroblasts was significantly elevated, the oral mucosal wounds showed significantly less contraction than did the skin wounds over time.

Conclusions

Earlier resolution of the inflammatory reaction and reduced wound contraction may promote scarless oral mucosal wound healing. In addition, scar formation likely depends not only on the number of myofibroblasts but also on the extracellular environment which regulates their function.

Keywords: Wound healing, Scar, Oral mucosa, Skin, Transforming growth factor-beta