The effect of topical tretinoin on tissue strength and skin components in a murine incisional wound model.
BACKGROUND
Vitamin A derivatives modulate the inflammatory phase in wound healing. Retinoic acid can restore decreased tensile strength and collagen content in steroid- or diabetes-impaired wounds. It is hypothesized that retinoic acid can lead to accelerated healing with improved breaking strength in unimpaired incisional wounds.


METHODS
Skin incisions were made in 45 CD-1 mice. The sutured wounds were treated once daily with topical all-trans-retinoic acid 0.1% (n = 15), vehicle ointment (n = 15), or left untreated (n = 15). Skin biopsies at 1-, 2-, and 3-week intervals were examined using hematoxylin and eosin (H&E), Masson's trichrome, and immunoperoxidase staining methods. Wound breaking strength was determined by biomechanical analysis.


RESULTS
Incisions treated with retinoic acid exhibited a significantly reduced breaking strength at week 1 when compared to the vehicle and control group. Histologic examination showed a prolonged inflammatory reaction with abundant deposition of granulation tissue. Despite an increased fibroplastic proliferation in the tretinoin-treated wounds, the production of collagen was diminished.


CONCLUSIONS
Topical retinoic acid does not enhance the healing of unimpaired incisional wounds. The inadequate tensile strength in the early phase of the healing process is possibly the result of an increased dermal inflammatory response and the decreased collagen content. Although these adverse effects disappeared by 3 weeks postwounding, we found no discernible benefit of supplemental retinoic acid in unimpaired wounds.
Muehlberger
Thomas
T
Department of Plastic Surgery, Park-Klinik Weissensee, Charité Medical School, Berlin, Germany. muehlberger@park-klinik.com
Moresi
J Margaret
JM
Schwarze
Hartmut
H
Hristopoulos
Georgios
G
Laenger
Florian
F
Wong
Lesley
L
D000287:Administration, Topical; D000818:Animals; D003094:Collagen / Q000032:analysis; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D012867:Skin / Q000033:anatomy & histology / Q000737:chemistry; D013718:Tensile Strength / Q000187:drug effects; D014212:Tretinoin / Q000008:administration & dosage* / Q000627:therapeutic use; D014945:Wound Healing / Q000187:drug effects*; D014951:Wounds, Stab / Q000188:drug therapy / Q000473:pathology
D014212:Tretinoin; D003094:Collagen