Proapoptotic effect of control-released basic fibroblast growth factor on skin wound healing in a diabetic mouse model.
The ability of basic fibroblast growth factor (bFGF) to improve wound healing is attenuated by its short half-life in free form. This study aimed to enhance skin wound healing in a diabetes mouse model while concomitantly decreasing scar formation using control-released bFGF together with acidic gelatin hydrogel microspheres (AGHMs). Bilateral full-thickness wounds (10 mm in diameter) were made on the backs of db/db mice. Forty-five mice were divided into three groups, and the base of the wound under the panniculus carnosus and the wound periphery were injected with phosphate-buffered saline (300 μL) containing (1) control-released bFGF (50 μg), (2) control-released bFGF (20 μg), or (3) AGHMs alone. The size of the wound area was recorded on each postoperative day (POD). Mice were sacrificed on postoperative day 4, 7, 10, 14, and 28, and skin wound specimens were obtained to assess the endothelium/angiogenesis index via cluster of differentiation 31 immunohistochemistry, the proliferation index via Ki-67 immunohistochemistry, and the myofibroblast and fibroblast apoptosis indices by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and alpha-smooth muscle actin or vimentin staining, respectively. Epithelialization rates and indices of proliferation and myofibroblast/fibroblast apoptosis were higher in the bFGF groups than in the AGHM group, mainly within 2 weeks of injury. No dose-effect relationship was found for control-released bFGF, although the actions of 50 μg bFGF seemed to last longer than those of 20 μg bFGF. Therefore, control-released bFGF may accelerate diabetic skin wound healing and induce myofibroblast/fibroblast apoptosis, thereby reducing scar formation.
Department of Plastic, Reconstructive and Aesthetic Surgery, Nippon Medical School, Tokyo, Japan.|Department of Plastic and Reconstructive Surgery, Medical Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China.|Department of Plastic Surgery, Meitan General Hospital, Beijing, China.
Chenyu
C
Huang
Department of Plastic, Reconstructive and Aesthetic Surgery, Nippon Medical School, Tokyo, Japan.
Hakan
H
Orbay
Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Morikuni
M
Tobita
Department of Cardiology, Nippon Medical School, Tokyo, Japan.
Masaaki
M
Miyamoto
Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Yasuhiko
Y
Tabata
Department of Plastic, Reconstructive and Aesthetic Surgery, Nippon Medical School, Tokyo, Japan.
Hiko
H
Hyakusoku
Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Hiroshi
H
Mizuno
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003692:Delayed-Action Preparations; D003921:Diabetes Mellitus, Experimental; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects; D005780:Gelatin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008863:Microspheres; D058628:Myofibroblasts / Q000187:drug effects; D062326:Re-Epithelialization / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014746:Vimentin / Q000187:drug effects / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
D000199:Actins; D003692:Delayed-Action Preparations; D014746:Vimentin; C544013:alpha-smooth muscle actin, mouse; D016222:Fibroblast Growth Factor 2; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin