Combination of stromal cell-derived factor-1 and collagen-glycosaminoglycan scaffold delays contraction and accelerates reepithelialization of dermal wounds in wild-type mice.
While dermal substitutes can mitigate scarring and wound contraction, a significant drawback of current dermal replacement technologies is the apparent delay in vascular ingrowth compared with conventional skin grafts. Herein, we examined the effect of the chemokine stromal cell-derived factor-1 (SDF-1) on the performance of a porous collagen-glycosaminoglycan dermal analog in excisional wounds in mice. C57BL/6 mice with 1 cm × 1 cm dorsal full-thickness wounds were covered with a collagen-glycosaminoglycan scaffold, followed by four daily topical applications of 1 μg SDF-1 or phosphate-buffered saline vehicle. Some animals were also pretreated with five daily doses of 300 mg/kg granulocyte colony-stimulating factor. Animals treated with SDF-1 and no granulocyte colony-stimulating factor reepithelialized 36% faster than vehicle controls (16 vs. 25 days), and exhibited less wound contraction on postwounding day 18 (∼ 35% greater wound area) plus three-fold longer neoepidermis formed than controls. Conversely, granulocyte colony-stimulating factor promoted contraction and no epidermal regeneration. Early (postwounding Day 3) inflammatory cell infiltration in the SDF-1-treated group was 86% less, while the fraction of proliferating cells (positive Ki67 staining) was 32% more, when compared with controls. These results suggest that SDF-1 simultaneously delays contraction and promotes reepithelialization and may improve the wound-healing performance of skin substitutes.
Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Aparajita
A
Sarkar
Soner
S
Tatlidede
Saja Sandra
SS
Scherer
Dennis P
DP
Orgill
François
F
Berthiaume
D000818:Animals; D054377:Chemokine CXCL12 / Q000627:therapeutic use*; D003094:Collagen; D020405:Dermis / Q000293:injuries*; D006025:Glycosaminoglycans; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017768:Skin, Artificial; D054457:Tissue Scaffolds; D014945:Wound Healing / Q000502:physiology*; D014950:Wounds, Penetrating / Q000473:pathology / Q000628:therapy*
D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D006025:Glycosaminoglycans; D016179:Granulocyte Colony-Stimulating Factor; D003094:Collagen