Abstract
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.
Highlights
In light of the various known chemotactic properties of stromal cell-derived factor-1 (SDF-1) toward stem cells and progenitor cells that may be beneficial to wound healing, we investigated the effect of an exogenous application of SDF-1 on the healing of wounds extending deep into the dermis when used in combination with a dermal skin substitute
We investigated the effect of systemic granulocyte colony-stimulating factor (GCSF) pretreatment to increase the number of circulating stem cells before SDF-1 application
We found that topically applied SDF-1, when used in combination with a crosslinked collagen–chondroitin sulfate matrix scaffold, delayed wound contraction and led to faster closure of a full-thickness excision wound in normal wild-type mice as compared with control animals grafted with the scaffold but otherwise treated with phosphate-buffered saline (PBS) vehicle
Summary
Digital images of the stained sections were obtained at 4× magnification to measure the relative percentage of the α-SMA-positive cell area in the wound area using NIH ImageJ software.[16] H&E stain was performed to visualize and compare the infiltration of inflammatory cells into the wound area among the animal groups at an early time point (Day 3). The inflammatory cell density was evaluated among the control and the GCSF+SDF-1 animal groups by assessing three fields per histological stained slide (one in the middle of the wound scaffold area and two on either lateral aspect) at ×40 magnification.
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