Influence of electrospun collagen on wound contraction of engineered skin substitutes

The treatment of massive full-thickness burns with engineered skin substitutes has shown promise in clinical trials. The majority of skin substitutes are comprised of fibroblasts and/or keratinocytes on collagen scaffolds, commonly generated by freeze drying which can generate significant structural heterogeneity. Electrospinning may generate collagen scaffolds with greater homogeneity. Skin substitutes were fabricated using either freeze-dried (FD) or electrospun (ES) collagen scaffolds. Cell distribution, proliferation, organization, and maturation were assessed on each scaffold type in vitro, and engraftment and healing of full thickness wounds in athymic mice were tested. In vitro evaluation of freeze-dried collagen skin substitutes (FCSS) and electrospun collagen skin substitutes (ECSS) revealed no significant differences in cell proliferation, surface hydration, or cellular organization between the ECSS and FCSS groups. Both groups exhibited excellent stratification with a continuous layer of basal keratinocytes present at the dermal–epidermal junction. After grafting to full thickness wounds in athymic mice, both skin substitutes had high rates of engraftment: 87.5% in the FCSS group and 100% in the ECSS group. Histological evaluation of wounds revealed that bovine collagen persisted in the wound at week 8 in the FCSS group while no bovine collagen was seen in the ECSS group. At 8 weeks post-grafting, the ECSS grafts were 61.3±7.9% original graft area whereas the FCSS grafts were 39.2±8.8% original area (p<0.01). These results indicate that ES scaffolds can be used to fabricate skin substitutes with optimal cellular organization and can potentially reduce wound contraction compared to FD scaffolds. These advantages may lead to reduced morbidity in patients treated with skin substitutes fabricated from ES collagen.