Design matters: A comparison of natural versus synthetic skin substitutes across benchtop and porcine wound healing metrics: An experimental study.

Background and Aims: Skin substitutes, essential tools for helping close full thickness wounds with minimal scarring, are available in both collagen-based and synthetic polyurethane constructions. Here we explore fundamental differences between two frequently used skin substitutes and discuss how these differences may impact in vivo performance. Methods: Polyurethane- and collagen-based matrices were characterized in vitro for pore size via scanning electron microscopy, hydrophobicity via liquid contact angle, conformability via bending angle, and biocompatibility via fibroblast and keratinocyte adhesion and proliferation. These matrices were then evaluated in a full-thickness excisional pig wound study followed by histological analysis. Statistical analysis was performed using Results: Average pore diameter in the tested polyurethane matrix was over four times larger than that of the collagen matrix (589 ± 297 µm vs. 132 ± 91 µm). Through liquid contact angle measurement, the collagen matrix (not measurable) was found to be hydrophilic compared to the hydrophobic polyurethane matrix (>90°). The collagen matrix was significantly more conformable than the polyurethane matrix (9 ± 2° vs. 84 ± 5° bending angle, respectively). Fibroblast and keratinocyte adhesion and proliferation assays elucidated a significantly greater ability of both cell types to attach and proliferate on collagen versus polyurethane. While the porcine study showed minimal contraction of either matrix material, histological findings between the two treatments were markedly different. Collagen matrices were associated with early fibroblast infiltration and fibroplasia, whereas polyurethane matrices elicited a strong multinucleated giant cell response and produced a network of comparatively aligned collagen fibrils. Conclusions: The more favorable in vitro properties of the collagen matrix led to less inflammation and better overall tissue response in vivo. Overall, our findings demonstrate how the choice of biomaterial and its design directly translate to differing in vivo mechanisms of action and overall tissue quality.