Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.
Sunnybrook Research Institute, Toronto, ON, Canada.
J Anat. 2019 Apr;234(4):523-531. doi: 10.1111/joa.12941. Epub 2019 Feb 20.
Severe cutaneous wounds expose the body to the external environment, which may lead to impairments in bodily functions and increased risk of infection. There is a need to develop skin substitutes which could effectively promote complete skin regeneration following an injury. Murine models are used to test such skin substitutes, but their healing involves contraction of the dermis not found in human wounds. We have previously described a device called a dome, which comes in two models, that is used to prevent skin contraction in mice. One model provides a physical barrier to minimize contraction, and the other model has additional perforations in the barrier to allow cellular contribution from the surrounding intact skin. Taking advantage of an enhanced version of these two models, we compared granulation tissue formation, the extent of vascularization, and the transition to myofibroblastic phenotype between the models. We enhanced the dome by developing a twist open cap dome and applied the two models of the dome into the excisional wound biopsy in mice. We demonstrate that the dome can be used to prevent skin contraction in mice. The control model prevented skin contraction while barricading the contribution of surrounding intact skin. When not barricaded, the intact skin enhances wound healing by increasing the number of myofibroblasts and neovascularization. Using a novel model of inhibition of skin contraction in rodents, we examined the contribution from the surrounding intact skin to granulation tissue formation, myofibroblastic differentiation, and neovascularization during the course of skin healing in mice.
严重的皮肤创伤使身体暴露于外部环境中，这可能导致身体功能受损和感染风险增加。因此，需要开发能够在受伤后有效促进完全皮肤再生的皮肤替代物。鼠类模型被用于测试这种皮肤替代物，但它们的愈合过程涉及到真皮的收缩，而人类伤口中不存在这种收缩。我们之前描述过一种名为穹顶的装置，它有两种型号，用于防止小鼠皮肤收缩。一种型号提供物理屏障以最小化收缩，另一种型号在屏障上增加了穿孔，以允许周围完整皮肤的细胞贡献。利用这两种型号的增强版本，我们比较了两种型号之间肉芽组织形成、血管化程度和向肌成纤维表型的转变。我们通过开发一种扭开式帽穹顶来增强穹顶，并将两种穹顶模型应用于小鼠的切除性伤口活检中。我们证明穹顶可用于防止小鼠皮肤收缩。对照模型在阻挡周围完整皮肤贡献的同时，防止了皮肤收缩。当不被阻挡时，完整皮肤通过增加肌成纤维细胞和新生血管的数量来增强伤口愈合。我们使用一种新型的抑制啮齿动物皮肤收缩的模型，研究了在皮肤愈合过程中，来自周围完整皮肤对肉芽组织形成、肌成纤维分化和新生血管形成的贡献。
