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.

Introduction Burned human skin, which is routinely excised and discarded, contains viable mesenchymal stromal/stem cells (burn-derived mesenchymal stromal/stem cells; BD-MSCs). These cells show promising potential to enable and aid wound regeneration. However, little is known about their cell characteristics and biological function. Objectives This study had two aims: first, to assess critical and cellular characteristics of BD-MSCs and, second, to compare those results with multipotent well-characterized MSCs from Wharton’s jelly of human umbilical cords (umbilical cord mesenchymal stromal/stem cells, UC-MSCs). Methods BD- and UC-MSCs were compared using immunophenotyping, multi-lineage differentiation, seahorse analysis for glycolytic and mitochondrial function, immune surface markers, and cell secretion profile assays. Results When compared to UC-MSCs, BD-MSCs demonstrated a lower mesenchymal differentiation capacity and altered inflammatory cytokine secretomes at baseline and after stimulation with lipopolysaccharides. No significant differences were found in population doubling time, colony formation, cell proliferation cell cycle, production of reactive oxygen species, glycolytic and mitochondrial function, and in the expression of major histocompatibility complex I and II and toll-like receptor (TLR). Importance, translation This study reveals valuable insights about MSCs obtained from burned skin and show comparable cellular characteristics with UC-MSCs, highlighting their potentials in cell therapy and skin regeneration.

Skin healing a complex and well-orchestrated process that involves the coordination and activity of many cell types. Myeloid lineage cells are inflammatory cells recruited to the wound site that remove injured tissue and invading pathogens. Besides this role, due to their ability to secrete a variety of growth factors and cytokines, myeloid cells influence each stage of wound healing (primarily inflammation and proliferation phases). Abnormalities in myeloid cell function lead to pathologies such as excessive and deficient healing. Therapies based on modulating myeloid cells may hold therapeutic potential. However, further research is needed to fully elucidate the spatial and temporal mechanisms of myeloid cells in skin healing. The objective of this review is to discuss recent findings on the role of myeloid lineage cells in skin healing and regeneration.