Abstract
Wound healing is a complex phenomenon that involves different cell types with various functions, i.e., keratinocytes, fibroblasts, and endothelial cells, all influenced by the action of soluble mediators and rearrangement of the extracellular matrix (ECM). Physiological angiogenesis occurs in the granulation tissue during wound healing to allow oxygen and nutrient supply and waste product removal. Angiogenesis output comes from a balance between pro- and antiangiogenic factors, which is finely regulated in a spatial and time-dependent manner, in order to avoid insufficient or excessive nonreparative neovascularization. The understanding of the factors and mechanisms that control angiogenesis and their change following unloading conditions (in a real or simulated space environment) will allow to optimize the tissue response in case of traumatic injury or medical intervention. The potential countermeasures under development to optimize the reparative angiogenesis that contributes to tissue healing on Earth will be discussed in relation to their exploitability in space.
Highlights
The skin is the largest organ by surface area in the human body
Chemotaxis of ECs is driven by growth factors (VEGF and fibroblast growth factor-2 (FGF-2), among the most important), haptotaxis is related to increased EC migration activated in response to integrins, bound to extracellular matrix (ECM) components, and mechanotaxis is associated to a polarization of cytoskeleton and cell-ECM interactions in the blood flow direction (Lamalice et al, 2007)
Inhibition of cell proliferation and angiogenesis was verified in skeletal muscles of rats exposed to hindlimb unloading through RNA sequences analysis (Cui et al, 2020). These results suggest that keratinocyte and EC functions may be impaired during the wound healing process under periods of prolonged inactivity or bed rest
Summary
The skin is the largest organ by surface area in the human body. Its structure is highly organized with different cell types (epithelial, stromal, and endothelial cells-ECs), which finely cooperate in order to guarantee a constant functioning and structural homeostasis of the organ. The skin is the first defensive barrier of our body that protects internal tissues from microbial infections, mechanical damages, UV radiations, dangerous substances, and high temperatures. The maintenance of its integrity is fundamental for our survival and skin repair, following a mechanical or physical injury, implying very complex and delicate processes to recover its integrity and barrier function (Sorg et al, 2017; Rodrigues et al, 2019). We report the state-of-the art of tissue wound healing phases and factors, the role of angiogenesis and the potential pharmacological, cellular, and physical countermeasures acting on ECs. The aim of the article is to understand how to apply all these findings in the space environment as the one that astronauts face during long duration missions. The review article is based on the recent/most cited
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