Page 97 - IJB-10-3

International Journal of Bioprinting 3D bioprinting for vascularized skin tissue engineering

Figure 2. (A) The wound-healing process is influenced by both vasculogenesis and angiogenesis. (B) Four stages of cutaneous wound healing in mature mice: (a)
immediate reactions, including blood-clot formation and neutrophil recruitment (0–2 h); (b) inflammatory responses involving the recruitment of neutrophils
and monocytes from the peripheral bloodstream, as well as the activation of tissue-resident cells (1–72 h); (c) re-epithelialization, where keratinocytes proliferate
and migrate to repair the wound, accompanied by the formation of fibrotic granulation tissue, collagen deposition, and angiogenic sprouting (3–10 days); and
(d) contraction of the wound through myofibroblasts, wound closure, resolution of inflammatory processes, and scar remodeling (14 months).

vascular structure. The hypodermis—the innermost layer During skin implantation, improving vascularization
of the skin—is composed mostly of adipocytes. It serves is essential. Vasculogenesis can be achieved by means
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as a connection between muscle tissue and the dermal of pre-vascularization and angiogenesis. Due to poor
layer. Damage to or loss of the hypodermis caused by deep microvessel development (about 5 µm/h) in large skin
wounds that extend to this layer presents a significant implants, angiogenesis alone encounters challenges.
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obstacle to the wound-healing process. 27,28 Before transplantation, pre-vascularization generates
microvessels inside the tissue layers to ensure an increased
3. Enhancing vascularization strategies in supply of blood. Table 2 presents an overview of
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human skin tissue for effective in vitro skin various factors that may influence the vascularization of
modeling and in vivo wound healing skin constructs.
3.1. Importance of vascularization in human skin for The neovascularization in native skin (Figure 2A)
in vitro modeling and in vivo wound healing involves the formation of new blood vessels by angiogenesis
The clinical efficacy of tissue engineered skin and vasculogenesis process. These processes occur when
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transplantation depends on effective vascularization. The endothelial progenitor cells (EPCs) differentiate into ECs,
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limited blood flow can result in problems with necrosis. forming a complex vascular network where blood supply
Volume 10 Issue 3 (2024) 89 doi: 10.36922/ijb.1727