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

The skin consists of epidermis and dermis. The epidermis— tissue. Additionally, bioactive molecules like vascular
the outermost layer of the skin—functions as a barrier endothelial growth factor (VEGF) can be incorporated into
that protects the skin from external chemical, physical, the construct at specific locations using 3D bioprinting.
and biological risks. The dermis—the second layer—is a These growth factors play a pivotal role in stimulating ECs
complex structure with many components that are crucial to form functional vascular network. In summary, the
for proper skin function. It contains a network of blood 3D bioprinting technique allows for the development of
vessels responsible for supplying oxygen and nutrients to functional vascular networks through precise control over
the cells that constitute the skin tissue. 3,4 the distribution of relevant cells and growth factors. These
Damage to dermal layer containing vascular advancements would not only enhance the functionality
networks impairs efficient wound-healing process, and integration of transplanted tissues and organs but also
which involves a sequence of cellular functions such as unlock the potential of regenerative medicine.
hemostasis, inflammation, proliferation, maturation, The purpose of this review is to introduce various
and remodeling. Vascular regeneration process, which aspects of vascularization strategies and important
1,5
facilitates the reconstruction of vascular networks in the components of wound healing used to explore the
wounded skin, can be slightly accelerated using wound development of engineered human functional vascular
dressings. However, traditional dressings such as gauze skin tissues. Through continuous development, 3D
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and tulle are not suitable for patients who need continuous bioprinting techniques have become increasingly efficient
treatment and have significant exuding wounds. Despite for producing vascularized skin. Additionally, we discuss
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the development of advanced polymeric dressing devices the advantages of different 3D bioprinting techniques
utilizing materials such as poly (vinyl alcohol), chitosan, and ideal candidates for bioinks used in vascular 3D skin
polyurethane, poly(ε-caprolactone) (PCL), and alginate, bioprinting. We also address future perspectives and
these devices have inherent limitations when it comes to provide solutions in this highly dynamic field of research
promoting essential vascularization for effective wound skin that involves 3D-bioprinted skin tissue for the successful
treatment. This is because they primarily address moisture formation of vascularized functional skin in vitro and
retention and the prevention of secondary infections. in vivo.
Tissue engineering, which employs biomaterials,
bioactive compounds, and cells, has recently emerged as a 2. Human skin structure and functions
promising approach to tackle these challenges. The supply Human skin is composed of several appendages (Table 1),
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of nutrients to engineered tissue is limited to a distance each of which serves a distinct biological function and
up to 200 µm, accomplished through diffusion from the possesses a unique architecture and properties that
surface in contact with the culture media. 10,11 Consequently, collectively provide protection for the underlying organs.
15
most tissue engineering scaffolds have been designed with In general, the skin comprises three layers: the epidermis,
high porosity to facilitate tissue reconstruction by allowing dermis, and hypodermis (Figure 1).
the infiltration of blood vessels from the host tissue. The epidermis serves as a vital protective barrier,
15
Nevertheless, this approach inherently results in sluggish protecting against stress and regulating the absorption
vascularization. Typically, vascularization processes at of water and chemicals. An epidermis is composed of
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an average rate of about 5 µm/h, implying that it takes five sublayers, including the stratum corneum, stratum
several months to achieve complete vascularization for spinosum, stratum granulosum, stratum lucidum, and
larger wounds that span several millimeters in length. stratum basale. 17,18 In the stratum corneum, basal-layer
13
Moreover, delayed vascularization can have adverse effects keratinocyte stem cells are replenished by lower-layer
on cell viability and lead to uneven nutrient distribution keratinocytes. 19,20 Found in the stratum spinosum,
within the scaffold, ultimately hindering cell growth Langerhans cells play a role in triggering immune
and function. 14
responses. Between the epidermis and dermis, a cutaneous
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Hence, the establishment of vascularization from basement membrane region integrates the underlying
within the engineered construct itself is critically essential keratinocytes with collagen fibers. Its primary function
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to ensure its survival, functionality, and integration. From is to act as an adhesive between the two layers. Because
this perspective, three-dimensional (3D) bioprinting has the epidermis lacks blood vessels, the basement membrane
emerged as a promising solution to address this challenge. zone facilitates the transfer of nutrients and oxygen from
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It accomplishes this by precisely depositing bioinks the vascular and non-vascular dermis to the epidermis.
containing bioactive molecules and endothelial cells (ECs) The dermis is essential for providing structural support
into predetermined patterns, thereby enabling the creation and cushioning for the body. It consists of connective
of intricate vascular structures within the engineered tissue, including vascular structures, lymphatic vessels,

Volume 10 Issue 3 (2024) 87 doi: 10.36922/ijb.1727