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International Journal of Bioprinting 3D bioprinted vascularized tissue models

osteogenesis. As another application, the skin has been constructs in desired complexity and arrangement,
a major focus of cosmetic research as it performs many which holds tremendous promise to tackle multiple
essential physiological functions including protection, questions in human biology and medicine that could be
conditioning, and sensation. Faced with the restrictions on insufficiently addressed using conventional biofabrication
animal testing for cosmetic products, engineering 3D skin techniques . Recent advances in bioprinting techniques,
[24]
model provides a valuable alternative to animal models. 3D material science, cell biology, and many other disciplines
bioprinting bolsters development of vascularized human have increased the possibility for engineering novel
skin equivalents as a novel in vitro skin model for drug in vitro model system to reflect organ physiology and
or cosmetic testing platform. Kim et al. constructed a disease states as closely as possible. In the last few decades,
[68]
perfusable and vascularized 3D skin equivalent mimicking significant progress has been made in the bioprinting
the structural complexity of the human skin. In the of in vitro vascularized tissue models for applications
custom-made polycaprolactone transwell chambers, the to biomedical research and drug screening. Despite the
bioprinted full-thickness skin models consisted of an significant advances described above, the structural,
epidermis (primary human epidermal keratinocytes), cellular, and molecular features of vascular networks
dermis (human dermal fibroblast‐loaded skin dECM with have yet to be fully achieved. With current bioprinting
fibrinogen), and hypodermis (preadipocyte‐laden adipose approaches, the clinical availability of bioprinted in vitro
dECM with fibrinogen). Gelatin and thrombin (sacrificial models is still elusive, and important practical challenges
material) loaded with HUVECs was utilized to form need to be addressed, including the construction of
vascular channels. They demonstrated that the engineered fully functional multi-scale vasculature, the assembly of
full-thickness skin models replicated the structural diverse cellular populations and tissue-specific matrices,
complexity of native human skin more realistically and prolonged functionality.
compared to the conventional dermal and epidermal In general, extrusion-based approaches have not
skin models. Moreover, the vascularized dermal and yet led to the fabrication of refined, fully functional
hypodermal compartments promoted interactions with the multi-scale vasculature due to the lack of resolution and
epidermal compartment, emulating native-like epidermal precision in the printed tissue constructs. Most vital
morphogenesis. The unique 3D-bioprinted platform of a organs, including the liver, kidneys, lungs, and brain,
perfusable vascularized human skin equivalents exhibited have a rich vascular system representing a complex
tissue development and closely mimicked natural human hierarchy of dimensions and compositions, from micro-
skin. Therefore, 3D bioprinting has provided a viable scaled capillaries to millimeter-sized vessels. Thus,
solution to the development of in vitro vascularized models more advanced bioprinting strategies with improved
of various tissues for interrogating human pathophysiology resolution and precision are necessary to produce
and pre-screening drug candidates. complex and scalable human vasculature. In addition,

4. Conclusion and future outlook replicating the cellular and compositional heterogeneity
of vascularized tissues in an organ-specific manner is
An unrelenting pressure exists to ascertain alternatives critical. Most of the reported bioprinting model studies
to traditional pre-clinical models, such as simple cell have been demonstrated by incorporating tissue-relevant
culture or animal testing, for better replicating biological parenchymal cell lines, thus making it difficult to fulfill
or therapeutic responses detected in humans [5,69] . This has the organ-specific requirements. The advancement of
led to the emergence of 3D in vitro models owing to their stem cell technology has allowed the isolation of induced-
ability to faithfully recapitulate the key architectural and pluripotent stem cells and organoids from adult or fetal
physiological characteristics within an in vitro setting. tissue biopsy samples . Leveraging high-quality human
[70]
Such models are expected to serve as reliable tools to cells, such as tissue-resident stem (embryonic or adult) or
narrow the gap between oversimplified planar culture induced-pluripotent stem cells and organoids, will pave
systems and species-discrepant animal models. Note that the way for a paradigm shift in developing more reliable in
vascularization is of utmost importance for the supply vitro models that emulate critical aspects of organ-specific
of oxygen and nutrients and for the manipulation of physiology and function. Moreover, the selection of ink
communication between cells and their extracellular materials that provide cells with a microenvironmental
environment. Therefore, engineering biomimetic and niche is essential for effective cell growth and
multi-scale vascular networks is essential for establishing function [22,71,72] . Among prevailing ink materials used
physiologically relevant 3D in vitro models. in 3D bioprinting, tissue-specific dECMs have received
increased attention as the most promising biomimetic
As cutting-edge biofabrication technology, 3D
bioprinting enables the production of 3D living ink material that can better provide the intrinsic natural

Volume 9 Issue 5 (2023) 29 https://doi.org/10.18063/ijb.748