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International Journal of Bioprinting 3D bioprinted vascularized tissue models

the key aspects of human physiology and disease [1,2] . vascular environments, including anatomical structure,
Although many biomedical studies have typically used biochemical and biophysical dynamics, and relevant
two-dimensional (2D)/3D cell culture methods or animal physiological functions, have not yet been successfully
experiments, such conventional pre-clinical models face engineered.
significant drawbacks, including the lack of biological
complexity, cross-species discrepancies, and ethical To tackle this problem, 3D bioprinting has emerged
issues [2,3] . Alternatively, 3D in vitro models facilitate as a promising tool for developing an advanced in vitro
biomedical experimentations through the inclusion of model with functional vasculature. 3D bioprinting
relevant cell sources and organized biological structures allows for the generation of prescribed biomimetic tissue
in controlled microenvironments. Therefore, these structures through precise depositions of biomaterials,
models have received increasing interests as the next- cells, and biomolecules [17,18] . As each organ has its own
generation research platform to investigate human (patho) unique physiological role and contains distinct cell types
physiology and impact drug discovery pipelines [1,4] . Given and structures, a suitable design, materials, and fabrication
their inherent advantage of replicating physiological strategy are needed to emulate tissue/organ specificity
organ functions in a robust and reproducible manner, and functionality in vascularized tissue models. A high-
humanized in vitro models offer intriguing opportunities precision, multi-material 3D bioprinting system has been
to replace traditional cell cultures and animal models for considered a promising tool to fabricate tissue models that
clinical translation. mimic native tissue structures and reproduce complex
biological environments in a tissue-specific manner. In
The ultimate goal of 3D in vitro models is to reproduce addition, to obtain reliable in vitro models, advanced
physiologically and biologically realistic human model strategy is necessary for providing guidance cues within
systems outside the body. To date, substantial progress an organ-mimicking 3D environment, which could
has been made in the development of in vitro models to further enrich the structural similarity and functional
mimic the natural microenvironment and to understand maturity of the engineered tissues . Despite the advances
[19]
organ-specific function and pathological behavior [5-7] . in biofabrication techniques for engineering complex
However, the current models cannot reliably recapitulate vascular networks, unresolved issues remain, including
the key structural and physiological properties of their poorly defined structural organization, unmet size
their native counterparts. In particular, the lack of scale, and immaturity [5,20,21] . In this respect, 3D bioprinting
vascularization in the engineered tissues is one of the with multi-scale and multi-material fabrication process
paramount issues . In the human body, the vascular is useful to achieve robust vascularization in printed
[8]
network represents hierarchical organization and serves tissue models. Given the great importance of systematic
for the efficient exchange of nutrient and oxygen and interaction between vasculature and engineered tissues
for the removal of wastes within and between tissues/ in the developmental process, numerous bioprinting
organs . In addition, the presence of vascularization methods have been extensively explored to vascularize
[9]
in engineered tissues not only maintains cell viability in vitro tissues, including by spatial patterning of vascular
and function, but also supports cross-talk between precursors or generating a readily perfusable vascular
diverse cell and tissue types, effectively mimicking structures.
human biological responses [10] . Thus, engineering
functional vasculature is a prerequisite for the successful This review highlights the recent advances in 3D
engineering of physiologically relevant in vitro models. bioprinting strategies for vascularized tissue model
Over the past few decades, significant efforts have been development. First, we introduce the main bioprinting
devoted to developing 3D vascular tissues that replicate approaches for the fabrication of vascular structures and
the physiological properties of human vasculature within describe the key elements to rebuild functional vasculature
an in vitro biological system by introducing several in engineered tissues using 3D bioprinting. In the context of
intrinsic/extrinsic elements [9-11] . Numerous approaches engineered tissue vascularization, we focus on delineating
for generating vascularized tissues using various the 3D bioprinting strategies that not only build readily
biofabrication techniques (e.g., nano-/micro-fabrication, perfusable vascular channels, but also incorporate vascular
soft lithography, and replica molding for micro-fluidics) networks into bioprinted tissues via intrinsic/extrinsic
have already been explored [3,12,13] . Recently, self- induction. Next, we discuss the recent achievements in
assembling approaches have been attempted to create engineering 3D vascularized in vitro models using 3D
tubular structures by systematically modulating the co- bioprinting. Finally, the current challenges and future
assembling components [14-16] ; nevertheless, vascularized perspectives of engineering 3D bioprinting-based
tissues reflecting the complexity and multifariousness of vascularized tissue models are delineated.

Volume 9 Issue 5 (2023) 16 https://doi.org/10.18063/ijb.748