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International Journal of Bioprinting 3D bioprinted vascularized tissue models

conduits with tunable geometry and dimensions by heterotypic cell–cell communication and cell–ECM
controlling the nozzle moving speed and extrusion flow interactions. Third, proper biomechanical and biochemical
rate. They designed a tri-layered coaxial nozzle containing cues must be introduced to orchestrate cellular activities
sacrificial PF-127 in the core region, endothelial cells and direct tissue maturity and function. Finally, the model
(ECs)-laden vascular tissue-derived decellularized ECM should be easy to reproduce and amenable to commonly
(VdECM) bioink in the intermediate region, and smooth used tissue culture and engineering methods, thus
muscle cells-laden VdECM in the shell region according to facilitating the application of standard evaluation methods
the native blood vessel structure, enabling the emulation of of molecular analysis and live imaging. Accordingly, the 3D
more complex vascular structures with multiple layers and bioprinting platform can provide fascinating insights into
heterogeneous cell populations. vascularized model development that can not only recreate
The inherent benefits of coaxial bioprinting involve the vascular networks, but also allow biological elements
precise control of concentric multi-material deposition, (cells, biomolecules, and their products) to dynamically
one-step facile manufacturing process, flexibility of reorient or remodel an integrated vascular system. This
dimensions (e.g., diameter, wall thickness, and length), review does not cover the details of cell type, matrix type,
and the fabrication of vascular structure with high aspect and biomaterials used for engineering vasculature, which
[6,7,9,13]
ratio. However, creating a branched vascular network is have been featured elsewhere ; however, note that
difficult owing to the continuous deposition of a uniform more advanced materials and optimized protocols from
tubular structure, which further requires technological cell and molecular biology are necessary for the continued
convergence and advancements. advancement of 3D bioprinting multi-scale functional
vasculature. Collectively, the ideal 3D-bioprinted in vitro
2.5. Key elements in 3D bioprinting in vitro model recapitulates the compositional and structural
vascularized models heterogeneity of the target tissue in living organisms
Complex blood vessels pervade virtually all tissues in and is amenable to assemble them. We envision that
the body and affect diverse physiological functions in an 3D-bioprinted models may provide a much more
organ-specific manner . To better understand how blood economical option for advancing the translational research
[7]
vessels develop and function as well as their pathological and drug discovery pipeline.
implications, researchers have strived to engineer 3D living
vascular systems that resemble the structure and function 3. Applications of 3D bioprinting in
of native blood vessels. Innovative approaches to fulfill modeling 3D in vitro vascular tissues
this critical need have been employed with 3D bioprinting
technology. The specific methods of 3D bioprinting applied Because vascularization is a vital component to reconstitute
to vascularization can be categorized into (i) coordinated organ-level physiological functions, an emerging
patterning, (ii) sacrificial, (iii) embedding, and (iv) coaxial direction in establishing a solid vascularized tissue has
bioprinting methods for engineering vascularized tissue been pursued to resemble the in vivo state within organ-
models in vitro. Specifically, coordinated pattering strategy specific vasculature. With advances in 3D bioprinting
was mainly used to promote vascular assembly (e.g., techniques and biomaterials, 3D in vitro models of
vasculogenesis and angiogenesis) for vascular network numerous vital organs and diseases have been developed
formation in the bioprinted constructs via endogenous/ and validated [6,25,41] . In this section, we discuss recent
exogenous induction. Meanwhile, sacrificial, embedding, 3D bioprinting strategies for constructing vascularized
and coaxial bioprinting strategies were primarily used tissue models, including specific designs, materials, and
to create hollow vascular channels within the bioprinted fabrication approaches as well as the notable achievements
tissue models. Given the functional importance of of their applications (Table 2). Here, taking vessel, liver,
vasculatures, 3D bioprinting has made transformative kidney, and tumor as examples, we review the pioneering
progress in reproducing the complex vascular network and representative work in 3D-bioprinted in vitro models.
within engineered tissues.
3.1. 3D bioprinting of perfusable vessel models
To establish a functional vascularized model, identifying Blood vessels are fundamental in circulating nutrients,
the key elements to be pursued is crucial. First, the model oxygen, and metabolic wastes and vitalizing most tissues
should include all relevant cell types pertaining to target and organs. Given the diffusion limit of living tissues within
tissues and should be spatially organized according to 200 μm from the nearest capillary, the lack of vasculature
the anatomical structures. Second, complex and dynamic in engineering tissues hinders oxygen and nutrient supply
ECM environments found in healthy and diseased states and the maintenance of normal physiological conditions.
of vascularized tissues should be realized to manipulate More importantly, manufacturing techniques need to be

Volume 9 Issue 5 (2023) 19 https://doi.org/10.18063/ijb.748