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International Journal of Bioprinting 3D bioprinting for vascular system
are unsuitable for cell culture. Zhang et al. demonstrated a underwent angiogenesis at a rate significantly faster than
bioprinting method that uses cells to simulate two-phase individual EVC cells (Figure 4B) .
[61]
water systems (ATPS) . The new ATPS used poly-lysine Support cells around blood vessels, such as perivascular
[54]
(PLL) aqueous solution as ink and oxidized bacterial cells, mesenchymal stem cells, and fibroblasts, provide
cellulose (oxBC) aqueous solution as a cell-containing mechanical support for blood vessel wall cells, shape the
medium. When the PLL ink loaded with cells was deposited microenvironment around blood vessels, and promote
into the oxBC medium phase, oxBC and PLL formed a angiogenesis. Therefore, adding support cells to vascular
condensed complex through electrostatic interaction at the printing, which utilizes hydrogels, is a recommended strategy.
water–water interface, successfully constructing a 3D cell
interconnection network lined with perfusion channels . As perivascular support cells, adipose-derived stem
[54]
cells (ASCs) express various angiogenic factors that
Laser-assisted technology has exceptionally high stimulate endothelial and smooth muscle cell proliferation.
resolution and can print feature sizes of less than 10 μm. For 7 days, Benmeridja et al. co-cultured ASCs with
Two-photon polymerization (TPP) is a laser direct writing HUVECs, forming a network of capillaries in the printed
technique that uses near-infrared femtosecond lasers adipose tissue . Using three-culture spheres containing
[62]
to induce crosslinking reactions in monomer solutions, HUVECs, human preputial fibroblasts (HFF), and adipose
enabling nanoscale resolution . Dobos et al. tested various tissue-derived mesenchymal stem cells (ADSC), de Moor
[57]
TPP parameters on the small-diameter channel structure, et al. found that HUVECs spontaneously organized into a
including voxel size, layer spacing, etc., which improved capillary-like network throughout the sphere .
[63]
the accuracy and throughput of the printing process, and
successfully built a microvascular network with a diameter The vascular wall comprises endothelium, smooth
of 10–30 μm . muscle, and outer membrane. When natural blood vessels
[58]
are damaged, vascular stem cells that are located in the outer
Stereolithography (SLA) allows patterning in membrane of blood vessel wall differentiate into smooth
photoreactive hydrogels and fabrication of blood vessels at muscle cells or endothelial cells that repair themselves.
the scale of millimeters and micrometers at high printing
speeds. Xue et al. used the system to manufacture a variety To fully mimic the natural vascular wall hierarchy,
of bracket architectures, ranging from regular geometries Dogan et al. used human iPSC-derived mesodermal
such as serpentine, spiral, and fractal shapes to more progenitor cells (hiMPCs), instead of mature endothelial or
[64]
irregular/complex geometries such as bionic trees and smooth muscle cells, to print the vascular network . Using
capillary networks, with channel widths ranging from hiMPCs, they induced de novo generation of small and
tree trunks (width >1100 μm) to small branches (about large containers with multi-walled structures that possess
[64]
17 μm in width) . Thomas et al. used SLA to construct the inner, medium, and outer membrane-like layers .
[59]
perfusable endothelialized blood vessels successfully .
[52]
4.4. Micropatterns that induce angiogenesis
4.3. Suitable sources of cells Endothelial cells form the vascular networks in artificial
A layer of endothelial cells usually forms the capillary tissues mainly through self-assembly. Biomaterials and
wall. Adding endothelial cells directly to the bio-ink for biomaterial inks that precisely control cell adhesion are
printing is the primary way to create hollow endothelial essential for creating functional microvasculature systems.
tubes. Three common endothelial cell types used for tissue Since the lumen formation of endothelial cells depends on
engineering include human umbilical vein endothelial cell–matrix interactions, the vascular system formed by
cells (HUVECs), human microvascular endothelial cells self-assembly is often subject to hemodynamic disorder.
(HMVECs), and induced pluripotent stem cell-derived By designing high-resolution patterns, 3D bioprinting
endothelial cells (iPSC-ECs). The globular aggregates of can exert a degree of exogenous control over the self-
cells better mimic the function of living tissue and promote assembly process of blood vessels. It creates biological cues
the formation of microvascular networks, compared to that guide the formation of blood vessels by depositing
the dispersed individual cells. The spherical culture chips endothelial cells and collagen fibers in artificial tissue .
[65]
made by Anada et al. can produce 500 spheroids per The printing of the microvascular network contains two
device at a time and allow for the collection of spheroids aspects: endothelial cell mapping and extracellular matrix
[60]
in a quick and non-invasive manner (Figure 4A) . Liu mapping. The arranged and formed cord of endothelial
et al. extracted small balls of early vascular cells (EVCs) cells defines the structure of neovascularization in vivo. The
from human embryonic stem cells (hESCs) to construct patterned matrix structure can give mechanical clues to
microvascular networks. When the spherical vascular cells endothelial cells’ adhesion and proliferation and promote
were mixed into the hydrogel, the spherical vascular cells vascular network formation.
Volume 9 Issue 6 (2023) 265 https://doi.org/10.36922/ijb.0012

