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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
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