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International Journal of Bioprinting 3D-printed nanocomposites: Synthesis & applications
organization and cellular functionality. CNT-containing inside the scaffold. 154,155 These approaches show success in
constructs exhibited desired electrical conductivity, native forming microvascular networks. However, the fabrication
heart tissue-like mechanical property, and enhanced of perfusable vascularized tissue still remains challenging.
gene expression, suggesting that CNTs are preferred in To this end, two bioprinting techniques—indirect
regenerating cardiac tissues. Zhu et al. incorporated and direct bioprinting—have been developed to fabricate
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gold nanorod into GelMA/alginate bioink to print layered perfused vasculature. Sacrificial materials are deposited
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constructs to address the problems of poor conductivity of into a cell-laden crosslinkable supporting bioink in indirect
the existing artificial cardiac tissue and inefficient cardiac bioprinting. The sacrificial materials are removed after
cell communication via electrical coupling. Cardiac printing through temperature-induced phase transition
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fibroblasts (CFs) were co-cultured with cardiomyocytes under mild condition, forming a perfused open lumen,
as CFs are important in essential physiological activities, which is infused with endothelial cells to realize the
but CFs tend to over-proliferate, breaking the initial endothelialization of the microchannels. 45-47 For example,
cardiomyocytes-to-CFs ratio. The conductive gold nanorod Kolesky et al. were successful in creating microvascular
46
could help balance the growth and proliferation between networks using Pluronic F127 which liquefies at 4°C to
cardiomyocytes and CFs. In addition, gold nanorods produce mirochannels within a covalently crosslinked
promoted synchronized contraction of the cardiac tissue. hydrogel matrix. By employing this strategy, multilayered
This study implies that the gold nanorods nanocomposite vascularized tissue structures with multiple cells types
bioink shows great potential in fabricating conductive and ECM were constructed. Human neonatal dermal
cardiac tissue, which could be used for drug screening and fibroblasts and 10T1/2 cells were encapsulated in
implantation. Further, not only cardiac tissues but also
other electrogenic tissues, such as brain tissue, could be GelMA while HUVECs were suspended in fugitive
regenerated via this technique. Notably, the length of the Pluronic F127. It was noticed that on day 7, cells in the
nanowire should be larger than the average wall thickness bioink have comparable cell viability to cells cultured in
of the hydrogel pore in order for cells on either side to medium, indicating that the bioinks and bioprinting are
46
interact with each other and increase their electrical signal not harmful to cells. The strategy was adopted by Noor
transmission. et al. to fabricate thick, perusable vascularized cardiac
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patches (Figure 6a). iPSC-derived cardoimyocytes were
6.5. Vessel tissues blended with decellularized ECM (dECM), and iPSC-
Bioprinting has not yet produced functional large- derived endothelial cell was mixed with gelatin, serving as
scale tissues with physiological heterogeneity that a sacrificial bioink. A customized vascularized patch has
perfectly simulate the morphological, biochemical, and been successfully created with high cell viability. After 7
physiological characteristics. This is primarily caused by days, a continuous layer of endothelial cells was formed
the complexity of human tissue and organs, particularly on the inner side of the lumen (~300 μm in diameter), as
the vasculature which includes millimeter-scale arteries shown in Figure 6b. Moreover, in vivo test revealed that the
and micrometer-scale capillaries. The artificial vessel printed lumen remained in rat, and the encapsulated cells
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permits the exchange of vital nutrients and metabolic were elongated and aligned, showing that 3D bioprinting
waste products but prevents the exchange of immunogenic may be used for engineering vascularized tissues that
molecules. When creating large tissues, a vascular mimic biological matrix.
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network is necessary to support cell survival because the Apart from the vasculature embedded within a
distance at which oxygen and nutrient can diffuse is only hydrogel matrix, stand-alone vascular structure can be
100–200 μm. Blood compatibility is also important. The fabricated through direct bioprinting strategy, including
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vessels can be modified through the creation of bioactive coaxial and embedded bioprinting. A vessel phantom
antithrombotic surface, surface passivation, and surface was created by coaxially printing cell-laden bioinks in the
endothelialization to eliminate thrombosis in the vessels. shell and sacrificial ink in the core, followed by forming a
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Additionally, since endothelial layers are inherently anti- confluent monolayer of cells.
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thrombogenic and hemocompatible, a layer of endothelial
cells would inhibit thrombus formation. Strategies, such Alginate is the most commonly used material in
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as incorporation of angiogenic growth factor and co- fabricating hollow fibers as it could be readily in situ
culturing with pericytes and smooth muscle cells (SMCs), crosslinked with CaCl solution which is injected through
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have been devised to promote the vascularization of the the core nozzle. For example, Dolati et al. used alginate
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scaffold. Additionally, sacrificial materials, such as and MWCNTs hybrid bioink as the shell material and
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Pluronic F127 and gelatin, were blended with polymers, CaCl as the core materials to construct vascular conduits.
2
followed by washing, leaving microporous network The addition of CNTs had a significant effect on the
Volume 10 Issue 2 (2024) 93 doi: 10.36922/ijb.1637

