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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
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            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
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            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.
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            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
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