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International Journal of Bioprinting                             Bioprinted tissue-on-a-chip in drug screening




            not trigger an immune response from encapsulated cells,   lines, and the restored bioink after the shear thinning state
            leading  to  the  reserved  biocompatibility  of  dECM.  In   retained most of the structural features, demonstrating
            contrast, non-animal-derived bioink causes an immune   its self-healing ability. The pore structure within the
            response as well as the change of pH and temperature in   microarchitecture plays a crucial role in material diffusion
            microenvironments.                                 and cell migration. Wang et al.  developed a bioink with
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               Like other bioinks, the addition of dECM enables   an  emulsion  system,  which  facilitated  the  generation  of
            bioprinted bioinks to regulate viscosities, reduce shear   multiple interconnected micropores. These micropores in
            stress, and help cells proliferate after printing and form   bioink were beneficial for the proliferation and distribution
            a self-supporting structure.  However, the mechanical   of cells in deep structures. When taking GelMA as the
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            properties of dECM do not meet the requirements of   dispersed phase and dextran as the continuous phase,
            supporting 3D constructs. Moreover, dECM fails to be   methacrylated galactoglucomannan, acting  as the
            perfectly copied in vitro because of the differences between   emulsifier in this system, was added to enhance cell
            individuals, organs, and even tissues. dECM is extracted   viability promote intercellular communication (Figure
            from ECM via methods of cell removal. Uncontrolled and   3A). Two-component bioink is subjected to oxidation
            unstandardized methods lead to degradation of dECM at   or modification to obtain specific chemical groups that
            different degrees during extraction processes, contributing   interact with groups in other components, resulting in
            to differences between batches. The strong specificity of   more stable covalent bonds. Biological substances, such
            dECM could explain why popularizing dECM on a large   as polypeptides, are introduced to enhance cell adhesion
            scale remains challenging.                         and biomimetic properties. In general, bioinks mimicking
                                                               functions of ECM provide gas exchange, facilitate material
            3.1.2. Examples of hydrogel bioinks                transport and removal, and offer physical support for
            The   single-component  natural  bioink  cannot    experimental cultures. Moreover, advanced hydrogels
            simultaneously meet the requirements for molding during   can selectively enrich or deplete molecules. For example,
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            the printing process and the suitability of viscosity on the   Zhang et al.  exploited a functional hydrogel system that
            growth of cells encapsulated in bioinks, so two-component   consumed reactive oxygen, thus protecting cells from
            and even multi-component hydrogels are applied to break   oxidative stimulation (Figure 3B).
            the mutual limitation of molding and cell culture. Moreover,   3.1.3. Synthetic polymers
            the  mechanical  properties  of  bioink  may  be  improved   Despite non-natural sources, research certified that
            through  crosslinking.  The alginate  component  in  the   synthetic bioink has biological correlations in cell culture.
            alginate/GelMA bioink enabled the initial consolidation of   Synthetic polymers with high inertness and resistance
            the bioink, and GelMA formed the covalent bonds after   are artificially produced for specific purposes. Synthetic
            photocrosslinking  to  conglutinate  the  interlayer  bioink.   polymers are blended with natural bioink to promote the
            This process completed the entity construction of a cell-  mechanical properties of the mixed bioink and offset the
            friendly bioink at a low concentration.  Soltan et al.    disadvantages of natural bioink.  Since the polymers are
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            investigated the synthesis of alginate dialdehyde because   non-animal and non-human derived, their toxicity may
            the human body lacked alginate sodium enzymes, and   restrict cell viability. Moreover, the targeted cells can not
            the increased oxidation degree of alginate dialdehyde   adhere to the synthetic polymers, contributing to cell loss
            promoted biodegradation. The oxidized and methacrylate   at the beginning of model constructions.
            alginate (OMA) bioink also underwent ion crosslinking
            and photocrosslinking. However, the methacrylate bonds   Polyethylene glycol (PEG) is an ethylene oxide
            for photocrosslinking were obtained by the esterification   polymer with high cytocompatibility, commonly seen as a
            of the groups in alginate rather than the involvement of   constituent of capsules. It is used in wound dressing for
            GelMA. On the premise of ensuring mechanical stability,   hemostasis and pharmaceutic preparations to enhance the
            this bioink showed a high resolution and rapid recovery   stability of the drug-loaded nanoparticles. 80-82  The ability
            capability, simultaneously supporting a high survival rate   of PEG to support cell adhesion allows for its further
            of cultured stem cells.  Cui et al.  developed a three-  application in tissue engineering.  Aliphatic polyester,
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            component bioink using natural proteins/polyphenols/  polycaprolactone (PCL) consisting of acetate, has a
            polysaccharides. The hydrogel construct was shaped   melting point of 56–66°C. Notwithstanding that PCL is
            through hydrogen bonding and electrostatic interactions   degraded by most natural microorganisms, it is difficult
            after the ion crosslinking of alginate. The addition of   to be enzymatically degraded in vivo.  Liu et al.  printed
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            polyphenols disrupted the protein structure in gelatin,   the gelatin solution between PCL bands for cell support
            exposing more reactive sites for crosslinking. The initial   (Figure 3C-I). Notably, 92% cell viability was maintained
            hydrogel had structural features in the form of sheets and   after  a  7-day  culture  (Figure  3C-II).  Furthermore,  the
            Volume 10 Issue 3 (2024)                       179                                doi: 10.36922/ijb.1951
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