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International Journal of Bioprinting                          3D bioprinting of tissue with carbon nanomaterials



            single component or heterogeneous components combined   2. CFNs in biomedical applications
            with additives, such as copolymers, nanoparticles, and   CFNs, composed of carbon elements, represent various
            crosslinking agents [39,40] . There is less toxicity in hydrogel   spatial arrangements, such as zero-dimensional carbon
            composites with the use of naturally available polymers,   quantum dots, nanodiamonds, fullerenes, one-dimensional
            including gelatin, chitosan, alginate, and pectin. Synthetic   CNTs, nanofibers, nanowires, two-dimensional (2D)
            polymers including pluronic, methacrylic acid, poly(vinyl   graphene nanosheets, and 3D networks or their bulk
            alcohol) (PVA), and  poly(ethylene  glycol) (PEG) have   counterparts [59-63] . Their carbon atoms are organized in a
            been blended with natural polymers to increase the   cubic or hexagonal lattice following sp  or sp  hybridization
                                                                                             2
                                                                                                  3
            stability, biodegradation time, and mechanical strength   in  conventional  allotropes,  including  diamond  and
            of the produced hydrogel composites . Gelatin      graphite [64,65] . Since the discovery of fullerenes (1985), CNTs
                                                [41]
            methacrylate (GelMA) is a commonly employed        (1991), and graphene (2004), CFNs have been extensively
            polymeric component of printable gels in microextrusion   researched on in recent decades [66-68] . CNTs are widely
            and laser-based bioprinters because it exhibits    used in various fields, including energy production and
            photocurable properties by UV radiation [42,43] . Pluronic   storage, material science, environmental sciences, as well
            F127 (poloxamer 407) hydrogel is thermoresponsive, and   as biomedical sciences, owing to their unique properties
            it is often used as a sacrificial material, mold, and track   (small size, large surface area, and ultrathin thickness) [69-75] .
            patterning in TE . When functionalized with the cell-  When the colloidal stability of CFNs in aqueous suspensions
                          [44]
            adhesive peptide arginyl-glycyl-aspartic acid (RGD),   is poor, the surface of the material is modified using
            photoactive PVA hydrogels augment cell attachment and   covalent and non-covalent functionalization techniques,
            enhance fibroblast spreading . The choice of polymer   such as oxidation, dehydrogenation, plasma treatments,
                                    [45]
            affects the crosslinking reactions and mechanisms   and ozonolysis [76,77] . Oxidized carbon nanomaterials
            involved in printable gel. Photopolymerization is a   may have 5% to 50% oxygen content depending on the
            prominent crosslink reaction in printable bioinks, as   synthetic procedures, thus making them water-dispersible
            it enables control in space and during gelation . Free   when used in several biological applications, including TE
                                                   [39]
            radical polymerization of acrylate derivatives is often   and tissue regeneration , as shown in Figure 2. Carbon
                                                                                  [78]
            used to fabricate photoresponsive bioinks; however,   nanomaterials like GO and CNTs have been reported to
            many researchers have employed photoinitiated thiol-ene   exhibit superior optical absorption and near-infrared (NIR)
            crosslinking as an alternative to the former method to form   conversion properties . The supramolecular π–π stacking
                                                                                [79]
            homogeneous hydrogel networks [46,47] . Thermosensitive   in the structure enables them to adsorb a large amount of
            polymers, which form supramolecular hydrogels through   drug, while their tunable surface chemistry enables them
            hydrophobic  interactions  within  a  certain  temperature   to control drug release [80-82] . Yin et al. formulated a multi-
            range, have been used in bioprinting formulations [48,49] .   functionalized monolayer GO composite to deliver small
            Small molecule-mediated cross-linkages, such as calcium   interfering RNAs to target pancreatic cancer cells MIA
            chloride, glycerylphytate, and curcumin, have also   PaCa-2. The tumor volume was reduced by more than
            supported the fabrication of printable gels with highly fine   80% with the synergistic combination of gene silencing
            printability and customizable mechanical properties [50-52] .   and NIR light thermotherapy of the composite . Various
                                                                                                    [83]
            In order to improve viscosity and printability as well as   electrochemical sensors and label-free CFNs-based
            enhance cellular activities, researchers are now creating   biosensors have also been developed in consideration
            complex 3D printable structures that incorporate   of their remarkable electronic properties . In a study,
                                                                                                 [84]
            nanomaterials into bioinks, which leads to the fabrication   a composite of antibodies-grafted CNTs was used as an
            of functional tissues. Carbonaceous nanomaterials,   immunosensor  for  detecting  adiponectin,  an  obesity
            hydroxyapatite,  silica-based  bioceramics,  nanosilicates,   biomarker. Cyclic voltammetry was used to monitor
            bioactive glasses, strontium carbonate, and their doped   the reaction of secondary antibodies conjugated with
            nanocomposites [53-56]  have been used as  additives  in   horseradish peroxidase-streptavidin with adiponectin and
            printable inks for the fabrication of varying scaffolds   to quantify them, thus enabling fast detection .
                                                                                                   [85]
            for TE. In view of their biocompatibility, electrical
            conductivity,  and mechanical strength,  carbon-based   The introduction of CFNs into soft materials, such
            nanomaterials are frequently used in printable inks [57,58] .   as hydrogels, enhances the functional properties of the
            In this review, we discuss the contribution of carbon-  resulting  3D multicomponent  systems; the  features of
            family nanomaterials (CFNs), such as graphene, graphene   CFNs-containing hydrogels meet the requirements of
            oxide (GO), and carbon nanotubes (CNTs), in bioink   the promising strategies, which makes them advanced
            formulation and their biomedical applications for tissue   biomaterials in biomedical research [78,86] . Hossein  et al.
            regeneration.                                      have reported that CNT-loaded nanocomposite hydrogels

            Volume 9 Issue 1 (2023)                        184                      https://doi.org/10.18063/ijb.v9i1.635
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