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International Journal of Bioprinting                       3D-printed nanocomposites: Synthesis & applications




            cartilage matrix. By adding anisotropic fillers, such as   and the strut thickness of the engineered constructs were
            nanocellulose, into alginate solution, the printability of the   optimized to provide sufficient strength and induce the
            bioink was significantly improved. 130,131  The nanocellulose-  osteoinductive effect as well.
            incorporated bioink exhibited enhanced cell spreading,   Byambaa et al.  fabricated pyramidal microstructured
            proliferation, and ECM formation, demonstrating its   bone-like tissue constructs that mimic the architecture of
            great potential in 3D printing of living tissue and organs.   natural bone tissue.  Rapidly degradable GelMA hydrogel
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            Researchers have also demonstrated that the anisotropic   encapsulated with HUVECs and human mesenchymal
            gradient-structured cartilage exhibited better cartilage   stem cells (hMSCs) was printed in the center of the
            repair effect both in vivo and in vitro as the anisotropic   construct, which was surrounded by gelatin methacryloyl
            structure can provide desirable mechanical characteristics   (GelMA)/silicate nanoplatelets hydrogel (Figure 5a). The
            and signaling pathway required for chondrogenic    vessel was formed via the degradation of GelMA overtime
            differentiation. 132,133   To  closely  resemble  the  anisotropic   (Figure 5b). The encapsulated hMSCs and HUVECs could
            heterogeneous multilayered structure of natural cartilage,   migrate and proliferate in the constructs, and the hMSCs
            a novel strategy combining microfluidic and 3D printing   promoted vasculogenesis. In addition, hMSCs in silicate
            technique to construct engineered zonal cartilage was   nanoplatelets hydrogels differentiated into osteoblasts.
            developed. 134,135  The technology relies on a microfluidic   Chiesa et al. also developed vascularized bone model
            printing head connected to a coaxial needle extruder   with controlled pore geometry, size, and interconnectivity
            to print muscle precursor cells onto hydrogel fibers in a   by printing gelatin-nanohydroxyapatite hydrogel in a
            high-resolution 3D bioprinting process. The advanced   supporting bath composed of Pluronic F127 (Figure 5c–f).
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            approach enables the deposition of chemical, physical,   A  wood-pile  scaffold  was  first  printed  and  kept  in  the
            and biological cues, making it possible to fabricate   supporting bath. Gelatin was crosslinked with genipin,
            scaffolds with exceptionally high shape fidelity and cell   followed by removing sacrificial materials. Cylinders with
            viability. Zone-specific matrix was observed after human   a diameter of 4 mm were cut from the scaffolds for further
            articular chondrocytes and human bone marrow-derived   investigation, including pore connectivity, compressive
            mesenchymal stem cells were cultured for 3 weeks   modulus, osteogenic differentiation, and vascularization.
            in vitro. 134                                      The  engineered  bone  model   exhibited  robust
                                                               vascularization  and  HUVECs-supported  osteogenesis,
            6.3. Bone tissues                                  indicating that vascularized bone model could be readily
            Bone is one of the rigid body tissues and composed of two   fabricated via 3D bioprinting.
            main components, i.e., collagen and calcium phosphate.
            Bone tissue constructs that are hierarchically porous are   6.4. Cardiac tissues
            helpful for vascularization and cell proliferation.  To treat   Similar to chondrocytes, cardiomyocytes have limited
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            bone defects, tough but light, biocompatible substitutes   regenerative capacity. This signals a crucial need to
            endowed with the capability of preventing any allergic   regenerate cardiac tissues. The cardiomyocytes are aligned
            reactions  are  required.  Traditional  fabrication  methods,   in cardiac tissues to execute spontaneous, synchronous,
            such as freeze-casting, foam replica, high-pressure   and rhythmic contractions.  The hierarchical  property of
            pressing, and injection molding, cannot control the   native myocardium and complicated blood vessels are the
            porous structure, but the recently developed 3D printing   main challenges in fabricating cardiac tissues.
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            techniques could overcome the  limitations  to fabricate
            customized scaffolds.                                 Lee et al. had attempted to fabricate a model of
                                                               left ventricle of human heart via embedded printing.
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               As one of the main bone components, calcium     Collagen was crosslinked by changing the pH of supporting
            phosphate  supports  osteoblast  adhesion,  proliferation,   bath, and the geometry could be maintained for over 28
            and osteoinduction. Additionally, it regenerates bone   days. Cell viability achieved 96%, and the ventricular
            marrow stromal cells to induce bone formation.  Besides   contraction was noticed after 4 days of culturing.
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            calcium phosphate, other nanomaterials, such as silicate   Moreover, wall thickening, an evidence of ventricular
            nanoplatelets and hydroxyapatite, are commonly used   contraction, was observed during peak systole. They also
            in bone tissue engineering. Nyberg et al. fabricated PCL   printed a functional robust tri-leaflet heart valve that was
            scaffolds functionalized with tricalcium phosphate,   mounted to a pulsatile pump. Cyclical opening and closing
            hydroxyapatite, or decellularized bone matrix and co-  of the valve leaflets were observed under the pulsatile
            cultured with adipose-derived stromal/stem cells.  The   flow. Further, a monolayer of HUVECs was formed on the
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            addition  of  minerals  increased the viscosity  of the PCL   leaflets. However, the limitation of this study is that the cell
            melts. By tuning the 3D printing parameters, the porosity   density was too low to mimic the real tissue as it requires


            Volume 10 Issue 2 (2024)                        91                                doi: 10.36922/ijb.1637
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