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International Journal of Bioprinting                                         Hydrogels for 3D bioprinting



            in biomedical research, including nanowires, nanorods,   5.1. Flat tissue
            and nanospheres .                                  The skin is the largest tissue in the human body and has a
                          [95]
               Some   researchers  used  conductive  hydrogels  complex multi-layer structure. The treatment to severe skin
            containing GNRs in cardiac tissue. Navaei  et al.    damage due to diabetes, ulcers, and other wounds that cannot
                                                        [95]
            developed GNR-GelMA hybrid hydrogels as a functional   heal by themselves is hampered by insufficient skin source for
            cardiac  patch. When  GNRs  were  introduced,  the   transplantation. Tissue-engineered skin provides a new way
                                                                                [137,138]
            mechanical and biological properties of the hydrogel were   of treating skin damage  . Compared with traditional skin
            enhanced. High concentrations of GNRs (1 and 1.5 mg/  tissue engineering technologies, 3D bioprinting technology
            mL) promote the electrical conductivity of the hydrogel,   has the characteristics of accurate cell positioning and
            which is conducive to the conduction of electrical   efficient layer-by-layer printing, which can greatly shorten
                                                                                                         [139,140]
            signals between cardiomyocytes (CMs) and improves the   the manufacturing cycle and increase efficiency  .
            contractility of the tissue. Figure 6D shows the TEM image   Despite the considerable benefits in burns and chronic
            of GNRs incorporated into GelMA hydrogel. However, the   wounds, the current 3D-printed tissue-engineered skins still
            functional heart patch is a 2D structure, which cannot meet   cannot satisfy the requirements of human skin’s functions,
            the requirements of certain tissue and cell regeneration   as they are incapable of pigmentation and vascularization,
                                                                                                 [60]
            in the 3D environment in the body. In 2017, Zhu et al.    and lack of hair follicles and sweat glands . At present,
                                                        [94]
            developed a gold nanocomposite bioink for 3D bioprinting.   there are still tremendous challenges in manufacturing
            They firstly coated the surface of GNRs to obtain C-GNRs.   skins  with  complete  functions.  However,  bioprinting
            GelMA molecules are then wrapped on the surface of   relying on highly automated devices is conducive to the
            C-GNRs to obtain G-GNRs, which can be evenly dispersed   construction of layered skin tissue composed of a variety
            in water. Next, they mixed G-GNRs (with a concentration   of cells and materials, which can enhance the homology
            of 0.1–0.5 mg/mL) with GelMA and SA polymer solution   with human natural skin and also improve its barrier and
                                                                               [141]
            to obtain gold nanocomposite bioink. They chose 0.1 mg/  complexity functions  .
            mL G-GNRs compound hydrogel bioinks to suspend and    Compared with other printing methods,  in situ
            print the complex structure in the support medium of the   bioprinting has attracted more and more attention from
            gelatin solution. This spiral structure has a high shape   researchers and made great improvements. It can print
            fidelity. The CMs and cardiac fibroblasts (CFs) (the ratio   on the skin and external damaged areas or previously
            of CMs and CFs is 1:1) obtained from newborn rats were   exposed parts of surgery [142,143] . In 2018, the Wake Forest
            jointly loaded into bioinks for printing. After a few days   Institute of Regenerative Medicine made important
            of culture, the cells fuse in the scaffold structure to form   progress in in situ bioprinting of autologous skin cells [144] .
            a new organizational layer. They also found that G-GNRs   They used a new mobile skin printing system to quickly
            can promote signal transmission between heart cells, and   print large-scale wounds in situ, using autologous dermal
            the contraction behavior of 3D-bioprinted constructs   fibroblasts  and  epidermal  keratinocytes  mixed  with
            has been improved, which could be due to the ability   hydrogel to form cell therapy. The treatment effect of
            of  GNRs  to inhibit the  excessive  proliferation  of  CFs.   in situ bioprinting on wound defects of rats and pigs was
            Compared with the 2D manufacturing of  heart patches,   observed. These two kinds of cells can be distributed layer
            3D-bioprinted  heart  structures  have  great  advantages  in   by layer to form a double skin structure. Compared with
            terms of functionality, bionics, and simplicity.   the untreated control group, in situ printing of autologous
                                                               cells can quickly promote wound closure, prevent wound
            5. Pre-clinical research on printed                contraction, and has a layered structure similar to healthy
            organs in vitro                                    skin regeneration, which can accelerate the formation
                                                               of normal skin functions (Figure 7A). In 2020, Urciuolo
            Although the studies of tissue engineering have only been   et al. [143]  performed bioprinting in the tissues of living mice.
            developed for only three decades, many basic theories   Cells are loaded with photosensitive biopolymer hydrogels
            have been proposed, and tissue construction and in vivo   as bioinks, making it possible to create 3D structures and
            implantation in animals have been vastly conducted a   functional tissues in living animals for organ repair or
            great volume of basic theory, tissue construction and   reconstruction. They named this concept “3D bioprinting.”
            in vivo implantation in animals have been accomplished.   In living 3D bioprinting, skin becomes the best target
            With the rapid progress of cytology, molecular biology,   tissue. There is no need for open surgery, the complexity
            and biomaterials research, the research and application of   of the operation is minimized, and the success rate of 3D
            tissue engineering of various tissues in the clinic have also   bioprinting is also improved. It is particularly noteworthy
            made great progress.                               that they combined coumarin derivatives with the backbone


            Volume 9 Issue 5 (2023)                        224                         https://doi.org/10.18063/ijb.759
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