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International Journal of Bioprinting                      Functional materials of 3D bioprinting for wound healing



            (quinoline derivatives, doxorubicin, and paclitaxel) [94,95] .    biological materials, cells, or other active substances in
            The mechanism of antitumor materials killing or    a controllable space, so as to repeatedly manufacture 3D
            inhibiting cancer cells can be divided into three aspects.   functional structures of various shapes and sizes with
            Chemotherapy drugs such as doxorubicin and paclitaxel   high flexibility [104] . According to the molding principles
            inhibit tumor growth by interfering with DNA, RNA, or   and printing materials, current bioprinting technologies
            protein synthesis of tumor cells. Some photosensitizers such   mainly include extrusion-based bioprinting, laser-
            as indocyanine green and berberine can induce apoptosis   assisted bioprinting, digital light processing-based
            of cancer cells by producing ROS or singlet oxygen . In   bioprinting, inkjet bioprinting, and microfluidics-assisted
                                                     [32]
            addition,  polyphenols,  such  as  anthocyanin,  curcumin,   bioprinting [105,106] .
            and quercetin, can increase the content of active oxygen
            and downregulate cancer cell migration and proliferation   Extrusion-based bioprinting is the most popular
            by regulating several signaling pathways, such as EGFR/  form of bioprinting that applies mechanical actuation
            MAPK signaling pathway .                           or pneumatic pressure to extrude a bioink from a nozzle
                                [63]
                                                               continuously, and deposit it layer-by-layer to form a 3D
               Long-term  controlled  release  of  either  natural   structure [107,108]  (Figure 3a). Extrusion bioprinting systems
            anticancer drugs or chemotherapy drugs is very important   can be classified into screw, piston, and pneumatic type
            for  tumor  treatment.  3D  porous  scaffolds  have  been   according to their working principles [109] . Compared
            widely used in cancer therapy and tissue engineering due   with other  bioprinting technologies,  extrusion-based
            to their good capabilities in drug controlled release [96-99] .   bioprinting is relatively simple and low-cost, can handle
            Zhao  et al.  designed and  developed a multifunctional   high-viscosity bioinks, and has excellent compatibility
                     [32]
            biomimetic cellulose nanofiber (CNF) in situ liquid wound   with multiple materials (decellularized extracellular matrix
            dressing  (CNF-ILWD).  CNF-ILWD  was  simultaneously   [dECM], microcarriers, polymers, hydrogels, and cell
            loaded with photothermal agent (indocyanine green)   aggregates) [110] . However, this system suffers from lower
            and chemotherapeutic drugs (doxorubicin) during the   print resolution (50–400 microns) and longer production
            preparation process. NIR, temperature, and pH multiple   times due to the small nozzle diameter. Furthermore, when
            response switches could efficiently control the drug release   the cell density in the ink is too high, the high shear stress
            of CNF-ILWD to kill residual tumor cells in wounds and   during extrusion reduces the number of viable cells [101,110] .
            deep layers of skin, and eliminate bacterial biofilms and
            harmful bacteria. Therefore, drug-loaded CNF-based    Laser-assisted bioprinting uses an energy source
            wound dressings can be used for postoperative tumor   (continuous  monochromatic  laser  energy  or  pulses)
            therapy and to promote the repair of infected wounds. The   to irradiate a light-absorbing layer, thereby causing
            functional material products recently used for skin wound   the bioinks to be deposited as droplets on the printing
            repair are presented in Table 1.                   platform by light [111]  (Figure 3b). Depending on the laser
                                                               source, laser-assisted bioprinting can be subdivided into
               Despite the significant advancements in the field   laser direct writing (LDW), laser-induced forward transfer
            of tissue engineering, a large number of functional or   (LIFT), and matrix-assisted pulsed laser evaporation
            multifunctional wound healing materials are still afflicted   (MAPLE) [112] . Laser-assisted bioprinting has a high system
            with problems such as morphological inconsistencies with   resolution and open nozzle structure, which can precisely
            wounds, difficulty in generating natural vascular networks   arrange small volume of cell droplets in 3D spatial
            and skin appendages, and difficulty in nutrient and oxygen   positions, eliminating the problem of nozzle blockage.
            exchange between tissue cells [100,101] . Also, it is hard to meet   In addition, as a noncontact printing technology, it can
            the diverse needs of wounds in complex situations. In recent   prevent cell and bioink contamination to a certain degree.
            years, 3D bioprinting technology has emerged as an ideal   However, this technology can only select photosensitive
            strategy to replace traditional low-precision cell spraying   polymers for printing, and photopolymerization requires
            and seeding techniques to deposit cells, biomaterials, and   additional chemical modification of materials, which
            bioactive molecules into precise 3D geometric patterns.   limits  the  extensive  use  of  various  biological  materials.
            Computer control provides tools for the development of   In addition, this technology has high maintenance cost
            vascular and adnexal regeneration, thereby replicating the   and long production time, which leads to low printing
            anisotropy of natural skin [102,103] .             efficiency and difficulty in printing large tissues and
                                                               organs [113,114] .
            4. 3D bioprinting technology                          Digital light processing-based (DLP) 3D bioprinting

            3D bioprinting is an advanced additive manufacturing   uses a digital micromirror device (DMD) to project
            technology, which can distribute bioink containing   a designed optical pattern onto an ink container, by


            Volume 9 Issue 5 (2023)                        173                         https://doi.org/10.18063/ijb.757
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