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



            Table 2. 3D-bioprinted skin wound dressings for wound healing applications
             Main components              Representative functional materials  Properties for accelerating wound healing  Ref.
             Gel/Alg/HA/PPV               PPV                           Antibacterial                   [130]
             GMA/CMC/ε-PL                 ε-PL                          Antibacterial, antioxidant      [128]
             GelMA/CMC/Xanthan gum/CeO /   APSGH-Cl                     Antibacterial                   [131]
                                  2
             N-halamine (APSGH-Cl)
             Gel/AgNO                     AgNO                          Antibacterial                   [132]
                    3                         3
             AgNW/MAA                     AgNW/MAA                      Antibacterial, conductive, flexible  [133]
             HA/SiO /CINP                 SiO /CINP                     Antitumor, antioxidant, antibacterial  [134]
                  2                         2
             CNC/Chit-MA/Gentamicin/AgNPs  AgNPs                        Antibacterial                   [135]
             PEGDA/Gallium maltolate (GaM)  GaM                         Antibacterial                   [136]
             PAM/HPMC/AgNPs               AgNPs                         Antibacterial                   [137]
             N-halamine (PSPH-Cl)/TiO /GelMA/   PSPH-Cl                 Antibacterial                   [138]
                               2
             Xanthan gum
             GO-CS-Calcium silicate       CS                            Antitumor, antibacterial        [19]
            Abbreviations: Alg, alginate; AgNPs, silver nanoparticles; AgNW, silver nanowire; Chit-MA, chitosan methacrylamide; CINP, nanoparticle derived from
            cuttlefish ink; CMC, carboxymethylcellulose sodium; CNC, cellulose nanocrystal; CS, chitosan; ε-PL, ε-polylysine; GaM, gallium maltolate; Gel, gelatin;
            GelMA, gelatin methacryloyl; GMA, glycidyl methacrylate; GO, graphene oxide; HA, hyaluronic acid; HPMC, hydroxypropyl methylcellulose; MAA,
            methacrylic acid; PAM, polyacrylamide; PEGDA, poly(ethylene glycol)-diacrylate; PPV, polyphenylene vinylene derivative;
            The results of LIVE/DEAD staining indicated that ePatch   thickness  wound  skin  regeneration  due  to  their  unique
            enhanced  the  proliferation  and  migration  of  NIH  3T3   properties. Therefore, combining functional materials
            fibroblasts by electrical stimulation (Figure 5d). A rat   (antibacterial materials, antioxidant, hemostatic materials,
            model of full-thickness wound repair demonstrated that   flexible material, and antitumor material) and bioactive
            the soft and stretchable ePatch fitted tightly to the rats   molecules (cell-binding peptides, growth factors, bioactive
            curved back and shortened the wound healing time to only   nanoparticles, and other specific additives) with 3D
            7 days, significantly promoting wound closure (Figure 5e   bioprinting technology can produce functionalized
            and  f). In addition, antimicrobial performance testing   skin substitutes that maintain tissue homeostasis, thus
            showed the ability of ePatch to prevent Gram-positive and   providing a new strategy for on-demand preparation
            Gram-negative infections both in vitro and in vivo. This   of multifunctional hydrogels in the area of skin tissue
            3D bioprinting-based multifunctional biomaterial system   engineering [154] .
            with antibacterial, conductive, and soft properties provides   When the skin is injured, microbes can easily irrupt the
            a new approach to promote wound healing.  Table  2   wound and arouse serious infections that hinder wound
            summarizes  the  reports  of  3D-bioprinted  antibacterial   healing [42,128] . The general solution is to encapsulate metal
            wound dressing used for wound healing. The addition of   nanomaterials, antibiotics, and/or antibacterials into
            various functional materials has promoted the design and   scaffolds to prevent and treat wound site infections .
                                                                                                           [42]
            innovation of 3D-bioprinted wound dressings.
                                                               Wan et al.  fabricated a bilayer scaffold with silver-loaded
                                                                       [25]
            5.2. Skin tissue engineering scaffolds             gelatin cryogel as the top layer and platelet-derived growth
            Skin tissue engineering is a complex process that involves   factor-BB (PDGF-BB)-loaded 3D-printed gelatin as the
            mimicking the tissue-specific microenvironment of native   bottom layer (Figure 6a). This bilayer design is designed
            tissue [116] . Traditional tissue-engineered skin scaffolds   to protect the wound from infection through the release
            are usually made of live cell-loaded natural or synthetic   of silver nanoparticles in the upper layer, while delivering
            materials, which are easily limited by the printability   growth factors that adjust cell growth and division to the
            and biocompatibility of the materials [152] . 3D bioprinting   granulation tissue of the wound bed through the basal
            technology  has  been  extensively  used  in  the  fabrication   layer. A diabetic mouse wound model showed that PDGF-
            of organs, tissues, and blood vessels because of its ability   BB-loaded scaffolds could accelerate granulation tissue
            to accurately simulate living cells in confined spatial   formation, neovascularization, and collagen deposition
            configurations to generate complex tissue analogs [128,153] .   (Figure 6b).
            Furthermore, functional materials have important clinical   The microenvironment around the damaged skin
            value  in  accelerating  wound  healing  and  inducing  full-  is harsh, and a large amount of ROS will accumulate in


            Volume 9 Issue 5 (2023)                        178                         https://doi.org/10.18063/ijb.757
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