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International Journal of Bioprinting                    Fabrication of 3D functional hydrogel for wound dressings



            1. Introduction                                       In order to prevent bacterial infestation, trauma
                                                               dressings should have good antimicrobial activity [21,22] .
                                                        [1]
            Skin, the largest organ and the first barrier of our body ,   Although antibacterial agents have been widely developed
            plays a vital role in protecting our body, but often becomes   and used, it has been a big problem to maintain excellent
            fragile when encountering different kinds of accidents,   biocompatibility while having antibacterial properties .
                                                                                                           [22]
            such as physical cuts and chemical reagent corrosion   Some researchers have chosen to address this problem
            injury [2,3] . In addition to the acute wounds caused by   by adding antibiotics to the dressing. Antibiotics are
            these accidents, chronic wounds such as diabetic foot   efficient in destroying bacteria by inhibiting bacterial cell
            ulcers (DFU), which are difficult to heal and cause serious   wall  production  or  inhibiting  protein  and  nucleic  acid
            physical damage, have become a major threat to human   production within bacteria [23,24] , but the problems caused
            health and can lead to amputation and even death [4,5] . As   by antibiotics cannot be ignored, and some reports have
            a temporary substitute, wound dressings provide durable   mentioned that bacterial resistance and bacterial mutations
            protection in accelerating wound healing . Traditional   are associated with heavy antibiotic use [25,26] . Compared
                                               [6]
            wound  dressings,  such  as  bandages  and  gauze,  have   with antibiotics, biomacromolecular antimicrobial agents
            protective effects on wound surface, but often lack of   are safer and have sustained antimicrobial properties.
            ability to absorb tissue fluid and may cause secondary   Chitosan (CS) is the product of the deacetylation of
            injuries due to adhesion on the wound surface . To solve   chitin, a positively charged alkaline polysaccharide with
                                                 [7]
            these problems, membrane, sponge, rubber, hydrogel   low solubility in water . In order to improve its water
                                                                                  [27]
            dressing, and other new dressings [8-11]  have been widely   solubility, quaternized groups are introduced to obtain
            studied and used. Among the dressings described above,   quaternized chitosan (QCS). The cationic moieties of
            hydrogels can provide a moist  environment  to  promote   QCS are preferentially attracted to the negatively charged
            skin tissue regeneration and have structural characteristics   surfaces of bacteria, resulting in the disruption of bacterial
            similar to those of the extracellular matrix, as well as good   membranes and efflux of internal material and ultimately
            slippery elasticity to avoid secondary injuries caused by   in bacteria death [28,29] . At the same time, its low biotoxicity
                    [12]
            lacerations . In addition, with the new modification and   and the addition of gelatin and SA as described above
            structural design, the hydrogel dressings are endowed   ensure that it will not cause damage to skin cells.
            with a variety of excellent properties, such as antibacterial,
            anti-inflammatory, and antioxidative properties, which are   In  damaged skin, inflammation-induced  over-
            beneficial to the four stages of wound repair (hemostasis   reactive oxygen species (ROS), including superoxide-free
            and coagulation, inflammation, proliferation, and   radicals and non-free radical hydrogen peroxides, alter
            remodeling) .                                      or  degrade  extracellular  matrix  (ECM)  proteins,  destroy
                      [13]
                                                               skin fibroblasts, and reduce keratinocyte function [30,31] .
               Since hydrogel  dressings are applied directly to the   Hydrogels loaded with free radical scavenging drugs have
            skin surface, it is essential to ensure that hydrogels are   been shown to significantly improve the wound healing
            skin-friendly , which involves the choice of hydrogel   process in  patients, avoiding oxidative damage [32,33] .
                      [14]
            materials. Gelatin, a protein that partially hydrolyzed   However, gelatin, SA, and QCS materials selected above
            from collagen, has good biocompatibility and temperature   have no antioxidant properties. Fortunately, the antioxidant
            sensitivity, and it is favored for its excellent viscoelasticity   capacity of hydrogels can be improved by grafting
            after solidification at low temperature (below 20°C) . Dou   dopamine. As a neurotransmitter secreted by human body,
                                                    [15]
            et al.  introduced gelatin into poly (γ-glutamic acid) by   dopamine has good biocompatibility and a large amount of
                [16]
            physical crosslinking to improve the structural stability and   catechol structure, which makes it an excellent free radical
            cellular adhesion properties and form an excellent double-  eliminator [34,35] .
            network bio-based wound dressing. Sodium alginate (SA)
            is a harmless natural polysaccharide extracted from brown   Due to the accident of wounds, the randomness of the
            algae . When a large number of high-valued metal cations   size and location of wounds, the dressing could not adapt
                [17]
            such as Ca , Mg , and Cu  exist in the aqueous solution,   to the changes of wounds [36,37] . In order to fulfill different
                         2+
                                 2+
                    2+
            they will be rapidly crosslinked with SA through replacing   requirement of patients, 3D printing technology can be
            Na  to form gel networks . Hence, SA is widely used in   introduced to prepare hydrogel dressings according to
              +
                                [18]
            hydrogel dressings due to mild reaction conditions . For   their wound conditions. Moreover, the simple printing
                                                     [19]
            example, Chen et al.  used sodium alginate as a reducing   principle, cheap bioink material,  and stable  printing
                            [20]
            agent and stabilizer to reduce Ag  into silver nanoparticles.   equipment make extrusion-based 3D printing conducive
                                      +
                                                                                                 [38]
            Thereby, the nano-silver-loaded polyvinyl alcohol/sodium   to the mass production of wound dressings . In addition,
            alginate wound dressings were prepared by using nano-  further  research  on  3D  printing  technology  can  pave
            silver as an antibacterial agent.                  the way for the emerging 4D printing technology and
            Volume 9 Issue 2 (2023)                        439                          https://doi.org/10.18063/ijb.689
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