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



               As science and technology continue to advance,   dressings [43,140] . Over the past few decades, thousands of
            current bioprinting techniques are also improved. For   wound dressings have been developed to treat wounds
            example, microfluidics-assisted extrusion bioprinting is a   or burns [141] . In addition to basic barrier functions, some
            micro-device printing technology based on microfluidics,   wound dressings have antimicrobial and moisturizing
            which enables precisely controlled deposition of multiple   properties, in addition to mechanical strength and
            materials to obtain 3D structures in a relatively short   histocompatibility [135] .
            period of time [124]  (Figure 3f  and  3f ). As an additive                                    [6]
                                           2
                                    1
            bio-manufacturing technique, 3D bioprinting can offer   At present, there are many types of wound dressings .
            an essential strategy for wound dressings or skin tissue   Traditional wound dressings mainly prevent infection
            engineering to manufacture personalized construct   and help wound healing by providing a physical barrier
            precisely and dexterously in a short time, which would   and absorbing wound exudate, but they are still unable to
            shorten the waiting time and reduce the suffering of the   prevent and treat wound infection, and thus, there is still
                                                                                                           [19]
            patients as well as accelerate regeneration of skin function.  a need to develop fully functional wound dressings .
                                                               With the development of biomatrix materials, the
            5. Applications of functional materials            application of 3D bioprinting technology and the addition
            for 3D-bioprinted dressings and tissue             of functional materials, the manufactured 3D-bioprinted
                                                               wound dressings not only have the functions of traditional
            engineering scaffolds                              wound dressings, but also can stimulate cell migration and
            Every year, many people suffer from skin damage or burns   promote ECM production during wound healing [44,142] .
            of  varying  degrees  due to  carelessness  or  force  majeure.   [130]
            In wound treatment, wound dressings and skin tissue   Zhao  et al.   used photoactive cationic conjugated
            engineering scaffolds, which have become an integral part   polyphenylene vinylene derivatives (PPV), gelatin (Gel),
            of clinical skin defect treatment, can protect wounds and   hyaluronic acid (HA), and alginate (Alg) for the fabrication
            accelerate wound healing [127,128] .               of bioinks (Figure 4a), where cationic PPV conferred
                                                               excellent photodynamic therapy (PDT)-based resistance
               The application of traditional wound dressings and   to S. aureus to the artificial skin patch. Figure 4b shows
            skin  tissue  engineering  scaffolds  in promoting  wound   the process of printing a skin patch using a 3D bioprinter.
            healing have attained great progress, but there are still   The  3D-bioprinted  large-scale  antibacterial  skin  patch
            limitations such as inability to fit irregular wounds and   Gel/Alg/HA/PPV has a certain flexibility, as shown in
            poor vascularization . 3D bioprinting technology   Figure 4c. While printing the letters “ICCAS” using Gel/
                              [19]
            has advantages in treating wound healing and tissue   Alg/HA/PPV bioink, further demonstrating printability
            regeneration, and can make geometric shape accurately   (Figure 4d). In vivo anti-infection test of the artificial skin
            match tissue defects. In recent years, many researchers   patch using a rat model of  S. aureus infection showed
            have combined 3D bioprinting technology with various   that on the fourth day after photodynamic therapy, no
            matrix biomaterials, functional materials, and other active   infection occurred around the dry wounds treated with
            ingredients in a controlled manner to generate viable   the PPV skin patch, indicating that it has the ability to
            structures  to  fabricate  wound  dressings  and  skin  tissue   resist infection in vivo (Figure 4e). Diffusion plate assay
            engineering scaffolds that fully adapt to irregular wounds   of  S. aureus-infected wound sites further demonstrated
            to promote wound repair and tissue regeneration [129] .  the excellent antimicrobial properties of PPV skin patch
                                                               (Figure 4f). In addition, the antibacterial skin patch Gel/
            5.1. Wound dressings                               Alg/HA/PPV also had accelerated in vivo biodegradability
            Wound dressings are applied to the wound surface to   and wound healing.
            support various stages of wound healing [139] . The earliest
            use of wound dressings dates back to 2500 BC, when the   Although topical wound dressings promote wound
            Sumerians used resin, honey, or mud and herbs to cover   healing by preventing or reducing skin inflammation, the
            wounds  after  washing  them  with  milk  or  water .  In   development of new alternative dressings to effectively
                                                      [6]
            460–370 BC, the ancient Greeks used wine or vinegar to   clear excess inflammation and infection in the initial stages
            clean wounds. In the late 20th century, people began to   of the healing mechanism is warranted . Recently, Yang
                                                                                               [50]
            use occlusive dressings to provide moisture to wounds,   et al. [131]  added CeO /N-halamine hybrid nanoparticles
                                                                                2
            protect wounds, and reduce wound infection [140] . With   (NPs) as antibacterial components into the matrix of
            the remarkable development of microbiology and     gelatin methacryloyl (GelMA), carboxymethylcellulose
            cytopathology, Winter proposed in 1962 that a moist   sodium (CMC), and xanthan gum, and then prepared a
            wound microenvironment could accelerate wound repair,   new 3D-bioprinted GCX-CeO /APSGH-Cl antibacterial
                                                                                        2
            laying the foundation for the development of wound   dressing by photocrosslinking. The results of antibacterial

            Volume 9 Issue 5 (2023)                        175                         https://doi.org/10.18063/ijb.757
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