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International Journal of Bioprinting                      3D printed hydrogel for infected wound healing via PDT



            1. Introduction                                    today. It has the advantage of simplicity of operation, but
                                                               cell viability is reduced . For this experiment, extrusion-
                                                                                 [18]
            Skin is the largest organ of the human body and is   based bioprinting was chosen because the hydrogel
            vulnerable to various types of traumas, such as wounds.   dressings are cell-free, and the structure does not require
            Wound healing has been an ongoing topic of research and   high-resolution  printing.  Hydrogels  can  be  deposited
                                         [1]
            an area of concern in the medical field . When skin trauma   layer by layer to fabricate artificial skin tissue with porous
            occurs, the skin’s protective barrier is damaged, leaving   structures customized through computer-aided design [19,20] .
            the wound site vulnerable to invasion by microorganisms   Moreover, various photo-crosslinked polymers have been
                                                        [2]
            in the environment, which can lead to severe infection .   widely incorporated as a material for 3D-bioprinted tissue-
            Moreover, bacteria-associated wound infection prevents   engineered scaffolds due to their mild reaction conditions,
            wound healing and may be life-threatening [3,4] . Therefore,   highly tunable mechanical and structural properties,
            wound management in the early stages is essential for   printability, biodegradability, and biocompatibility [19,21] .
            preventing wound infection and promoting wound     Natural polymers, which can be used as biological inks,
            healing. Currently, wound dressings that contain   such as alginate, gelatin, and SF, have recently attracted
            antiseptics or antibiotics are commonly used to prevent   wide attention [22-26] .
            and treat wound infections. However, these dressings have
            significant limitations, including long-term treatment,   Silk fibroin (SF) extracted from Bombyx mori, which
            inefficacy, and high cost [5-7] . Long-term use of antibiotics   has good biocompatibility, adjustable biodegradability,
            can lead to bacterial resistance, which is a major clinical   and mechanical properties, has been used in various
            problem [8,9] . Therefore, it is necessary to develop a new type   biomedical applications and was approved by the U.S. Food
            of non-antibiotic multifunctional wound dressing with   and Drug Administration (FDA) for use in drug delivery
            antibacterial properties that can reduce the risk of wound   and surgical suture applications [27,28] . SF can be prepared
            infection caused by bacteria and promote wound healing.  into scaffolds, films, hydrogels,  etc., to meet different
                                                               clinical needs. It was reported that ultrasound or chemical
               Hydrogels have been widely used in skin, fat, and vessel   crosslinkers could induce the formation of SF hydrogels .
                                                                                                           [29]
            tissue engineering due to their advantages including good   However, the addition of ultrasound or toxic chemical
            hydrophilicity and biocompatibility . Hydrogels have a   crosslinkers is not conducive to the clinical promotion of
                                         [10]
            similar 3D porous structure to the extracellular matrix,   SF hydrogels. Photo-crosslinking technology can be used
            making them one of the most competitive candidates for   to prepare SF hydrogels in a controllable manner without
            wound dressings [11-13] . Meanwhile, hydrogels can maintain   chemical grafting or the introduction of toxic chemical
            the high moisture level of the wound bed; therefore,   crosslinking  agents .  Previous  studies  have shown  that
                                                                              [30]
            hydrogels can provide an optimal  3D environment  for   by using riboflavin (RPS) and sodium persulfate (SPS) as
            cells to promote soft tissue regeneration . Furthermore,   a photoinitiator under blue light irradiation, the tyrosine
                                            [14]
            hydrogels can be a platform for loading cells, antimicrobial   (Tyr) on the molecular chain of SF can be combined to
            agents, growth factors, and unique complementary and   form a stable tyrosine–tyrosine (Tyr–Tyr) bond .
                                                                                                     [30]
            biological macromolecules .
                                 [15]
                                                                  Moreover, the SF hydrogel may have difficulty meeting
               3D bioprinting is a promising technology in the   the needs of tissue regeneration due to its relatively dense
            manufacture of hydrogels, offering a high degree of   internal pores and slow degradation . The β-sheet
                                                                                               [29]
            flexibility and reproducibility. The three most commonly   formation in SF hydrogels could cause changes to the
            used bioprinting techniques according to the American   internal  structure, compressing the internal  pores and
            Society for Testing and Materials are jetting-based,   water content. Therefore, it is necessary to introduce other
            extrusion-based, and vat photopolymerization-based   components to control the conformational changes of SF.
            bioprinting processes. The inkjet technique offers the   The introduction of other polymers can reduce the contact
            advantages of low cost and fast printing speed but has the   between SF molecules, thereby preventing the formation of
            limitations of low accuracy and need for low-viscosity   the β-sheet as well as regulating the mechanical properties
            bioinks . The vat photopolymerization technique offers   for soft tissue engineering . Gelatin, a natural polymer
                                                                                    [31]
                  [16]
            higher resolution and accuracy than other bioprinting   with high biocompatibility and a cell attachment sequence
            techniques. The high-resolution printing facilitates   that  is  similar  to the extracellular matrix,  has  excellent
            the fabrication of bionic mircoorganisms. However, its   performance in cell fixation and proliferation . It contains
                                                                                                  [32]
            complex design, limited choice of biocompatible materials,   about 1% of Tyr residues in the amino acid sequence of
            and cumbersome operation hinder its wide application in   the gelatin strands, which can be crosslinked with the SF
            the field of tissue engineering . Extrusion bioprinting   molecular chain through Tyr–Tyr bonding without chemical
                                     [17]
            is the most common bioprinting technology available   modifications. Adding gelatin as a spacer molecule to the

            Volume 9 Issue 5 (2023)                        460                         https://doi.org/10.18063/ijb.773
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