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International Journal of Bioprinting                     3D printed bioactive dressings for burn wound treatment




            promotes moist wound healing for longer time periods,   immense need to develop advanced wound dressings
            and the non-adhesive porous texture of the 3D-printed   for  second-degree  burn wound  treatment with desired
            dressings with increased wound-dressing interactions.   features, such as bioactive formulation, soothing effect,
            Our findings provided proof of concept for the synergistic   tunable  water absorption/release, non-adhesive contact,
            effect of bioactive formulation and the porous texture   and skin-like mechanical properties [6,16,23,24] .
            of the 3D-printed hydrogel dressings incorporated with   Bioactive glass materials are a class of bioceramics that
            BBG on continuous water release and, consequently, on   have the ability to bond with living tissues and promote
            second-degree burn wound healing.                  specific biological responses when exposed to body fluids.
                                                               These materials have been studied extensively for their
            Keywords: Hydrogel wound dressing; Burn wound      potential use in hard tissue engineering and implant
            healing; 3D printing; Bioactive borate glass;      coating [25,26] . Bioactive glass materials comprise a mixture
            Continuous water release                           of oxides from biologically active elements, such as Si, B,
                                                               Ca, Mg, Ag, Ce, Cu, and Zn, among others. The multiple
                                                               therapeutic ions released from bioactive glass can react
                                                               with proteins and enzymes to stimulate the proliferation
            1. Introduction                                    and differentiation of cells involved in wound healing, such
                                                               as  mesenchymal  stem  cells,  fibroblasts,  and endothelial
            Burn wound healing is a complex and delicate molecular-  cells [26,27] . There are three major types of bioactive glass
            cellular process to restore skin functions and repair   which are classified based on the dominant network
                       [1]
            tissue damage . Burn injuries represent a major public   forming oxide in the glass formulation: silicate glass,
            health issue and are among the most severe injuries ,   phosphate glass, and borate glass, among which the latter
                                                        [2]
            with approximately 10,000 annual deaths in the United   has the fastest degradation rate . Recently, the US Food
                                                                                        [28]
            States . Each year approximately 1.1 million patients   and Drug Administration (FDA) has cleared a bioactive
                [3]
            suffering from burn wounds are admitted to hospitals in   borate glass (BBG) product (Mirragen, ETS Wound Care,
            the United States, and approximately 660,000 among them   Missouri, USA) for treatment of chronic wound healing .
                                                                                                           [29]
            are diagnosed with second-degree burn wounds [4-6] .  In addition to its ability to promote cellular activity, BBG
               Second-degree burn is characterized by damage to the   can enhance wound healing by (i) regulating the secretion
            integrity of the entire epidermis and varied depths of the   of essential growth factors and matrix metalloproteinase
                                                        [7]
            dermis that typically require immediate medical care .   (MMPs) to promote angiogenesis and extracellular
            The current standard of care in clinical practice for second-  matrix (ECM) remodeling [30-37] , (ii) preventing bacterial
            degree burn wound treatment includes topical antimicrobial   growth [32,38,39] , and (iii) alleviating the adverse inflammatory
            agents and advanced dressings such as  contact dressing   response  by  scavenging  the  reactive  oxygen  species [40,41] .
            and hydrogel dressings. The primary goal of the advanced   Several studies showed that boron in BBG positively affects
            dressings is to promote optimal wound healing while   different stages of wound healing. It has been shown that
            providing  pain relief and  protection  from infection [8,9] .   boron can promote angiogenesis by stimulating tissues to
            Although the existing advanced wound dressings cover   secrete specific growth factors and modulate keratinocytes
            a broad range of moderate to high exuding wounds, a   and endothelial cellular responses [26,31,36,42,43] . One of the
            small number of wound care products are specifically   key advantages of using BBG over other additives is its
            designed for low exuding wounds,  e.g., second-degree   potential for incorporating a wide variety of dopants,
            burns. Despite good clinical outcomes for wet wounds, the   including copper and zinc to promote the release kinetics
            majority of these products end up with inadequate healing   of bioactive ions, regulate degradation rate, and potentially
                                                                                                           [44]
            and  poor  hydration  in  second-degree  burn  wounds [10,11] .   impart additional  therapeutic  properties to the glass .
            Topical  agents,  such  as  silver  sulfadiazine,  are  typically   Copper has been shown to stimulate the proliferation of
            associated with pain and prolonged healing due to wound   endothelial cells by inducing local hypoxia to stimulate
            dehydration, poor re-epithelialization, traumatic removal,   the expression of vascular endothelial growth factor
                                                                     [33,45]
            and non-transparent appearance [10-22] . Hydrogel dressings   (VEGF)  . Several studies have reported the positive
            provide a moist environment for the second-degree wound   effect of zinc dopant on the antimicrobial activity and
                                                                                 [46-48]
            and help with pain relief. However, frequent changes of   inflammatory response  .
            hydrogel dressings in second-degree burn wounds can   Despite the good clinical outcome for wet wounds,
            be time-consuming, potentially traumatic to the healing   however, BBG alone is ineffective in treating dry wounds,
            tissue, and may lead to complications such as dehydration   e.g., burn wounds, due to the wound dehydration and
            or maceration if poorly managed. Hence, there is an   lack of reacting medium. Besides, the fast degradation


            Volume 9 Issue 6 (2023)                        133                         https://doi.org/10.36922/ijb.0118
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