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RESEARCH ARTICLE

           3D-Printed Gelatin-Alginate Hydrogel Dressings for

           Burn Wound Healing: A Comprehensive Study


           Fateme Fayyazbakhsh *, Michael J. Khayat , Ming C. Leu    1,2
                                                        3
                                  1,2
           1 Department of Mechanical and Aerospace Engineering, Missouri University of Science and Technology, Rolla, Missouri,
           United States
           2 Intelligent System Center, Missouri University of Science and Technology, Rolla, Missouri, United States
           3 Department of Materials Engineering, McGill University, Montréal, Quebec, Canada


           Abstract: Burn wound treatment is still a clinical challenge due to the severity of tissue damage and dehydration. Among
           various wound dressings, hydrogel materials have gained significant attention for burn wound treatment in clinical practice
           due to their soothing and moisturizing activity. In this study, 3D-printed dressings were fabricated using clinically relevant
           hydrogels for deep partial-thickness burn (PTB) wounds. Different ratios of gelatin and alginate mixture were 3D-printed and
           examined in terms of rheological behavior, shear thinning behavior, mechanical properties, degradation rate, and hydration
           activity to tune the hydrogel composition for best functionality. The cell-laden dressings were bioprinted to evaluate the effect
           of the gelatin: alginate ratio on the proliferation and growth of human dermal fibroblasts. The present findings confirm that
           the higher alginate content is associated with higher viscosity and Young’s modulus, while higher gelatin content is associated
           with faster degradation and higher cell viability. Together, the 3D-printed dressing with 75% gelatin and 25% alginate showed
           the best tradeoff between mechanical properties, hydration activity, and in vitro biological response. Findings from in vivo test
           using the most effective dressing showed the positive effect of 3D-printed porous pattern on wound healing, including faster
           wound closure, regenerated hair follicles, and non-traumatic dressing removal compared to the non-printed hydrogel with the
           same composition and the standard of care. Results from this research showed that 3D-printed dressings with an adequate
           gelatin: alginate ratio enhanced wound healing activity for up to 7 days of moisture retention on deep PTB wounds.

           Keywords: Burn wound; Moist wound healing; Advanced dressings; 3D printing; Gelatin; Alginate

           *Correspondence to: Fateme Fayyazbakhsh, 316 Engineering Research Lab, 500 West 16  Street, Rolla, Missouri 65401, USA; f.fba@mst.edu
                                                                        th
           Received: June 15, 2022; Accepted: July 21, 2022; Published Online: September 19, 2022
           Citation: Fayyazbakhsh F, Khayat MJ, Leu MC. 2022. 3D-printed gelatin-alginate hydrogel dressings for burn wound healing: A comprehensive
           study. Int J Bioprint, 8(4): 618. DOI: http://doi.org/10.18063/ijb.v8i4.618

           1. Introduction                                     treatment in clinical practices, while the current standard
                                                               of care for deep partial-thickness burns (PTB) includes
           Burn wound is one of the most challenging and       petrolatum gauze, topical antimicrobial agents, contact
           debilitating wound types leading to significant disability,   dressings, and hydrogels . However, limitations such
                                                                                    [8]
           morbidity, and mortality . There is ~1% of the global   as prolonged healing, pain, traumatic removal, poor
                                [1]
           burden of diseases related to burns, leading to more   mechanical stability, limited body movement, scarring,
           than 9 million injuries and 120,000 deaths in 2017 [2,3] .   and poor regeneration of skin appendages have fostered
           Approximately 1.1 million Americans suffer from burn   the development of dermal tissue engineering (DTE)
           injuries that require medical attention, accounting for   solutions as an advanced approach to wound healing [9-13] .
           over 60% of the acute hospitalizations in the United   The desired features for burn wound dressings are
           States [4,5] . Burn wound healing is a complex and delicate   considered to be antimicrobial, soothing, tunable water
           molecular-cellular process for restoring skin functions   absorption/release, easy to remove, and transparent [14] . It
           and repairing tissue damage [6,7] . Autologous skin grafts   is also a key feature for burn wound dressings to provide
           are still the gold standard for full-thickness burn   a non-adhesive contact that is elastic enough to support

           © 2022 Author(s). This is an Open-Access article distributed under the terms of the Creative Commons Attribution License, permitting distribution and
           reproduction in any medium, provided the original work is properly cited.
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