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      Incorporating redox-sensitive nanogels into bioabsorbable nanofibrous membrane to acquire ROS-balance capacity for skin regeneration

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          Abstract

          Facing the high incidence of skin diseases, it is urgent to develop functional materials with high bioactivity for wound healing, where reactive oxygen species (ROS) play an important role in the wound healing process mainly via adjustment of immune response and neovasculation. In this study, we developed a kind of bioabsorbable materials with ROS-mediation capacity for skin disease therapy. Firstly, redox-sensitive poly(N-isopropylacrylamide-acrylic acid) (PNA) nanogels were synthesized by radical emulsion polymerization method using a disulfide molecule as crosslinker. The resulting nanogels were then incorporated into the nanofibrous membrane of poly( l -lactic acid) (PLLA) via airbrushing approach to offer bioabsorbable membrane with redox-sensitive ROS-balance capacity. In vitro biological evaluation indicated that the PNA-contained bioabsorbable membrane improved cell adhesion and proliferation compared to the native PLLA membrane. In vivo study using mouse wound skin model demonstrated that PNA-doped nanofibrous membranes could promote the wound healing process, where the disulfide bonds in them were able to adjust the ROS level in the wound skin for mediation of redox potential to achieve higher wound healing efficacy.

          Graphical abstract

          ROS-balance nanofibrous bioabsorbable membrane enables an accelerated wound healing process via promoting cell proliferation and neovascularization.

          Highlights

          • Redox-sensitive nanogels are synthesized using a disulfide molecule as crosslinker.

          • Nanofibrous membrane is fabricated via nanogel hybridization by an airbrushing approach.

          • Nanogel-modified membrane presents adjustable hydrophilicity and redox status, promoting cell adhesion and proliferation.

          • The ROS-balance membrane can create good microenvironments to promote wound healing efficacy.

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          Most cited references47

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          Reactive oxygen species in inflammation and tissue injury.

          Abstract Reactive oxygen species (ROS) are key signaling molecules that play an important role in the progression of inflammatory disorders. An enhanced ROS generation by polymorphonuclear neutrophils (PMNs) at the site of inflammation causes endothelial dysfunction and tissue injury. The vascular endothelium plays an important role in passage of macromolecules and inflammatory cells from the blood to tissue. Under the inflammatory conditions, oxidative stress produced by PMNs leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. The migrated inflammatory cells not only help in the clearance of pathogens and foreign particles but also lead to tissue injury. The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury.
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            A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish

            Barrier structures (e.g. epithelia around tissues, plasma membranes around cells) are required for internal homeostasis and protection from pathogens. Wound detection and healing represent a dormant morphogenetic program that can be rapidly executed to restore barrier integrity and tissue homeostasis. In animals, initial steps include recruitment of leukocytes to the site of injury across distances of hundreds of micrometers within minutes of wounding. The spatial signals that direct this immediate tissue response are unknown. Due to their fast diffusion and versatile biological activities, reactive oxygen species (ROS), including hydrogen peroxide (H2O2), are interesting candidates for wound-to-leukocyte signalling. We probed the role of H2O2 during the early events of wound responses in zebrafish larvae expressing a genetically encoded H2O2 sensor1. This reporter revealed a sustained rise in H2O2 concentration at the wound margin, starting ∼3 min after wounding and peaking at ∼20 min, which extended ∼100−200 μm into the tail fin epithelium as a decreasing concentration gradient. Using pharmacological and genetic inhibition, we show that this gradient is created by Dual oxidase (Duox), and that it is required for rapid recruitment of leukocytes to the wound. This is the first observation of a tissue-scale H2O2 pattern, and the first evidence that H2O2 signals to leukocytes in tissues, in addition to its known antiseptic role.
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              Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process.

              Reactive oxygen species (ROS) play a pivotal role in the orchestration of the normal wound-healing response. They act as secondary messengers to many immunocytes and non-lymphoid cells, which are involved in the repair process, and appear to be important in coordinating the recruitment of lymphoid cells to the wound site and effective tissue repair. ROS also possess the ability to regulate the formation of blood vessels (angiogenesis) at the wound site and the optimal perfusion of blood into the wound-healing area. ROS act in the host's defence through phagocytes that induce an ROS burst onto the pathogens present in wounds, leading to their destruction, and during this period, excess ROS leakage into the surrounding environment has further bacteriostatic effects. In light of these important roles of ROS in wound healing and the continued quest for therapeutic strategies to treat wounds in general and chronic wounds, such as diabetic foot ulcers, venous and arterial leg ulcers and pressure ulcers in particular, the manipulation of ROS represents a promising avenue for improving wound-healing responses when they are stalled. This article presents a review of the evidence supporting the critical role of ROS in wound healing and infection control at the wound site, and some of the new emerging concepts associated with ROS modulation and its potential in improving wound healing are discussed.
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                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                21 March 2021
                October 2021
                21 March 2021
                : 6
                : 10
                : 3461-3472
                Affiliations
                [a ]The Key Laboratory for Ultrafine Materials of Ministry of Education, State Key Laboratory of Bioreactor Engineering, Engineering Research Center for Biomedical Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, China
                [b ]Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
                [c ]Heilongjiang Key Laboratory of Anti-fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang, 157011, China
                [d ]Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
                [e ]Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, College of Chemistry and Chemical Engineering, Hubei University, Wuhan, 430062, China
                Author notes
                []Corresponding authors. wuyan@ 123456mdjmu.edu.cn
                [∗∗ ]Corresponding author. jmsx2021@ 123456shu.edu.cn
                [∗∗∗ ]Corresponding authors. liucs@ 123456ecust.edu.cn
                [∗∗∗∗ ]Corresponding author. The Key Laboratory for Ultrafine Materials of Ministry of Education, State Key Laboratory of Bioreactor Engineering, Engineering Research Center for Biomedical Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, China yulinli@ 123456ecust.edu.cn
                [1]

                The authors contribute equally.

                Article
                S2452-199X(21)00110-9
                10.1016/j.bioactmat.2021.03.009
                7988352
                33817421
                74f1aa96-25d4-4249-9f23-f2e06e86ad88
                © 2021 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 22 November 2020
                : 3 March 2021
                : 3 March 2021
                Categories
                Article

                polylactide,nanofibrous membrane,redox sensitivity,ros-balance capacity,skin regeneration

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