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      A strongly adhesive hemostatic hydrogel for the repair of arterial and heart bleeds

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          Abstract

          Uncontrollable bleeding is a major problem in surgical procedures and after major trauma. Existing hemostatic agents poorly control hemorrhaging from traumatic arterial and cardiac wounds because of their weak adhesion to wet and mobile tissues. Here we design a photo-reactive adhesive that mimics the extracellular matrix (ECM) composition. This biomacromolecule-based matrix hydrogel can undergo rapid gelling and fixation to adhere and seal bleeding arteries and cardiac walls after UV light irradiation. These repairs can withstand up to 290 mm Hg blood pressure, significantly higher than blood pressures in most clinical settings (systolic BP 60–160 mm Hg). Most importantly, the hydrogel can stop high-pressure bleeding from pig carotid arteries with 4~ 5 mm-long incision wounds and from pig hearts with 6 mm diameter cardiac penetration holes. Treated pigs survived after hemostatic treatments with this hydrogel, which is well-tolerated and appears to offer significant clinical advantage as a traumatic wound sealant.

          Abstract

          Uncontrollable bleeding is a major problem in surgery and after trauma. Here the authors design a photo-reactive adhesive that mimics the composition of connective tissue and is able to stop high pressure bleeding within half a minute.

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          Most cited references27

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          A Novel Wound Dressing Based on Ag/Graphene Polymer Hydrogel: Effectively Kill Bacteria and Accelerate Wound Healing

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            Tissue Adhesive Catechol-Modified Hyaluronic Acid Hydrogel for Effective, Minimally Invasive Cell Therapy

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              Engineering a highly elastic human protein–based sealant for surgical applications

              Surgical sealants have been used for sealing or reconnecting ruptured tissues but often have low adhesion, inappropriate mechanical strength, cytotoxicity concerns, and poor performance in biological environments. To address these challenges, we engineered a biocompatible and highly elastic hydrogel sealant with tunable adhesion properties by photocrosslinking the recombinant human protein tropoelastin. The subcutaneous implantation of the methacryloyl-substituted tropoelastin (MeTro) sealant in rodents demonstrated low toxicity and controlled degradation. All animals survived surgical procedures with adequate blood circulation by using MeTro in an incisional model of artery sealing in rats, and animals showed normal breathing and lung function in a model of surgically induced rat lung leakage. In vivo experiments in a porcine model demonstrated complete sealing of severely leaking lung tissue in the absence of sutures or staples, with no clinical or sonographic signs of pneumothorax during 14 days of follow-up. The engineered MeTro sealant has high potential for clinical applications because of superior adhesion and mechanical properties compared to commercially available sealants, as well as opportunity for further optimization of the degradation rate to fit desired surgical applications on different tissues.
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                Author and article information

                Contributors
                linyongzhu@ecust.edu.cn
                zhangshufang@zju.edu.cn
                hwoy@zju.edu.cn
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                14 May 2019
                14 May 2019
                2019
                : 10
                : 2060
                Affiliations
                [1 ]ISNI 0000 0004 1759 700X, GRID grid.13402.34, Department of Orthopaedic Surgery, Second Affiliated Hospital and Zhejiang University-University of Edinburgh Institute and School of Basic Medicine, , Zhejiang University School of Medicine, ; Hangzhou, 310003 China
                [2 ]ISNI 0000 0004 1759 700X, GRID grid.13402.34, Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, , Zhejiang University School of Medicine, ; Hangzhou, 310003 China
                [3 ]ISNI 0000 0001 2163 4895, GRID grid.28056.39, Optogenetics and Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering, School of Chemistry and Molecular Engineering, , East China University of Science and Technology, ; 130 Mei Long Road, Shanghai, 200237 China
                [4 ]ISNI 0000 0004 1759 700X, GRID grid.13402.34, Department of Cardiothoracic Surgery, The First Affiliated Hospital, , Zhejiang University School of Medicine, ; Hangzhou, Zhejiang Province 310003 China
                [5 ]ISNI 0000 0004 1759 700X, GRID grid.13402.34, Clinical Research Center, The First Affiliated Hospital, , Zhejiang University School of Medicine, ; Hangzhou, Zhejiang Province 310003 China
                [6 ]China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou, 310003 China
                [7 ]ISNI 0000 0004 1759 700X, GRID grid.13402.34, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, , Zhejiang University School of Medicine, ; Hangzhou, 310003 China
                [8 ]ISNI 0000 0004 1759 700X, GRID grid.13402.34, Department of Sports Medicine, , Zhejiang University School of Medicine, ; Hangzhou, 310003 China
                Article
                10004
                10.1038/s41467-019-10004-7
                6517429
                31089131
                90028833-56fd-406d-861e-909207d16039
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 3 March 2019
                : 8 April 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 2017YFA0104902
                Award ID: 81672162
                Award ID: 81630065
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Uncategorized
                biomaterials,trauma
                Uncategorized
                biomaterials, trauma

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