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      Injectable antibacterial conductive nanocomposite cryogels with rapid shape recovery for noncompressible hemorrhage and wound healing

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          Abstract

          Developing injectable antibacterial and conductive shape memory hemostatic with high blood absorption and fast recovery for irregularly shaped and noncompressible hemorrhage remains a challenge. Here we report injectable antibacterial conductive cryogels based on carbon nanotube (CNT) and glycidyl methacrylate functionalized quaternized chitosan for lethal noncompressible hemorrhage hemostasis and wound healing. These cryogels present robust mechanical strength, rapid blood-triggered shape recovery and absorption speed, and high blood uptake capacity. Moreover, cryogels show better blood-clotting ability, higher blood cell and platelet adhesion and activation than gelatin sponge and gauze. Cryogel with 4 mg/mL CNT (QCSG/CNT4) shows better hemostatic capability than gauze and gelatin hemostatic sponge in mouse-liver injury model and mouse-tail amputation model, and better wound healing performance than Tegaderm™ film. Importantly, QCSG/CNT4 presents excellent hemostatic performance in rabbit liver defect lethal noncompressible hemorrhage model and even better hemostatic ability than Combat Gauze in standardized circular liver bleeding model.

          Abstract

          To improve trauma survival and surgical outcomes, hemostatic agents are needed. Here, the authors report on the development of injectable, biocompatible carbon nanotube reinforced quaternized chitosan cryogels with shape memory, conductivity and antibacterial properties for hemostatic control.

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          Most cited references58

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          Carbon-nanotube-embedded hydrogel sheets for engineering cardiac constructs and bioactuators.

          We engineered functional cardiac patches by seeding neonatal rat cardiomyocytes onto carbon nanotube (CNT)-incorporated photo-cross-linkable gelatin methacrylate (GelMA) hydrogels. The resulting cardiac constructs showed excellent mechanical integrity and advanced electrophysiological functions. Specifically, myocardial tissues cultured on 50 μm thick CNT-GelMA showed 3 times higher spontaneous synchronous beating rates and 85% lower excitation threshold, compared to those cultured on pristine GelMA hydrogels. Our results indicate that the electrically conductive and nanofibrous networks formed by CNTs within a porous gelatin framework are the key characteristics of CNT-GelMA leading to improved cardiac cell adhesion, organization, and cell-cell coupling. Centimeter-scale patches were released from glass substrates to form 3D biohybrid actuators, which showed controllable linear cyclic contraction/extension, pumping, and swimming actuations. In addition, we demonstrate for the first time that cardiac tissues cultured on CNT-GelMA resist damage by a model cardiac inhibitor as well as a cytotoxic compound. Therefore, incorporation of CNTs into gelatin, and potentially other biomaterials, could be useful in creating multifunctional cardiac scaffolds for both therapeutic purposes and in vitro studies. These hybrid materials could also be used for neuron and other muscle cells to create tissue constructs with improved organization, electroactivity, and mechanical integrity.
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            Error bars in experimental biology

            Error bars commonly appear in figures in publications, but experimental biologists are often unsure how they should be used and interpreted. In this article we illustrate some basic features of error bars and explain how they can help communicate data and assist correct interpretation. Error bars may show confidence intervals, standard errors, standard deviations, or other quantities. Different types of error bars give quite different information, and so figure legends must make clear what error bars represent. We suggest eight simple rules to assist with effective use and interpretation of error bars.
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              Development of a chitosan-based wound dressing with improved hemostatic and antimicrobial properties.

              Hemorrhage remains a leading cause of early death after trauma, and infectious complications in combat wounds continue to challenge caregivers. Although chitosan dressings have been developed to address these problems, they are not always effective in controlling bleeding or killing bacteria. We aimed to refine the chitosan dressing by incorporating a procoagulant (polyphosphate) and an antimicrobial (silver). Chitosan containing different amounts and types of polyphosphate polymers was fabricated, and their hemostatic efficacies evaluated in vitro. The optimal chitosan-polyphosphate formulation (ChiPP) accelerated blood clotting (p = 0.011), increased platelet adhesion (p=0.002), generated thrombin faster (p = 0.002), and absorbed more blood than chitosan (p 99.99% kill of Staphylococcus aureus consistently. The silver dressing also significantly reduced mortality from 90% to 14.3% in a P. aeruginosa wound infection model in mice. Although the dressing exerted severe cytotoxicity against cultured fibroblasts, wound healing was not inhibited. This study demonstrated for the first time, the application of polyphosphate as a hemostatic adjuvant, and developed a new chitosan-based composite with potent hemostatic and antimicrobial properties.
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                Author and article information

                Contributors
                baoling@mail.xjtu.edu.cn
                mapx@umich.edu
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                17 July 2018
                17 July 2018
                2018
                : 9
                : 2784
                Affiliations
                [1 ]ISNI 0000 0001 0599 1243, GRID grid.43169.39, Frontier Institute of Science and Technology and State Key Laboratory for Mechanical Behavior of Materials, , Xi’an Jiaotong University, ; 710049 Xi’an, China
                [2 ]ISNI 0000 0001 0599 1243, GRID grid.43169.39, Department of Orthopaedics, the First Affiliated Hospital, College of Medicine, , Xi’an Jiaotong University, ; 710061 Xi’an, China
                [3 ]ISNI 0000000086837370, GRID grid.214458.e, Department of Biomedical Engineering, , University of Michigan, ; Ann Arbor, MI 48109 USA
                [4 ]ISNI 0000000086837370, GRID grid.214458.e, Department of Biologic and Materials Sciences, , University of Michigan, ; 1011, North University Ave., Room 2209, Ann Arbor, MI 48109 USA
                [5 ]ISNI 0000000086837370, GRID grid.214458.e, Macromolecular Science and Engineering Center, , University of Michigan, ; Ann Arbor, MI48109 USA
                Author information
                http://orcid.org/0000-0001-6756-1441
                http://orcid.org/0000-0002-0191-9487
                Article
                4998
                10.1038/s41467-018-04998-9
                6050275
                30018305
                a6b879c1-df7d-4414-a8ff-df21f3f381c3
                © The Author(s) 2018

                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
                : 26 December 2017
                : 4 June 2018
                Funding
                Funded by: National Natural Science Foundation of China (grant number: 51673155)
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