Nucleic acid scavenging microfiber mesh inhibits trauma-induced inflammation and thrombosis

被引:47
作者
Lee, Jaewoo [1 ]
Jackman, Jennifer G. [2 ]
Kwun, Jean [1 ,4 ]
Manook, Miriam [1 ,4 ]
Moreno, Angelo [3 ]
Elster, Eric A. [5 ]
Kirk, Allan D. [1 ]
Leong, Kam W. [2 ,6 ]
Sullenger, Bruce A. [1 ,3 ]
机构
[1] Duke Univ, Dept Surg, Durham, NC 27710 USA
[2] Duke Univ, Dept Biomed Engn, Durham, NC 27710 USA
[3] Duke Univ, Dept Mol Genet & Microbiol, Durham, NC 27710 USA
[4] Duke Univ, Dept Surg, Duke Transplant Ctr, Durham, NC 27710 USA
[5] Uniformed Serv Univ Hlth Sci, Dept Surg, Walter Reed Natl Mil Med Ctr, Bethesda, MD 20814 USA
[6] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
Nucleic acid scavenger; Toll like receptor; Inflammation; Thrombosis; Microfiber mesh; TOLL-LIKE RECEPTORS; NEUTROPHIL EXTRACELLULAR TRAPS; INJURY SEVERITY; IN-VITRO; DNA; DAMPS; DENDRIMERS; QUANTIFICATION; CYTOTOXICITY; HEMOSTASIS;
D O I
10.1016/j.biomaterials.2016.12.024
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Trauma patients produce a host of danger signals and high levels of damage-associated molecular patterns (DAMPs) after cellular injury and tissue damage. These DAMPs are directly and indirectly involved in the pathogenesis of various inflammatory and thrombotic complications in patients with severe injuries. No effective therapeutic agents for the removal of DAMPs from blood or tissue fluid have been developed. Herein, we demonstrated that nucleic acid binding polymers, e.g., polyethylenimine (PEI) and polyamidoamine dendrimers, immobilized onto electrospun microfiber mesh can effectively capture various DAMPs, such as extracellular DNAs and high mobility group box 1 (HMGB1). Furthermore, treatment with PEI-immobilized microfiber mesh abrogated the ability of DAMPs, released from dead and dying cells in culture or found in patients following traumatic injury, to activate innate immune responses and coagulation in vitro and in vivo. Nucleic acid scavenging microfiber meshes represent an effective strategy to combat inflammation and thrombosis in trauma. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:94 / 102
页数:9
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