4.8 Article

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

Journal

BIOMATERIALS
Volume 120, Issue -, Pages 94-102

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.12.024

Keywords

Nucleic acid scavenger; Toll like receptor; Inflammation; Thrombosis; Microfiber mesh

Funding

  1. Duke Department of Surgery
  2. Duke University Shared Materials Instrumentation Facility, a member of the North Carolina Research Triangle Nanotechnology Network
  3. National Science Foundation as part of the National Nanotechnology Coordinated Infrastructure [ECCS-1542015]
  4. Opportunity Funds Management Core of the Centers for Medical Countermeasures against Radiation, National Institute of Allergy and Infectious Diseases [U19AI067773]
  5. National Institutes of Health (NIH) [U54HL112307, U19AI067798, 5R01HL065222]
  6. NIH [HL109442, AI096305, GM110494]
  7. Guangdong Innovative and Entrepreneurial Research Team Program [2013S086]
  8. DoD/SC2i initiative: Department of Defense Health Program - Joint Program Committee 6/Combat Casualty Care [USUHS HT9404-13-1-0032, USUHS HU0001-15-2-0001]

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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.

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