title: Nucleic acid scavenging microfiber mesh inhibits trauma-induced inflammation and thrombosis.
abstract: 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.
authors.affiliation: Department of Surgery, Duke University, Durham, NC, 27710, USA. Electronic address: jaewoo.lee@duke.edu.
authors.forename: Jaewoo
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, 27710, USA.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Jackman
authors.affiliation: Department of Surgery, Duke University, Durham, NC, 27710, USA; Duke Transplant Center, Department of Surgery, Duke University, Durham, NC, 27710, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Kwun
authors.affiliation: Department of Surgery, Duke University, Durham, NC, 27710, USA; Duke Transplant Center, Department of Surgery, Duke University, Durham, NC, 27710, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Manook
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, 27710, USA.
authors.forename: Angelo
authors.initials: A
authors.lastname: Moreno
authors.affiliation: Department of Surgery, Uniformed Services University of Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD, 20814, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Elster
authors.affiliation: Department of Surgery, Duke University, Durham, NC, 27710, USA; Duke Transplant Center, Department of Surgery, Duke University, Durham, NC, 27710, USA.
authors.forename: Allan D
authors.initials: AD
authors.lastname: Kirk
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, 27710, USA; Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA.
authors.forename: Kam W
authors.initials: KW
authors.lastname: Leong
authors.affiliation: Department of Surgery, Duke University, Durham, NC, 27710, USA; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, 27710, USA. Electronic address: bruce.sullenegr@duke.edu.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Sullenger
mesh_terms: D065966:Absorption, Physicochemical; D000067531:Alarmins / Q000276:immunology / Q000302:isolation & purification*; D000818:Animals; D002478:Cells, Cultured; D050091:Dendrimers / Q000737:chemistry*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000628:therapy*; D008422:Materials Testing; D051379:Mice; D057139:Nanofibers / Q000737:chemistry*; D009696:Nucleic Acids / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification*; D013927:Thrombosis / Q000276:immunology / Q000628:therapy*; D016896:Treatment Outcome; D014462:Ultrafiltration / Q000379:methods*
chemical_list: D000067531:Alarmins; D050091:Dendrimers; D009696:Nucleic Acids
keywords: Inflammation; Microfiber mesh; Nucleic acid scavenger; Thrombosis; Toll like receptor