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

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• 作者：Jaewoo Lee^a ; ^{jaewoo.lee@duke.edu} ; Jennifer G. Jackman^b ; Jean Kwun^a ; ^d ; Miriam Manook^a ; ^d ; Angelo Moreno^c ; Eric A. Elster^e ; Allan D. Kirk^a ; ^d ; Kam W. Leong^b ; ^f ; Bruce A. Sullenger^a ; ^c ; ^{bruce.sullenegr@duke.edu}
• 关键词：Nucleic acid scavenger ; Toll like receptor ; Inflammation ; Thrombosis ; Microfiber mesh
• 刊名：Biomaterials
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：120
• 期：Complete
• 页码：94-102
• 全文大小：1458 K
• 卷排序：120

文摘

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.