Nucleic acid scavenging microfiber mesh inhibits trauma-induced inflammation and thrombosis.
Nucleic acid scavenging microfiber mesh inhibits trauma-induced inflammation and thrombosis.
复制标题
核酸清除超细纤维网抑制创伤引起的炎症和血栓形成。
DOI：
10.1016/j.biomaterials.2016.12.024
复制
发表时间：
2017-03
期刊：
影响因子：
14
通讯作者：
Sullenger BA
中科院分区：
文献类型：
--
作者：
Lee J;Jackman JG;Kwun J;Manook M;Moreno A;Elster EA;Kirk AD;Leong KW;Sullenger BA
创伤患者在细胞损伤和组织损伤后产生大量危险信号和高水平的损伤相关分子模式（DAMP）。这些DAMP直接和间接参与严重损伤患者各种炎症和血栓并发症的发病机制。尚未开发出用于从血液或组织液中去除DAMP的有效治疗剂。在此，我们证明了核酸结合聚合物，例如，聚乙烯亚胺（PEI）和聚酰胺胺树状聚合物固定在静电纺丝微纤维网上可以有效地捕获各种DAMP，如细胞外DNA和高迁移率族蛋白1（HMGB1）。此外，用PEI固定的微纤维网治疗废除了DAMP的能力，DAMP从培养物中的死亡和垂死细胞释放或在创伤性损伤后的患者中发现，在体外和体内激活先天性免疫应答和凝血。核酸清除微纤维网代表了对抗创伤中的炎症和血栓形成的有效策略。
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.