Lee Jaewoo, Jackman Jennifer G, Kwun Jean, Manook Miriam, Moreno Angelo, Elster Eric A, Kirk Allan D, Leong Kam W, Sullenger Bruce A
Department of Surgery, Duke University, Durham, NC, 27710, USA.
Department of Biomedical Engineering, Duke University, Durham, NC, 27710, USA.
Biomaterials. 2017 Mar;120:94-102. doi: 10.1016/j.biomaterials.2016.12.024. Epub 2016 Dec 23.
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.
创伤患者在细胞损伤和组织损伤后会产生一系列危险信号以及高水平的损伤相关分子模式(DAMPs)。这些DAMPs直接或间接参与了重伤患者各种炎症和血栓形成并发症的发病机制。目前尚未开发出从血液或组织液中清除DAMPs的有效治疗药物。在此,我们证明,固定在电纺微纤维网上的核酸结合聚合物,如聚乙烯亚胺(PEI)和聚酰胺胺树枝状大分子,能够有效捕获各种DAMPs,如细胞外DNA和高迁移率族蛋白B1(HMGB1)。此外,用固定有PEI的微纤维网进行治疗,可消除培养中死亡和濒死细胞释放的或创伤后患者体内发现的DAMPs在体外和体内激活先天免疫反应和凝血的能力。核酸清除微纤维网是对抗创伤中炎症和血栓形成的有效策略。