Semprus BioSciences Corp., Cambridge, MA 02139, USA.
Sci Transl Med. 2012 Sep 26;4(153):153ra132. doi: 10.1126/scitranslmed.3004120.
Adherence of proteins, cells, and microorganisms to the surface of venous catheters contributes to catheter occlusion, venous thrombosis, thrombotic embolism, and infections. These complications lengthen hospital stays and increase patient morbidity and mortality. Current technologies for inhibiting these complications are limited in duration of efficacy and may induce adverse side effects. To prevent complications over the life span of a device without using active drugs, we modified a catheter with the nonleaching polymeric sulfobetaine (polySB), which coordinates water molecules to the catheter surface. The modified surface effectively reduced protein, mammalian cell, and microbial attachment in vitro and in vivo. Relative to commercial catheters, polySB-modified catheters exposed to human blood in vitro had a >98% reduction in the attachment and a significant reduction in activation of platelets, lymphocytes, monocytes, and neutrophils. Additionally, the accumulation of thrombotic material on the catheter surface was reduced by >99% even after catheters were exposed to serum in vitro for 60 days. In vivo, in a highly thrombogenic canine model, device- and vessel-associated thrombus was reduced by 99%. In vitro adherence of a broad spectrum of microorganisms was reduced on both the external and the internal surfaces of polySB-modified catheters compared to unmodified catheters. When unmodified and polySB-modified catheters were exposed to the same bacterial challenge and implanted into animals, 50% less inflammation and fewer bacteria were associated with polySB-modified catheters. This nonleaching, polySB-modified catheter could have a major impact on reducing thrombosis and infection, thus improving patient health.
蛋白质、细胞和微生物对静脉导管表面的黏附作用会导致导管堵塞、静脉血栓形成、血栓栓塞和感染。这些并发症会延长住院时间,增加患者的发病率和死亡率。目前抑制这些并发症的技术在疗效持续时间上存在局限性,并且可能会引起不良反应。为了在不使用活性药物的情况下预防整个装置使用期间的并发症,我们用非浸出性聚合物磺酸甜菜碱(polySB)对导管进行了修饰,该聚合物可以使水分子与导管表面配位。修饰后的表面可有效减少体外和体内的蛋白质、哺乳动物细胞和微生物黏附。与商业导管相比,暴露于体外人血液中的 polySB 修饰导管的黏附率降低了>98%,血小板、淋巴细胞、单核细胞和中性粒细胞的激活显著降低。此外,即使在体外将导管暴露于血清中 60 天后,导管表面血栓形成物质的积累也减少了>99%。在体内,高度血栓形成的犬模型中,装置和血管相关的血栓减少了 99%。与未修饰导管相比,polySB 修饰导管的内外表面对广谱微生物的黏附均减少。当未修饰和 polySB 修饰的导管暴露于相同的细菌挑战并植入动物体内时,polySB 修饰的导管与炎症和细菌的相关性降低了 50%。这种非浸出的、polySB 修饰的导管可能会对减少血栓形成和感染产生重大影响,从而改善患者的健康状况。