Currently, one of the most promising treatments of lipopolysaccharides (LPS)-induced sepsis is based on hemofiltration. Nevertheless, proteins rapidly adsorbed on the artificial surface of membranes which leads to activation of coagulation impairing effective scavenging of the endotoxins. To overcome this challenge, we designed polymer-brush-coated microparticles displaying antifouling properties and functionalized them with polymyxin B (PMB) to specifically scavenge LPS the most common endotoxin. Poly[( N-(2-hydroxypropyl) methacrylamide)- co-(carboxybetaine methacrylamide)] brushes were grafted from poly(glycidyl methacrylate) microparticles using photoinduced single-electron transfer living radical polymerization (SET-LRP). Notably, only parts-per-million of copper catalyst were necessary to achieve brushes able to repel adsorption of proteins from blood plasma. The open porosity of the particles, accessible to polymerization, enabled us to immobilize sufficient PMB to selectively scavenge LPS from blood plasma.
- MeSH
- adsorpce MeSH
- akrylamidy metabolismus MeSH
- biokompatibilní potahované materiály farmakologie MeSH
- bioznečištění prevence a kontrola MeSH
- epoxidové sloučeniny metabolismus MeSH
- krevní plazma metabolismus MeSH
- lidé MeSH
- lipopolysacharidy metabolismus MeSH
- methakryláty metabolismus MeSH
- polymerizace účinky léků MeSH
- polymery chemie MeSH
- polymyxin B farmakologie MeSH
- povrchové vlastnosti účinky léků MeSH
- proteiny metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Nonthrombogenic modifications of membranes for extracorporeal membrane oxygenators (ECMOs) are of key interest. The absence of hemocompatibility of these membranes and the need of anticoagulation of patients result in severe and potentially life-threatening complications during ECMO treatment. To address the lack of hemocompatibility of the membrane, surface modifications are developed, which act as barriers to protein adsorption on the membrane and, in this way, prevent activation of the coagulation cascade. The modifications are based on nonionic and zwitterionic polymer brushes grafted directly from poly(4-methyl-1-pentene) (TPX) membranes via single electron transfer-living radical polymerization. Notably, this work introduces the first example of well-controlled surface-initiated radical polymerization of zwitterionic brushes. The antifouling layers markedly increase the recalcification time (a proxy of initiation of coagulation) compared to bare TPX membranes. Furthermore, platelet and leukocyte adhesion is drastically decreased, rendering the ECMO membranes hemocompatible.
