Design of a Polyethersulfone-Based Self-Anticoagulant Endotoxin Hemoperfusion Adsorbent for Sepsis Treatment
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
- 300 Bioengineering
- Li, Yupei, West China Hospital of Sichuan University, Chengdu, China
- Su, Baihai, West China Hospital of Sichuan University, Chengdu, China
Sepsis is life-threatening and associated with high mortality. Currently available endotoxin adsorption columns still face significant drawbacks, such as low endotoxin adsorption capacity and unwanted need for systemic heparin anticoagulation or regional citrate anticoagulation. This work aimed to develop a polyethersulfone-based self-anticoagulant endotoxin hemoperfusion adsorbent to evaluate its hemocompatibility and endotoxin adsorption performance in vitro and in vivo.
First, polyethersulfone-based self-anticoagulant beads (namely, RAHM beads) filled with polyacrylic acid and poly(2-acrylamide-2-methyl propane sulfonic acid) copolymer networks were prepared by phase inversion and in situ polymerization technology, and polyethyleneimine was grafted onto the surface of RAHM beads to obtain RAHM@PEI beads. Second, the surface morphology and specific surface area of RAHM and RAHM@PEI beads were systematically analyzed. Third, the hemocompatibility of RAHM and RAHM@PEI beads was evaluated by measuring complement C3a, platelet count, plasma clotting time and hemolysis ratio in vitro. Finally, the feasibility of the RAHM/RAHM@PEI-based endotoxin adsorption column in LPS-induced beagle sepsis models was investigated.
Both RAHM and RAHM@PEI beads had high specific surface areas and mesoporous structures and exhibited excellent anticoagulant properties by partially inhibiting the activity of the intrinsic coagulation factors FVIII, FIX, FXI and FXII. With PEI grafting on their surfaces, the endotoxin adsorption capacity of RAHM@PEI beads was significantly higher than that of RAHM beads (164.9 vs. 82.5 EU/g). In vivo animal experiments further showed that the RAHM/RAHM@PEI-based endotoxin adsorption cartridge significantly alleviated the decrease in leukocyte and neutrophil counts in LPS-induced beagle sepsis models without obvious adverse effects. Moreover, plasma levels of cytokines (IL-8 and TNF-α) and neutrophil infiltration and bleeding in the alveolars were also significantly reduced after the use of our endotoxin adsorption cartridge.
Our data show that the RAHM and RAHM@PEI beads have high endotoxin adsorption capacities and good anticoagulant properties and are thus promising hemoperfusion sorbents to treat severe septic patients.
- Government Support – Non-U.S.