A Nitric Oxide–Releasing Self-Assembled Peptide Amphiphile Nanomatrix for Improving the Biocompatibility of Microporous Hollow Fibers

Abstract

Oxygenators are critical components of extracorporeal circuits used frequently in cardiopulmonary bypass and intensive care, but platelet activation and induction of a complex inflammatory response are usually observed with their use. To improve the biocompatibility of oxygenators, we developed a nitric oxide (NO)-releasing, self-assembled peptide amphiphile nanomatrix. The nanomatrix formed a homogenous coating over the microporous hollow fibers as demonstrated by scanning electron microscopy. We quantitated platelet adhesion to the artificial fibers by measuring absorbance/area of platelets (Abs/A; nm/m2) using acid phosphatase assay. There was a 17-fold decrease in platelet adhesion to the nanomatrix (Abs/A = 0.125) compared to collagen controls (Abs/A = 2.07; p<0.05) and a 22-fold decrease compared to uncoated fibers (Abs/A = 2.75; p<0.05). Importantly, the nanomatrix coating did not impede oxygen transfer in water through coated and uncoated fiber modules (p>0.05) in a bench top test circuit at different flow rates as estimated by change in partial pressure of oxygen in relation to water velocity through fibers. These findings demonstrate the feasibility of coating microporous hollow fibers with a NO-releasing, self-assembled amphiphile nanomatrix that may improve the biocompatibility of the hollow fibers without affecting their gas exchange capacity.

Anti-thrombogenic Surface Coatings for Extracorporeal Membrane Oxygenation: A Narrative Review

“…Two PAs were developed to form the nanomatrix: PA–Tyr-Ile-Gly-Ser-Arg (PA–YIGSR), containing enzyme-mediated degradable metalloproteinase (MMP)-2 sensitive sequences and YIGSR (working as endothelial cell adhesive ligands); PA–KKKKK, a polylysine (KKKKK) group to form NO-donating residues. The coating did not affect the gas exchange efficacy of the fibers, whereas it significantly reduced platelet (from citrated human blood) adhesion by 22-fold compared with uncoated fibers under static incubation for 90 min . Future studies evaluating the effect of shear stress on the release of NO and the stability of the coating as well as the effect of NO on the multitude of biological systems are warranted as proposed by the authors.…”

“…16 NO) on PP hollow fibers by soaking PP fibers in the PA solution. 67 This NO-releasing PA nanomatrix was originally designed for coating implantable cardiovascular devices, 81 and in this study it was explored for ECMO membrane. Two PAs were developed to form the nanomatrix: PA−Tyr-Ile-Gly-Ser-Arg (PA−YIGSR), containing enzyme-mediated degradable metalloproteinase (MMP)-2 sensitive sequences and YIGSR (working as endothelial cell adhesive ligands); PA−KKKKK, a polylysine (KKKKK) group to form NO-donating residues.…”

“…The coating did not affect the gas exchange efficacy of the fibers, whereas it significantly reduced platelet (from citrated human blood) adhesion by 22-fold compared with uncoated fibers under static incubation for 90 min. 67 Future studies evaluating the effect of shear stress on the release of NO and the stability of the coating as well as the effect of NO on the multitude of biological systems are warranted as proposed by the authors.…”

“…Overall, the exploration of novel anti-thrombogenic coatings follows the two main directions as categorized above. Heparin-based coatings, − nitric oxide (NO) releasing coatings, and C1-esterase inhibitor (C1-INH) coatings are bioactive coatings. Zwitterionic polymers exemplified by 2-methacryloyloxyethyl phosphorylcholine (MPC), SB- co -methacrylic acid (MA) block copolymer (SBMAb-COOH) and polycarboxybetaine (pCB), tethered liquid perfluorocarbon (TLP), poly­(ethylene glycol acrylate) (PEGA), and non-ionic polymers are classified as biopassive coatings.…”

“…However, there have been minimal efforts on NO-releasing coatings for oxygenator membranes. El-Ferzli et al developed a NO-releasing, self-assembled peptide amphiphile (PA) nanomatrix (PA–YK–NO) on PP hollow fibers by soaking PP fibers in the PA solution . This NO-releasing PA nanomatrix was originally designed for coating implantable cardiovascular devices, and in this study it was explored for ECMO membrane.…”