An effective surface grafting method for chemically inert and elaborately porous medical expanded-polytetrafluoroethylene (ePTFE) was developed. Although surface graft polymerization onto basic polymeric biomaterials has been widely studied, successful modification of the ePTFE surface has been lacking due to its high chemical resistance. Herein, we succeeded in surface graft polymerization onto ePTFE through glycidyl methacrylate (GMA) as a bridge linkage following argon (Ar) plasma treatment. The epoxy group of GMA was expected to react with the peroxide groups produced on ePTFE by Ar plasma exposure, and its methacrylic groups can copolymerize with various monomers. In the present study, we selected 2-methacryloyloxyethyl phosphorylcholine (MPC) as a model monomer and the blood compatibility of modified ePTFE was evaluated. Two sequences of surface grafting were compared. In a two-step graft polymerization, GMA was first immobilized onto Ar plasma treated ePTFE, and then MPC was polymerized. In a one-step graft copolymerization, MPC and GMA were mixed and copolymerized simultaneously onto Ar plasma treated ePTFE, resulting in a poly(MPC-co-GMA) (PMG) graft surface. The roughness of the node-and-fibril structure of ePTFE was reduced by the uniform polymer layer, and the modified ePTFE had a good hydrophilic nature even after being stored in an aqueous environment for 30 days. The indispensable GMA in graft polymerization improved the surface grafting on ePTFE. The one-step and two-step graft polymerization methods could decrease the number of adhered platelets, and almost inhibit platelet activation. We concluded that graft polymerization with the GMA linker provides a novel strategy to modify the chemically inert ePTFE surfaces for functionalizing as new medical devices.

Blood compatibility generally requires two contradictory characteristics: reduced protein/platelet adhesion and excellent endothelium-related cell affinity. To understand the effect of cell adhesion peptides on blood compatibility, the peptides REDV, RGD, and hemocompatible peptide-1 (HCP-1) were immobilized on an expanded polytetrafluorethylene (ePTFE) surface and evaluated in vitro, in situ, and in vivo. Since the terminal amino groups of functional peptides often have an important effect, a cysteine residue was added to the C terminal and used for immobilization to keep the terminal amino groups free. Maleimide groups were added to carboxylic groups of highly hydrophilic and biologically inert (bioinert) polymer chains grafted onto ePTFE and coupled with cysteine residues. In vitro tests revealed that free N-terminal HCP-1 and RGD-immobilized surfaces improved the adhesion and spread of human umbilical vein endothelial cells (HUVECs), while, unexpectedly, a free N-terminal adjacent to REDV suppressed cell affinity. In situ evaluation with a porcine closed-circuit system for 2 h showed that no platelets adhered to the modified ePTFE sutures due to the bioinert graft chain containing phosphorylcholine groups. Simultaneously, leukocyte-related and endothelium-related cells were observed on RGD-immobilized ePTFE sutures because RGD was recognized by broad types of cells. These cells were not observed on the HCP-1- and REDV-immobilized ePTFE sutures, which may be due to insufficient exposure time. HCP-1-modified ePTFE graft implantation in a porcine femorofemoral (FF) bypass model for 10 days showed that the thrombus layer was clearly mitigated by HCP-1 immobilization. This study suggests that the HCP-1-immobilized ePTFE surface has potential for long-term application by mitigating thrombus and supporting endothelial cell adhesion.

To modify the surface properties of segmented polyurethane (SPU), effects of the molecular architecture of the 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers on the performance of the SPU/MPC polymer membrane were investigated. We combined the random-type, block-type, and graft-type of the MPC polymers with a typical SPU, Tecoflex^® using double solution casting procedure. The graft-type MPC polymers composed of a poly(MPC) main chain and poly(2-ethylhexyl methacrylate (EHMA)) side chains were synthesized through the combination of two different living radical polymerization techniques to regulate the density and chain length of the side chains. The SPU membranes modified with the MPC polymers were characterized using X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. The results revealed that the MPC units were located on the SPU surface. Although the breaking strength of the SPU membranes modified with block-type poly(MPC-block-EHMA) and graft-type poly(MPC-graft-EHMA) was lower than that of SPU membranes modified with random-type poly(MPC-random-EHMA), their breaking strengths were adequate for manufacturing medical devices. On the other hand, better stability was observed in the MPC polymer layer on the SPU membrane after immersion in an aqueous medium, wherein the SPU membrane had been modified with the poly(MPC-graft-EHMA). This was because of the intermixing of the hydrophobic poly(EHMA) segments in the domain of the hard segments in the SPU membrane. After this modification, each SPU/MPC polymer membrane showed hydrophilic nature based on the MPC polymers and a dramatic suppression of protein adsorption. From these results, we concluded that the SPU membrane modified with the poly(MPC-graft-EHMA) was one of the promising polymeric biomaterials for making blood-contacting medical devices.

A nanofiber mesh was prepared for the adsorption of indoxyl sulfate (IS), a toxin associated with chronic kidney disease. Removing IS is highly demanded for efficient blood purification. The objective of this study is to develop a zeolite composite nanofiber mesh to remove IS efficiently. Eight zeolites with different properties were used for IS adsorption, where a zeolite with a pore size of 7 Å, H⁺ cations, and a silica to aluminum ratio of 240 mol/mol exhibited the highest adsorption capacity. This was primarily attributed to its suitable silica to aluminum ratio. The zeolites were incorporated in biocompatible poly (ethylene-co-vinyl alcohol) (EVOH) nanofibers, and a zeolite composite nanofiber mesh was successfully fabricated via electrospinning. The nanofiber mesh exhibited an IS adsorption capacity of 107 μg/g, while the adsorption capacity by zeolite increased from 208 μg/g in powder form to 386 μg/g when dispersed in the mesh. This also led to an increase in cell viability from 86% to 96%. These results demonstrated that this zeolite composite nanofiber mesh can be safely and effectively applied in wearable blood purification devices.