Cytokine Adsorption Effects of a Novel Hemofiltration Column for the Treatment of Experimental Endotoxemia.

INTRODUCTION: The TKM-101 is a new hemofiltration column packed with a polymer alloy membrane consisting of polyethersulfone, polyvinylpyrrolidone, and sulfonated poly (arylene ether) copolymers. We examined the ability of the TKM-101 column to remove cytokines and humoral mediators from blood in vitro and the effects of extracorporeal treatment with the TKM-101 column on the mortality rate and inflammatory responses to endotoxic shock in vivo. METHODS: In vitro and in vivo laboratory investigations were conducted. In the in vitro experiment, the adsorption abilities of TKM-101, AN69-ST, and control columns for cytokine-related sepsis in blood were compared using human serum samples. In the in vivo experiment, male Sprague-Dawley rats were anesthetized and injected with Escherichia coli endotoxin (15 mg/kg, intravenously). Afterward, the rats were assigned (in a double-blind manner) to one of three groups (n = 17 per group): apheresis with a control column (control group), apheresis with an AN69-ST column (AN69-ST group), or apheresis with a TKM-101 column (TKM-101 group). Outcomes were compared among the groups. RESULTS: In vitro, the concentrations of all evaluated cytokines significantly decreased with the TKM-101 column compared to those with the control column; however, there were no significant differences between the TKM-101 and AN69-ST columns. In vivo, the mortality rates 8 h after endotoxin injection were 65%, 29%, and 29% for the control, AN69-ST, and TKM-101 groups, respectively. Hypotension and elevated plasma cytokine concentrations were less prominent in the TKM-101 and AN69-ST groups compared to those in the control group. CONCLUSIONS: TKM-101 effectively removed proteins of varying sizes, from small-sized proteins such as interleukin (IL)-8 to mid-sized protein such as IL-10 in vitro. Moreover, TKM-101 treatment reduced mortality and had inhibitory effects on inflammatory responses in endotoxemic rats. These findings suggest that TKM-101 treatment may be available for use in patients with sepsis and/or endotoxemia.

Immobilization of polyphosphoesters on poly(ether ether ketone) (PEEK) for facilitating mineral coating.

Poly(ether ether ketone) (PEEK) is an alternative material to metals for orthopedic applications. However, the compatibility of PEEK with hard tissues needs to be improved. To address this issue, this study proposes a novel technique for PEEK surface modifications. A polyphosphodiester macromonomer (PEPMA·Na) was synthesized via the demethylation of polyphosphotriester macromonomer obtained via the ring-opening polymerization of cyclic phosphoesters using 2-hydroxypropyl methacrylamide as the initiator. The surface modification of PEEK was performed via photoinduced and self-initiated graft polymerization of PEPMA·Na without using any photoinitiators. The amount of phosphorus due to poly(PEPMA·Na) immobilized on PEEK increased with an increase in the photoirradiation time. The PEEK surface turned hydrophilic due to poly(PEPMA·Na) grafting, with almost similar advancing and receding contact angles, implying that the modified PEEK surface (PEEK-g-poly(PEPMA·Na)) was homogeneous. Specimens were mineral coated by simple static soaking in ×1.5 simulated body fluid (1.5SBF) and by an alternative process that included additional soaking steps in 200 mM CaCl2 aq. and 200 mM K2HPO4 aq. before static soaking in 1.5SBF. Specimens were immersed in 1.5SBF for 28 days in simple static soaking, after which the PEEK-g-poly(PEPMA·Na) surface was completely covered with spherical cauliflower-like mineral deposits that resembled octacalcium phosphate (OCP). Their structural similarities were confirmed via X-ray diffraction (XRD), energy dispersive X-ray spectrometry (EDS), and X-ray fluorescence (XRF) analyses. However, these mineral deposits were not observed on the bare PEEK surface. Due to the additional soaking steps (alternative soaking) undertaken before the static soaking of the specimens in 1.5SBF, the mineral coating on the PEEK-g-poly(PEPMA·Na) was dramatically accelerated and the surface was fully covered with mineral deposits in only one day of soaking. The mineral deposits resulting from both the soaking processes had similar structures. Compared with bare PEEK, osteoblastic MC3T3-E1 cells proliferated more actively on mineral-coated PEEK-g-poly(PEPMA·Na). Thus, the surface immobilization of poly(PEPMA·Na) on a PEEK surface is effective for mineral coating and may be useful to provide hard-tissue compatibility on PEEK.