Masaya Iwaki

Ion implantation and protein coating of detachable coils for endovascular treatment of cerebral aneurysms: Concepts and preliminary results in swine models

OBJECTIVEnComplete anatomic obliteration remains difficult to achieve with endovascular treatment of wide-necked aneurysms using Guglielmi detachable platinum coils (GDCs). Ion implantation is a physicochemical surface modification process resulting from the impingement of a high-energy ion beam. Ion implantation and protein coating were used to alter the surface properties (thrombogenicity, endothelial cellular migration, and adhesion) of GDCs. These modified coils were compared with standard GDCs in the treatment of experimental swine aneurysms.nnnMETHODSnIn an initial study, straight platinum coils were used to compare the acute thrombogenicity of standard and modified coils. Modified coils were coated with albumin, fibronectin, or collagen and underwent Ne+ ion implantation at a dose of 1 x 10(15) ions/cm2 and an energy of 150 keV. Coils were placed in common iliac arteries of 17 swine for 1 hour, to evaluate their acute interactions with circulating blood. In a second study, GDCs were used to treat 34 aneurysms in an additional 17 swine. GDCs were coated with fibronectin, albumin, collagen, laminin, fibrinogen, or vitronectin and then implanted with ions as described above. Bilateral experimental swine aneurysms were embolized with standard GDCs on one side and with ion-implanted, protein-coated GDCs on the other side. The necks of aneurysms were evaluated macroscopically at autopsy, by using post-treatment Day 14 specimens. The dimensions of the orifice and the white fibrous membrane that covered the orifice were measured as the fibrous membrane to orifice proportion. Histopathological evaluation of the neck region was performed by light microscopy and scanning electron microscopy.nnnRESULTSnFibronectin-coated, ion-implanted coils showed the greatest acute thrombogenicity (average thrombus weight for standard coils, 1.9 +/- 1.5 mg; weight for fibronectin-coated coils, 8.6 +/- 6.2 mg; P < 0.0001). By using scanning electron microscopy, an intensive blood cellular response was observed on ion-implanted coil surfaces, whereas this was rare with standard coils. At Day 14, greater fibrous coverage of the necks of aneurysms was observed in the ion-implanted coil group (mean fibrous membrane to orifice proportion of 69.8 +/- 6.2% for the ion-implanted coil group, compared with 46.8 +/- 15.9% for the standard coil group; P = 0.0143).nnnCONCLUSIONnThe results of this preliminary experimental study indicate that ion implantation combined with protein coating of GDCs improved cellular adhesion and proliferation. Future application of this technology may provide early wound healing at the necks of embolized, wide-necked, cerebral aneurysms.

Endothelial cell adhesion to ion implanted polymers

Abstract The biocompatibility of ion implanted polymers has been studied by means of adhesion measurements of bovine aorta endothelial cells in vitro. The specimens used were polystyrene (PS) and segmented polyurethane (SPU). Na+, N2+, O2+ and Kr+ ion implantations were performed at an energy of 150 keV with fluences ranging from 1 × 1015 to 3 × 1017 ions/cm2 at room temperature. The chemical and physical structures of ion-implanted polymers have been investigated in order to analyze their tissue compatibility such as improvement of endothelial cell adhesion. The ion implanted SPU have been found to exhibit remarkably higher adhesion and spreading of endothelial cells than unimplanted specimens. By contrast, ion implanted PS demonstrated a little improvement of adhesion of cells in this assay. Results of FT-IR-ATR showed that ion implantation broke the original chemical bond to form new radicals such as OH, z.lbond2;C=O, SiH and condensed rings. The results of Raman spectroscopy showed that ion implantation always produced a peak near 1500 cm−1, which indicated that these ion implanted PS and SPU had the same carbon structure. This structure is considered to bring the dramatic increase in the extent of cell adhesion and spreading to these ion implanted PS and SPU.

Fabrication of a stable p–n junction in a polyacetylene film by ion implantation

A stable p–n junction has been fabricated in high-density p-type polyacetylene film by sodium ion implantation.

Ion implantation into collagen for the substrate of small diameter artificial grafts

Abstract Ion implantation into collagen coated inner surface of the test tube with a diameter of 2 and 3 mm, length of 50 mm was performed to develop the hybrid type small diameter artificial vascular grafts. Substrates used were polystyrene tubes with a inner diameter of 2 mm and polytetrafluoroethylene (ePTFE) tubes with a inner diameter of 3 mm. Ne + ion implantation at an energy of 150 keV with a fluence of 3 × 10 15 ions/cm 2 was performed as a pre-treatment of protein coating. Ion implanted test tubes were coated with collagen (type I). He + , Ne + and Kr + ion implantation into inner surface of collagen coated tubes were performed at an energy of 150 keV with a fluence of 1 × 10 14 ions/cm 2 . Grafts were exposed to blood for one hour up to 120 days. He + ion implanted collagen coated specimens exhibit cell attachment and inhibition of platelet adhesion. Replaced He + ion implanted collagen coated grafts with carotid artery demonstrated 100% patency for 120 days. In contrast, Ne + and Kr + ion implanted grafts were occluded. He + ion broke the ligand which corresponds to platelet and the ligands corresponding to endothelial cell were still existent after ion implantation. Ion implantation technology into inner surface of the collagen coated test tube may develop a new small diameter artificial vascular grafts.

Plasma protein adsorption onto cell attachment controlled ion implanted collagen

Abstract Ion implantation into collagen (Type I) coated inner surfaces of test tubes with a length of 50 mm and inner diameter of 2 and 3 mm were performed to develop hybrid type small-diameter artificial vascular grafts. He+ ion implanted collagen coated grafts with a fluence of 1×10 14 ions / cm 2 replacing femoral arteries exhibited excellent graft patency. To obtain information about the relationship between plasma protein adsorption and antithrombogenicity of ion implanted collagen surfaces, protein adsorption measurements, platelet adhesion test, and animal study were performed. The amount of fibrinogen, fibronectin and albumin showed minimum value at a fluence of 1×10 14 ions / cm 2 . The adsorption of fibrinogen and fibronectin to surfaces is known to promote the adhesion of platelets. The results indicated that antithrombogenicity of He+ ion-implanted collagen with a fluence of 1×10 14 ions / cm 2 was caused by the reduction of the amount of adsorbed proteins.

Ion implantation into ePTFE for application of a dural substitute

Abstract The ideal synthetic dural substitute consists of two different sides: a cell adhesive ossa cranii and non-adhesive cerebral surfaces. The development of new materials that combine these cell adhesive and cell non-adhesive properties is the focus of this research. We report on the preparation of novel cell adhesive materials for dural substitutes by ion implantation. A cell-adhesive ion-implanted expanded polytetrafluoroethylene (ePTFE) sheet was applied as a substitute for the dura mater. Ne+ ions were implanted into ePTFE at an energy of 150 keV with fluences between 1xa0×xa01013 and 1xa0×xa01015 ions/cm2. An in vivo study demonstrated that ePTFE implanted at with 1xa0×xa01015 ions/cm2 exhibited much greater adhesion and spreading of living cells in a body compared to the non-implanted one. The internodal distance, density between the nodes and Cue605O radicals produced by ion implantation were the major factors that influenced cell invasion in ion-implanted ePTFE.

Ion bombardment into inner wall surfaces of tubes and their biomedical applications

Abstract A study has been made of ion bombardment into the inner wall surfaces of tubes to develop hybrid type, small diameter artificial vascular grafts. Substrates used were polystyrene with an inside diameter of 2 mm and segmented polyurethane (SPU) coated glass tube with an inside diameter of 1.5 mm. Ne-ion bombardment into inner wall surfaces of tubes was performed at an energy of 150 keV with an average fluence of 4 × 10 14 ions/cm 2 at an incident angle of about 88.3°. The surface modification of inner wall surfaces was examined by X-ray photoelectron spectroscopy, which showed the presence of amorphous carbon structures in the inner surfaces of Ne bombarded tubes. Endothelialization was performed on the Ne-bombarded SPU coated inner wall of a glass tube, although it could not be done without ion bombardment. A femoral artery has been replaced by the new artificial graft, and exposed to blood for 24 hours. The new graft demonstrated 100% patency. The development of artificial vascular grafts will be feasible by ion beam modification of inner wall surfaces of tubes.

Effects of Ion Implantation on Protein Adsorption onto Silicone Rubber

A study has been made on the surface wettability, atomic ratio, chemical structure, chemical bonding states and plasma protein adsorption of ion implanted silicone rubbers. C + -, N 2 + -, 0 2 + -, Ar + - and Na + -ion implantations were performed at an energy of 150 keV at room temperature. The doses ranged from 1x10 12 to 1x10 17 ions/cm 2 . Ion implantation caused the surface roughness to increase by 1–5 times. Surface wettability was estimated by means of a sessile drop method using water. With increasing ion dose, the contact angle of water decreased from 98.9° to 48.5°. However, if the sample was in the air, the contact angle of water returned to its initial valve in time elapsed. The results of XPS measurements showed that implanted elements were incorporated in a gaussian like distribution and host elements were redistributed in the polymer matrix. No change of binding energies of 0 1s , C IS , Si 2p and Si 2p can be observed upon ion implantation. Results of FT-IR-ATR showed that C + -, N 2 + -, 0 2 + -, and Ar + -ion implantation decomposed the original chemical bonds to form the new radicals. The amounts of new radicals are related to doses of implanted ions. In contrast, Na + -ion implantation hardly formed new radicals. The amount of albumin adsorbed onto 0 2 + -, Ar + -, N 2 + -, and C + - ion implanted silicone is less than that on unimplanted specimens, but more fibrinogen is adsorbed. Na + -ion implantation produced an increase in the amount of adsorbed albumin as the dose increased. In summary, Na+ion implantation produces effects that are attributable to the additional implanted constituent in the surface of the silicone, and 0 2 + -, N 2 + -, C + -, and Ar + -ion implantations primarily cause radiation effects on silicone rubber.

Formation of a super-thin film and a self-assembly cellular sheet by ion-beam irradiation

Abstract We performed ion-beam irradiation of biodegradable polymer sheets to develop a super-thin film and self-assembly cellular sheets, which exfoliated spontaneously from the substrate in a water solution. Poly- l -lactic acid sheets were used as substrates. We performed He+ and Kr+ ion-beam irradiation at energies of 50, 100 and 150 keV with fluences between 1xa0×xa01014 and 1xa0×xa01015 ions/cm2. He+ ion-beam irradiation formed a super-thin film at an energy of 50 keV with a fluence of 1xa0×xa01015 ions/cm2 and thickness of 500 nm. Kr+ ion-beam irradiation did not form a film. Simultaneous He+ and Kr+ ion-beam irradiation improved cell attachment properties. We obtained self-assembly cellular sheets by combining these two techniques. The film thickness can be controlled by controlling the ion species and acceleration energy. The experimental values agreed well with the theoretical results. This technique should be useful for new medical devices.

Cell adhesion control by ion implantation into polymeric materials and extra-cellular matrix

Abstract The bio-compatibility of ion implanted polymers and extra-cellular matrix has been studied by means of adhesion measurements of bovine aorta endothelial cells and the carcinoma of the cervix (HeLa cell). The specimens used were polystyrene (PS), oxygen plasma treated polystyrene (PS-O), extra-cellular matrix (Collagen: Type I) coated polystyrene (PS-C), and gelatin coated polystyrene (PS-G). Ne + , Na + and Ar + ion implantations were performed at energies of 50, 100 and 150 keV with fluence of 1×10 15 ions/cm 2 at room temperature. Ion implanted PS demonstrated improvement of adhesion of endothelial cells and dramatic improvement of adhesion of HeLa cell. HeLa cell adhered only to ion implanted circular domains of a diameter about 100 μm on PS. By contrast, ion implanted PS-C, PS-G and PS-O domain inhibited HeLa cell adhesion. These phenomena were observed on Ne + , Na + and Ar + implanted specimens at energies of 50, 100 and 150 keV. The results of cell adhesion to ion implanted PS was caused by carbon structure and new radicals induced by ion implantation. The inhibition of HeLa cell adhesion to ion implanted PS-C, PS-G and PS-O was caused by the destruction of cell adhesion properties of amino acid, OH and > Cue5fbO by the radiation effects. A difference between endothelial and HeLa cell adhesion to the 150 keV-Ne + ion implanted domain is recognized. It seems that 150 keV-Ne + ion implantation with a fluence of 1×10 15 ions/cm 2 broke ligands on the collagen that corresponds to HeLa cell adhesive domain, and did not break ligands which corresponding to endothelial cell.