Occlusion of Experimental Aneurysms with Heparin-loaded, Microporous Stent Grafts

Nishi, Shogo; Nakayama, Yasuhide; Ishibashi‐Ueda, Hatsue; Matsuda, Takehisa

doi:10.1227/01.neu.0000093427.89827.12

Cited by 18 publications

(22 citation statements)

References 35 publications

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“…This raises questions on how PMMPI interacts with MMPs at the liquid-solid interface or whether the MMPI binding to the zinc ion located at the active site of the MMP is a reversible reaction or not. Irrespective of these processes, however, the present results support the reasonable application of PMMPI as a coating for metal stents and polymer-covered stents 32,33 to prevent restenosis after stent implantation. An additional advantage is the extremely low drug concentrations in blood and high local concentration at the treatment site provided by this polymer, which is a potentially significant prerequisite for DES.…”

Section: Discussionsupporting

confidence: 65%

Development of a polymeric matrix metalloproteinase inhibitor as a bioactive stent coating material for prevention of restenosis

Nakayama

Masuda

2006

J Biomed Mater Res

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Abstract:Drug-eluting stents have been developed to prevent restenosis derived from excessive growth of smooth muscle cells (SMCs) after stenting. In almost every case, however, less-or non-biocompatible polymers were selected for the platform material for impregnating drugs on the stent strut. Consideration was given principally to the physical properties of the polymers, such as their adhesion to the strut and the drug dispersibility in the polymeric matrix. In this study, we designed a matrix metalloproteinase inhibitor (MMPI)-derivatized hydrophobic polymer (PMMPI) for use as a bioactive material for stent coating. This was a copolymer of n-butylmethacrylate and a vinyl monomer of synthetic MMPI (N-Hydroxy-5- carboxyethylcarbonyloxy-2(S)-methy-4(S)-(4-phenoxybenzoyl)amino-pentanamide:ONO-M11-335) with a molecular weight of about 32,000 and MMPI content of 45 per molecule. The precursor of the MMPI monomer produced significant activity in temporally inhibiting SMC proliferation without any cellular damage. After coating with the PMMPI, adhesion and proliferation of SMCs were manifestly prevented even when a small amount of MMPI was released from the polymer. The MMPI-immobilized surface may thus be effective for inhibiting both adhesion and proliferation of SMCs, which is the first step toward in vivo experimentation. It is very much expected that coating stent struts with PMMPI containing an appropriate combination of impregnated drugs will provide a powerful tool for prevention of restenosis with little cytotoxicity.

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Section: Discussionsupporting

confidence: 65%

Development of a polymeric matrix metalloproteinase inhibitor as a bioactive stent coating material for prevention of restenosis

Nakayama

Masuda

2006

J Biomed Mater Res

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“…20,21 As a stent platform, the Sendai stent (diameter: 4.5, 5.0, or 6.0 mm; length: 18 or 23 mm, Piolax), which is a self-expandable stent, was used. Segments of the Sendai stent are structured from 12 struts and each segment is linked at three joints.…”

Section: Fabrication Of Self-expandable Drug-eluting Covered Stentsmentioning

confidence: 99%

Development of self‐expandable covered stents

et al. 2007

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We newly developed self-expandable covered stents by combining two of our original technologies. Of these, the first is the dip-coating covering method that was developed previously for balloon-expandable stents; the other is the newly developed self-expandable Nitinol stents, namely, Sendai stents. The three types of covered stents with the expansion diameter of 4.5, 5.0, or 6.0 mm thus obtained had a laser-processed microporous elastomeric cover film (pore diameter: 100 microm, interpore distance: 250 microm). Although the film was extremely thin (approximately 15 microm), the film could be expanded without causing any damage, the strut was completely embedded within the film, and the luminal surface of the film was smooth and flat. Mechanical properties such as ideal flexibility to follow the shapes of arteries were almost retained even after covering. As appropriate drugs, the blood-contacting inner and tissue-contacting outer surfaces of the film were differentially coated with argatroban for antithrombogenicity or FK506 for anti-inflammation, respectively. The preliminary in vivo study indicated that the covered stents mounted in the delivery catheter were navigated and placed to appropriate position in the arteries, and permissible neointimal thickening after 1-month implantation was observed similarly in noncovered stents.

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“…Our microporous membrane induces early endothelialization capable of secreting tissue plasminogen 11 within one week of stent graft implantation, 3 thereby avoiding early thrombosis and controlling mid- to long-term hyperplasia. 12 Polyurethane has excellent elastomeric properties and is clinically used as a material for manufacturing blood pumps and arterial grafts; it also exhibits no toxicity or little biodegradation.…”

Section: Discussionmentioning

confidence: 99%

“…Micropores are circular, with a pore diameter and interpore distance of 100 µm and 250 µm, respectively, such that they achieve an opening ratio of 23.6% (calculated) after full expansion. 3 The uncoated stent was a bare stent with an opening ratio of 86%. The outer surface of the film of the microporous stent grafts was coated with argatroban (500 µg/cm 2 ), which was applied using a methanol solution (1% w/v); the solvent was subsequently volatilized for physical adsorption.…”

Section: Methodsmentioning

confidence: 99%

“…We established rabbit carotid aneurysms by intraluminal incubation of elastase within an endovascularly trapped segment of the proximal common carotid artery (CCA), 1,2 and we implanted hybrid stents equipped with micropores in these aneurysms. 3 Besides studying the occlusive effect of the hybrid stents in the aneurysms, we examined the patency of the side-branches arising from the right subclavian artery (SA), both angiographically and histologically.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of rabbit carotid aneurysms by hybrid stents (microporous thin polyurethane-covered stents): Preservation of side-branches

et al. 2013

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ObjectiveWe sought to determine the patency of normal arterial branches from the covered segments of an artery after stenting.BackgroundMost intracranial aneurysms occur at arterial branching points (bifurcations, side-branches, or perforators). The post-stenting patency of normal arterial branches from the covered segments of the artery is important. We have previously developed a hybrid stent with micropores to prevent early parent artery occlusion by more early endothelialization, and mid- to long-term parent artery stenosis by control of intimal hyperplasia after aneurysm occlusion.MethodsWe created aneurysms in 10 rabbits by distal ligation and intraluminal incubation of elastase within an endovascularly trapped proximal segment of the common carotid artery. All animals were treated with hybrid stents having micropores. Four animals were observed for one month and three each for three and 12 months. The patency of the side-branches of the subclavian artery was evaluated angiographically and in some cases, histologically.ResultsAneurysms were completely occluded at all time points other than 12 months. The subclavian artery and brachiocephalic artery were patent, without significant stenosis. All the side-branches of the subclavian artery detected on the preoperative angiogram remained patent at the final assessment.ConclusionThe use of hybrid stents for aneurysm repair and side-branch patency seems to be effective, as per the long-term results obtained in an animal model.

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Occlusion of Experimental Aneurysms with Heparin-loaded, Microporous Stent Grafts

Abstract: The stent graft we have developed seems to be highly promising for the treatment of aneurysms, especially with respect to immediate termination of blood inflow for aneurysm occlusion and rapid endothelialization in the aneurysm neck.

Cited by 18 publications

References 35 publications

Development of a polymeric matrix metalloproteinase inhibitor as a bioactive stent coating material for prevention of restenosis

Development of a polymeric matrix metalloproteinase inhibitor as a bioactive stent coating material for prevention of restenosis

Development of self‐expandable covered stents

Treatment of rabbit carotid aneurysms by hybrid stents (microporous thin polyurethane-covered stents): Preservation of side-branches

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