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Biomedical subjects

Yasuhide Nakayama

Publications and source records attributed to Yasuhide Nakayama.

At least 19 recordsLinked to original sources

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

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.

Animals↗

Encapsulation of chondrocytes in photopolymerizable styrenated gelatin for cartilage tissue engineering.

We have developed a photopolymerizable styrenated gelatin that can cross-link through polymerization induced by irradiation with visible light. The purpose of this study was to investigate the feasibility of using photopolymerizable styrenated gelatin as a cell carrier in chondrocyte transplantation. As visible light activates camphorquinone added as a photoinitiator, free radicals induce the polymerization of the gelatin macromer; the styrenated gelatin then becomes cross-linked. Rabbit articular chondrocytes were cultured in styrenated gelatin hydrogels and also in collagen gels as a control. After being cultured in the gels, the cells were collected from both gels and counted. Reverse transcriptase-polymerase chain reaction, histological examination, and quantification of the synthesized glycosaminoglycan were performed. On average, 26% of the embedded cells were collected from the gelatin hydrogel immediately after the crosslinking reaction. The surviving chondrocytes expressed the mRNA of type II collagen and aggrecan core protein and produced a cartilaginous matrix throughout the gelatin after 3 weeks. A slightly insufficient accumulation of the matrix was found in the internal region of the gelatin hydrogels, suggesting that less permeability for nutrients due to the high concentration and closely packed structure resulted in less cell viability. Although some limitations became evident, these results indicate that it may be possible to use photopolymerizable styrenated gelatin as a cell carrier in chondrocyte transplantation.

Animals↗

Improved gene expression in resting macrophages using an oligopeptide derived from Vpr of human immunodeficiency virus type-1.

Vpr, an accessory gene product of human immunodeficiency virus type-1, is thought to transport a viral DNA from the cytoplasm to the nucleus in resting macrophages. Previously, we reported that a peptide encompassing amino acids 52-78 of Vpr (C45D18) promotes the nuclear trafficking of recombinant proteins that are conjugated with C45D18. Here, we present evidence that C45D18, when conjugated with a six-branched cationic polymer of poly(N,N-dimethylaminopropylacrylamide)-block-oligo(4-aminostyrene) (SV: star vector), facilitates gene expression in resting macrophages. Although there was no difference between SV alone and C45D18-SV with respect to gene transduction into growing cells, C45D18-SV resulted in more than 40-fold greater expression of the exogenous gene upon transduction into chemically differentiated macrophages and human quiescent monocyte-derived macrophages. The data suggest that C45D18 contributes to improving the ability of a non-viral vector to transduce macrophages with exogenous genes and we discuss its further application.

Amino Acid Sequence↗

Differentiation from embryonic stem cells to vascular wall cells under in vitro pulsatile flow loading.

This study evaluated the possibility of differentiation from embryonic stem (ES) cells to vascular wall cells by physical (mechanical) stress loading in vitro. A cell mixture containing Flk1-positive cells (ca. 30%) derived from murine ES cells was added to a compliant microporous tube made of segmented polyurethane. The compliance of the tube was close to that of the human artery [the stiffness parameter (beta) = 57.2 (n = 5, SD < 5%)]. The luminal surface of the tube was fully covered with the cells by preincubation for two days in the presence of vascular endothelial growth factor (VEGF). After 2 days of additional incubation without VEGF under static conditions, layering of the grown cells, mostly smooth muscle actin (SMA)-positive cells, was observed only on the luminal surface of the tube. The cells were flat, polygonal, and randomly oriented. On the other hand, after a 2-day incubation under a weak pulsatile flow simulating the human venous systems [wall shear stress (WSS) from -0.98 to 2.2 dyn/cm(2); circumferential strain (CS) 4.6-9.6 x 10(4) dyn/cm(2)] without VEGF, cells in the superficial layer were regularly oriented in the direction of the pulsatile flow. The oriented cells exhibited endothelial-like appearance, indicating that they were platelet endothelial cell adhesion molecule 1 (PECAM1)-positive. In addition, the cells growing into the interstices in the deeper layer showed smooth muscle-like appearance, indicating that they were SMA-positive. Differentiation to two different cell types and segregation of incorporated ES cells may be simultaneously encouraged by the combination of WSS and CS. It is expected that the monobloc building of hierarchically structured hybrid vascular prostheses composed of several vascular wall cell types is possible by physically synchronized differentiation of ES cells.

Actins↗

Development of sutureless vascular connecting system for easy implantation of small-caliber artificial grafts.

A novel sutureless vascular connecting system, an assembly with a delivery rod, an introducing sheath, and a connecting device, was developed for easy implantation of small-caliber vascular grafts less than 2 mm in internal diameter. A microporous stainless tube (length 2 mm, external diameter 1.6 mm, wall thickness 65 microm, pore diameter 400 microm, pore-to-pore distance 500 microm) was designed to serve as a connecting device. The feasibility of the system was tested using two types of preliminary animal experiments. One animal model consisted of graft implantation into the rat abdominal aorta (1.5 mm in diameter). The connecting device was inserted into the proximal and distal ends of the aorta through the introducing sheath by pushing the delivery rod with the connecting device placed over it. Subsequently, the aortic segments were inserted into both ends of model grafts made of segmented polyurethane (1.8 mm in internal diameter) and were fixed with banding silk threads from the exterior. The procedure was completed within 20 min without requiring specialized microsurgery techniques. Blood leakage and obstruction did not occur. The second model consisted of an end-to-end anastomosis between rabbit common carotid arteries (2 mm in diameter), which was performed within several minutes of blood flow interruption. Scanning electron microscopy demonstrated that the luminal surface of the device was fully covered with endothelial cells (ECs) after 1 week as a result of transluminal ingrowth of native ECs through the micropores in the device. This endothelialization may prevent early thrombus-induced occlusion. This simple and "easy-to-learn" technique will promote the development of small-caliber arterial grafts, and furthermore, it may have potential for clinical application.

Anastomosis, Surgical↗

The potential of poly(N-isopropylacrylamide) (PNIPAM)-grafted hyaluronan and PNIPAM-grafted gelatin in the control of post-surgical tissue adhesions.

Poly(N-isopropylacrylamide)-grafted hyaluronan (PNIPAM-HA) and PNIPAM-grafted gelatin (PNIPAM-gelatin), which exhibit sol-to-gel transformation at physiological temperature, were applied as control of tissue adhesions: tissue adhesion prevention material and hemostatic aid, respectively. The rat cecum, which was abraded using surgical gauze, was coated with PNIPAM-HA-containing PBS (concentration: 0.5 w/v%). The coated solution was immediately converted to an opaque precipitate at body temperature, which weakly adhered to and covered the injured rat cecum. One week after coating, tissue adhesion between the PNIPAM-HA-treated cecum and adjacent tissues was significantly reduced as compared with that between non-treated tissue and adjacent tissues. On the other hand, the coating of bleeding spots of a canine liver with PNIPAM-gelatin-containing PBS (concentration: 20 w/v%) resulted in spontaneous gel formation on the tissues and subsequently suppressed bleeding. Although these thermoresponsive tissue adhesion prevention and hemostatic materials are still prototypes at this time, both thermoresponsive biomacromolecules bioconjugated with PNIPAM, PNIPAM-HA and PNIPAM-gelatin, may serve as a tissue adhesion prevention material and hemostatic aid, respectively.

Acrylic Resins↗

High performance gene delivery polymeric vector: nano-structured cationic star polymers (star vectors).

Nano-structured hyperbranched cationic star polymers, called star vectors, were molecularly designed for a novel gene delivery non-viral vector. The linear and 3, 4 or 6 branched water-soluble cationic polymers, which had same molecular weight of ca. 18,000, were synthesized by iniferter (initiator-transfer agent-terminator)-based photo-living-radical polymerization of 3-(N,N-dimethylamino)propyl acrylamide, initiated from respective multi-dithiocarbamate-derivatized benzenes as an iniferter. All polymers produced polyion complexes 'polyplexes' by mixing with pDNA (pGL3-control plasmid), in which the particle size was ca. 250 nm in diameter [the charge ratio < 2/1 (vevtor/pDNA)] and ca. 150 nm (the charge ratio > 2.5/1), and the zeta-potential was ca. +10 mV (the charge ratio > 1/1). When COS-1 cells were incubated with the polyplexes 12 h after preparation under the charge ratio of 5/1, higher gene expression was obtained as an increase in branching, with a little cytotoxicity. The relative gene expression to the linear polymer was about 2, 5, and 10 times in 3-, 4-, and 6-branched polymers, respectively. The precise change in branching of polymers enabled the control of the gene transfer activity.

Animals↗

Photo-control of the polyplexes formation between DNA and photo-cation generatable water-soluble polymers.

Photo-cation generatable water-soluble polymers (Mw: approximately 1x10(5)) were prepared by radical copolymerization of N,N-dimethylacrylamide and vinyl monomer of triphenylmethane leucohydroxide (malachite green), which generate a cation upon ultraviolet light (UV) irradiation at wavelengths of between 290 and 410 nm. The malachite green contents of the copolymers were 3.6 (0.4 mol%), 7.9 (0.7 mol%), and 15.0 (2.7 mol%) per molecule. When an aqueous solution of the photo-cationized copolymers generated by UV irradiation was mixed with a Tris-HCl buffer (pH 7.4) of DNA (pGL3-control plasmid), dynamic light scattering (DLS) measurements showed the formation of polyplexes between the cationic copolymers and anionic DNA by non-specific electrostatic interaction, which was visualized with a confocal laser scanning microscopy (CLMS). Their mean cumulant diameter was about 150 nm with low polydispersity irrespective of the malachite green content in the copolymers. In the copolymer with the lowest malachite green content, almost all of the amount of the polyplexes was maintained by repeated UV irradiation, but the amount gradually decreased in the dark at 37 degrees C due to dissociation of the polyplexes, synchronized with the neutralization of the cation form of malachite green. The photo-cation generatable copolymers designed here can undergo photo-induced formation of the polyplexes with DNA and thermal polyplex dissociation, which may be used as a model for a novel photo-induced gene delivery system into cells.

Cations↗

In vivo evaluation of poly(N-isopropylacrylamide) (PNIPAM)-grafted gelatin as an in situ-formable scaffold.

We examined whether poly(N-isopropylacrylamide)-grafted gelatin (PNIPAM-gelatin) with a lower critical solution temperature of approximately 34 degrees C, which was prepared by quasi-living radical graft polymerization, can serve as an in situ-formable three-dimensional extracellular matrix or cell scaffold. A mixture of fibroblasts stained with fluorescent dye and PNIPAM-gelatin in Dulbecco's modified Eagle's medium solution was injected into the subcutaneous tissue of Wistar rats, and immediately formed a white, opaque cell-incorporated gel. Fibroblasts immediately after injection were spherical in shape and were homogeneously distributed in the gel. Fibroblasts in the gel 2 weeks after injection had spread and proliferated. One day after injection, many macrophages and neutrophiles were observed around the gel. As the implantation period proceeded, the inflammation reaction subsided. One week after injection, fibroblasts in the native tissue and macrophages migrated into the gel. From 6 to 12 weeks after injection, some degree of calcification in the solid tissue was intermittently observed. The weight of the gel 6 weeks after implantation was reduced to almost one-half of the weight of the originally injected sample. The potential usefulness of PNIPAM-gelatin as an injectable scaffold is discussed.

Acrylic Resins↗

In vivo tissue-engineered small-caliber arterial graft prosthesis consisting of autologous tissue (biotube).

In this study, vascular-like tubular tissues called biotubes, consisting of autologous tissues, were prepared using in vivo tissue engineering. Their mechanical properties were evaluated for application as a small-caliber artificial vascular prosthesis. The biotubes were prepared by embedding six kinds of polymeric rods [poly(ethylene) (PE), poly(fluoroacetate) (PFA), poly(methyl methacrylate) (PMMA), segmented poly(urethane) (PU), poly(vinyl chloride) (PVC), and silicone (Si)] as a mold in six subcutaneous pouches in the dorsal skin of New Zealand White rabbits. For rods apart from PFA, biotubes were constructed after 1 month of implantation by encapsulation around the polymeric implants. The wall thickness of the biotubes ranged from about 50 to 200 microm depending on the implant material and were in the order PFA < PVC < PMMA < PU < PE. As for PE, PMMA, and PVC, the thickness increased after 3 months of implantation and ranged from 1.5-to 2-fold. None of the biotubes were ruptured when a hydrostatic pressure was gradually applied to their lumen up to 200 mmHg. The relationship between the intraluminal pressure and the external diameter, which was highly reproducible, showed a "J"-shaped curve similar to the native artery. The tissue mostly consisted of collagen-rich extracellular matrices and fibroblasts. Generally, the tissue was relatively firm and inelastic for Si and soft for PMMA. For PMMA, PE, and PVC the stiffness parameter (beta value; one of the indexes for compliance) of the biotubes obtained was similar to those of the human coronary, femoral, and carotid arteries, respectively. Biotubes, which possess the ability for wide adjustments in their matrices, mechanics, shape, and luminal surface design, can be applied for use as small-caliber blood vessels and are an ideal implant because they avoid immunological rejection.

Animals↗

Development of a water-soluble matrix metalloproteinase inhibitor as an intra-arterial infusion drug for prevention of restenosis after angioplasty.

To prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA) and/or stenting of atherosclerotic stenosed arteries, we designed and developed two water-soluble matrix metalloproteinases (MMPs) inhibitors. The first inhibitor was monomeric in type and was chemically synthesized by succinylation of the synthetic MMP inhibitor, N-hydroxy-5-hydroxy-2(S)-methyl-4(S)-(4-phenoxybenzoyl)aminopentanamide (ONO-M11-335). The second inhibitor was polymeric and was a radical copolymer of the vinyl derivative of ONO-M11-335 and a water-soluble monomer, N,N-dimethylacrylamide (DMAAm). For the second inhibitor, NMR analyses and UV-vis spectra measurements showed that the content of the ONO-M11-335 unit in the copolymers (M(n); ca. 10 000 and 20 000 by GPC measurements) was about 8 per molecule. The MMP inhibitors were all highly soluble in water, even under neutral pH. The succinylated derivative markedly inhibited MMP-2, MMP-9, and MMP-12 in vitro, as did ONO-M11-335. In contrast the copolymers, which can maintain effective plasma levels for extended periods by prevention of hepatic uptake, showed a ca. 100-fold reduced inhibition activity. Such water-soluble MMP inhibitors, developed in this study, may potentially be useful as an intra-arterial infusion drug for vascular injury.

Acrylamides↗

Novel visible-light-induced photocurable tissue adhesive composed of multiply styrene-derivatized gelatin and poly(ethylene glycol) diacrylate.

A novel photocurable tissue adhesive glue, which is composed of styrene-derivatized (styrenated) gelatin, poly(ethylene glycol) diacrylate (PEGDA), and carboxylated camphorquinone in phosphate-buffered saline (PBS), was prepared. The prototype formulation suitable for arterial repair was determined based on the gel yield, degree of swelling, tissue adhesive strength, and breaking (or burst) strength in vitro. The formulated photocurable tissue adhesive glue with an appropriate viscosity was converted to a water-swollen gel within 1 min of visible light irradiation. The tissue adhesive glue, which was coated on a rat abdominal aorta incised with a pair of scissors, was immediately converted to a swollen gel upon subsequent irradiation with visible light, and concomitantly hemostasis was completed. Histological examination showed that the produced gel was tightly adhered to the artery shortly after photoirradiation. The gel gradually degraded with time and was completely absorbed within 4 weeks after treatment. These results indicate that the photocurable glue developed here may serve as a tissue adhesive glue applicable to vascular surgery.

Animals↗

Coaxial double-tubular compliant arterial graft prosthesis: time-dependent morphogenesis and compliance changes after implantation.

In order to reduce the compliance mismatch between the native artery and the artificial graft, we have developed a coaxial double-tubular compliant graft, using multiply micropored segmented polyurethane (SPU) thin films, which mimics the relationship between the intraluminal pressure and vessel internal diameter (P-D) of the native artery (termed "J" curve). The graft was coaxially assembled by inserting a high-compliance inner tube with a heparin-immobilized photocured gelatin coating layer into a low-compliance outer tube with a photocured hydrophilic polymer coating layer. Twenty-eight coaxial double-tubular compliant grafts were implanted into the canine common carotid arteries in an end-to-end fashion for up to 12 months. The overall patency rate was 86% (24/28), and neither rupture nor aneurysmal formation was observed. A neoarterial wall was formed via transanastomotic and transmural tissue ingrowth, resulting in neoarterial tissue formation on the luminal surface and into the intertubular space of the double-tubular graft, accompanied by mainly myofibroblasts and inflammatory cells in the early stage and endothelialization and collagen-rich extracellular matrices in the late stage of implantation. Surrounding-tissue adhesion with the outer tube was prevented by the hydrophilic polymer coating. Although the J curve of the implanted prototype model was preserved 1 month after implantation, the impaired J curves were observed because of tissue ingrowth and tissue adhesion between the outer surface of the inner tube and the surrounding tissues 3 and 6 months after implantation. At 12 months after implantation, however, the implanted coaxial double-tubular graft exhibited high compliance due to biodegradation of the SPU films.

Animals↗

Photo-control of the interaction between endothelial cells and photo-cation generatable water-soluble polymers.

In this study photo-control of the non-biospecific interaction between endothelial cell membranes and photo-cation generatable water-soluble polymers were examined. The water-soluble polymers contained triphenylmethane leucohydroxide (malachite green) groups (contents: 0.4 and 1.6 mol%), which dissociate into triphenylmethyl cations and counter hydroxide ions upon ultraviolet light (UV) irradiation, and were prepared by free radical copolymerization of diphenyl(4-vinylphenyl)methane leucohydroxide and acrylamide. The nature and magnitude of the interaction was quantitatively assessed by direct luminescence measurement of the intracellular calcium ion concentration using a calcium-sensitive photoprotein, aequorin. When a PBS buffer of the photoreactive copolymers were added, prior to UV irradiation, to a PBS suspension of cultured bovine endothelial cells loaded with aequorin, no detectable elevation of Ca(2+) was measured. In contrast, cationic copolymers, derived from the photoreactive copolymers after UV irradiation at a wavelength of 290<lambda<410 nm, induced an immediate transient increase in the cytosolic free Ca(2+) concentration due to a Ca(2+) inflow from the extracellular space into the cells, which may be due to non-biospecific transmembrane stimulation. Longer UV irradiation exposures of the copolymers and higher concentrations of the polymers, with higher contents of the photodissociable group, resulted in more Ca(2+) inflow with little cellular damage. The photo-cation generatable copolymers developed here made possible to control the non-biospecific interaction with endothelial cell membranes by UV irradiation condition, and composition and amount of the copolymer.

Animals↗

In vivo leukocyte cytokine mRNA responses to biomaterials are dependent on surface chemistry.

An in vivo mouse cage implant system was used to determine whether leukocyte cytokine mRNA responses to implanted biomaterials were dependent on surface chemistry. Surfaces displaying various chemistries (hydrophobic, hydrophilic, anionic, and cationic) were placed into stainless steel cages and implanted subcutaneously. Semiquantitative RT-PCR analyses revealed that hydrophilic surfaces showed a decreased expression of proinflammatory cytokines, IL-6 and IL-8, and pro-wound healing cytokines, IL-10 and TGF-beta by adherent cells, and mRNA levels of the proinflammatory cytokine, IL-1beta, and the pro-wound healing cytokine IL-13 were decreased in surrounding, exudate cells. Cytokine responses by adherent and exudate cells to hydrophobic, anionic and cationic surfaces were similar and indicative of a strong inflammatory response at the earliest time point followed by a wound healing response at later time points. However, no differences in the types or levels of exudate cells for any of the surfaces or the empty cage at each of the respective time points were observed, indicating their respective biocompatibility. These studies identify hydrophilic surface chemistries as having significant effects on leukocyte cytokine responses in vivo by decreasing the expression of inflammatory and wound healing cytokines by inflammatory cells adherent to the biomaterial as well as present in the surrounding exudate.

Animals↗

Fabrication of micropored elastomeric film-covered stents and acute-phase performances.

To prevent thrombus formation in the acute phase and restenosis in the subacute to chronic phase after stenting of atherosclerotic arteries, we developed a covered stent with a micropored elastomeric film, the blood-contacting surface of which was coated with a photocured gelatin layer immobilized with heparin. Segmented polyurethane (SPU) film (30 microm in wall thickness) as a cover material was multiply micropored by excimer laser-directed microprocessing (pore diameter, 30 microm; interpore distance, 125 microm). An aqueous mixed solution of benzophenone-derivatized gelatin and heparin was coated on the micropored SPU film. Upon ultraviolet light irradiation, a thin layer of a gelatin gel immobilized with heparin was formed and simultaneously fixed on the SPU film. The fully covered stents were assembled by wrapping a balloon-expandable stent with gelatin/heparin gel-layered SPU film and subsequently suturing and then gluing. To assess the validity of this covered stent in vivo, "half-covered" stents, in which half at the distal side was covered with the gel-layered SPU film, was implanted in rabbit common carotid arteries (about 3 mm in diameter). After 3 months of implantation, all the half-covered stents (n = 7) were patent. Regardless of the covered or noncovered region of the stents, the entire luminal surface of the stents was fully endothelialized and a thin neointimal tissue was formed. The potential advantages of a covered stent as designed above are discussed.

Animals↗

Phosphorylcholine-endcapped oligomer and block co-oligomer and surface biological reactivity.

Phosphorylcholine (PC)-endcapped oligomer and block co-oligomer were prepared by employing a photoiniferter-based quasi-living polymerization technique. The designed oligomer had a PC polar head group attached to an alkylene chain at one end of the molecule and an oligo(styrene) (oligoST) segment at the other end. In the co-oligomer, an oligo(N,N-dimethylacrylamide) (oligoDMAAm) segment was inserted between both ends of the oligomer mentioned above. Surface coating of these amphiphilic substances, using an appropriate coating procedure, resulted in a very hydrophilic characteristic, suggesting that the oligoST anchored on the substrate and the PC polar head group was exposed to or located on the outer coating layer. Non-cell adhesivity in serum-containing medium was observed, while slightly reduced protein adsorption was observed. Thus, PC-endcapped oligomer and block co-oligomer appear to function as a biocompatible coating.

Biomimetic Materials↗

Occlusion of experimental aneurysms with heparin-loaded, microporous stent grafts.

OBJECTIVE: An embolization technique using a stent graft has been developed to replace the conventional type of direct surgery or neurointervention with platinum coils and/or bare stents. The utility of a commercially available metal stent wrapped with a microporous elastomeric film coated with a thin, heparin-loaded, photocured gelatinous layer for the treatment of experimental carotid artery sidewall aneurysms in dogs was evaluated. METHODS: The stent graft was used for embolization of experimental carotid artery aneurysms in dogs. The aneurysms were prepared bilaterally in canine carotid arteries with branching of an external jugular vein patch. RESULTS: The entries into all of the aneurysms were occluded immediately after placement of the stent grafts, and the aneurysms were embolized by thrombus formation even 1 week after deployment. All of the parent carotid arteries in which stent grafts were placed were patent, without severe stenosis, immediately (n = 2), 1 week (n = 4), 1 month (n = 3), and 3 months (n = 4) after placement. Scanning electron microscopy demonstrated that the luminal surfaces of the stent grafts were entirely endothelialized as soon as 1 week after placement, via transmural tissue ingrowth through the micropores formed in the covering film. CONCLUSION: 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.

Aneurysm↗