WO2000053121A1 - Improved autologous vein graft - Google Patents

Improved autologous vein graft Download PDF

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Publication number
WO2000053121A1
WO2000053121A1 PCT/EP2000/002059 EP0002059W WO0053121A1 WO 2000053121 A1 WO2000053121 A1 WO 2000053121A1 EP 0002059 W EP0002059 W EP 0002059W WO 0053121 A1 WO0053121 A1 WO 0053121A1
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use according
vein
casing
prosthesis
sheath
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PCT/EP2000/002059
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German (de)
French (fr)
Inventor
Jürgen C. FRÖLICH
Axel Haverich
Original Assignee
Froelich Juergen C
Axel Haverich
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Application filed by Froelich Juergen C, Axel Haverich filed Critical Froelich Juergen C
Priority to AU41045/00A priority Critical patent/AU4104500A/en
Publication of WO2000053121A1 publication Critical patent/WO2000053121A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06—Blood vessels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels

Definitions

  • the invention relates to the use of a covering of autologous veins as a material for arteriovenous and arterio- (aorto -) - arterial connections to improve the short and long-term function in vein transplants.
  • the sheath is able to successfully prevent the early and late failure of autogenous vein material.
  • autologous veins are routinely used as aorto-coronary bypasses or as arterio-arterial bypasses. This material is also used as an arteriovenous connection in dialysis shunts.
  • varicose veins have sack or nodular ectasia and differ fundamentally from pathologically unchanged, continuous vein tissue.
  • the metal grid improves the patency of the varicose veins.
  • a sheath is used for the routine manufacture of venous prostheses using non pathologically modified veins, increasing the shear force in the vein and preventing its expansion under arterial pressure.
  • transplanted veins are expanded strongly and irregularly and the walls are covered with thrombotic masses, through which a tiny blood clot meanders, which is inadequate in relation to the initial and necessary amount of blood.
  • thrombotic masses through which a tiny blood clot meanders, which is inadequate in relation to the initial and necessary amount of blood.
  • angina pectoris and myocardial infarction occur again, and in the case of arterio-arterial bypass, circulatory disorders.
  • NO also known as EDRF or nitric oxide
  • prostacyclin Both Substances inhibit platelet adhesion and aggregation and the adhesion of monocytes / macrophages and the expression of VCAM "1 (vascular celt adhesion molecule '1 ) (DeCatarina, R., P.
  • Nitnc oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokmes J. Clin. Invest. 1995, 96: 60-68).
  • the diameter also increases due to the high pressure and further growth (so-called remodeling) due to the growth factors described above This reduces the shear force and the production of the antithrombotic and antiproliferative mediators NO and PGI 2 , and the formation of wall-like thrombi as well as vasodilation and ectasia.
  • the invention has for its object to prevent the expansion of the vessel, to maintain the shear force and thus to ensure the production of NO, PGI 2 and other shear force-dependent mediators. This prevents the wall thrombi and the release of the growth factors and thus the remodeling.
  • the prevention of the expansion of the vein under arterial pressure and the increase in shear force are achieved according to the invention in that a mesh, sheath or sleeve is placed around the vein, which brings the vein diameter to an optimal level and stops there Appropriate procedures and can be combined in different areas and in different ways to achieve optimal results.
  • the simplest variant is a sleeve made of structured PTFE or another plastic.
  • the plastic can be designed as a mesh.
  • a porous tube with a pore size that allows capillaries to sprout and thus integrate into the tissue (pore size 200 - 800 ⁇ m) can be used.
  • the covering can be elastic, for example so elastic that a pulse wave is passed on. It is known that pulsatile flow requires PGI 2 production from endothelial cells (JA Frangos, SG Eskin, LV Mclntire, CL Ives Flow effects on prostacyclin production by cultured human endothelial cells, Science, March 22, 1985, pp. 1477-79 )
  • the covering can also consist of resorbable biological or artificial material.
  • these materials are collagen, polyglycolic acid, polyhydroxyctanoid, poly-4-hydroxybutyrate and polylactidic acid.
  • growth factors or drugs can be incorporated into these materials which influence tissue formation and function, as well as the cells of the blood flowing through (e.g. granulocytes, thrombocytes)
  • the ends of the covering can be funnel-shaped, so that the terminal or lateral anastomotic areas are also covered and the covering can be fixed in this area by suitable measures.
  • the covering can taper from the high-pressure side to the low-pressure side, as in a normal blood vessel.
  • the cross-section of the covering can be non-circular (e.g. ehptoid) and thus increase the shear force.
  • the covering can be combined with a tube made of the body's own fibroblasts or exclusively from such consist of the body's own smooth muscle cells and combinations of fibroblasts and muscle cells with and without plastic
  • the sheath can also be coated with autogenous genetically engineered endothelial cells. Tissue glue can be used to fix the sheath or vein or to open certain areas after absorption.
  • the materials can be designed to deliver certain drugs that mimic or support the antithrombotic and growth-inhibiting effects of endothelial cells.
  • Example I A vein with an inner diameter of 4 mm and a length of 8 cm is perfused with Krebs-Henseleit buffer. Then it is pulled into a tube so that its inner diameter is now 2.0 mm. The NO production increased by 160% through this procedure.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Transplantation (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Dermatology (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Botany (AREA)
  • Vascular Medicine (AREA)
  • Cell Biology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pulmonology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Prostheses (AREA)

Abstract

The invention relates to the use of a flexible hose, sheath or tube as a vein envelope for a vein prosthesis to increase the shear force of the vein and prevent its expansion under arterial pressure.

Description

Verbessertes autologes Venentransplantat Improved autologous venous graft
Beschreibungdescription
Die Erfindung betrifft den Einsatz einer Ummantelung von autologen Venen als Material für arteriovenöse und arterio-(aorto-)-arterielle Verbindungen zur Verbesserung der kurz- und langfristigen Funktion bei Venentransplantationen. Die Ummantelung ist in der Lage, das Früh- und Spätversagen autogenen Venenmaterials erfolgreich zu verhindern.The invention relates to the use of a covering of autologous veins as a material for arteriovenous and arterio- (aorto -) - arterial connections to improve the short and long-term function in vein transplants. The sheath is able to successfully prevent the early and late failure of autogenous vein material.
Autologe Venen werden beispielhaft als aorto-koronare Bypässe oder als arterio- arterielle Bypässe routinemäßig eingesetzt. Weiterhin findet dieses Material als arteriovenöse Verbindung Verwendung bei Dialyse-Shunts.For example, autologous veins are routinely used as aorto-coronary bypasses or as arterio-arterial bypasses. This material is also used as an arteriovenous connection in dialysis shunts.
Manche Patienten haben unzulängliche, ausgeweitete Krampfadervenen. Es liegt ein Bericht vor, wo die Anwendung eines Metallgitters als Umhüllung die Verwendung derartiger Venen ermöglicht hat (Zurbrügg, H. R., H. Zimgibel: Improvement of venous diameter in bypass surgery: initial application of ultraflexible biocompound grafts in patients. Swiss Surg. 1996, Suppl. 1 : 8-12). Infolge einer Klappen- und Wandinsuffizienz weisen Krampfadervenen sack- oder knotenförmige Ektasien auf und unterscheiden sich grundlegend von pathologisch unverändertem durchgängigem Venengewebe. Wie aus diesem Dokument hervorgeht, verbessert das Metallgitter die Durchgängigkeit der Krampfadervenen. Im Gegensatz hierzu wird erfindungsgemäß eine Ummantelung verwendet zur routinemäßigen Herstellung von Venenprothesen unter Verwendung von nicht pathologisch veränderten Venen, wobei die Scherkraft in der Vene erhöht und ihre Dehnung unter arteriellem Druck verhindert wird.Some patients have inadequate, enlarged varicose veins. There is a report where the use of a metal grid as a covering has made it possible to use such veins (Zurbrügg, HR, H. Zimgibel: Improvement of venous diameter in bypass surgery: initial application of ultraflexible biocompound grafts in patients. Swiss Surg. 1996, Suppl. 1: 8-12). As a result of valve and wall insufficiency, varicose veins have sack or nodular ectasia and differ fundamentally from pathologically unchanged, continuous vein tissue. As can be seen from this document, the metal grid improves the patency of the varicose veins. In contrast to this, according to the invention a sheath is used for the routine manufacture of venous prostheses using non pathologically modified veins, increasing the shear force in the vein and preventing its expansion under arterial pressure.
Die bisherigen Erfahrungen lehren, daß transplantierte Venen zahlreiche Probleme verursachen. So kommt es zu Frühverschlüssen innerhalb der ersten Tage und Wochen und zu einem Spätversagen nach mehreren Jahren. Dabei zeigen die Venen charakteristische Veränderungen, die zum großen Teil darauf zurückzuführen sind, daß sie plötzlich einem ganz ungewöhnlich hohen Druck, dem arteriellen Blutdruck, ausgesetzt werden. Dies hat zur Konsequenz, daß die Endothelzellen auseinanderweichen, weil das Gefäß durch den hohen Druck gedehnt wird. Dadurch wird subendotheliales Gewebe gegenüber dem Blut exponiert. Dies bedeutet, daß Blutplättchen und Makrophagen mit dem subendothelialen Gewebe in unphysiologischer Weise direkt in Kontakt kommen. Dabei werden Wachstumsfaktoren wie PDGF (platelet derived growth factor), Thromboxan aus durch diesen Kontakt aktivierten Plättchen und zahlreiche andere Faktoren freigesetzt. Diese Faktoren zusammen mit den veränderten Druckverhältnissen tragen zur muskulären und endothelialen Hyperplasie und Ausweitung der Gefäße bei.Experience has shown that transplanted veins cause numerous problems. This leads to early closure within the first days and weeks and to late failure after several years. The veins show characteristic changes, which are largely due to the fact that they are suddenly exposed to an unusually high pressure, arterial blood pressure. The consequence of this is that the endothelial cells diverge because the vessel is stretched by the high pressure. This exposes subendothelial tissue to the blood. This means that platelets and macrophages come into direct contact with the subendothelial tissue in an unphysiological manner. Growth factors such as PDGF (platelet derived growth factor), thromboxane from platelets activated by this contact and numerous other factors are released. These factors together with the changed pressure conditions contribute to muscular and endothelial hyperplasia and dilation of the vessels.
Im Endstadium sind die transplantierten Venen stark und unregelmäßig erweitert und die Wände mit thrombotischen Massen belegt, durch die sich ein winziges Blutgerinnsel schlängelt, welches im Vergleich zur initialen und notwendigen Blutmenge in keinem ausreichenden Verhältnis steht. Im Falle des koronaren Bypasses kommt es erneut zu Angina pectoris und Herzinfarkt, im Falle des arterio-arteriellen Bypasses zu Durchblutungsstörungen.In the final stage, the transplanted veins are expanded strongly and irregularly and the walls are covered with thrombotic masses, through which a tiny blood clot meanders, which is inadequate in relation to the initial and necessary amount of blood. In the case of coronary bypass, angina pectoris and myocardial infarction occur again, and in the case of arterio-arterial bypass, circulatory disorders.
Ein weiterer Faktor, dessen Bedeutung in den letzten 2 Jahren mit zunehmender Deutlichkeit erkannt worden ist, betrifft die Fähigkeit der Gefäßwand, speziell der Endothelzellen, antithrombotisch zu wirken. Diese Fähigkeit ist in den transplantierten Venen nicht oder nur mangelhaft vorhanden, weshalb sich die massenhaften thrombotischen Ablagerungen vorfinden. Die zwei wichtigsten Faktoren, die physiologisch gegen die Thrombosierung gerichtet sind, sind NO (auch als EDRF oder Stickstoffmonoxyd bezeichnet) und Prostacyclin. Beide Substanzen hemmen Plättchen-Adhäsion und -Aggregation sowie die Haftung von Monocyten/Makrophagen sowie die Expression von VCAM"1 (vascular celt adhesion molecule'1) (DeCatarina, R., P. Libby, H. B. Peng et al.. Nitnc oxide decreases cytokine induced endothelial activation: Nitnc oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokmes J. Clin. Invest. 1995, 96: 60-68).Another factor, the importance of which has been recognized with increasing clarity in the past two years, relates to the ability of the vascular wall, especially the endothelial cells, to have an antithrombotic effect. This ability is not or only inadequately present in the transplanted veins, which is why the mass thrombotic deposits are found. The two most important factors that are physiologically directed against thrombosis are NO (also known as EDRF or nitric oxide) and prostacyclin. Both Substances inhibit platelet adhesion and aggregation and the adhesion of monocytes / macrophages and the expression of VCAM "1 (vascular celt adhesion molecule '1 ) (DeCatarina, R., P. Libby, HB Peng et al. Nitnc oxide decreases cytokine induced endothelial activation: Nitnc oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokmes J. Clin. Invest. 1995, 96: 60-68).
Von entscheidender Bedeutung ist die Tatsache, daß die bei den von den Endothelzellen produzierten antithrombotischen Substanzen NO und Prostacyclin in ihrer Synthese weitestgehend von der Scherkraft des Blutes auf die Endothelzelle abhängen (J Niebauer, J P Cooke Cardiovascular effects of exercise: Role of endothelial shear stress J Am Coll Cardiol 1996, 28 1652- 63). Die Scherkraft ist in den transplantierten Venen aber sehr niedrig, weil der Durchmesser dieser Venen viel größer ist als der Durchmesser der Arterien, mit denen sie typischerweise verbunden werden. So wird typischerweise bei einem aorto-koronaren Bypass eine Vene von 4 mm Durchmesser von der Aorta in eine Koronararterie von 2 mm Durchmesser geleitet Außerdem nimmt der Durchmesser durch den hohen Druck und durch weiteres Wachstum (sogen. remodeling) durch die oben beschriebenen Wachstumsfaktoren noch weiter zu Damit sinken die Scherkraft und die Produktion der antithrombotischen und antiproliferativen Mediatoren NO und PGI2, und es kommt zur Bildung der wandständigen Thromben sowie von Gefäßerweiterung und Ektasien.Of crucial importance is the fact that the synthesis of the antithrombotic substances NO and prostacyclin produced by the endothelial cells largely depend on the shear force of the blood on the endothelial cell (J Niebauer, JP Cooke Cardiovascular effects of exercise: Role of endothelial shear stress J Am Coll Cardiol 1996, 28 1652-63). However, the shear force in the transplanted veins is very low because the diameter of these veins is much larger than the diameter of the arteries with which they are typically connected. In an aorto-coronary bypass, a vein with a diameter of 4 mm is typically passed from the aorta into a coronary artery with a diameter of 2 mm. The diameter also increases due to the high pressure and further growth (so-called remodeling) due to the growth factors described above This reduces the shear force and the production of the antithrombotic and antiproliferative mediators NO and PGI 2 , and the formation of wall-like thrombi as well as vasodilation and ectasia.
Der Erfindung liegt die Aufgabe zugrunde, die Dehnung des Gefäßes zu verhindern, die Scherkraft zu erhalten und somit die Produktion von NO, PGI2 und anderen Scherkraft-abhängigen Mediatoren zu gewahrleisten. Dadurch werden die wandständigen Thromben und die Freisetzung der Wachstumsfaktoren und damit das Remodeling verhindert.The invention has for its object to prevent the expansion of the vessel, to maintain the shear force and thus to ensure the production of NO, PGI 2 and other shear force-dependent mediators. This prevents the wall thrombi and the release of the growth factors and thus the remodeling.
Die Verhinderung der Dehnung der Vene unter arteriellem Druck und die Erhöhung der Scherkraft werden erfindungsgemaß dadurch erreicht, daß um die Vene ein Netz, Mantel oder eine Hülse gelegt wird, die den Venendurchmesser auf ein optimales Maß bringt und dort halt Dabei sind zahlreiche Vorgehensweisen sinnvoll und können in unterschiedlichen Gefaßgebieten und auch in unterschiedlichen Weisen kombiniert werden, um optimale Ergebnisse zu erzielen.The prevention of the expansion of the vein under arterial pressure and the increase in shear force are achieved according to the invention in that a mesh, sheath or sleeve is placed around the vein, which brings the vein diameter to an optimal level and stops there Appropriate procedures and can be combined in different areas and in different ways to achieve optimal results.
Als einfachste Variante bietet sich eine Hülse aus strukturiertem PTFE oder einem anderen Kunststoff an. Der Kunststoff kann als Netz ausgebildet sein Ein poröser Schlauch mit Porengröße, die das Einsprossen von Kapillaren und damit die Integration ins Gewebe erlaubt (Porengröße 200 - 800 μm) kann verwendet werden. Die Umhüllung kann elastisch sein, z B so elastisch, daß eine Pulswelle weitergeleitet wird. Es ist bekannt, daß pulsatiler Fluß die PGI2-Produktιon von Endothelzellen fordert (J A Frangos, S G Eskin, L V Mclntire, C L Ives Flow effects on prostacyclin production by cultured human endothelial cells, Science, March 22, 1985, S. 1477-79)The simplest variant is a sleeve made of structured PTFE or another plastic. The plastic can be designed as a mesh. A porous tube with a pore size that allows capillaries to sprout and thus integrate into the tissue (pore size 200 - 800 μm) can be used. The covering can be elastic, for example so elastic that a pulse wave is passed on. It is known that pulsatile flow requires PGI 2 production from endothelial cells (JA Frangos, SG Eskin, LV Mclntire, CL Ives Flow effects on prostacyclin production by cultured human endothelial cells, Science, March 22, 1985, pp. 1477-79 )
Die Umhüllung kann auch aus resorbierbarem biologischem oder kunstlichem Material bestehen Beispiele für diese Materialien sind Kollagen, Polyglycolsaure, Polyhydroxyoktanoid, Poly-4-hydroxybutyrat und Polylactidsaure Wünschenswert ist auch hier eine Elastizität, die die natürliche Situation imitiert In diese Materialien können Wachstumsfaktoren oder Arzneimittel inkorporiert sein, die Einfluß auf die Gewebebildung und Gewebefunktion nehmen, sowie auf die Zellen des durchströmenden Blutes (z B Granulozyten, Thrombozyten)The covering can also consist of resorbable biological or artificial material. Examples of these materials are collagen, polyglycolic acid, polyhydroxyctanoid, poly-4-hydroxybutyrate and polylactidic acid. Here too it is desirable to have an elasticity that imitates the natural situation. Growth factors or drugs can be incorporated into these materials which influence tissue formation and function, as well as the cells of the blood flowing through (e.g. granulocytes, thrombocytes)
Die Enden der Umhüllung können trichterförmig ausgebildet sein, so daß die endständigen oder seitstandigen Anastomosenbereiche mit bedeckt werden und die Umhüllung in diesem Bereich durch geeignete Maßnahmen fixiert werden kann. Die Umhüllung kann sich von der Hochdruckseite zur Niederdruckseite verjüngen, wie bei einem normalen Blutgefäß Der Querschnitt der Umhüllung kann nicht-kreisformig (z B ehptoid) sein und so die Scherkraft erhohen Die Umhüllung kann mit einer Rohre aus körpereigenen Fibroblasten kombiniert werden oder ausschließlich aus solchen bestehen Weiterhin können auch körpereigene glatte Muskelzellen sowie Kombinationen aus Fibroblasten und Muskelzellen mit und ohne Kunststoffanteil kombiniert werden Auch kann die Ummantelung mit autogen gentechnologisch hergestellten Endothelzellen beschichtete sein. Gewebekleber können eingesetzt werden, um Ummantelung oder Vene zu fixieren oder nach Resorption bestimmte Areale zu öffnen.The ends of the covering can be funnel-shaped, so that the terminal or lateral anastomotic areas are also covered and the covering can be fixed in this area by suitable measures. The covering can taper from the high-pressure side to the low-pressure side, as in a normal blood vessel. The cross-section of the covering can be non-circular (e.g. ehptoid) and thus increase the shear force. The covering can be combined with a tube made of the body's own fibroblasts or exclusively from such consist of the body's own smooth muscle cells and combinations of fibroblasts and muscle cells with and without plastic The sheath can also be coated with autogenous genetically engineered endothelial cells. Tissue glue can be used to fix the sheath or vein or to open certain areas after absorption.
An Materialien können verschiedene Kunststoffe, Metalle und biologische Fäden, Gerüste, Schläuche, Hüllen und Röhren mit und ohne Poren und in den verschiedensten Kombinationen verwendet werden.Various plastics, metals and biological threads, scaffolds, hoses, casings and tubes with and without pores and in various combinations can be used as materials.
Die Materialien können so konstruiert werden, daß sie bestimmte Wirkstoffe abgeben, die die antithrombotische und wachstumshemmende Wirkung der Endothelzellen imitieren oder unterstützen.The materials can be designed to deliver certain drugs that mimic or support the antithrombotic and growth-inhibiting effects of endothelial cells.
Beispiel I: Eine Vene mit einem inneren Durchmesser von 4 mm und einer Länge von 8 cm wird mit Krebs-Henseleit-Puffer perfundiert. Danach wird sie in eine Röhre gezogen, so daß ihr innerer Durchmesser jetzt 2.0 mm beträgt. Die NO- Produktion stieg um 160 % durch dieses Vorgehen an. Example I: A vein with an inner diameter of 4 mm and a length of 8 cm is perfused with Krebs-Henseleit buffer. Then it is pulled into a tube so that its inner diameter is now 2.0 mm. The NO production increased by 160% through this procedure.

Claims

Patentansprüche claims
1. Verwendung eines Schlauches, Mantels oder einer Röhre als Ummantelung einer Vene für eine Venenprothese zur Erhöhung der Scherkraft der Vene und zur Verhinderung ihrer Dehnung unter arteriellem Druck.1. Use a tube, sheath, or tube to sheath a vein for a prosthetic vein to increase the shear force of the vein and prevent its expansion under arterial pressure.
2. Verwendung gemäß Anspruch 1 , wobei die Ummantelung zur Etablierung einer Pulswelle (pulsatiler Fluß) elastisch ist.2. Use according to claim 1, wherein the casing for establishing a pulse wave (pulsatile flow) is elastic.
3. Verwendung gemäß Anspruch 1 , wobei die Ummantelung aus einem strukturierten Polymer mit und ohne Poren gebildet ist.3. Use according to claim 1, wherein the casing is formed from a structured polymer with and without pores.
4. Verwendung gemäß Anspruch 1 , wobei die Ummantelung netzförmig ausgebildet ist.4. Use according to claim 1, wherein the casing is formed in a mesh.
5. Verwendung gemäß Anspruch 1 , wobei die Venenprothese mit trichterförmigen Enden, die die Anastomosenbereiche überdecken, ausgestattet ist.5. Use according to claim 1, wherein the vein prosthesis is equipped with funnel-shaped ends that cover the anastomotic areas.
6. Verwendung gemäß Anspruch 1 , wobei die ummantelte Venenprothese so ausgeführt ist, daß das venöse Gefäß sich von der Hoch- zur Niederdruckseite hin verjüngt.6. Use according to claim 1, wherein the covered vein prosthesis is designed so that the venous vessel tapers from the high to the low pressure side.
7. Verwendung gemäß Anspruch 1 , wobei die Ummantelung Fibroblasten, Myocyten oder einer Kombination mit und ohne Matrix aus biologischem oder künstlichem Material umfaßt.7. Use according to claim 1, wherein the coating comprises fibroblasts, myocytes or a combination with and without a matrix of biological or artificial material.
8. Verwendung gemäß Anspruch 1 , wobei die Venenprothese unter Anwendung von Gewebekleber hergestellt wird.8. Use according to claim 1, wherein the vein prosthesis is made using tissue glue.
9. Verwendung gemäß Anspruch 1 , wobei die Ummantelung Kunststoffe, biologische Materialien oder Kombinationen umfaßt. 9. Use according to claim 1, wherein the casing comprises plastics, biological materials or combinations.
10. Verwendung gemäß Anspruch 1 , wobei die Ummantelung die wiederholte Punktion gestattet.10. Use according to claim 1, wherein the sheath allows repeated puncture.
11. Verwendung gemäß Anspruch 1 , wobei die Venenprothese derart ausgestaltet ist, daß ein bestimmter Wirkstoff oder bestimmte Wirkstoffe an die Vene zur Verbesserung und Erhaltung ihrer Funktion abgegeben werden können.11. Use according to claim 1, wherein the vein prosthesis is designed such that a certain active substance or certain active substances can be released to the vein to improve and maintain their function.
12. Verwendung gemäß Anspruch 1 unter Verwendung von Venenersatz- Konstrukten wie Bioprothesen aus körpereigenen und körperfremden Gerüsten mit eigenen oder genetisch unterschiedenen oder genetisch modifizierten Fibrozyten, Muskel- und/oder Endothelzellen. 12. Use according to claim 1 using vein replacement constructs such as bioprostheses from the body's own and foreign bodies with their own or genetically different or genetically modified fibrocytes, muscle and / or endothelial cells.
PCT/EP2000/002059 1999-03-09 2000-03-09 Improved autologous vein graft WO2000053121A1 (en)

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AU41045/00A AU4104500A (en) 1999-03-09 2000-03-09 Improved autologous vein graft

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DE19910340.2 1999-03-09
DE19910340A DE19910340A1 (en) 1999-03-09 1999-03-09 Improved autologous venous graft

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DE19910340A1 (en) 2000-09-21

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