CA2004833A1 - Prosthesis of foam polyurethane and collagen and uses thereof - Google Patents

Prosthesis of foam polyurethane and collagen and uses thereof

Info

Publication number
CA2004833A1
CA2004833A1 CA 2004833 CA2004833A CA2004833A1 CA 2004833 A1 CA2004833 A1 CA 2004833A1 CA 2004833 CA2004833 CA 2004833 CA 2004833 A CA2004833 A CA 2004833A CA 2004833 A1 CA2004833 A1 CA 2004833A1
Authority
CA
Canada
Prior art keywords
prosthesis
collagen
comprises
composition
polyurethane
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
CA 2004833
Other languages
French (fr)
Inventor
Leonard Armand Trudell
Anthony D. Whittemore
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Brigham and Women's Hospital
Original Assignee
Leonard Armand Trudell
Anthony D. Whittemore
Brigham And Women's Hospital
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to US28136488A priority Critical
Priority to US281,364 priority
Application filed by Leonard Armand Trudell, Anthony D. Whittemore, Brigham And Women's Hospital filed Critical Leonard Armand Trudell
Publication of CA2004833A1 publication Critical patent/CA2004833A1/en
Application status is Abandoned legal-status Critical

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/26Mixtures of macromolecular compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/04Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06Blood vessels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56Porous materials, e.g. foams or sponges
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08LCOMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L89/00Compositions of proteins; Compositions of derivatives thereof
    • C08L89/04Products derived from waste materials, e.g. horn, hoof or hair
    • C08L89/06Products derived from waste materials, e.g. horn, hoof or hair derived from leather or skin, e.g. gelatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/24Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/04Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2002/041Bile ducts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/04Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2002/047Urethrae
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/04Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2002/048Ureters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/28Bones
    • A61F2002/2835Bone graft implants for filling a bony defect or an endoprosthesis cavity
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30003Material related properties of the prosthesis or of a coating on the prosthesis
    • A61F2002/3006Properties of materials and coating materials
    • A61F2002/30069Properties of materials and coating materials elastomeric
    • A61F2002/3007Coating or prosthesis-covering structure made of elastic material, e.g. of elastomer
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30667Features concerning an interaction with the environment or a particular use of the prosthesis
    • A61F2002/30677Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2250/00Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/0067Means for introducing or releasing pharmaceutical products into the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2310/00Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00005The prosthesis being constructed from a particular material
    • A61F2310/00365Proteins; Polypeptides; Degradation products thereof

Abstract

The present invention provides an implantable medical prosthesis comprising a uniform mixture of foam polyurethane and collagen. A73-03.WP 120189

Description

TITLE OF THE INVEHTION
~PROSTHESIS OF FOAM POLYURETHANE AND COLLQ6EN

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-;n-part of U.S. Patent Application Serial No. 07/281,364 filed December 8, 1988.

FIELD OF THE INVENTIPN

The present invention is in the field of ~medical prostheses. More specifically, the present ~invention is directed to a prosth~esis composed of a uniform mixture of collagen and foam polyurethane which is suitable for use, for example, as a vascular prosthesis cr soft tissue replacement.
.
BACKGROUND OF THE INVENTION ~ ~ -The use of prostheses for the replacement of blood vessels and other anatomical ducts ;s of great ;nterest in medicine and veter;nary work. The use of b;omaterials ;n prostheses and biomed;cal dev;ces is reviewed in~Hanker, J.S.
et al., Sc;ence ~ 885-892 (1988), and by Gebele;n, C.G., "Prosthet;c and B;omedical Devices'i in Kirk-Othmer, Concise EncYclopedla of Chemical Techno1OqY, M. Grayson, ed., W;ley &

Sons, 1985, pp. 965-9~8, both incorporated herein by refer-ence. To be acceptable in a given applicakion, a prosthesis must exhibit the proper mechanical properties and bio-accep-table composition for the given application. For example, vascular prostheses must provide a bio-acceptable surface which is conducive to cellular attachment and sustained blood flow, but yet is strong enough not to split or tear.
Especially it is critical that the vascular prosthesis not tear along the body of the prosthesis or at the site of the sutures.
Collagen has been proposed as a biomaterial which has many properties desirable of a medical prosthesis Collagen is a family of fibrous proteins that have been classified into a number of structurally and genetically distinct types (Stryer, L. Biochemistrv, 2nd Edition, W.H. Freeman ~ Co.7 1981, pp. 184-199).
Type I collagen is the most prevalent form. Type I
collagen is found in skin, tendons, and bones and consists of two subunits of ~l(IJ collagen and one subunit of a different sequence termed ~2. Other types of collagen have three identical subunits or chains, each consisting of about 1,000 amino acids.
Different tissues express different types of collagen, depending upon their structural needs. For example, type II
collagen is found in cartilage, type TII collagen is found in blood vessels and the cardiovascular system, and type IV
collagen is localized in basement membranes. Collagen is a unique protein in that it forms insoluble fibers that have a high tensile strength.
Tubes made of pure collagen have been proposed for use as vascular prostheses (Noishiki, Y. et al., U.S. Patent No.
4,690,973; Chu, G. U.S. Patent No. 4,655,980; and Huc, A. J.
Am. Leather Chem. Assoc. 80:195-212 (1985)); arterial prostheses (Maurer, P. et al., Eur. Surg. Res. Sept.-Oct., p.90, (1983)); ureteral replacements, ~Tachibana, M. et al., J. Urol w Y 133:866 869 (1985)); and as a microencapsulation material for the oral administration or implantation of controlled release substances (Huc, A., et al., U.S. Patents No. 4,711,783 and No. 4,670,014; Sanders, N.J., Chem. Enq.
News, April 1, 1985, p. 30-48).
However, the mechanical properties of prostheses made solely of collagen are not satisfactory for many purposes due to a tendency to tear or split. Especially, protheses made solely of collagen are not satisfactory for replacement of vessels with a small diameter (Huc, A., J. Am. Leather Chem.
Assoc. 80:195-212 (1985)). Attempts to strengthen the mechanical characteristics of collagen by fixing or tanning it have not been successful. Grillo found collagen tubes too weak to allow fine silk suturing without splitting at the sites of the needle puncture (Grillo, H.C. et al., J. Sura.
Res II (1): 69-82 (1962)).
To avoid the mechanical def;ciencies of collagen tubular prostheses, prostheses composed of other polymers such as Dacron and polyurethane have been prepared (Robert, A.-M. et al., Pathol. Biol. (Paris) 24-Supp.:42-47 (1976); Maupepit, P., EP Patent Application Publication No. 058623); as well as combinations of plast;cs and polyurethane (Hanson, S.R., U.S.
Patent No. 4,687,482; Mano, H. et al., U.S. Patent No. RE
31,618; and Buddecke, E., DE Ratent No. 1,4g4,939~. However, these prostheses lack the biocompatability of collagen, and do not promote the revascularization of the prosthesis in the manner that collagen does (Huc, A., J. Am. Leather Chem.
Assoc. 80: 195-212 (1985)). In addition, prostheses made solely from synthetic materials often evoke a foreign body response, suffer from fatigue or are potentially toxic or car-cinogenic (Grillo, H.C. et al., J. Sur~1. Res. II (1):69-82 (1982)~.

A composition comprising foam polyurethane and collagen has been used as a contraceptive sponge (Vorhaur, B., Bioflu;d Mechanics, vol. 2, 1980, Plenum, pp. 93-124) and to promote neovascular;zation (Lamberton, P. et al., ASAIO Abstracts 16:29 (1987)). Lamberton also proposed the use of a collagen impregnated polyurethane sponge to promote neovascularization in endocrine or hepatic transplantation, soft tissue prosthesis, bone graft or drug delivery systems (Lamberton, P.
et al., ASAIO Abstracts 16:29 (1987)).
But there remains a need for a prosthesis which provides the bio-compatibility of collagen with the required pliancy and mechanical strength for use in medical applications such as conduits for the replacement of a missing, diseased or damaged biological vessel and especially a biological vessel with a small diameter.

SummarY of the Invention The present invention provides a composition co~prising foam polyurethane and collagen which can be shaped into bio-compatible un;ts for implantation as prostheses wherein the collagen is an integral part of the matrix which forms the backbone of the prosthetic structure.
The present invention further provides a tubular prosthesis useful for implantation in an animal comprising an elongated hollow body tube, said hollow body tube being open at both ends and defining a confined-flow passageway, wherein said prosthesis comprises a uniform mixture of foam polyure-thane and collagen, of one or more layers; the ~ascular prosthesis so produced has the strength and pliancy consistent with replacement of the human artery.
The present ~nvention further provides a composition of collagen and foam polyurethane that can be shaped into bio-compatible units, of one or more layers, for use as soft-t;ssue rep~acements or as matrices for sustained-release vehicles. Such biocompatible units may also supply medicinal substances such as hormones or drugs at a controlled rate to the host.

Brief DescriDtion of the Drawinqs Figure 1 is a graph representative of a typical tensile strength response of a canine carotid artery.
Figure 2 is a graph representative of results typical of the tensile strength of a polyurethane/collagen graft (1.0 mg/ml collagen), single layer.

Detailed Description of the Invention The invention provides a composition comprising a mixture of foam polyurethane and collagen wh;ch is capable of being shaped into a wide variety of bio-compatible conduits and especially into a tube, suitable for implantation as an artificial device, a prosthesis, to replace a missing, diseased or damaged part of the body of a human or other animal. Additionally this composition of foam polyurethane and collagen is capable of forming a vascular prosthesis with mechanical characteristics consis~ent with replacement of the human artery. Additionally, this composition of foam poly-urethane and collagen is capable of forming implantable bio-compatible units capable of use as soft-tissue replacements and as sustained-release vehicles.
The prosthesis composition of the present invention derives from the inventors' discovery that foam polyurethane is capable of correcting the mechanical deficiencies of collagen prostheses. The prostheses of the invention, comprising a mixture of foam polyurethane and collagen, for the first time allow the implantation of a prosthesis with the bio-compatibility advantages of collagen and the mechanical advantages of ~olymerized foam polyurethane. The incorporation of collagen during the cross-linking reaction makes collagen an integral chemical component of the structure of the molded polyurethane prosthesis. Surprisingly, unex-pected and advantageous mechanical properties are realized when collagen is incorporated into the polyurethane matrix as the prosthesis is formed. These unexpected and advantageous mechan;cal properties include unexpected strength and res;s-tance to tear;ng at the site of the sutures.
By prosthesis is meant an artificial device designed to replace a missîng, diseased or damaged part of the body of an animal.
By a prosthesis containing at least one "layer" of the composition of the invention (a uniform mixture of foam polyurethane and collagen) is meant a prosthesis containing at least one discrete ply or strata of the composition of the invention. ~his layer may be joinedj in the final product, to additional layers wherein each layer surrounds the other but wherein each layer, that is each ply or stratum, had originally been molded separately or at a separate time, from the other layers. The layers containing the composition of the invention may be directly adjacent to each other or physically separated by a layer(s) of a substance with a differing composition. A layer or layers of a substance with a composition different from that of the composition of the invention may also be used to "coat" the prosthesis on its inner and/or outer surface. For example, the layered prosthesis may be molded so as to contain an outer layer conta;ning polyurethane and silicone.
By animal or host is meant a human or other member of the kingdom Animelia which is developed enough to have separate organ systems and a circulatory system.

By biocompatible is meant compatible with living tissue;
a biocompatible substance does not harm the host nor does it evoke a severe foreign body reaction. In a severe foreign body react;on, the func~ion of the prosthesis becomes severely compromised by the host's response to its presence.
By implant is meant to fix or set securely in a living site, such as in tissue or as a replacement for a biological vessel or conduit, a prosthesis which promotes tissue growth, slow release of a medicinal substance, or formation of an organic union with the surrounding tissue.
By conduit is meant a channel through which something (as a fluid) flows or is conveyed.
By tubular is meant the form of a tube; that is, resembling a hollow, sometimes elongated, cylinder. When the prosthesis of the invention is in the shape of a hollow tube, it has an inner and an outer surface; the inner surface being that surrounding the liquid being conveyed through the prosthesis.
By uniform mixture is meant a mixture which has the same composition or physical properties throughout the entire physical structure of the mixture.
By sustained-release vehicle is meant a biocompatible vehicle capable of supplying a prolonged release of substance such as a drug or hormone, for a relatively long period of t;me, such as hours~ days, months or even years.
The chemistry of the urethanes is reviewed in Billmeyer, F.W., Textbook of PolYmer Science, Wiley ~ Sons, 1984, incorporated herein by reference. Polyurethanes are polymers conta;ning the group:
O
l c o and are typically formed through the reaction of a diisocyanate and a glycol:

xOCNRCNO ~ xHOR'OH --> -[OCONHRNHCOOR'-]X.

In the production of polyurethane foams, excess isocyanate groups in the polymer react with water or carboxylic acids to produce carbon dioxide which 'blows' the foam at the same time that crosslinking is occurring. This results in a crosslinked product containing bubbles of trapped carbon dioxide. As discussed in Billmeyer, supra, upon curing, the polyurethane foam may be either flexible or rigid depending on the nature of the polymer and the type of crosslinking. Because of the rapid curing of the polyure-thane, it is especially compatible with reaction injection molding (RIM) wherein the polymerization and crosslinking are effected simultaneously with molding of the material into its final shape.
Urethane foams are made in several steps. First9 there is a basic intermediate which comprises a polyether made of poly(l,4-butylene glycol), sorbitol polyether, or other polyethers of a molecular weight around 1,000 daltons. If flexible foams are desired, this intermediate is bifunctional and if rigid foams are desired this intermediate is polyfunc-tional.
The basic intermediate reacts with an aromatic diisocyanate, usually tolylenediisocyanate, to give a prepoly-mer. Catalysts are then added to the prepolymer to effect rapid production of foam as described above with crosslinking forming through the synthesis of urea bridges. Crosslinking increases the melting point, decreases the solubility and moisture regain and strengthens the interstrand bonding.
In some cases, a low-boiling inert liquid such as a fluorocarbon has been used to replace the blowing action of carbon dioxide. This results in a foam with some altered characteristics, such as a lower thermal conductivity due to .

the entrapped fluorocarbon gas, when compared to the carbon dioxide blown foams. Alternatively, a two-step synthes;s may be used, wherein the foam ;s f;rst partly frothed with the inert gas and then foamed with carbon dioxide.
In the one-step process for the synthesis of flexible foams, the polyeth~r intermediate tolylenediisocyanate and catalysts are mixed just before foaming.
Hypol 2002 (sold by W.R. Grace and Co., Lexington, MA) is preferred because it is a special medical grade of polyureth-ane prepolymer which, upon mixing with water and other aqueous solutions, produces a hydrophilic foam having no extractable toluene diamine, toluene disocyanate or other primary aromatic am;nes. Foam extracts of this product are inert in the body and are not mutagenic. In addit;on, the cured product has been shown to be a good biomaterial for supporting cellular growth and, potentially, a good biomaterial to serve as a blood/surface interface. Hypol is described in U.S.
4,127,200, incorporated herein by reference. An elastic biomaterial is necessary for the fabrication of implantable medical devices such as vascular grafts, small diameter vascular grafts, atrial patches, ventricular patches, prosthetic valve cusps and arterial patches.
Additionally, the foamed polyurethane (polyurethane isocyanate) may be manufactured such that the end product may be biodegradable, thus allowing the product to be~ slowly absorbed by the host. The material can be engineered to any point along a scale of from rapidly biodegradable to biodurable where biodurable is defined as a substance as stable as Dacron in the host. Biodegradability, of the final polymer, is determined by the inclusion, ;n the reacting liquid, of chemical species (or groups) that are scissionable (or "digestible") ir, a living mammalian system. An example of how to increase the biodegradability of the final polymer would be to react the Hypol w;th lactic acid groups that can be broken down in vivo. In that example, the total number of scissionable lactic acid bonds per unit material would determine the time course of degradation.
Any non-antigenic, non-specific collagen such as, for example, a synthesized collagen is useful in the invention.
When used as a vascular graft, type III collagen is preferred because it is the type of collagen native to blood vessels.
Vascular collagen (type III) can be obtained commercially from Sigma Chemical Company, St. Louis, Missouri. The collagen solution is dissolved in O.dO5 M acetic acid solution. The collagen goes into solution readily, in the cold (4-6C) in 24-48 hours.
The prosthesis described herein has at least three essential characteristics. First, the prosthesis is com-patible with animal tissues and does not provoke a severe foreign body reaction. Second, the prosthesis is strong enough to a) resist tearing at the site of suture and b) resist splitting due to physiological pressures of a liquid such as blood being conveyed through it. Third, the pros-thesis potentially promotes neovascularization of the implant site and may provide a surface conducive to the ingrowth and proliferation of cells from adjacent areas and the development of new tissue. These three characteristics are achieved by including collagen in the reaction mtxture at the time of chemical cross-linking of the polyurethane during formation or molding of the prosthetic structure.
Especially, the composition is compatible with grafts of a small diameter; that is, with a graft having an inner diameter of 5.0 mm or smaller. A standard size graft of 6.0 mm or greater such as those commonly used in clinical peripheral vascular surgery is also compatible with the composition of the invention.
Preferably, the prepolymer is Hypol 2002 and is mixed with a stock solution of saline or Lactated Ringer's Solution conta;ning 1.0 mg/ml collagen, 2 units/ml heparin, and 2 ml of 0.1%/liter of Triton X-100 as a surfactant. Lactated Ringer's solution U.S.P. is composed of 600 mg of sodium chloride; 300 mg of sodium lactate; 30 mg of potassium chloride; and 20 mg of calcium chloride in a total of 100 ml of distilled water.
Preferably, Hypol 2002 is added to the solution of vascular collagen in a 1:1 volumetric ratio such as 1 ml Hypol 2002 per ml of the collagen solution and the reaction between collagen and polyurethane is allowed ~o proceed, the reaction proceeding in the mold. In a preferred embodiment the solutions of Hypol 200~ and collagen are mixed at 4-5C and the reaction time is complete within two minutes.
The polyurethane is activated as a function of tempera-ture, releasing C02. The temperature and hence the rate at which C02 is released controls the number and size of the C02 bubbles in the final product, and thus the foam;ness, permeability and strength of the prosthesis wall. In a preferred embodiment, the reaction is run at 4-6C and results in a product in which the bubbles are small and uniformly distributed throughout the prosthesis.
A bubble is considered to be small if its diameter is less than 0.2 mm, of medium size if its diameter is between 0.2~0.5 mmj and large if its diameter is 1 mm or greater.
Large bubbles are undesirable and tend to lend to failure of the prosthesis at the site of the large bubble.
The molded prosthesis has a compliance at least as good as a human artery where compliance is understood by those in the art to be the ease with which a vessel segment can expand to hold a larger volume. Compliance is generally looked upon as an indicator of the overall health of a given blood vessel.
The foam polyurethane-collagen grafts of the invention are considerably more "compliant," that is, "stretchy," than a natural vessel and have the ability to be elongated to twice their original length with not much plastic deformation.

, ~ 1 2~

Plastic deformation is that phase where a material is stretched beyond its abil ity to reooil to normal form or to snap back. It is the part of the deformation curve just prior to Failure or breakage of the material.
Triton X-100 is a nonionic detergent composed of various polyoxyethylene ethers and other surface-active compounds.
Triton X-100 is available commercially and is produced by Rohm & Haas Co. In this invention, Triton X-100 serves only as a surfactant and does not participate in the reaction between collagen and polyurethane. Therefore, other surface active agents which are non-ionic such as Brij, Tween or silicon oils would be useful in this capacity. A surface active compound may not be necessary and may be omitted if desired. The decision on whether or not to include a surface active compound will depend upon the performance of the collagen-polyurethane solution in forming a suitable prosthesis. For example, prostheses made using the synthet;c collagen "Vitro-gen" (Collagen Corp.), do not require the addition of a surface active compound in the solution forming the molded prosthecis to yield a desirable prodùct.
Heparin serves as an endothelial cell growth factor and as an anticoagulant and is not a required participant in the reaction between collagen and polyurethane. The presence of heparin in the collagen solution at the time of the reaction ensures that the prosthesis will be thoroughly impregnated with the compound. As an endothelial cell growth factor, heparin serves to encourage the establishment of endothelial cells as a confluent endothelial lining of the prosthesis after implantation. When seeded prior to implantation, a lining of endothelial cells reduces the thrombogenicity of a prosthesis (Shindo, S., et al., J. Vasc. Surg. 6:325-332 (1987)).
In a highly preferred embodiment, the prosthesis of the invention is an "active" prosthesis as opposed to a "pasive"

prosthesis. An "active prosthesis" performs a mechanical function Examples of mechanical functions include (a) the mechanical function of confined transport of a fluid, and especially blood, (b) the mechanical ~unction of fluid flow r~gulation, for example, opening and/or closing an aperture, such as a valve, and (c) the mechanical function of e~pansion and/or contraction in harmony with the physiological demands of the supporting environment, for example, the expansion and contraction requirements of an aortic patch.
The prostheses prepared by the method of the invention can be stored in distilled water with antibiotics, antimycotics and the like to prevent contamination of the graft. Alternatively, the prostheses can be dried and then ethylene oxide sterilized. The prostheses may also be sterilized by gamma radiation.
In one embodiment, the wall thicknesses between the natural biological vessel and the prosthesis are essentially the same. The wall thickness of the prosthesis is limited only by that thickness which is required to provide sufficient mechanical strength so as not to tear, split or produce undesired fluid or hemodynamic flow problems under physio-logical conditions. It is not necessary to exactly match the thickness of the natural biological vessel with that of the prosthesis.
In a preferred embodiment, a prosthesis is constructed which contains more than one layer of the collagen-polyure-thane mixture, each layer surrounding the other. In a highly preferred embodiment, a prosthesis of at least two layers is constructed and the outer layer includes a silicone elastomer in place of the collagen. A prosthesis with two layers can be constructed, for example, by molding the first prosthesis layer around a mandrel and then molding a second layer around the structure of the first prosthesis without removing the mandrel. By this method the two layers are "joined." In addition, those of ordinary skill in the art will recognize other ways of joining two molded layers of the composition of the invention, such as chemically linking two molded units.
The advantage of a prosthesis comprising layers of the collagen-polyurethane m;xture rather than only one layer ;s that the layered prosthes;s is stronger and prov;des better protect;on aga;nst potential fluid leakage. An outer layer sonta;n;ng a s;l;cone elastomer or a similar substance which adds strength to the prosthesis is advantageous when it is desired to prevent any tendency of the prosthesis to leak in the desired application. Examples of substances which may be used in place of, or in addition to silicone include other polyurethanes or elastomer polymers with similar elastic properties.
Prostheses comprising layers of the molded collagen-polyurethane mixture may be constructed so that the collagen-polyurethane layers are physically attached to each other or they may be constructed with a layer of a different substance, polymer, mesh or netting between the layers. It is only necessary that, in the final product, the various layers do not separate under physiological conditions. Different layers may be impregnated with different drugs, medicinal substances or other biological agents to provide a localized delivery of these agents to specific surfaces o~ the prosthesis. The different layers may also comprise compositions with differing rates of biodegradability.
Medicinal substances such as drugs, hormones, immunosup-pressants, biological agents and the like may be included in the collagen solution and incorporated into the molded prosthesis structure to provide a loralized exposure or a controlled delivery of said substance in the host at the site of the implant. Appropriate antibiotic solutions include penicillinj 10,000 U/ml; streptomycin, 10,000 mcgs/ml; or fungizone, 25 mcgs/ml.

In a preferred embodiment, the conduit of the invention is used for a vascular prosthesis in the implantation of a vascular graft, small diameter vascular graft, atrial patch, prosthetic valve cusp or arterial patch. In another preferred embodiment, the invention is used to replace or graft a blood vessel with a small diameter, especially one less than 5 mm in diameter.
The prosthesis or conduit of the invention is also useful as a ureteral, urethral or biliary prosthesis. As is under-stood by those skilled in the art, the composition of the invention results in a conduit which would be applicable to any biological dra;n, catheter, cannula, shunt, tube, or tube-like organ such as the windpipe or intestine.
The prosthesis of the ;nvention is also useful as a soft-tissue substitute for example, in bioartificial systems including endocrine or hepatic transplantation, soft-tissue prothetic materials and bone grafts.
In another embodiment, the composition of the invention is used to create a sustained-release vehisle to deliver a prolonged dose of a compound internally. Such a vehicle would be useful to deliver prolonged, localized doses of drugs, medical agents, biological agents, and the like used in the treatment of many diseases, including heart disease, glaucoma, angina, motion sickness, narcotics addiction, cancer, diabetes, pollen allergies and high blood pressure. In addition, such a vehicle would be useful for the sustained release of such compounds in the digestive system, for example, for weight control, or, for the delayed release of drugs till they passed the stomach. The composition of the invention would also be capable of providing a unit containing a matrix system to prolong the effectiveness of cosmetics, pesticides, fertilizers, detergents, cleaning agents and the like.

.

When embodied in a layered form, the sustained-release vehicle of the ;nYent;on may be used to deliver d;fferent compounds at different rates or to different sites of action.
For example, a compound of interest ;ncorporated into the outer layer of the vehicle may d;ffuse from the vehicle faster than one contained only in an inner layer. Alternatively, a vehicle may be designed to deliver one drug to the stomach and one to the lower intestine, for example, by incorporating the drug designed for release in the lower intestine into an inner layer of the vehicle and incorporating the drug designed for release in the stomach into the outer layer.
Having now generally described this invention, the same wili be better understood by reference to certain examples which are included herein for purposes of illustration only and are not intended to be limiting unless otherwise speci-fied.

Example l Procedure for Making a Layered Graft of PolYurethane/Collaqen/Silicone Elastomer Silicone tubing to be used as the mandrel is placed on a rotating device such as a lathe. Hypol 2002 is mixed with the stock collagen solution in a 1:1 ratio (the stock solution is l mg collagen/ml). The polyurethane/collagen mixture is layered onto the rotating mandrel and allowed to cure while continuously rotating, normally for approximately 3Q minutes.
A mixture of polyurethane and silicone is made by mixing equal amounts of Hypol 2002 and Dow Corning #92-009 Silicone Dispersion Fluid, then mixing in the Stock Saline Solution (0.9% NaCl, 2 units/ml heparin and 2 ml/liter 0.1% triton X-lO0) (without collagen). Each constituent comprises one-third of the total mixture. The polyurethane/silicone mixture is then layered onto the rotating mandrel over the first layer of cured Hypol/collagen and allowed to cure while rotating.

Approximately 4g of Silicone Dispersion #92-009 ;s mixed with approximately 2-3g of table salt pr;or to curing to ensure that the final silicone layer will be porous. The Silicone Dispersion salt mixture is then layered onto the rotating mandrel over the previous layers. This coating is allowed to cure while rotating and takes hours to cure completely. Normally this layer is allowed to cure overnight.
The rotation can be terminated after approximately 2 hours after which the silicone elastomer will hold its form without further rotation. The salt does not dissolve in the silicone dispersion and after the layer cures, crystals of salt can be visually observed.
The mandrel-with-graft can now be removed from the lathe and soaked in distilled water to dissolve out the salt.
Removing the salt crystals results in a porous material compatible with the uses described in the application. The resultant silicone elastomer layer is porous yet thin and strong enough to resist tearing at the site of sutures.
The graft can now be removed from the mandrel and stored.
The graft can be stored dry or it can be stored in the saline stock solution (with antibiotics). If it is stored dry it is necessary to rehydrate the graft prior to use.

Example 2 Tensile Measurements Graft prototypes were made by hand by smoothly mixing the prepolymer Hypol 2090 with an equal volume of stock solution containing 1 mg~ml collagen dissolved in lactated Ringer's solution (or 0.9% NaCl) containing 2 units/ml heparin and 2 ml/llter 0.1% triton X-100. A glass rod was used for the mixing and allowed to remain in the test tube as the mandrel for the graft's lumen. Smooth mixing, rather than vigorous shaking, was necessary to avoid generating large bubbles.

After be;ng mixed ;n a cup using a wooden tongue depressor, the polyurethane-collagen mixture was poured into a tubular mold to react and cure. Virtually any size graft can be made this way. As the mixture foamed, it overflowed the mold through the longitudinal opening through which the fluid was poured. After the material cured, the excess was trimmed off. The graft was then lifted out of the mold on the piece forming the lumen. That piece was then pulled away leaving the tubular cast. Any remaining excess material was again trimmed away.
The samples were tested for their tensile strength by inserting a ring, 0.5 cm in length, cut from the graft into a Tensile Tester (Instron~ sample holders.
As shown in Figure 1, stress and strain testing demon-strated excellent elongation properties (approximately 2x) with very little plastic deformation before material failure.
Prosthesis samples which did not have the bubbles uniformly distributed throughout their structure were inferior and gave poor results in the stress and strain testing.

Example 3 Compliance Measurements Tensile strength and elongation measurements for a prosthesis made as described in Example 1 are shown in Figure

2. Over a range that is two to three times physiologic, the total graft elongation was approximately 40%, or 4 mm. The experimental grafts produced thus far demonstrate approxi-mately 10% diameter expansion (dynamic compliance) in an in vitro circuit with flow pressure at 150 mm Hg.

.; . , . . .

Example 4 - Bioloq;cal ComDatibilitY of HYDO1 Preliminary cell culture experiments were done to examine the cured Hypol 2002 as a host material for endothelial cells.
Small discs of cured Hypol 2002 of approximately 2 cm2 were placed into cell culture wells and seeded with canine endothelial cells. The same cell culture procedures were followed as are standard in our laboratory for all cell culture experiments. (Shindo, S., et al., J. Vasc. Surq.
6:325-332 (1987)). The cells overgrew the Hypol material and grew to confluence in fairly short order. This indicates that Hypol is a biologically acceptable substrate for endothelial cells and seeded protheses.

Example 5 Animal Implants Collagen-polyurethane-silicone prostheses as prepared in Example 1 were implanted ;n the carotid position in six sheep.
Grafts subsequently harvested after four weeks ~were observed to maintain satisfactory integrity and patency for use as vascular prostheses.
Having now fully described this- invention, it will be understood by those with skill in the art that the scope may be performed within a wide and equivalent range of conditions, parameters, and the like, without affecting the spirit or scope of the invention or of any embodiment thereof.

. .
"'`~'' '

Claims (17)

WHAT IS CLAIMED IS:
1. A prosthesis useful for implantation in an animal wherein said prothesis comprises at least one layer containing a uniform mixture of foam polyurethane and collagen.
2. The prosthesis of claim 1, wherein said prosthesis further comprises two or more layers of a uniform mixture of foam polyurethane and collagen.
3. The prosthesis of claim 1, wherein said prosthesis further comprises an outer layer which contains a silicone elastomer.
4. The prosthesis of any one of claims 1-3, wherein said prosthesis comprises an elongated hollow body tube, said hollow body tube being open at both ends and defining a confined-flow passageway.
5. The prosthesis of claim 4, wherein the confined-flow passageway has an inner diameter of 10 mm or less.
6. The prosthesis of claim 4, wherein the confined-flow passageway has an inner diameter of 5 mm or less.
7. The prosthesis of any one of claims 1-3, wherein said prosthesis is used for implantation of a vascular graft, atrial patch, ventricular patch, prosthetic valve cusp, arterial patch, ureteral prosthesis, urethral prosthesis, biliary prothesis soft-tissue substitute, or bone graft.
8. The prosthesis of any one of Claims 1-3, wherein said prosthesis contains an antibiotic.
9. The prosthesis of any one of Claims 1-3, wherein said prosthesis contains a hormone.
10. The prosthesis of any one of Claims 1-3, wherein said prosthesis contains an immunosuppressant agent.
11. A method for implanting a vascular prosthesis which comprises suturing the prosthesis of any one of Claims 1-3 into a blood vessel, tissue or other organ.
12. A method for implanting a ureteral prosthesis which comprises replacement of the ureter, or a portion thereof, with the prosthesis of any one of Claims 1-3.
13. A method of implanting a urethral prosthesis which comprises replacement of the urethra, or a portion thereof, with the prosthesis of any one of Claims 1-3.
14. A method for implanting a biliary prosthesis which comprises replacement of the bile duct, or a portion thereof, with the prosthesis of any one of Claims 1-3.
15. A composition for use as a sustained-release vehicle wherein said composition comprises a uniform mixture of foam polyurethane and collagen.
16. The composition of Claim 15, wherein said vehicle further comprises two or more layers of said mixture.
17. The composition of any one of Claims 14 or 15, wherein said vehicle contains a drug.
CA 2004833 1988-12-08 1989-12-07 Prosthesis of foam polyurethane and collagen and uses thereof Abandoned CA2004833A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US28136488A true 1988-12-08 1988-12-08
US281,364 1988-12-08

Publications (1)

Publication Number Publication Date
CA2004833A1 true CA2004833A1 (en) 1990-06-08

Family

ID=23076977

Family Applications (1)

Application Number Title Priority Date Filing Date
CA 2004833 Abandoned CA2004833A1 (en) 1988-12-08 1989-12-07 Prosthesis of foam polyurethane and collagen and uses thereof

Country Status (5)

Country Link
EP (1) EP0447487A4 (en)
JP (1) JPH04502416A (en)
AU (1) AU636325B2 (en)
CA (1) CA2004833A1 (en)
WO (1) WO1990006094A1 (en)

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0604022A1 (en) * 1992-12-22 1994-06-29 Advanced Cardiovascular Systems, Inc. Multilayered biodegradable stent and method for its manufacture
US5443458A (en) * 1992-12-22 1995-08-22 Advanced Cardiovascular Systems, Inc. Multilayered biodegradable stent and method of manufacture
US5441515A (en) * 1993-04-23 1995-08-15 Advanced Cardiovascular Systems, Inc. Ratcheting stent
US5782907A (en) * 1995-07-13 1998-07-21 Devices For Vascular Intervention, Inc. Involuted spring stent and graft assembly and method of use
US20070161967A1 (en) * 1996-06-04 2007-07-12 Vance Products Inc., Dba Cook Urological Inc. Implantable medical device with pharmacologically active ingredient
US10028851B2 (en) 1997-04-15 2018-07-24 Advanced Cardiovascular Systems, Inc. Coatings for controlling erosion of a substrate of an implantable medical device
US6540780B1 (en) 1998-11-23 2003-04-01 Medtronic, Inc. Porous synthetic vascular grafts with oriented ingrowth channels
US6702848B1 (en) 1999-07-20 2004-03-09 Peter Paul Zilla Foam-type vascular prosthesis with well-defined anclio-permissive open porosity
US6554857B1 (en) 1999-07-20 2003-04-29 Medtronic, Inc Transmural concentric multilayer ingrowth matrix within well-defined porosity
US6702849B1 (en) 1999-12-13 2004-03-09 Advanced Cardiovascular Systems, Inc. Method of processing open-celled microcellular polymeric foams with controlled porosity for use as vascular grafts and stent covers
US6527801B1 (en) 2000-04-13 2003-03-04 Advanced Cardiovascular Systems, Inc. Biodegradable drug delivery material for stent
NL1016040C2 (en) * 2000-08-29 2002-03-01 Giles William Melsom Porous attachment material for cells, a process for the manufacture thereof, as well as applications.
US6863683B2 (en) 2001-09-19 2005-03-08 Abbott Laboratoris Vascular Entities Limited Cold-molding process for loading a stent onto a stent delivery system
US20050214339A1 (en) 2004-03-29 2005-09-29 Yiwen Tang Biologically degradable compositions for medical applications
US9283099B2 (en) 2004-08-25 2016-03-15 Advanced Cardiovascular Systems, Inc. Stent-catheter assembly with a releasable connection for stent retention
US9248034B2 (en) 2005-08-23 2016-02-02 Advanced Cardiovascular Systems, Inc. Controlled disintegrating implantable medical devices
US20070156230A1 (en) 2006-01-04 2007-07-05 Dugan Stephen R Stents with radiopaque markers
US20130325105A1 (en) 2006-05-26 2013-12-05 Abbott Cardiovascular Systems Inc. Stents With Radiopaque Markers
US8333000B2 (en) 2006-06-19 2012-12-18 Advanced Cardiovascular Systems, Inc. Methods for improving stent retention on a balloon catheter
US9072820B2 (en) 2006-06-26 2015-07-07 Advanced Cardiovascular Systems, Inc. Polymer composite stent with polymer particles
US7757543B2 (en) 2006-07-13 2010-07-20 Advanced Cardiovascular Systems, Inc. Radio frequency identification monitoring of stents
US9173733B1 (en) 2006-08-21 2015-11-03 Abbott Cardiovascular Systems Inc. Tracheobronchial implantable medical device and methods of use
RU2558365C2 (en) 2009-03-06 2015-08-10 Байополимер Текнолоджиз, Лтд. Emulsions and adhesives containing proteins, producing and using them
EP2403886A2 (en) * 2009-03-06 2012-01-11 Biopolymer Technologies, Ltd. Protein-containing foams, manufacture and use thereof
US8568471B2 (en) 2010-01-30 2013-10-29 Abbott Cardiovascular Systems Inc. Crush recoverable polymer scaffolds
US8808353B2 (en) 2010-01-30 2014-08-19 Abbott Cardiovascular Systems Inc. Crush recoverable polymer scaffolds having a low crossing profile
EP2576661B1 (en) 2010-06-07 2016-12-14 Evertree Protein-containing adhesives, and manufacture and use thereof
JP2014050412A (en) * 2010-12-28 2014-03-20 Tokyo Univ Of Agriculture & Technology Production method of artificial blood vessel
US8726483B2 (en) 2011-07-29 2014-05-20 Abbott Cardiovascular Systems Inc. Methods for uniform crimping and deployment of a polymer scaffold
US20130065012A1 (en) 2011-09-09 2013-03-14 Anthony A. Parker Protein-containing adhesives, and manufacture and use thereof
WO2014020447A2 (en) 2012-07-30 2014-02-06 Biopolymer Tecnologies, Ltd. Protein adhesives containing an anhydride, carboxylic acid, and/or carboxylate salt compound and their use
US9999527B2 (en) 2015-02-11 2018-06-19 Abbott Cardiovascular Systems Inc. Scaffolds having radiopaque markers
ITUB20153348A1 (en) 2015-09-02 2017-03-02 Tensive S R L Biodegradable medical device for reconstruction and / or breast augmentation

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4374669A (en) * 1975-05-09 1983-02-22 Mac Gregor David C Cardiovascular prosthetic devices and implants with porous systems
US4327195A (en) * 1980-09-29 1982-04-27 Seton Company Polyurethane containing polypeptides
US4604762A (en) * 1981-02-13 1986-08-12 Thoratec Laboratories Corporation Arterial graft prosthesis
US4699141A (en) * 1986-01-16 1987-10-13 Rhode Island Hospital Neovascularization

Also Published As

Publication number Publication date
AU636325B2 (en) 1993-04-29
JPH04502416A (en) 1992-05-07
AU4813090A (en) 1990-06-26
EP0447487A1 (en) 1991-09-25
EP0447487A4 (en) 1991-10-30
WO1990006094A1 (en) 1990-06-14

Similar Documents

Publication Publication Date Title
Xue et al. Biomaterials in the development and future of vascular grafts
Yarlagadda et al. Recent advances and current developments in tissue scaffolding
Pariente et al. In vitro biocompatibility assessment of naturally derived and synthetic biomaterials using normal human urothelial cells
CA2273077C (en) Tubular grafts from purified submucosa
EP0831755B1 (en) Bioresorbable heart valve support
EP1460972B1 (en) Layered stent-graft and methods of making the same
Godbey et al. In vitro systems for tissue engineering
US5697967A (en) Drug eluting stent
Langer Tissue engineering: a new field and its challenges
US6187053B1 (en) Process for producing a natural implant
US7217294B2 (en) Acellular matrix implants for treatment of articular cartilage, bone or osteochondral defects and injuries and method for use thereof
Ramakrishna et al. Biomedical applications of polymer-composite materials: a review
US6334872B1 (en) Method for treating diseased or damaged organs
Panduranga Rao Recent developments of collagen-based materials for medical applications and drug delivery systems
US8318193B2 (en) Crosslinked porous biomaterials
US7084082B1 (en) Collagen material and its production process
JP4489437B2 (en) Immobilized bioactive hydrogel matrix of the surface coating
US5628785A (en) Bioelastomeric stent
US5849034A (en) Intraluminal stent
EP1471952B1 (en) Coated vascular prosthesis and methods of manufacture and use.
Conklin et al. Development and evaluation of a novel decellularized vascular xenograft
EP1018977B1 (en) Method and implantable article for promoting endothelialization
US7004977B2 (en) Soft tissue substitute and method of soft tissue reformation
EP0814852B1 (en) Surgical prostheses
US5413597A (en) Three-layer vascular prostheses

Legal Events

Date Code Title Description
FZDE Dead