WO2016014259A1 - Prothèses vasculaires renforcées - Google Patents

Prothèses vasculaires renforcées Download PDF

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Publication number
WO2016014259A1
WO2016014259A1 PCT/US2015/039868 US2015039868W WO2016014259A1 WO 2016014259 A1 WO2016014259 A1 WO 2016014259A1 US 2015039868 W US2015039868 W US 2015039868W WO 2016014259 A1 WO2016014259 A1 WO 2016014259A1
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WO
WIPO (PCT)
Prior art keywords
extracellular matrix
vascular graft
tubular member
growth factor
group
Prior art date
Application number
PCT/US2015/039868
Other languages
English (en)
Inventor
Robert G. Matheny
Original Assignee
Cormatrix Cardiovascular, Inc.
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 claimed from US14/337,915 external-priority patent/US10052189B2/en
Application filed by Cormatrix Cardiovascular, Inc. filed Critical Cormatrix Cardiovascular, Inc.
Publication of WO2016014259A1 publication Critical patent/WO2016014259A1/fr

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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
    • A61L27/36—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
    • A61L27/3604—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 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3629—Intestinal tissue, e.g. small intestinal submucosa
    • 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
    • A61L27/3604—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 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3633—Extracellular matrix [ECM]
    • 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
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/48—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with macromolecular fillers
    • 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
    • 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
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A61L2300/414—Growth factors
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/64—Animal cells

Definitions

  • the present invention relates to methods and apparatus for treating damaged or diseased cardiovascular vessels. More particularly, the present invention relates to reinforced vascular grafts or prostheses for treating and/or reconstructing damaged or diseased
  • vascular grafts often employed to reconstruct (or replace) damaged or diseased cardiovascular vessels are autologous arteries and veins, e.g., internal mammary artery or saphenous vein; particularly, in situations where small diameter (i.e. 3-4 mm) vessels are required, such as below the knee and coronary artery bypass grafting.
  • autologous arteries and veins e.g., internal mammary artery or saphenous vein; particularly, in situations where small diameter (i.e. 3-4 mm) vessels are required, such as below the knee and coronary artery bypass grafting.
  • biodegradable materials and, hence, prostheses formed therefrom often break down at a faster rate than is desirable for the application.
  • a further disadvantage is that the materials can, and in many instances will, break down into large, rigid fragments that can cause obstructions in the interior of the vessel.
  • vascular grafts comprising various rcmodelable materials, such as extracellular matrix sheets, have been developed to treat and reconstruct damaged or diseased cardiovascular vessels.
  • Illustrative are the vascular grafts disclosed in Applicant's Co- Pending App. No. 13/573,226.
  • such grafts typically comprise one or more sheets of ECM tissue, e.g., small intestine submucosa, which is secured at one edge to form a tubular structure.
  • ECM tissue e.g., small intestine submucosa
  • the secured edge or seam can, and in many instances will, disrupt blood flow tlirough the graft.
  • a poorly secured edge also poses a significant risk of thrombosis.
  • the ECM graft comprises two or more sheets, i.e. a multi-sheet laminate, such as disclosed in Co-pending Application No. 14/031,423, the laminate structure is prone to delamination.
  • vascular grafts including “endografts” that substantially reduce or eliminate (i) the risk of thrombosis, (ii) intimal hyperplasia after intervention in a vessel, (iii) the harsh biological responses associated with conventional polymeric and metal prostheses, and (iv) the formation of biofilm, inflammation and infection.
  • vascular grafts that can effectively replace or improve biological functions or promote the growth of new tissue in a subject.
  • the present invention is directed to reinforced vascular grafts or prostheses for treating, reconstructing or replacing damaged or diseased cardiovascular vessels.
  • the vascular grafts comprise tubular members having first (or proximal) and second (or distal) ends.
  • the tubular members comprise a decellularized ECM material from a mammalian tissue source, i.e. tubular ECM members.
  • the ECM material can be derived from a variety of mammalian tissue sources, including, without limitation, small intestine submucosa (SIS), urinary bladder submucosa (UBS), stomach submucosa (SS), central nervous system tissue, epithelium of mesodermal origin, i.e. mesothelial tissue, dermal extracellular matrix, subcutaneous extracellular matrix, gastrointestinal extracellular matrix, i.e.
  • SIS small intestine submucosa
  • UBS urinary bladder submucosa
  • SS stomach submucosa
  • central nervous system tissue epithelium of mesodermal origin, i.e. mesothelial tissue, dermal extracellular matrix, subcutaneous extracellular matrix, gastrointestinal extracellular matrix, i.e.
  • the ECM material can also comprise collagen from mammalian sources.
  • the mammalian tissue source comprises an adolescent mammalian tissue source.
  • the tubular ECM members and, hence, vascular grafts formed therefrom further comprise at least one additional biologically active agent or composition, i.e. an agent that induces or modulates a physiological or biological process, or cellular activity, e.g., induces proliferation, and/or growth and/or regeneration of tissue.
  • additional biologically active agent or composition i.e. an agent that induces or modulates a physiological or biological process, or cellular activity, e.g., induces proliferation, and/or growth and/or regeneration of tissue.
  • the biologically active agent comprises a cell, such as a human embryonic stem cell, fetal cardiomyocyte, myofibroblast, mesenchymal stem cell, etc.
  • the biologically active agent comprises a growth factor, such as a transforming growth factor-alpha (TGF-a), transforming growth factor-beta (TGF- ⁇ ), fibroblast growth factor-2 (FGF-2), basic fibroblast growth factor (bFGF), and vascular epithelial growth factor (VEGF).
  • TGF-a transforming growth factor-alpha
  • TGF-beta TGF- ⁇
  • FGF-2 fibroblast growth factor-2
  • bFGF basic fibroblast growth factor
  • VEGF vascular epithelial growth factor
  • the tubular ECM members and, hence, vascular grafts formed therefrom further comprise at least one pharmacological agent or composition (or drug), i.e. an agent or composition that is capable of producing a desired biological effect hi vivo, e.g., stimulation or suppression of apoptosis, stimulation or suppression of an immune response, etc.
  • pharmacological agent or composition or drug
  • Suitable pharmacological agents and compositions include any of the
  • agents including, without limitation, antibiotics, anti-viral agents, analgesics, steroidal anti-inflammatories, non-steroidal anti-infiammatories, anti-neoplastics, antispasmodics, modulators of cell-extracellular matrix interactions, proteins, hormones, enzymes and enzyme inhibitors, anticoagulants and/or antithrombic agents, DNA, RNA, modified DNA and RNA, NSAIDs, inhibitors of DNA, RNA or protein synthesis, polypeptides, oligonucleotides, polynucleotides, nucleoproteins, compounds modulating cell migration, compounds modulating proliferation and growth of tissue, and vasodilating agents.
  • the pharmacological agent comprises a statin, i.e. a HMG-CoA reductase inhibitor, such as cerivastatin.
  • tubular ECM members and, hence, vascular grafts formed therefrom further comprise reinforcement means, i.e. reinforced vascular prostheses.
  • the reinforcement means comprises a thin strand or thread of reinforcing material that is wound around the tubular member.
  • the reinforcing strand comprises a biocompatible and biodegradable polymeric material.
  • the reinforcing strand comprises an ECM strand or thread.
  • the reinforcing strand comprises a biocompatible metal, such as stainless steel or Nitinol®, or a biocompatible and biodegradable metal, such as magnesium.
  • the reinforcement means comprises a braided or mesh configuration.
  • tubular ECM members and, hence, vascular grafts formed therefrom further comprise at least one anchoring mechanism.
  • FIGURE 1 A is a perspective view of one embodiment of a tubular ECM vascular graft, in accordance with the invention.
  • FIGURE IB is a side or edge plan view of the tubular ECM vascular graft shown in FIGURE 1A, in accordance with the invention.
  • FIGURE 2A is a perspective view of one embodiment of a coated ECM vascular graft, in accordance with the invention.
  • FIGURE 2B is a side or edge plan view of the coated ECM vascular graft shown in FIGURE 2A, in accordance with the invention.
  • FIGURE 3 A is a perspective view of one embodiment of a reinforced ECM vascular graft, in accordance with the invention.
  • FIGURE 3B is a side or edge plan view of the reinforced ECM vascular egraft shown in FIGURE 3A, in accordance with the invention.
  • FIGURE 4A is a perspective view of another embodiment of a reinforced ECM vascular graft, in accordance with the invention.
  • FIGURE 4B is a side or edge plan view of the reinforced ECM vascular graft shown in FIGURE 4A, in accordance with the invention.
  • ranges can be expressed herein as from “about” or “approximately” one particular value, and/or to “about” or “approximately” another particular value. " When such a range is expressed, another embodiment includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about” or “approximately”, it will be understood that the particular value forms another embodiment. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint.
  • graft and “endograft” are used interchangeably herein, and mean and include a structure that is configured for implantation in a cardiovascular structure, e.g., a cardiovascular vessel.
  • extracellular matrix , "ECM” and “ECM material” are used interchangeably herein, and mean and include a collagen-rich substance that is found in between cells in mammalian tissue, and any material processed therefrom, e.g. decellularized ECM.
  • the ECM material can be derived from a variety of mammalian tissue sources, including, without limitation, small intestine submucosa (SIS), urinary bladder submucosa (UBS), stomach submucosa (SS), central nervous system tissue, epithelium of mesodermal origin, i.e. mesothelial tissue, dermal extracellular matrix, subcutaneous extracellular matrix, gastrointestinal extracellular matrix, i.e.
  • the ECM material can also comprise collagen from mammalian sources.
  • UBS urinary bladder submucosa
  • SIS small intestine submucosa
  • SS stomach submucosa
  • the ECM material can also be derived from basement membrane of mammalian tissue/organs, including, without limitation, urinary basement membrane (UBM), liver basement membrane (LBM), and amnion, chorion, allograft pericardium, allograft acellular dermis, amniotic membrane, Wharton's jelly, and combinations thereof.
  • UBM urinary basement membrane
  • LBM liver basement membrane
  • Additional sources of mammalian basement membrane include, without limitation, spleen, lymph nodes, salivary glands, prostate, pancreas and other secreting glands.
  • the ECM material can also be derived from other sources, including, without limitation, collagen from plant sources and synthesized extracellular matrices, i.e. cell cultures.
  • angiogenesis means a physiologic process involving the growth of new blood vessels from pre-existing blood vessels.
  • '"neovascularization means and includes the formation of functional vascular networks that can be perfused by blood or blood components.
  • Neovascularization includes angiogenesis, budding angiogenesis, intussuceptive angiogenesis, sprouting angiogenesis, therapeutic angiogenesis and vasculogenesis.
  • Article means a poly(urethane urea) material distributed by Artimplant AB in Goteborg, Sweden.
  • biologically active agent and “biologically active composition” are used interchangeably herein, and mean and include agent that induces or modulates a physiological or biological process, or cellular activity, e.g., induces proliferation, and/or growth and/or regeneration of tissue.
  • biologically active agent and “biologically active composition” thus mean and include, without limitation, the following growth factors: platelet derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor alpha (TGF- alpha), transforming growth factor beta (TGF-beta), fibroblast growth factor - 2 (FGF-2), basic fibroblast growth factor (bFGF), vascular epithelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin-like growth factor (IGF), nerve growth factor (NGF), platlet derived growth factor (PDGF), tumor necrosis factor alpha (TNA-alpha), and placental growth factor (PLGF).
  • PDGF platelet derived growth factor
  • EGF epidermal growth factor
  • TGF- alpha transforming growth factor alpha
  • TGF-beta transforming growth factor beta
  • FGF-2 fibroblast growth factor-2
  • basic fibroblast growth factor bFGF
  • VEGF vascular epithelial growth factor
  • HGF he
  • biologically active agent and “biologically active composition” also mean and include, without limitation, human embryonic stem cells, fetal cardiomyocytes, myofibroblasts, mesenchymal stem cells, autotransplated expanded cardiomyocytes, adipocytes, totipotent cells, pluripotent cells, blood stem cells, myoblasts, adult stem cells, bone marrow cells, mesenchymal cells, embryonic stem cells, parenchymal cells, epithelial cells, endothelial cells, mesothelial cells, fibroblasts, osteoblasts, chondrocytes, exogenous cells, endogenous cells, stem cells, hematopoietic stem cells, bone-marrow derived progenitor cells, myocardial cells, skeletal cells, fetal cells, undifferentiated cells, multi- potent progenitor cells, unipotent progenitor cells, monocytes, cardiac myoblasts, skeletal myoblasts, macrophages,
  • biologically active agent and “biologically active composition” also mean and include, without limitation, the following biologically active agents (referred to interchangeably herein as a "protein”, “peptide” and “polypeptide “ ): collagen (types I-V), proteoglycans, glycosaminoglycans (GAGs), glycoproteins, growth factors, cytokines, cell- surface associated proteins, cell adhesion molecules (CAM), angiogenic growth factors, endothelial ligands, matrikines, cadherins, immuoglobins, fibril collagens, non-fibrallar collagens, basement membrane collagens, multiplexins, small-leucine rich proteoglycans, decorins, biglycans, fibromodulins, keratocans, lumicans, epiphycans, heparin sulfate proteoglycans, perlecans, agrins, testicans, syndecan
  • biologically active agents referred
  • pharmacological agent means and include an agent, drug, compound, composition of matter or mixture thereof, including its formulation, which provides some therapeutic, often beneficial, effect.
  • the terms "pharmacological agent”, “active agent”, “drug” and “active agent formulation” thus mean and include, without limitation, antibiotics, anti-arrhythmic agents, anti-viral agents, analgesics, steroidal anti-inflammatories, non-steroidal antiinflammatories, anti-neoplastics, anti-spasmodics, modulators of cell-extracellular matrix interactions, proteins, hormones, growth factors, matrix metalloproteinases (MMPS), enzymes and enzyme inhibitors, anticoagulants and/or antithrombic agents, DNA, RNA, modified DNA and RNA, NSAlDs, inhibitors of DNA, RNA or protein synthesis,
  • polypeptides oligonucleotides, polynucleotides, nucleoproteins, compounds modulating cell migration, compounds modulating proliferation and growth of tissue, and vasodilating agents.
  • the terms "pharmacological agent”, “active agent”, “drug” and “active agent formulation” thus include, without limitation, atropine, tropicamide, dexamethasone, dexamethasone phosphate, betamethasone, betamethasone phosphate, prednisolone, triamcinolone, triamcinolone acetonide, fluocinolone acetonide, anecortave acetate, budesonide, cyclosporine, FK-506, rapamycin, ruboxistaurin, midostaurin, flurbiprofen, suprofen, ketoprofen, diclofenac, ketorolac, nepafenac, lidocaine, neomycin, polymyxin b, bacitracin, gramicidin, gentamicin, oyxtetracycline, ciprofloxacin, ofloxacin, tobramycin, amikacin, vanco
  • the terms "pharmacological agent”, “active agent”, “drug” and “active agent formulation” further mean and include the following Class I - Class V antiarrhythmic agents: (Class la) quinidine, procainamide and disopyramide; (Class lb) lidocaine, phenytoin and mexiletine; (Class Ic) flecainide, propafenone and moricizine; (Class II) propranolol, esmolol, timolol, metoprolol and atenolol; (Class III) amiodarone, sotalol, ibutilide and dofetilide; (Class IV) verapamil and diltiazem) and (Class V) adenosine and digoxin.
  • Class la quinidine, procainamide and disopyramide
  • Class lb lidocaine, phenytoin and mexiletine
  • Class Ic flecainide, propafenone and mor
  • trimethoprim-sulfamethoxazole and vancomycin are trimethoprim-sulfamethoxazole and vancomycin.
  • the terms “pharmacological agent “ , “active agent”, “drug” and “active agent formulation” further include, without limitation, the following steroids: andranes (e.g., testosterone), cholestanes, cholic acids, corticosteroids (e.g., dexamethasone), estraenes (e.g., estradiol) and pregnanes (e.g., progesterone).
  • steroids e.g., testosterone
  • cholestanes cholestanes
  • cholic acids e.g., corticosteroids (e.g., dexamethasone)
  • estraenes e.g., estradiol
  • pregnanes e.g., progesterone
  • narcotic analgesics including, without limitation, morphine, codeine, heroin, hydromorphone, levorphanol, meperidine, methadone, oxycodone, propoxyphene, fentanyl, methadone, naloxone, buprenorphine, butorphanol, nalbuphine and pentazocine.
  • compositions can further include one or more classes of topical or local anesthetics, including, without limitation, esters, such as benzocaine, chloroprocaine, cocaine,
  • Local anesthetics can also include, without limitation, amides, such as articaine, bupivacaine, cinchocaine/dibucaine, etidocaine, levobupivacaine, lidocaine/lignocaine, mepivacaine, prilocaine, ropivacaine, and trimecaine. Local anesthetics can further include combinations of the above from either amides or esters.
  • anti-inflammatory and anti-inflammatory agent are also used interchangeably herein, and mean and include a “pharmacological agent” and/or “active agent fomiulation”, which, when a therapeutically effective amount is administered to a subject, prevents or treats bodily tissue inflammation i.e. the protective tissue response to injury or destruction of tissues, which serves to destroy, dilute, or wall off both the injurious agent and the injured tissues.
  • Anti-inflammatory agents thus include, without limitation, alclofenac, alclometasone dipropionate, algestone acetonide, alpha amylase, amcinafal, amcinafide, amfenac sodium, amiprilose hydrochloride, anakinra, anirolac, anitrazafen, apazone, balsalazide disodium, bendazac, benoxaprofen, benzydamine hydrochloride, bromelains, broperamole, budesonide, carprofen, cicloprofen, cintazone, cliprofen, clobetasol propionate, clobetasone butyrate, clopirac, cloticasone propionate, cormethasone acetate, cortodoxone, decanoate, deflazacort, delatestryl, depo-testosterone, desonide,
  • composition means and includes a composition comprising a "pharmacological agent " and/or a "biologically active agent " and/or any additional agent or component identified herein.
  • terapéuticaally effective means that the amount of the "pharmacological agent” and/or “biologically active agent” and/or “pharmacological composition” administered is of sufficient quantity to ameliorate one or more causes, symptoms, or sequelae of a disease or disorder. Such amelioration only requires a reduction or alteration, not necessarily elimination, of the cause, symptom, or sequelae of a disease or disorder.
  • the term "adolescent”, as used herein, means and includes a mammal that is preferably less than three (3) years of age.
  • patient and “subject” are used interchangeably herein, and mean and include warm blooded mammals, humans and primates; avians; domestic household or farm animals, such as cats, dogs, sheep, goats, cattle, horses and pigs; laboratory animals, such as mice, rats and guinea pigs; fish; reptiles; zoo and wild animals; and the like.
  • the present invention is directed to vascular grafts or prostheses for treating, reconstructing or replacing damaged or diseased cardiovascular vessels.
  • the tubular members comprise a decellularized ECM material from a mammalian tissue source.
  • the ECM material can be derived from a variety of mammalian tissue sources, including, without limitation, small intestine submucosa (SIS), urinary bladder submucosa (UBS), stomach submucosa (SS), central nervous system tissue, epithelium of mesodermal origin, i.e. mesothelial tissue, dermal extracellular matrix, subcutaneous extracellular matrix, gastrointestinal extracellular matrix, i.e.
  • the ECM material can also comprise collagen from mammalian sources.
  • the mammalian tissue source comprises an adolescent mammalian tissue source, i.e. an adolescent mammal, such as a piglet, which is preferably less than three (3) years of age.
  • the ECM material is decellularized and, hence, remodelable.
  • the ECM material can be decellularized by various conventional means.
  • the ECM material is decellularized via one of the unique Novasterilis processes disclosed in U.S. Pat. No. 7,108,832 and U.S. Pat. App. No. 13/480,204; which are incorporated by reference herein in their entirety.
  • the vascular graft upon implanting a vascular graft of the invention in a cardiovascular system of a subject, the vascular graft induces host tissue proliferation, bioremodeling, including neovascularization, e.g., vasculogenesis, angiogenesis, and intussusception, and regeneration of tissue structures with site-specific structural and functional properties.
  • the graft also provides a vessel having a smooth, non-thrombogenic interior surface.
  • the vascular grafts further comprise at least one additional biologically active agent or composition, i.e. an agent that induces or modulates a physiological or biological process, or cellular activity, e.g., induces proliferation, and/or growth and/or regeneration of tissue.
  • additional biologically active agent or composition i.e. an agent that induces or modulates a physiological or biological process, or cellular activity, e.g., induces proliferation, and/or growth and/or regeneration of tissue.
  • the biologically active agent is similarly derived from an adolescent mammal, i.e. a mammal less than three (3) years of age.
  • Suitable biologically active agents include any of the aforementioned biologically active agents, including, without limitation, the aforementioned cells and proteins.
  • the biologically active agent comprises a growth factor selected from the group comprising transforming growth factor-alpha (TGF-a), transforming growth factor-beta (TGF- ⁇ ), fibroblast growth factor-2 (FGF-2), basic fibroblast growth factor (bFGF) and vascular epithelial growth factor (VEGF).
  • TGF-a transforming growth factor-alpha
  • TGF- ⁇ transforming growth factor-beta
  • FGF-2 fibroblast growth factor-2
  • bFGF basic fibroblast growth factor
  • VEGF vascular epithelial growth factor
  • the growth factors link to and interact with at least one molecule in the vascular graft and further induce and/or control host tissue proliferation, bioremodeling, and regeneration of new tissue structures.
  • the biologically active agent comprises a protein selected from the group comprising proteoglycans, glycosaminoglycans (GAGs), glycoproteins, heparins, chondroitin sulfate B (dermatan sulfate), chondroitin sulfate A, heparin sulfates, and hyaluronic acids.
  • the protein comprises a cytokine selected from the group comprising a stem cell factor (SCF), stromal cell-derived factor- 1 (SDF-1), granulocyte macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN- gamma), interleukin-3, interleukin-4, interleukin-10, interleukin-13, leukemia inhibitory factor (LIF), amphiregulin, thrombospondin 1 , thrombospondin 2, thrombospondin 3, thrombospondin 4, thrombospondin 5, and angiotensin converting enzyme (ACE).
  • SCF stem cell factor
  • SDF-1 stromal cell-derived factor- 1
  • GM-CSF granulocyte macrophage colony-stimulating factor
  • IFN- gamma interferon gamma
  • interleukin-3 interleukin-4
  • interleukin-10 interleukin-13
  • LIF leukemia inhibitory
  • the proteins upon implanting a vascular graft of the invention in a cardiovascular system of a subject, similarly link to and interact with at least one molecule in the graft and further induce and/or control host tissue proliferation,
  • the vascular grafts further comprise at least one
  • pharmacological agent or composition i.e. an agent or composition that is capable of producing a desired biological effect in vivo, e.g., stimulation or suppression of apoptosis, stimulation or suppression of an immune response, etc.
  • Suitable pharmacological agents and compositions include any of the
  • agents including, without limitation, antibiotics, anti-viral agents, analgesics, steroidal anti-inflammatories, non-steroidal anti-inflammatories, anti-neoplastics, antispasmodics, modulators of cell-extracellular matrix interactions, proteins, honnones, enzymes and enzyme inhibitors, anticoagulants and/or antithrombic agents, DNA, RNA, modified DNA and RNA, NSAIDs, inhibitors of DNA, RNA or protein synthesis, polypeptides, oligonucleotides, polynucleotides, nucleoproteins, compounds modulating cell migration, compounds modulating proliferation and growth of tissue, and vasodilating agents.
  • the pharmacological agent comprises one of the aforementioned anti-inflammatories.
  • the pharmacological agent comprises a statin, i.e. a HMG-CoA reductase inhibitor.
  • suitable statins include, without limitation, atorvastatin (Lipitor®), cerivastatin, fluvastatin (Lescol®), lovastatin (Mevacor®, Altocor®, Altoprev®), mevastatin, pitavastatin (Livalo ®, Pitava®), pravastatin (Pravachol®, Selektine®, Lipostat®), rosuvastatin (Crestor®), and simvastatin (Zocor®, Lipex®).
  • actives comprising a combination of a statin and another agent, such as ezetimbe/simvastatin (Vytorin®), are also suitable.
  • statins exhibit numerous beneficial properties that provide several beneficial biochemical actions or activities.
  • the properties and beneficial actions are set forth in Applicant's Co-Pending Application Nos. 13/373,569, filed on
  • the vascular grafts further comprise at least one outer coating.
  • the outer coating comprises a pharmacological composition.
  • the vascular grafts further comprise reinforcement means, i.e. reinforced vascular grafts.
  • the reinforcement means comprises a thin strand or thread of reinforcing material that is wound around the tubular graft.
  • the reinforcing strand can comprise various biocompatible materials.
  • the reinforcing strand comprises a biocompatible and biodegradable polymeric material.
  • suitable biodegradable polymeric materials similarly include, without limitation, polyhydroxyalkonates (PHAs), polylactides (PLLA) and polyglycolides (PLGA) and their copolymers, polyanhydrides, and like polymers.
  • a further suitable polymeric material comprises "Artelon", i.e. a poly(urethane urea) material distributed by Artimplant AB in Goteborg, Sweden.
  • the reinforcing strand can also comprise an ECM strand or thread, such as a small intestine or urinary bladder submucosa suture.
  • the reinforcing strand can be disposed on the outer surface of the graft manually or via an electro-spin procedure.
  • the reinforcing strand can also comprise a
  • biocompatible metal such as stainless steel or Nitinol®, or a biocompatible and
  • biodegradable metal such as magnesium
  • the reinforcement means comprises a braided or mesh configuration or other conventional stent structure.
  • the vascular grafts further comprise at least one anchoring mechanism, such as disclosed in Co-pending Application Nos. 13/782,024 and 13/686,131 ; which are incorporated by reference herein in their entirety.
  • the graft 10a comprises a continuous tubular member 12 having proximal 14 and distal 16 ends, and a lumen 18 that extends therethrough.
  • the tubular member 12 comprises a decellularized ECM material.
  • the ECM material is derived from an adolescent mammal, i.e. a mammal less than three (3) years of age.
  • the tubular member 12, and, hence vascular graft 10a (and grafts ] 0b-10d, discussed below) formed therefrom can have various diameters, e.g. 3.0 mm, 10.0 mm, etc.
  • the vascular graft 10a further comprises at least one additional biologically active agent or composition, i.e. an agent that induces or modulates a physiological or biological process, or cellular activity, e.g., induces
  • Suitable biologically active agents include any of the aforementioned biologically active agents, including, without limitation, the aforementioned cells, growth factors and proteins.
  • the vascular graft 10a further comprises at least one pharmacological agent or composition (or drug), i.e. an agent or composition that is capable of producing a desired biological effect in vivo, e.g., stimulation or suppression of apoptosis, stimulation or suppression of an immune response, etc.
  • pharmacological agent or composition or drug
  • Suitable pharmacological agents and compositions include any of the
  • agents including, without limitation, antibiotics, anti-viral agents, analgesics, steroidal anti-inflammatories, non-steroidal anti-inflammatories, anti-neoplastics, antispasmodics, modulators of cell-extracellular matrix interactions, proteins, hormones, enzymes and enzyme inhibitors, anticoagulants and/or antithrombic agents, DNA, RNA, modified DNA and RNA, NSAIDs, inhibitors of DNA, RNA or protein synthesis, polypeptides, oligonucleotides, polynucleotides, nucleoproteins, compounds modulating cell migration, compounds modulating proliferation and growth of tissue, and vasodilating agents.
  • the pharmacological agent comprises a statin, i.e. a HMG-CoA reductase inhibitor.
  • Figs. 2A and 2B there is shown another embodiment of a vascular graft of the invention.
  • the endograft 10b similarly comprises a continuous tubular member 12 having proximal 14 and distal 16 ends, and a lumen 18 that extends therethrough.
  • the vascular endograft 10b further comprises at least one outer coating 20.
  • the outer coating 20 comprises a pharmacological composition.
  • the vascular grafts of the invention further comprise reinforcement means, i.e. reinforced vascular grafts.
  • reinforcement means i.e. reinforced vascular grafts.
  • Figs. 3A and 3B there is shown one embodiment of a reinforced vascular graft of the invention.
  • the graft 10c similarly comprises a continuous tubular member 12 having proximal 14 and distal 16 ends, and a lumen 18 that extends therethrough.
  • the graft 10c further comprises reinforcement means, which, in the illustrated embodiment, comprises a thin strand or thread of reinforcing material 30, which is wound around the tubular endograft 10c, and, hence, disposed proximate the outer surface 1 1 thereof.
  • reinforcement means which, in the illustrated embodiment, comprises a thin strand or thread of reinforcing material 30, which is wound around the tubular endograft 10c, and, hence, disposed proximate the outer surface 1 1 thereof.
  • the reinforcing strand 30 can comprise various biocompatible materials.
  • the reinforcing strand 30 comprises a biocompatible and biodegradable polymeric material.
  • Suitable biodegradable polymeric materials similarly include, without limitation, polyhydroxyalkonates (PHAs), polylactides (PLLA) and polyglycolides (PLGA) and their copolymers, polyanhydrides, and like polymers.
  • the reinforcing strand 30 can alternatively comprise an ECM strand or thread, such as a small intestine or urinary bladder submucosa suture.
  • the ECM strand comprises a cross-linked ECM material.
  • the reinforcing strand 30 can also comprise a biocompatible metal, such as stainless steel or Nitinol®, or a biocompatible and
  • biodegradable metal such as magnesium
  • the reinforcement means comprises a braided or mesh configuration.
  • graft lOd includes a braided reinforcing structure 32.
  • the braided structure 32 can comprise various configurations and can be formed by various conventional means.
  • the braided structure 32 can also comprise any of the aforementioned biocompatible and biodegradable materials.
  • the braided structure 32 comprises one of the aforementioned biodegradable polymeric materials.
  • the vascular grafts 10a- l Od further comprise at least one anchoring mechanism, such as disclosed in Co-pending Application Nos. 13/782,024 and 13/686,131 , which are incorporated by reference herein in their entirety.
  • the present invention provides numerous advantages compared to prior art prosthetic valves. Among the advantages are the following:

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Abstract

L'invention concerne des greffons vasculaires pour le traitement, la reconstruction et le remplacement de vaisseaux cardiovasculaires endommagés ou malades qui sont formés à partir d'une matrice extracellulaire (MEC) décellularisée. Les greffons vasculaires comprennent des moyens de renforcement structural, tel qu'un brin de matériau polymère biodégradable enroulé placé à proximité de la surface externe du greffon.
PCT/US2015/039868 2014-07-22 2015-07-10 Prothèses vasculaires renforcées WO2016014259A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US14/337,915 2014-07-22
US14/337,915 US10052189B2 (en) 2012-10-08 2014-07-22 Reinforced vascular prostheses

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5628782A (en) * 1992-12-11 1997-05-13 W. L. Gore & Associates, Inc. Method of making a prosthetic vascular graft
US20020169499A1 (en) * 1998-11-23 2002-11-14 Medtronic, Inc. Porous synthetic vascular grafts with oriented ingrowth channels
US20050187604A1 (en) * 2004-02-09 2005-08-25 Cook Incorporated Cast bioremodelable graft
US20120059487A1 (en) * 2010-08-24 2012-03-08 Cunanan Crystal M Biomaterials with enhanced properties and devices made therefrom
US20140100648A1 (en) * 2012-10-08 2014-04-10 Robert G. Matheny Multi-Layer Vascular Prosthesis

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5628782A (en) * 1992-12-11 1997-05-13 W. L. Gore & Associates, Inc. Method of making a prosthetic vascular graft
US20020169499A1 (en) * 1998-11-23 2002-11-14 Medtronic, Inc. Porous synthetic vascular grafts with oriented ingrowth channels
US20050187604A1 (en) * 2004-02-09 2005-08-25 Cook Incorporated Cast bioremodelable graft
US20120059487A1 (en) * 2010-08-24 2012-03-08 Cunanan Crystal M Biomaterials with enhanced properties and devices made therefrom
US20140100648A1 (en) * 2012-10-08 2014-04-10 Robert G. Matheny Multi-Layer Vascular Prosthesis

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