WO2000035372A2 - Matrices multiples pour tissus modifies - Google Patents

Matrices multiples pour tissus modifies Download PDF

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Publication number
WO2000035372A2
WO2000035372A2 PCT/US1999/029489 US9929489W WO0035372A2 WO 2000035372 A2 WO2000035372 A2 WO 2000035372A2 US 9929489 W US9929489 W US 9929489W WO 0035372 A2 WO0035372 A2 WO 0035372A2
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Prior art keywords
matrix
matrices
blood vessel
collagen
cells
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PCT/US1999/029489
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English (en)
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WO2000035372A3 (fr
Inventor
Timothy J Ryan
Original Assignee
Ryan, Timothy, J.
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Publication date
Application filed by Ryan, Timothy, J. filed Critical Ryan, Timothy, J.
Priority to AU24798/00A priority Critical patent/AU2479800A/en
Publication of WO2000035372A2 publication Critical patent/WO2000035372A2/fr
Publication of WO2000035372A3 publication Critical patent/WO2000035372A3/fr

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Classifications

    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L89/00—Compositions of proteins; Compositions of derivatives thereof
    • C08L89/04—Products derived from waste materials, e.g. horn, hoof or hair
    • C08L89/06—Products derived from waste materials, e.g. horn, hoof or hair derived from leather or skin, e.g. gelatin
    • 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

Definitions

  • Neointimal hyperplasia also known as intimal hyperplasia, is the proliferation of the smooth muscle cells (SMCs) and excessive production by these cells of extracellular matrix. Generally, this phenomenon is seen at the sites of anastomoses, that is, where the vascular graft is sutured to the parent or recipient vessel. It is also the phenomenon described by restenosis, that is, closure of a vessel after some intervention (e.g., PTCA).
  • the SMCs adopt a synthetic phenotype; they proliferate, migrate, and secrete more matrix than is appropriate. Some of this phenotypic shift is due to a shift in signal transduction by surface integrins on the SMCs, especially those specific for the adhesion proteins, laminin and fibronectin.
  • One aspect of the invention features a method of producing a multilayered cellular structure, including (i) forming a plurality of matrices; seeding at least one of the matrices with living cells; and (iii) assembling the matrices into a single multilayered cellular structure.
  • the matrices are tubular and of different diameters.
  • the matrices include a copolymer of collagen and a glycosaminoglycan
  • the living cells include smooth muscle cells, endothelial cells, fibroblasts, or any combination thereof.
  • the matrices differ in their mechanical properties.
  • the mechanical property which differs between matrices is pore size, pore orientation, mean molecular weight between crosslinks (Mc), or percent porosity (void fraction).
  • the matrices contain different amounts of elastin, laminin, fibronectin, or Tissue Factor Pathway Inhibitor (TFPI), or any combination thereof.
  • the invention features a method of producing a prosthetic blood vessel, including the steps of (i) forming a plurality of tubular matrices of different diameters; (ii) seeding at least one of the tubular matrices with living cells; and (iii) assembling the tubular matrices into a single, concentric multilayered tube.
  • the invention features a method of producing a prosthetic blood vessel, including the steps of (i) forming a plurality of matrices; (ii) seeding at least one of the matrices with living cells; (iii) shaping the matrices to form tubular matrices of different diameters; and (iv) assembling the tubular matrices into a single multilayered tube.
  • the invention features a method of producing a prosthetic blood vessel, including the steps of (i) forming a tubular matrix; and (ii) seeding the tubular matrix with living cells.
  • the matrix includes a co-polymer of collagen and a glycosaminoglycan.
  • the matrix also includes elastin, laminin, fibronectin, or Tissue
  • the living cells include smooth muscle cells, endothelial cells, or any combination thereof.
  • the invention features a method of producing a prosthetic blood vessel, including the steps of (i) forming a matrix; (ii) seeding the matrix with living cells; and (iii) shaping the matrix to form a tube.
  • the matrix includes a co-polymer of collagen and a glycosaminoglycan.
  • the matrix can also include elastin, laminin, fibronectin, or Tissue Factor Pathway Inhibitor (TFPI), or any combination thereof.
  • the living cells include smooth muscle cells, endothelial cells, or any combination thereof.
  • the invention features a matrix including a co-polymer of collagen and glycosaminoglycan, and also includes at least two of the following: elastin, laminin, fibronectin, and Tissue Factor Pathway Inhibitor
  • the glycosaminoglycan is chondroitin sulfate or heparin.
  • the collagen is type I or type IV collagen.
  • the co-polymer of collagen and glycosaminoglycan is acid precipitated.
  • the matrix also includes TFPI, elastin, laminin, and/or fibronectin.
  • the invention features a multilayered blood vessel prosthesis which includes (i) an inner layer comprising type I collagen, type IN collagen, GAG, elastin, and laminin; and (ii) an outer layer comprising type I collagen, GAG, elastin, and fibronectin.
  • the inner layer is seeded externally with smooth muscle cells and is seeded internally with endothelial cells.
  • the outer layer is seeded internally with smooth muscle cells and is seeded externally with fibroblasts.
  • the multilayered blood vessel prostheses also includes at least one medial layer comprising collagen, GAG, elastin, and fibronectin. In a related embodiment, the medial layers are seeded internally and externally with smooth muscle cells.
  • Biocompatible polymers include poly- ⁇ -acetylglucosamine (chitin), polyurethanes, polyether block amides, fluoropolymers such as polytetrafluoroethylene, polyethylene, polyester, and polyethylene terephthalate. Biocompatible polymers also include collagen-based polymers, with or without associated glycosaminoglycans, elastin, fibronectin, laminin, or combinations thereof. Any of the 20-odd collagens thus far identified can be used; those most preferred are Type I and Type IV collagens. A biocompatible polymer is intended to contact cells, biological fluids, and preparations derived from cells.
  • Cells include individual cells; animal tissues such as blood, muscle, nerves, tendons, cartilage, bone, and vasculature including veins, arteries, valves, placental and umbilical material, and organs of animals; and tissues of plants.
  • a biocompatible polymer of the invention is generally nontoxic. In some cases, the polymer can be designed to release, leech, degrade, or selectively bind biologically active substances, and direct favorable cellular processes.
  • a “bioresorbable material,” in amounts used with the invention, can be degraded in, or by, the body without producing unacceptable levels of harmful metabolites or stimulation of adverse immune responses including cellular proliferation, calcification, or synthesis of excessive fibrotic tissue.
  • the degradation occurs gradually, at a predetermined rate, to allow fibroblasts, endothelial cells, or other vascular, muscular, or other tissue to replace the bioresorbable material.
  • the time interval can be days, weeks, months or years.
  • the rate of degradation can be regulated by regulating the matrix components.
  • Compliance is a measure of the degree to which a material stretches as a result of an applied stress.
  • compliance is defined as a change in volume of the structure divided by the change in pressure necessary to cause the change in volume
  • Abbot Biological and Synthetic Vascular Prostheses, J.C. Stanley (ed), Grune and
  • compliance is the percent change in diameter per unit of pressure.
  • the compliance of the prosthesis should closely match that of the adjacent living tissue to which the prosthesis is being attached.
  • compliance is generally between 4% and 12%. and preferably between 6% and 9%.
  • 4% compliance means that an artery or vascular graft stretches 4% as a result of the difference between systolic and diastolic pressures—that is, at 120mm Hg, a graft or artery would have a diameter that is 4% larger than at 80mm Hg.
  • the collagen material as precipitated with a glycosaminoglycan, is nearly insoluble in water (or saline) at physiologic pH prior to crosslinking.
  • the crosslinking makes it less susceptible to degradation.
  • Crosslinking reduces aqueous solubility of a collagen-bound material and increases fracture stress and resistance to enzymatic degradation (for example, by collagenase, which cleave the collagen into smaller, soluble fragments).
  • Crosslinking conditions can be selected to provide the desired level of crosslink density, to reduce the surface functional groups, or otherwise modulate mechanical or biological properties.
  • GAG Glycosaminoglycans
  • GAGs include, but are not limited to, chondroitin-6-sulfate, chondroitin-4-sulfate, heparin sulfate, dermatan sulfate, keratin sulfate, chitosan, hyaluronic acid, and heparin.
  • Combinations of glycosaminoglycans can also be used.
  • Porcity is the estimate or index of the ratio of the void within a material to the total volume occupied by the material including the voids, expressed as a percentage void to the total volume.
  • the invention provides improved vascular grafts which resist failure, particularly at anastomoses.
  • the invention also provides vascular grafts with excellent mechanical and biological properties in a much shorter time period than is possible by other methods.
  • tubular or bifurcated matrix analogs constructed of a biocompatible polymer matrix analog which can be comprised of type I and type IV collagen, a glycosaminoglycan such as chondroitin sulfate or heparin sulfate, elastin, an adhesion protein such as laminin, or fibronectin, and Tissue Factor Pathway Inhibitor (TFPI).
  • a biocompatible polymer matrix analog which can be comprised of type I and type IV collagen, a glycosaminoglycan such as chondroitin sulfate or heparin sulfate, elastin, an adhesion protein such as laminin, or fibronectin, and Tissue Factor Pathway Inhibitor (TFPI).
  • a biocompatible polymer matrix analog which can be comprised of type I and type IV collagen, a glycosaminoglycan such as chondroitin sulfate or heparin sulfate, elastin,
  • the matrix includes collagen/GAG, precipitated in an acidic medium (pH ⁇ 4.25) and freeze dried.
  • both pathways of thrombus formation are inhibited and the resulting conduit is largely non- thrombogenic.
  • adhesion proteins such as laminin or fibronectin, to regulate SMC phenotype.
  • Elastin can also be included to increase compliance and to increase fracture toughness.
  • the extracellular matrix (ECM) analog can be formed into at least two tubes, sized such that one tube fits snugly inside the other.
  • the tubes can be manufactured such that the chemical or physical compositions, or both, are different in each of the tubes. It is particularly useful to construct the inner tube such that the pores in the ECM are smaller than those in the outer tube. For example, it can be desirable for the inner tube to have pores of between one and 10 microns in average size, while the outer or subsequent tube can be optimal with pores that average 40-80 microns in diameter. Additionally, the inner tube can be much thinner than the outer tube, and the inner tube can be also have a higher concentration of elastin.
  • SMCs Collected endothelial or SMCs, after isolation and sufficient growth, a then seeded onto one or more of the tubes.
  • Some of the tubes can be seeded with SMCs internally and externally, while others are only seeded externally. Additionally, the inner-most tube can be seeded externally with SMCs, then cultured for a few days, then seeded internally with endothelial cells.
  • the tubes are eventually assembled and further grown, yielding a construct of concentric layers of tissue containing endothelial cells and SMCs.
  • Fibroblasts can be added to the outermost surface for the final culture period, or it can be beneficial to construct a similar adventitial layer comprised of ECM and fibroblasts, and then assemble the adventitial layer onto the medial and intimal layers. This method yields an arterial graft with excellent mechanical and biological properties in a much shorter time period than is possible by other methods.
  • the matrices are formed into sheets.
  • the sheets can be manufactured such that the chemical or physical composition, or both, are different for each sheet.
  • endothelial or SMCs are seeded.
  • the matrix sheets are shaped into tubes.
  • the matrix sheet can be overlaid and allowed to attach to each other prior to forming tubes.
  • the sheets can be shaped individually into tubes of different sizes and then assembled into a multicellular structure.
  • culture medium can be forced through the lumen of the tube in a pulsatile fashion in addition to bathing the tube in the culture medium. This will orient the SMCs in a circumferential direction, as in a natural artery. The pulsatile flow will also cause the endothelial cells to adopt an elongate, 'cobblestone' appearance, as in a normal artery.
  • the cells on the matrices can be made to produce more matrix proteins than usual by culturing the cells in the presence of ascorbic acid. This yields a high-strength prosthesis faster than would be otherwise possible. This also leads to more rapid integration of the concentric layers once they are assembled. After the layers are sufficiently fused, the arterial analog is then packaged for sterile transfer to the operation room, where it is implanted in the patient.
  • the matrix can include (i) a glycosaminoglycan, (ii) a collagen, (iii) an integrin receptor ligand such as laminin and fibronectin, (iv) elastin, and (v) TFPI. Each of these components is described further.
  • a matrix can include between 1% and 10% glycosaminoglycan (GAG) by dry weight, and preferably between 3% and 8% GAG by dry weight, such as 4% or 7%.
  • GAG glycosaminoglycan
  • N preferred GAG is chondroitin-6-sulfate.
  • a matrix can include between 50% and 99% collagen, such as Type IV or Type I collagen.
  • the degree of crosslinking of the collagen determines the mechanical and bioresorptive properties of the matrix. Increases in the collagen/elastin ratio will decrease elasticity and, to a minor extent, decrease the resorption rate.
  • the resorption rate primarily is determined by the mean molecular weight between crosslinks. The limit for this value is a function of the GAG content. How close one comes to that limiting value is determined by the processing after precipitation. Thus, two grafts with very different compositions could have identical crosslink densities (Mc), which would yield similar resorption rates.
  • a matrix can include between about 0.0001% and 0.1 % by dry weight of the integrin receptor ligand, and preferably between 0.001% and 0.01%.
  • Preferred integrin receptor ligands are laminin and fibronectin.
  • Laminin and fibronectin are both adhesion proteins which link the matrix with SMCs via the surface integrins on those cells.
  • laminin is the integrin receptor ligand present on the matrix, the laminin causes SMCs to migrate and undergo the phenotypic shift in from the desired contractile type to the undesirable synthetic type. For some grafts, or portions of grafts, the opposite result is desired.
  • the matrix ligand is fibronectin, which causes the SMCs to remain or become contractile, and, thus, to not migrate and proliferate.
  • the composition of the matrices of the invention can be varied to control SMC phenotype.
  • TFPI can be included in the matrix in amounts to at least partially inhibit thrombus formation.
  • TFPI in amounts up to 0.5% of the matrix weight can be used, preferably between 0.00 1% and 0. 1%.
  • a matrix can also include elastin.
  • Elastin is added to the matrix to increase its compliance and to increase fracture toughness. Up to 30% by weight elastin can be used, preferably between 5 and 20%.
  • Pore size can be used alone or in combination with ligands to assist in directed migration of cells toward a desired region of the shaped mate.
  • the shaped material can be, for example, a sheet, a tube, a bifurcated tube, or tapered tube.
  • one portion such as an inner surface of a tube, has smaller pores than another surface, such as an outer surface of a tube, or vice versa.
  • the shaped material is a vascular graft, it is desirable to encourage migration of SMCs toward the outer surface or middle portion of the graft, and migration of vascular endothelial cells along the inner surface of the graft.
  • Matrices can also include other substances on the surface of the shaped polymer composition, or throughout the polymer composition.
  • examples include ligands which promote selective migration of desired cells towards or adherence to a surface, or which reduce migration or adherence of undesirable cells, such as platelets.
  • platelet activation is inhibited by the use of prostacyclin, a prostacyclin analog, or other platelet-activating factor antagonists.
  • Other targeting, repelling, or nutrient substances include VEGF, TGF-beta, or any other desired growth factor or inhibitor.
  • the three main cell types that make up an artery are SMCs, endothelial cells, and fibroblasts.
  • SMCs SMCs
  • endothelial cells SMCs
  • fibroblasts fibroblasts.
  • the cells can be collected from the patient and cultured.
  • the cells can be allogenic, coming from donated placental or umbilical tissue.
  • the cells can arise from embryonic stem cells which have become SMCs, endothelial cells, or fibroblasts (or precursors to these cells) through a cell- intrinsic program, response to exogenously-applied factors, or a combination of both.
  • the cells can be increased in number through extended culturing prior to being seeded onto the matrix.
  • SMCs, endothelial cells, and fibroblasts respond differently to matrix and adhesion proteins.
  • different regions of a graft require different proportions of cell types.
  • the amount of fibronectin and/or laminin in any region of the graft can be varied according to the needs of that region.
  • the concentrations of these proteins will vary depending on the properties required at individual radial and longitudinal positions in the graft.
  • endothelial cells eventually line the inner surface of the graft, and therefore collagen GAG/laminin is used to mimic basement membrane in this region. Small pores at the inner surface of the graft will prevent the SMCs from contacting the laminin, and thus discourage SMC migration and proliferation.
  • the medial matrix can have both fibronectin and laminin, and the relative amounts of the two adhesion proteins can vary with the length of the graft. For example, because of the problem with anastomotic hyperplasia, it is desirable to have no laminin or fibronectin at the ends of the graft. Moving towards the central portion of the graft, it can be beneficial to have higher laminin and fibronectin content in order to encourage the SMCs to continue to migrate, so that they can eventually populate the entire graft.
  • the outer portion of an artery, the adventitia, is largely populated by fibroblasts.
  • a third composition of the ECM analog can be employed in this outer region of the graft.
  • this outer fibroblast layer is critical in that the collagenous matrix of the adventitia provides much of the ultimate mechanical strength of the artery.
  • a thin layer of relatively dense collagen with fibronectin, perhaps with little GAG, can be appropriate for the outer section of the graft.
  • This outer layer must serve two functions initially; it must provide the ultimate strength to prevent rapture of the graft while other cells are migrating, and it must also provide a hospitable environment for proliferation and matrix turnover by fibroblasts.
  • the inner portion of the graft will have high laminin content and small pores.
  • the small pore size prevents the SMCs from interacting with the laminin, thus encouraging endothelialization, and discouraging migration, proliferation and synthesis by the SMCs.
  • the medial portion of the graft will have larger pores and a mixture of laminin and fibronectin, which will lead to control of the phenotype of the SMCs and also of the eventual population of the entire medial portion of the graft with SMCs of the contractile phenotype.
  • the outer portion of the graft will likely be more dense, and will have more fibronectin than the other two regions if it is needed to encourage fibroblast growth.
  • Vascular grafts The invention features prosthetic devices and methods for producing such devices for cardiovascular grafting.
  • Shapes for prosthetic devices in the cardiovascular system include valves, elbows, T-joints, tubes, branched tubes, and tubes with varying or tapering diameters.
  • Cardiovascular prostheses include small and large diameter vascular prostheses, aortic valves, venous valves, mitral valves, and prostheses used in techniques such as coronary artery bypass grafting, coronary stenting, coronary stent-grafting, transvascular shunting, transmyocardial revascularization, and endovascular grafting of aortic, peripheral, or carotid disease.
  • Cardiovascular prostheses preferably approximate the mechanical and performance properties of the natural tissue, particularly puncture-resistance, kink resistance, self-sealing, non-thrombogenicity, and infection resistance. Additional physical characteristics include suture retention, water permeability, integral water leakage, water entry pressure, circumferential tensile strength, longitudinal tensile strength, burst strength, diaphragm burst strength, probe burst strength, pressurized burst strength, strength after repeated puncture, usable length, relaxed internal diameter, pressurized internal diameter, and wall thickness. International quality control standards and safety testing procedures are known in the art and are described, for example, in ISO/DIS 7198 (ISO/TC 1501SC 2 N169), CEN/TC 28/WG 3/TF2, and the Revised A.A.M.I. Standard.
  • a small diameter vascular graft has an inner diameter between 1.0 mm and 6.0 mm, preferably between 1.5 and 4.0 mm; and a wall thickness between 0.25 mm and 3 mm, preferably between 0.5 mm. and 1.5 mm.
  • a vascular graft can have branches (e.g., a bifurcated or trifurcated graft), or tapering ends such that the diameter at one end is smaller than the diameter at another end, or have both branches and tapering portions.
  • the vascular conduit can have a variable modulus along the length, without varying the diameter.
  • bifurcated graft is between 3 and 9 inches long, preferably between 5 and 8 inches long, and has a proximal diameter of about 6 mm at the end to be attached to the descending aorta.
  • the two distal ends have diameters of about 2.5 mm and are to be attached to the coronary arteries.
  • the proximal end will stretch more than the distal ends, as the elasticity of each end should match the natural tissue (aortic and coronary arterial, respectively).
  • the proximal end of a graft is sewn to the ascending aorta.
  • a matrix tube is formed by creating an acidic dispersion of type I collagen in acetic acid at pH of ⁇ 4.2. Chondroitin-6-sulfate, also in acetic acid, is slowly added to the collagen suspension with mixing. The precipitate is then centrifuged to concentrate, and the concentrated slurry is injected into a mold, which defines an annular space of 2.5 mm. ID and 3.0 mm OD. The mold is submerged in a bath of liquid nitrogen, and rapidly frozen. The mold is then vented, and placed in a freeze-drying chamber. The aqueous solution of acetic acid is sublimed, and the collagen/GAG matrix is stabilized by the formation of crosslinks by a dehydration reaction.
  • the tube is then cultured in DMEM with 10%> fetal bovine serum and 50 ⁇ g/ml sodium ascorbate in a CO 2 incubator, 92%o air, 8% CO 2 at 37° C. After 24 hours, the tube is connected to a pulsatile apparatus, which forces the same culture medium through the lumen of the tube with slowly increasing force. After one week, this tube is placed within a series of slightly larger, similarly constructed tubes, and this assembly is then returned to the incubator and connected to the pulsatile apparatus for further culturing of two weeks. A similar layer of matrix seeded with fibroblasts is added externally, and after one more week of culture, the graft is ready for implantation.
  • a flat sheet matrix is made by pouring the slurry onto the steel sheet, and spreading the slurry to a uniform thickness of 0.005 inches. This sheet is then placed on the shelf in the freeze dryer, and rapidly frozen. Subsequent steps are as in Example 1, until SMCs are seeded onto the sheet at a density of

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Abstract

L'invention concerne une technique de production de prothèse de vaisseau sanguin au moyen de plusieurs matrices contenant un copolymère de collagène lyophilisé, précipité à l'acide, et un glycosaminoglycane. La matrice présente ainsi moins de structure quaternaire que le collagène natif. Par conséquent, la matrice, in vivo, active des plaquettes dans une moindre mesure que le collagène natif.
PCT/US1999/029489 1998-12-16 1999-12-13 Matrices multiples pour tissus modifies WO2000035372A2 (fr)

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AU24798/00A AU2479800A (en) 1998-12-16 1999-12-13 Multiple matrices for engineered tissues

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US21297398A 1998-12-16 1998-12-16
US09/212,973 1998-12-16

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WO2000035372A2 true WO2000035372A2 (fr) 2000-06-22
WO2000035372A3 WO2000035372A3 (fr) 2001-12-13

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Cited By (10)

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EP1609492A1 (fr) * 2003-03-31 2005-12-28 Teijin Limited Article en elastine moule et son procede de production
US7053051B2 (en) 2003-10-28 2006-05-30 Medtronic, Inc. Methods of preparing crosslinked materials and bioprosthetic devices
WO2006099016A2 (fr) * 2005-03-09 2006-09-21 Providence Health System Greffe composite
WO2007138269A2 (fr) * 2006-05-25 2007-12-06 Intercytex Limited Réparation tissulaire
WO2009047347A1 (fr) * 2007-10-11 2009-04-16 Inserm (Institut National De Sante Et De La Recherche Medicale) Procédé de préparation d'un échafaudage poreux pour l'ingénierie tissulaire
WO2011123665A1 (fr) * 2010-03-31 2011-10-06 Biolife Solutions, Inc. Procédés et compositions pour le traitement des brûlures et des blessures
US9051550B2 (en) 2009-04-09 2015-06-09 Arizona Board Of Regents, On Behalf Of The University Of Arizona Cellular seeding and co-culture of a three dimensional fibroblast construct
CN108404219A (zh) * 2018-02-11 2018-08-17 华中科技大学 一种基于冷冻铸造技术的小口径人工血管及其制备方法
CN115998953A (zh) * 2023-02-07 2023-04-25 苏州大学 一种双重仿生取向的人工小血管及其制备方法
US11890395B2 (en) 2017-06-16 2024-02-06 Avery Therapeutics, Inc. Three dimensional tissue compositions and methods of use

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US5336256A (en) * 1986-04-17 1994-08-09 Uab Research Foundation Elastomeric polypeptides as vascular prosthetic materials
US5716394A (en) * 1994-04-29 1998-02-10 W. L. Gore & Associates, Inc. Blood contact surfaces using extracellular matrix synthesized in vitro
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