WO2011115612A1 - Tissu collagène mince pour des applications de dispositifs médicaux - Google Patents

Tissu collagène mince pour des applications de dispositifs médicaux Download PDF

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Publication number
WO2011115612A1
WO2011115612A1 PCT/US2010/027341 US2010027341W WO2011115612A1 WO 2011115612 A1 WO2011115612 A1 WO 2011115612A1 US 2010027341 W US2010027341 W US 2010027341W WO 2011115612 A1 WO2011115612 A1 WO 2011115612A1
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tissue
tissue specimen
cross
vapor
specimen
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PCT/US2010/027341
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English (en)
Inventor
Kemal Schankereli
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Peridyne Medical, Llc
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Priority to PCT/US2010/027341 priority Critical patent/WO2011115612A1/fr
Priority to EP10848096.3A priority patent/EP2550029A4/fr
Priority to US13/097,837 priority patent/US8137411B2/en
Publication of WO2011115612A1 publication Critical patent/WO2011115612A1/fr

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    • 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
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/005—Ingredients of undetermined constitution or reaction products thereof
    • 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
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/005—Ingredients of undetermined constitution or reaction products thereof
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/40—Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking

Definitions

  • This invention relates to bioprosthetic transcatheter valve and implant material, processes for preparing bioprosthetic transcatheter valve and implant material from animal tissue, and methods of use thereof. Specifically, the invention relates to the preparation of animal tissue, in which the tissue is cleaned, chemically cross-linked using both vaporized and liquid cross-linking agents, and compressed, resulting in an improved bioprosthetic or implantable material that is substantially non-antigenic, non-thrombogenic, resistant to calcification, durable, and thin enough to be used in applications requiring extremely small valves or implants.
  • animal tissue specimens for surgical use were prepared by first harvesting the selected tissue from beef cattle or other meat supplying animals at the slaughter house. The harvested tissues were then transported to a laboratory where the material was cleaned by mechanically stripping away fat tissue and other undesired components from the harvested specimen material. Next, the cleaned tissue specimen was subjected to a "wet" cross-linking operation in which it is soaked for a predetermined time in a glutaraldehyde solution and finally was dehydrated in an alcohol solution. Subsequently, the sample was thoroughly rinsed to remove traces of the ethyl alcohol and glutaraldehyde and then was packaged in a vial containing a one percent propylene oxide solution as a sterilant.
  • U.S. Patent No. 6,468,313 to Bio-Vascular, Inc. discloses an implant material in the form of a natural animal tissue cross-linked into a pre-formed shape, the tissue being adapted to substantially retain its shape when implanted into a body,
  • U.S. Patent No. 5,507,810 to Osteotech, Inc. discloses fibrous connective tissue for surgical implantation is made substantially antigen-free by contact with one or more extraction agents.
  • U.S. Patent No. 4,681,588 to Ketharanathan discloses material for use in a biological environment is produced by subjecting a sheet of parietal pleura to glutaraldehyde tanning.
  • U.S. Patent No. 4,399,123 to Oliver discloses a fibrous tissue preparation suitable for homo or heterotransplantation obtained by treating mammalian fibrous tissue with a proteolytic enzyme followed, if desired, by further treatment with a carbohydrate splitting enzyme.
  • tissue thickness too large for surgical use in applications requiring a smaller valve or implant.
  • Tissue samples of this thickness can limit the use of smaller gauge catheters in delivering the tissue sample to the area of the human body in which surgery is to be performed, or limit the types of patients that may be treated to large patients only.
  • bovine pericardial tissue used in the products Duraguard®, Peri- Guard®, and Vascu-Guard®, all products currently used in surgical procedures, are marketed as being harvested generally from cattle less than 30 months old.
  • pericardial tissue from older animals is thicker than younger animals, and thus limits the thinness that can be achieved.
  • biocompatible animal tissues may disclose thin tissues, however, these tissues are used only as biocompatible "jackets" or sleeves for implantable stents. Accordingly, these tissues do not have the biomechanical, e.g. strength and durability, necessary for the construction of bioprosthetic transcatheter valves, or implants.
  • 5,554,185 to Block discloses an inflatable prosthetic cardiovascular valve which is constructed so as to be initially deployable in a deflated "collapsed" configuration wherein the valve may be passed through the lumen of a cardiovascular catheter and subsequently inflated to an "operative" configuration so as to perform its intended valving function at its intended site of implantation within the cardiovascular system.
  • a covered stent assembly comprising a tubular, expandable stent having a metallic framework covered with a cylinder of biocompatible, non-thrombogenic expandable material, such as heterologous tissue.
  • U.S. Patent No. 6,440,164 to Scimed Life Systems, Inc. discloses a prosthetic valve for implantation within a fluid conducting lumen within a body includes an elongate generally cylindrical radially collapsible valve body scaffold defining a fluid passageway therethrough for retentive positioning within the lumen.
  • a process of preparing a bioprosthetic or implant tissue material for use in surgical procedures on humans comprising the steps of: (a) vapor cross-linking a pre-digested compressed tissue specimen by exposing the tissue specimen to a vapor of a cross-linking agent selected from the group consisting of aldehydes, epoxides, isocyanates, carbodiimides, isothiocyanates, glycidalethers, and acyl azides; and (b) chemically cross-linking the vapor-cross-linked tissue specimen by exposing the vapor- crosslinked tissue specimen to an aqueous crosslinking bath for a predetermined time, such crosslinking bath containing a liquid phase of a crosslinking agent selected from the group consisting of aldehydes, epoxides, isocyanates, carbodiimides, isothiocyanates,
  • tissue material prepared according to the process herein.
  • the tissue specimen is harvested from a porcine, ovine or bovine animal.
  • the predetermined tissue specimen is taken from a bovine animal 30 days old or less.
  • the tissue specimen is taken from an animal that is not more than about 10 days old, and in a preferred embodiment about 5 days old.
  • the harvested tissue specimen comprises a collagen-based tissue selected from the group consisting of pericardium, dura mater, heart valves, blood vessels, fascia, ligaments, tendons, and pleura tissue.
  • the tissue specimen is subjected to chemical dehydration/ compression and mechanical compression before cross-linking, and/or the pre-digested tissue specimen is provided by digesting a harvested, cleaned pericardial tissue in a solution containing a surfactant.
  • the surfactant is 1 % sodium laurel sulfate.
  • the chemical dehydration/compression comprises subjecting the tissue specimen to hyperosmotic salt solution.
  • the mechanical compression may preferably comprise subjecting the tissue specimen to a roller apparatus capable of compressing the tissue specimen to a thickness ranging from about 0.003' (0.0762 mm) to about 0.010" (0.254 mm).
  • a process of preparing animal- derived collagen tissue material for use in surgical procedures on humans comprising the steps of: (a) vapor cross-linking a pre-digested collagen tissue specimen by exposing the tissue specimen to a formaldehyde vapor phase; and (b) subjecting the vapor-crosslinked collagen tissue specimen to an aqueous glutaraldehyde bath for a predetermined time,
  • tissue for bioprosthetic or implant use in the human body prepared according to the process herein.
  • a process of preparing a bioprosthetic transcatheter valve material for use in surgical procedures on humans comprising the steps of: (a) vapor cross-linking a pre-digested compressed bovine pericardium tissue specimen by exposing the tissue specimen to a formaldehyde vapor phase; and (b) subjecting the vapor-crosslinked tissue specimen to an aqueous glutaraldehyde bath for a predetermined time.
  • the pre-digested tissue specimen is provided by digesting a harvested, cleaned bovine pericardial tissue in a solution containing a surfactant.
  • the surfactant is 1 % sodium laurel sulfate.
  • the chemical dehydration/compression comprises subjecting the tissue specimen to hyperosmotic salt solution and wherein the mechanical compression comprises subjecting the tissue specimen to a roller apparatus capable of compressing the tissue specimen to a thickness ranging from about 0.003' (0.0762 mm) to about 0.010" (0.254 mm),
  • a process of converting pericardial tissue specimen taken from a bovine animal not more than 30 days old to a non- antigenic, non-thrombogenic, calcification-resistant implantable material for use in surgical procedures on humans wherein the pericardial tissue specimen is cleaned, digested by surfactant, compressed to approximately 0.003" in thickness, vapor cross-linked by exposing the tissue to a vapor-phase cross-linking agent selected from the group consisting of aldehydes, epoxides, isocyanates, carbodiimides, isothiocyanates, glycidalethers, and acyl azides , and liquid-phase cross-linked by immersing the tissue in a liquid cross-linking agent selected from the group consisting of aldehydes, epoxides, isocyanates, carbodiimides, isothiocyanates, glycidalethers, and acyl azides.
  • a liquid cross-linking agent selected from the group consisting of alde
  • a process of converting pericardial tissue specimen taken from a bovine animal not more than 30 days old to a non- antigenic, non-thrombogenic, calcification-resistant implantable material for use in surgical procedures on humans wherein the pericardial tissue specimen is cleaned, digested by surfactant, compressed to approximately 0.003" in thickness, vapor cross-linked by exposing the tissue to formaldehyde vapor for approximately 10 minutes, and further cross-linked by immersing in a glutaraldehyde solution for at least 24 hours.
  • tissue material as claimed herein in dehydrated state for dry packaging.
  • tissue material as claimed for use wherein such material is trimmed and/or configured to an appropriate shape as replacement tissue for any of the following surgical purposes: stented or stentless pericardial valve replacement, stented or stentless pulmonic valve replacement, transcatheter valvulare prosthesis, aortic bioprosthesis/valve replacement or repair, annuloplasty rings, bariatric surgery, dural patching, enucleation wraps, gastric banding, herniation repair, lung surgery e.g. lung volume reduction, peripheral arterial or venous valve replacement, pericardial patching, rotator cuff repair, uretheral slings, valve repair, vascular patching, valve conduit insertion, or arterial conduit insertion.
  • the tissue material as claimed in any of claims comprises a very thin, durable material that ranges from about 0.002" (0.0508 mm) to about 0.020" (0.508 mm) as the average cross-sectional thickness.
  • the focus is on being able to create materials, tissues, and devices that can access applications where a very thin, very durable material is needed.
  • the focus may not necessarily be on the thinness of the material compared to the 0.002" (0.0508 mm) materials; however, the durability, and the ability to form materials, tissues and devices from a wider range of starting materials and sources.
  • the present invention ranges from about 0.002" (0.0508 mm) and about 0.010" (0.254 mm) in thickness. In another preferred embodiment, the present invention ranges from about 0.002" (0.0508 mm) and about 0.005" (0.127 mm) in thickness. In one preferred embodiment, the present invention averages approximately 0.003" (0.0762 mm) in thickness.
  • tissue material as claimed wherein the tissue material is provided in sterile form and is adapted to be implanted into a body and attached in place.
  • the material may be configured in a spherical form to wrap an orbital implant, or configured to form leaflets in a prosthetic transcatheter valve.
  • a stent assembly for maintaining the patency of a body lumen comprising an expandable stent with or without a biocompatible jacket, and a prosthetic transcatheter valve made from the inventive tissue material disposed therein to function as a valve replacement.
  • a prosthetic transcatheter valve made from the tissue material configured for delivery within an intravenous catheter measuring 18 or less in french gauge, or even within a gauge 14 or less french gauge.
  • the harvested tissue specimen comprises a collagen-based tissue selected from the group consisting of pericardium, dura mater, heart valves, blood vessels, fascia, ligaments, tendons, and pleura tissue,
  • Methods of use include using the tissue configured to an appropriate shape as replacement tissue for any of the following surgical purposes: stented or stentless pericardial valve replacement, stented or stentless pulmonic valve replacement, transcatheter valvulare prosthesis, aortic bioprosthesis/valve replacement or repair, annuloplasty rings, bariatric surgery, dural patching, enucleation wraps, gastric banding, herniation repair, lung surgery e.g. lung volume reduction, peripheral arterial or venous valve replacement, pericardial patching, rotator cuff repair, uretheral slings, valve repair, vascular patching, valve conduit insertion, or arterial conduit insertion.
  • FIGURE 1 is a flow chart evidencing the steps of the process claimed herein.
  • “Bobby calf as used herein means a male or a female calf of a dairy cow that is slaughtered before weaning, usually not more than 30 days from birth.
  • "Collagen” is the most abundant protein in all animal tissue, and is the primary component of connective tissue. Collagen consists of a protein with three polypeptide chains, each containing approximately 1000 amino acids and having at least one strand of repeating amino acide sequence Gly-X-Y, where X and Y can be any amino acid but usually are proline and hydroxyproline, respectively. Collagen assembles into different supramolecular structures and has exceptional functional diversity.
  • Natural collagen sources contemplated as within the scope of the present invention include porcine, ovine, or bovine animals 30 days old or less.
  • the tissue specimen is taken from an porcine, ovine, or bovine animal that is not more than about 10 days old, and in a preferred embodiment about 5 days old.
  • Preferred embodiments include specific tissues, wherein the harvested tissue specimen comprises a collagen-based tissue selected from the group consisting of pericardium, dura mater, heart valves, blood vessels, fascia, ligaments, tendons, and pleura tissue.
  • Crosslinks are bonds that link one polymer chain to another. They can be covalent bonds or ionic bonds.
  • Polymer chains can refer to synthetic polymers or natural polymers, including proteins such as collagen. Examples of some common crosslinkers are the dimethyl suberimidate, formaldehyde and glutaraldehyde. Each of these crosslinkers induces nucleophilic attack of the amino group of lysine and subsequent covalent bonding via the crosslinker.
  • Pyridyl encompasses a set of functional groups in the pyridine derivative chemical class with the common structure C5N1. A pyridyl group will bond an aldehyde compound to a collagen protein through the cross-linking process.
  • surfactants are wetting agents that lower the surface tension of a liquid, allowing easier spreading, and lower the interfacial tension between two liquids.
  • the term surfactant is a blend of "surface active agent”.
  • Surfactants are usuallyorganic compounds that are amphiphilic, meaning they contain both hydrophobic groups (their "tails”) and hydrophilic groups (their "heads”). Therefore, they are soluble in both organic solvents and water.
  • Surfactants are also often classified into four primary groups: anionic, cationic, non-ionic, and zwitterionic (dual charge).
  • a non- limiting preferred surfactant contemplated herein is sodium laurel sulfate, although various other surfactants known to a person of ordinary skill in the art are also contemplated as within the scope of the invention.
  • BC pericardial tissue is known to be extremely thin, typically in the range of 0.005" to
  • Pericardial tissue from such animals also has a very high natural collagen content, providing the tissue both high strength and a variety of
  • biocompatibility benefits including low antigenicity, thrombogenicity and calcification potential; high endothelialization; high suture retention; and high bursting strengths. As the animal ages, the natural collagen content of its tissue decreases, and these biocompatibility benefits also decrease.
  • Formation of a flat sheet of tissue allows for later trimming and manipulation to form shapes specifically tailored to individual surgeries.
  • a thinner sample means a lower gauge catheter, and easier intravenous or percutaneous insertion, and thus the ability to treat a higher percentage of the patient population requiring such an intervention.
  • BC pericardial tissue that has been surfactant treated and attained a very high collagen content becomes ideally suited to compression to further thin the tissue sample.
  • BC pericardial tissue of the present invention may be about at least 95% to about at least 99% collagen. In a non-limiting preferred embodiment, the collagen content is about 99%.
  • Collagen-enhanced and partially dehydrated BC pericardial tissue may be further thinned by means of mechanical compression, and the high bursting strength of such tissue will prevent tearing or weakening of the tissue in the process.
  • a preferred method of mechanically compressing a tissue sample is to place it between two sheets of polyethylene film, each larger in surface area than the tissue sample, and covering the entire upper and lower surfaces of the tissue sample, and placing the sample and film into one of (i) a wringer apparatus comprising upper and lower electrically or manually driven rollers, with the gap between such rollers set at approximately 0.002" to 0.020" using a feeler gauge, wherein the tissue sample and film are fed through the apparatus, or (ii) a press apparatus comprising upper and lower plates, wherein the plates are compressed via manual or electrically driven turning mechanism until reaching a gap set at approximately 0.002" to 0.020" using a feeler gauge, wherein the tissue sample and film are fed through the apparatus.
  • BC pericardial tissue subjected to dehydration compression and mechanical compression as detailed herein is known to attain a tissue thickness of approximately 0.003" (0.0762 mm), making BC tissue at least 40% thinner than bovine tissue currently in use on the surgical market, without compromising the strength of the tissue, and therefore is highly desirable as a material for surgical implants and grafts. It is contemplated as within the scope of the invention that tissue thicknesses of about 0.002" (0.0508 mm) to about 0.007" (0.1778 mm), without limitation, may be manufactured according to the inventive process.
  • Cross-linking is a process well known in the art for improving the biocompatibility of collagen in a piece of tissue prior to surgical implantation. Processes for collagen cross-linking currently known in the art have been limited to the "tanning", or submersion of a tissue sample in a wet bath containing a cross-linking agent, such as an aldehyde, as a solute.
  • a cross-linking agent such as an aldehyde
  • An ideal primary method for cross-linking collagen in tissue comprises placing such tissue onto a pin frame such that the edges are held firmly in place.
  • the frame and tissue sample are then placed into a chamber equipped with each of an inlet and outlet port for submission to a "vapor cross-linking" process.
  • the inlet port is attached to a stoppered flask comprising each of an inlet and outlet port and containing a bolus of polyoxymethylene, which flask is gently heated as air flow is simultaneously initiated from the flask into the chamber containing the tissue sample, thereby producing formaldehyde vapors which flood the chamber for a period of 10 minutes, after which time such vapors are evacuated from the chamber and the pin frame and tissue sample are removed intact therefrom,
  • tissue material After completion of the vapor cross- linking, the tissue material is subjected to a liquid glutaraldehyde bath.
  • Glutaraldehyde provides a further cross-linking that results in additional cross-links that formaldehyde cannot achieve.
  • the presence of two aldehyde groups for cross-linking and the ability to be cross link over a distance since glutaraldehyde has a three-carbon chain connecting the two carbonyl moieties further strengthens the tissue material.
  • the pin frame and tissue sample are then transferred into an aqueous bath containing 1% 0.01M phosphate buffered glutaraldehyde and 10% isopropyl alcohol at a temperature of approximately 40 degrees C, and gently stirred for a period of not less than 24 hours, although variations of glutaraldehyde cross-linking are well known in the art and are considered within the scope of this step of the present invention.
  • the process of creating stable, non-reactive aromatics on the exposed surface of the collagen is believed to progress by nucleophilic attack by formaldehyde on the carbonyl of the glutaraldehyde-linked amine of the lysine, histidine, and/or arginine, improving the stability of the molecular structure of the sample and reducing the antigenicity of the sample compared to a sample treated with glutaraldehyde alone.
  • Aredcued inflammatory response and lower degree of capsule formation provides a distinct advantage.
  • the tissue sample After the completion of wet cross-linking, the tissue sample, still attached to the pin frame, is sterilized by transferring it to an aqueous bath consisting essentially of a 2% buffered glutaraldehyde solution containing 10% isopropyl alcohol, and is soaked therein at 42 degrees C for a period of no less than 24 hours. Upon completion of sterilization, the tissue sample is removed from the pin frame.
  • an aqueous bath consisting essentially of a 2% buffered glutaraldehyde solution containing 10% isopropyl alcohol
  • tissue sample is packaged for transport in a container together with a sterilizing 0.65%, 0.01M phosphate buffered glutaraldehyde solution, in which solution the tissue sample may either float freely or be held stationary by attachment to a mylar film, [para 76] Upon removal from packaging, the tissue sample may be trimmed, sutured or otherwise manipulated to form the size and shape necessary for any implantation surgery for which such tissue would be appropriate.
  • the tissue would be trimmed to fit for any necessary vascular or pericardial patching.
  • the tissue would be sutured to form a cylinder to cover a mesh stent.
  • the tissue would be cut into a leaflet shape for prosthetic transplantation into a mitral valve.
  • a strip of tissue would be cut and sutured into an annular shape for transplantation into a mitral valve.
  • Methods of use include using the tissue configured to an appropriate shape as replacement tissue for any of the following surgical purposes: stented or stentless pericardial valve replacement, stented or stentless pulmonic valve replacement, transcatheter valvulare prosthesis, aortic bioprosthesis/valve replacement or repair, annuloplasty rings, bariatric surgery, dural patching, enucleation wraps, gastric banding, herniation repair, lung surgery e.g. lung volume reduction, peripheral arterial or venous valve replacement, pericardial patching, rotator cuff repair, uretheral slings, valve repair, vascular patching, valve conduit insertion, or arterial conduit insertion,
  • FIGURE 1 shows a flow chart evidencing the steps and materials used in the BC pericardial tissue treatment process.
  • EXAMPLE 1 In this example, the pericardial sac from a bobby calf is washed with isotonic saline at room temperature, held in saline for processing, then inspected for acceptability and split into a flat sheet approximately 7x9cm in dimension. The washed sample is then subjected to "digestion", in which a detergent extraction to de -nucleate the tissue and remove non-collagenous proteins, preferably using a 1% sodium lauryl sulfate solution (SDS). The sample is held in this solution and gently stirred for up to 24 hours. Histological review of the tissue will indicate that the tissue has been de-nucleated and that non-collagenous proteins have been almost entirely removed. Gross observation of the tissue will indicate a color change from the original tan/white color to pure white. Digestion has the side effect of swelling the tissue.
  • Digestion has the side effect of swelling the tissue.
  • the swollen tissue is washed again in isotonic saline until the SDS is removed. This process also reverses some of the swelling from digestion.
  • the tissue is further "chemically compressed” by dehydration by placing it in a hyperosmotic NaCl solution for a period of 30 minutes, during which time the sample is gently stirred. Upon removal, the sample is placed between two sheets of polyethylene film and subjected to mechanical compression, either using mechanical rollers, a press, or similar mechanism, resulting in a flattened sample approximately 0.003" in thickness. The polymer films are then removed and the sample is momentarily held on a dry surface.
  • the compressed tissue is subjected to an initial cross-linking phase, in which the tissue is first placed onto a pin fame with all edges of the tissue held in place.
  • the tissue/ frame is then placed into a box or similar chamber with an outlet port, and an inlet port.
  • the inlet port is attached via a tube to an outlet port emanating from an Erlenmeyer flask, which flask is also equipped with a stopper and an inlet port, and contains a bolus of
  • the flask is gently heated, drawing air from the inlet port, releasing the cross-linking agent formaldehyde vapor, and pushing the vapor out the outlet port and into the chamber containing the tissue sample.
  • the chamber is flooded with vapor for approximately 10 minutes, after which the chamber is evacuated of vapor and the tissue/ frame is removed.
  • the tissue/frame is then transferred to an aqueous bath containing 1%, 0.01M phosphate buffered glutaraldehyde and 10% isopropyl alcohol for a second phase of cross- linking.
  • the glutaraldehyde solution will have been prepared according to the teaching of U.S. Patent 7,303,757.
  • the bath will be maintained at approximately 40 degrees C, and the submerged tissue will be gently stirred therein for no less than 24 hours. At such time, the bath solution will be discarded and replaced, and gentle stirring will resume for a second period of no less than 24 hours.
  • the tissue is removed from the pin frame and sterilized by immersion for a minimum of 24 hours in a 2% buffered glutaraldehyde solution containing 10% isopropyl alcohol, maintained at approximately 42 degrees C. Upon removal from this solution, the sterile tissue is packed for shipment into a 0.65%, 0.01M phosphate buffered glutaraldehyde solution, in which the sample may either float freely, or be attached to a mylar film and held stationary within the container,
  • EXAMPLE 2 In this example, pericardial tissue, valve tissue or tendon tissue from one of a bovine, porcine or ovine animal is washed with isotonic saline at room temperature, held in saline for processing, then inspected for acceptability and split into a flat sheet. The washed sample is then subjected to "digestion", in which a detergent extraction to de-nucleate the tissue and remove non-collagenous proteins, preferably using a solution in which the solute is sodium lauryl sulfate (SDS) or another surfactant. The sample is held in this solution and gently stirred for more than 24 hours.
  • SDS sodium lauryl sulfate
  • the swollen tissue is washed again in isotonic saline until the surfactant is removed. This process also reverses some of the swelling from digestion.
  • the tissue is further "chemically compressed" by dehydration by placing it in a hyperosmotic solution for a period of 30 minutes, during which time the sample is gently stirred. Upon removal, the sample is placed between two sheets of polyethylene film and subjected to mechanical compression, either using rollers, weights, a press, a vacuum or or similar mechanism, resulting in a flattened sample between about 0.003" (0.0762 mm) and about 0.007" ( 0.1778 mm) in thickness. The polymer films are then removed and the sample is momentarily held on a dry surface.
  • the compressed tissue is subjected to an initial cross-linking phase, in which the tissue is first placed onto a pin fame with all edges of the tissue held in place.
  • the tissue/ frame is then placed into a box or similar chamber with an outlet port, and an inlet port.
  • the inlet port is attached via a tube to an outlet port emanating from an Erlenmeyer flask, which flask is also equipped with a stopper and an inlet port, and contains a bolus of polyoxymethylene.
  • the flask is gently heated, drawing air from the inlet port, releasing the cross-linking agent formaldehyde vapor, and pushing the vapor out the outlet port and into the chamber containing the tissue sample.
  • the chamber is flooded with vapor for approximately 10 minutes, after which the chamber is evacuated of vapor and the tissue/ frame is removed.
  • the tissue/frame is then transferred to an aqueous bath containing between 0.1% - 5.0%, 0.01M phosphate buffered glutaraldehyde and 10% isopropyl alcohol for a second phase of cross-linking.
  • the glutaraldehyde solution will have been prepared according to the teaching of U.S. Patent 7,303,757, or any functionally similar method known to persons of ordinary skill in the art.
  • the bath will be maintained at approximately 40 degrees C, and the submerged tissue will be gently stirred therein for no less than 24 hours. At such time, the bath solution will be discarded and replaced, and gentle stirring will resume for a second period of no less than 24 hours.
  • the tissue is removed from the pin frame and sterilized by immersion for a minimum of 24 hours in a solution containing between 1% - 5% buffered glutaraldehyde and 10% isopropyl alcohol, maintained at approximately 42 degrees C. Upon removal from this solution, the sterile tissue is packed for shipment into a 0.65%, 0.01M phosphate buffered glutaraldehyde solution, in which the sample may either float freely, or be attached to a mylar film and held stationary within the container.

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  • Prostheses (AREA)

Abstract

La présente invention porte sur des procédés de préparation d'un matériau de greffe hétérogène à partir d'un tissu animal. De manière spécifique, l'invention porte sur la préparation d'un tissu animal, le tissu étant nettoyé et réticulé chimiquement à l'aide à la fois d'agents de réticulation vaporisés et d'agents de réticulation liquides, conduisant à des propriétés physiques améliorées, telles qu'un tissu mince et une antigénicité réduite, permettant ainsi respectivement d'accroître la facilité de pose du tissu pendant une chirurgie et de diminuer le risque de complication post-chirurgicale.
PCT/US2010/027341 2010-03-15 2010-03-15 Tissu collagène mince pour des applications de dispositifs médicaux WO2011115612A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
PCT/US2010/027341 WO2011115612A1 (fr) 2010-03-15 2010-03-15 Tissu collagène mince pour des applications de dispositifs médicaux
EP10848096.3A EP2550029A4 (fr) 2010-03-15 2010-03-15 Tissu collagène mince pour des applications de dispositifs médicaux
US13/097,837 US8137411B2 (en) 2010-03-15 2011-04-29 Thin collagen tissue for medical device applications

Applications Claiming Priority (1)

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PCT/US2010/027341 WO2011115612A1 (fr) 2010-03-15 2010-03-15 Tissu collagène mince pour des applications de dispositifs médicaux

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EP3185817A4 (fr) * 2014-08-27 2018-07-18 Amnis Therapeutics Ltd. Dispositifs implantables comprenant des membranes de greffe
CN113499478A (zh) * 2021-07-07 2021-10-15 成都纽脉生物科技有限公司 一种生物组织材料的处理方法

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US4902289A (en) * 1982-04-19 1990-02-20 Massachusetts Institute Of Technology Multilayer bioreplaceable blood vessel prosthesis
US5197977A (en) * 1984-01-30 1993-03-30 Meadox Medicals, Inc. Drug delivery collagen-impregnated synthetic vascular graft
US5037377A (en) * 1984-11-28 1991-08-06 Medtronic, Inc. Means for improving biocompatibility of implants, particularly of vascular grafts
US5104405A (en) * 1991-02-21 1992-04-14 The University Of Southern California Process for improving the biostability of tissue implant devices and bioprosthetic implants so produced
US20060253192A1 (en) * 2005-03-11 2006-11-09 Wake Forest University Health Sciences Production of tissue engineered heart valves

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3185817A4 (fr) * 2014-08-27 2018-07-18 Amnis Therapeutics Ltd. Dispositifs implantables comprenant des membranes de greffe
CN113499478A (zh) * 2021-07-07 2021-10-15 成都纽脉生物科技有限公司 一种生物组织材料的处理方法

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Publication number Publication date
EP2550029A1 (fr) 2013-01-30
EP2550029A4 (fr) 2014-06-18

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