WO2011028977A1 - Membranes de collagène reconstitué à haute résistance et rigidité élevées pour implantation biomédicale - Google Patents

Membranes de collagène reconstitué à haute résistance et rigidité élevées pour implantation biomédicale Download PDF

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Publication number
WO2011028977A1
WO2011028977A1 PCT/US2010/047772 US2010047772W WO2011028977A1 WO 2011028977 A1 WO2011028977 A1 WO 2011028977A1 US 2010047772 W US2010047772 W US 2010047772W WO 2011028977 A1 WO2011028977 A1 WO 2011028977A1
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WO
WIPO (PCT)
Prior art keywords
collagen
membrane
membranes
stiffness
water
Prior art date
Application number
PCT/US2010/047772
Other languages
English (en)
Inventor
David Cheung
Original Assignee
David Cheung
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
Application filed by David Cheung filed Critical David Cheung
Priority to CA2773165A priority Critical patent/CA2773165A1/fr
Priority to EP10814543A priority patent/EP2473134A4/fr
Publication of WO2011028977A1 publication Critical patent/WO2011028977A1/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
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24—Collagen
    • 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
    • A61L27/3683—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 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
    • 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
    • A61L27/56—Porous materials, e.g. foams or sponges
    • 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
    • A61F2/062—Apparatus for the production of blood vessels made from natural tissue or with layers of living cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/40—Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking

Definitions

  • Collagen molecules are present in virtually all animals. Collagen for medical implants is most often derived as a natural protein from animal sources, typically cow, pigs, horses or even cadaveric human tissue. Collagen composes approximately 35% of vertebrates by weight. Therefore, it is an abundantly available for use as allografts or xenografts in medical devices.
  • the ends of the collagen molecules contain a telopeptide which is immunogenic and can initiate an inflammatory response.
  • other components e.g., structural proteins and cells
  • the transplant tissue can initiate significant inflammatory responses, causing rejection and the failure to repair and regenerate.
  • Collagen membranes are conventionally manufactured by one of two processes: transplanting of connective tissue or reconstituted, purified collagen. Tissue directly obtained or transplanted from the donor maintains the complex composite nature of the connective tissue. Although these membranes principally contain collagen, they have other components, such as elastin which provides some of the strength, toughness and stiffness. They may also contain remnant cells and other immunogenic molecules. Theses biomaterials be extensively processed and cross-linked to further increase their strength and stability. These biomaterials are not highly purified. Consequently, they may contain immunogenic components that cause a tissue reaction in patients.
  • Sheets or membranes containing high concentrations of collagen are currently used by reconstructive surgeons as implantable medical devices. They serve as either barriers or trellis for a multitude of indications, including tissue repair and tissue regeneration. For many of these indications, collagen membranes must have significant biomechanical strength and stiffness.
  • Collagen membranes can be manufactured by a variety of methods. Transplanted connective tissues serve as membranes with high strength and high stiffness, but these membranes can initiate an inflammatory reaction because they are immunogenic. In addition, they are expensive and difficult to manufacture into precise shapes and dimensions. To decrease the immunogenicity and to increase the manufacturing efficiency, collagen can be reconstituted to its primary molecular form. When the collagen is purified by conventional, contemporary methods, the resulting membranes lack strength and stiffness.
  • Collagen implants typically are made of highly porous, reconstituted bovine (i.e., cow) collagen. These collagen implants are commercially sold to surgeons as rectilinear sheets with uniform thicknesses and porosity. Their low density, high porosity makes these collagen membranes supple and conformable. However, for the collagen membrane to function effectively as a containment device, it is a requirement that the membrane exhibit an adequate degree of stiffness. Unfortunately conventional collagen membranes have inadequate tensile strength and stiffness for many surgical applications, particularly after wetting with saline or blood.
  • the present invention relates to a process for producing collagen membranes for biomedical implantation which is capable of producing implantable collagen membranes with high strength and high stiffness in a variety of shapes and sizes by casting a solution of reconstituted collagen against a membrane, lyophilizing the membrane to foam, applying an alcohol/water solution, and air drying. Appropriate adjustments in the composition of the formulation of alcohol/water solution, the method for applying the solution, the air drying time and temperature allow the operator to control the mechanical properties and porosity of resulting collagen membranes to adapt them for specific applications.
  • the collagen membranes produced by the method of the invention may be used by reconstructive surgeons to replace or help repair torn ligament, tendons or fascia.
  • Collagen is a helical trimer, composed of monomers each containing approximately 1000 amino acids. The triple helix is bundled into fibrils which are bundled into fibers. This complex provides strength and stiffness to tissues. It also serves as a matrix or substructure for tissue formation. Thus collagen is inherently an excellent biomaterial for use by reconstructive surgeons to regenerate tissues.
  • a biocompatible and resorbable membrane For many bone reconstructive indications, a biocompatible and resorbable membrane is desirable. These membranes or sheets serve four possible functions. First, they act as a trellis for tissue regeneration. Second, the function as a barrier for separating tissues. Third, they serve as a structural biomaterial for containing biomaterials. Fourth, collagen membranes can also be used for load bearing, typically in tension.
  • Trellises of porous biomaterials serve as a framework on which and through which tissue grow. Most tissues proliferate only by attaching to a structure or matrix. Cells then multiply and expand on preexisting cells, extra-cellular matrix or biomaterials. Therefore, these matrices must have porosity. However, porosity generally decreases strength, typically non-linearly such that a small amount of porosity disproportionally decreases mechanical properties.
  • the optimal porosity has been characterized in the musculoskeletal, field, for various principal regenerative tissues. For neovascular tissue (i.e., new blood vessels), pore diameters must be larger than 20 micrometers. For osteoid (non-mineralized bone), pore diameters must be larger than 50 micrometers. For bone formation, pore diameters must be larger than 100 micrometers.
  • Collagen membranes according to the invention with three dimensional shapes can be produced to facilitate tissue regeneration, particularly bone. These three dimensional shapes are manufactured by casting collagen in male and female molds and lyophilizing, to form a highly porous structure. The collagen membranes are then collapsed and cross linked to provide high strength, stiff membranes. Collagen membranes can be formed into a variety of three dimensional shapes, such as capsules, wedges or balloons. For examples, capsules have been formed to contain and retain bone grafting materials to their desired location. These capsules can aid in the reconstruction of the buccal plate after tooth extraction.
  • the high strength collagen membranes of the invention are initially produced by casting a suspension of purified collagen.
  • the collagen desirably may have a native fibrous structure and an average fiber length of from about 0.2 to about 3 mm.
  • the collagen fibers may also be treated for implantation by the process of Cheung, US patent no.7,008,763, the entire disclosure of which is likewise incorporated herein by reference.
  • the treated (i.e., rehydrated) membrane is then dried. Drying may advantageously be effected by air drying at a temperature of 25°C to 37°C. Air drying at ambient temperature is ordinarily sufficient. If desired, the membrane may be subject to vacuum drying in addition to, or in lieu of, the air drying step.
  • the alcohol/water content is a controlling variable for strength/stiffness. Decreasing the alcohol/water ratio increases the strength/stiffness. Generally, the greater the proportion of water, the greater the density and the higher the strength and stiffness will be. However, too much water can cause the the collagen to degrade. Generally, a water content of 40-50% is optimal for super high strength/stiff membranes.
  • the membrane of the invention is non-fragile and exhibits sufficient sturdiness to enable it to be readily handled during implantation surgery without danger of damage of disintegration.
  • a capsule of relatively stiff, high density, low porosity collagen is ideal for containing bone grafting material and placing into the socket. The capsule restrains the bone grafting material to exactly the correct location for maximal bone formation.
  • Step 1 Casting
  • a collagen membrane was obtained having a a tensile strength of about 35 g/mm 2 , a tensile modulus of about 560 g/mm 2 , a porosity of more than 50%, and pore diameters of greater than 50 microns.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Botany (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Dispersion Chemistry (AREA)
  • Biophysics (AREA)
  • Prostheses (AREA)
  • Materials For Medical Uses (AREA)

Abstract

Procédé de fabrication d’une structure de collagène bioimplantable à porosité contrôlée, grande résistance et module élevé d’élasticité en traction. Le procédé consiste à couler une solution de collagène reconstitué sur une membrane, à lyophiliser cette membrane pour la transformer en mousse, à lui appliquer une solution d’alcool-eau et à la laisser sécher à l’air. Est décrite une structure de collagène bioimplantable obtenue ainsi à résistance et rigidité élevées.
PCT/US2010/047772 2009-09-04 2010-09-03 Membranes de collagène reconstitué à haute résistance et rigidité élevées pour implantation biomédicale WO2011028977A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CA2773165A CA2773165A1 (fr) 2009-09-04 2010-09-03 Membranes de collagene reconstitue a haute resistance et rigidite elevees pour implantation biomedicale
EP10814543A EP2473134A4 (fr) 2009-09-04 2010-09-03 Membranes de collagène reconstitué à haute résistance et rigidité élevées pour implantation biomédicale

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US23990709P 2009-09-04 2009-09-04
US61/239,907 2009-09-04

Publications (1)

Publication Number Publication Date
WO2011028977A1 true WO2011028977A1 (fr) 2011-03-10

Family

ID=43649660

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2010/047772 WO2011028977A1 (fr) 2009-09-04 2010-09-03 Membranes de collagène reconstitué à haute résistance et rigidité élevées pour implantation biomédicale

Country Status (3)

Country Link
EP (1) EP2473134A4 (fr)
CA (1) CA2773165A1 (fr)
WO (1) WO2011028977A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITUB20154229A1 (it) * 2015-10-08 2017-04-08 Novagenit S R L Un processo per la preparazione di film di collagene
US20210187156A1 (en) * 2018-05-18 2021-06-24 Cambridge Enterprise Limited Collagen Biomaterials And Methods For Manufacturing Collagen Biomaterials

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030114061A1 (en) * 2001-12-13 2003-06-19 Kazuhisa Matsuda Adhesion preventive membrane, method of producing a collagen single strand, collagen nonwoven fabric and method and apparatus for producing the same
US20030204023A1 (en) * 2000-06-01 2003-10-30 Shriners Hospital For Children, A Florida Corporation Polymer composite compositions
US20070009578A1 (en) * 2004-07-09 2007-01-11 Lene Moller Haemostatic composition comprising hyaluronic acid
US20080038352A1 (en) * 1999-02-25 2008-02-14 Virginia Commonwealth University Intellectual Property Foundation Electroprocessed Collagen and Tissue Engineering
US20090209020A1 (en) * 2005-11-07 2009-08-20 Kyoung-Chan Park collagenous matrix with improved porosity and tensile strength and preparation method therefore by using mechanical stimulation system

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010091223A1 (fr) * 2009-02-06 2010-08-12 David Cheung Membrane de collagène biphasique ou capsule pour une régénération tissulaire guidée
WO2010117766A1 (fr) * 2009-03-30 2010-10-14 Osseous Technologies Of America Cale de biomatériau de collagène
EP2467172A1 (fr) * 2009-08-10 2012-06-27 Osseous Technologies Of America Tunnel à collagène autoporteur pour la régénération tissulaire guidée et procédé d'utilisation de celui-ci

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080038352A1 (en) * 1999-02-25 2008-02-14 Virginia Commonwealth University Intellectual Property Foundation Electroprocessed Collagen and Tissue Engineering
US20030204023A1 (en) * 2000-06-01 2003-10-30 Shriners Hospital For Children, A Florida Corporation Polymer composite compositions
US20030114061A1 (en) * 2001-12-13 2003-06-19 Kazuhisa Matsuda Adhesion preventive membrane, method of producing a collagen single strand, collagen nonwoven fabric and method and apparatus for producing the same
US20070009578A1 (en) * 2004-07-09 2007-01-11 Lene Moller Haemostatic composition comprising hyaluronic acid
US20090209020A1 (en) * 2005-11-07 2009-08-20 Kyoung-Chan Park collagenous matrix with improved porosity and tensile strength and preparation method therefore by using mechanical stimulation system

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP2473134A4 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITUB20154229A1 (it) * 2015-10-08 2017-04-08 Novagenit S R L Un processo per la preparazione di film di collagene
US20210187156A1 (en) * 2018-05-18 2021-06-24 Cambridge Enterprise Limited Collagen Biomaterials And Methods For Manufacturing Collagen Biomaterials
US11998655B2 (en) * 2018-05-18 2024-06-04 Cambridge Enterprise Limited Collagen biomaterials and methods for manufacturing collagen biomaterials

Also Published As

Publication number Publication date
EP2473134A4 (fr) 2013-01-30
EP2473134A1 (fr) 2012-07-11
CA2773165A1 (fr) 2011-03-10

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