WO1993016739A1 - Collagen- and fibrin adhesive-based graft for osteocartilaginous reconstruction, and preparation method therefor - Google Patents

Collagen- and fibrin adhesive-based graft for osteocartilaginous reconstruction, and preparation method therefor Download PDF

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Publication number
WO1993016739A1
WO1993016739A1 PCT/EP1992/000344 EP9200344W WO9316739A1 WO 1993016739 A1 WO1993016739 A1 WO 1993016739A1 EP 9200344 W EP9200344 W EP 9200344W WO 9316739 A1 WO9316739 A1 WO 9316739A1
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Prior art keywords
collagen
graft
fibrin glue
reconstruction
volume
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PCT/EP1992/000344
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French (fr)
Inventor
Jean-Luc Eberlin
Original Assignee
Eberlin Jean Luc
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.)
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Publication date
Application filed by Eberlin Jean Luc filed Critical Eberlin Jean Luc
Priority to EP92904707A priority Critical patent/EP0626868A1/en
Priority to PCT/EP1992/000344 priority patent/WO1993016739A1/en
Publication of WO1993016739A1 publication Critical patent/WO1993016739A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0011Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using physical methods
    • A61L2/0029Radiation
    • A61L2/0035Gamma radiation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02Prostheses implantable into the body
    • A61F2/28Bones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/22Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/225Fibrin; Fibrinogen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/22Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24Collagen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56Porous materials, e.g. foams or sponges
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2310/00Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00005The prosthesis being constructed from a particular material
    • A61F2310/00365Proteins; Polypeptides; Degradation products thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2310/00Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00005The prosthesis being constructed from a particular material
    • A61F2310/00365Proteins; Polypeptides; Degradation products thereof
    • A61F2310/00377Fibrin

Definitions

  • the present invention relates to bone reconstruction after trauma or bone resection, especially for long bones, short or flat, and aims to provide a new filling material from a deficit or 5 of a solution of continuity in the said bones or intended to compensate for partial bone non-formation in the case of agenesis or dysplasia in particular.
  • the materials used are asked to be biocompatible, to present a healthy, clean, vascularized terrain, to be sufficiently rigid, to have an optimal congruence with the recipient site and to avoid as far as possible the laying of elements. external solidarity or restraint.
  • the object of the invention is to overcome these drawbacks by proposing a new material capable of constituting grafts for osteocartilaginous reconstruction ensuring total homogenization between the recipient bone and the graft and whose qualities, in particular mechanical, allow a suitable, easy, fast and solid reconstruction.
  • the subject of the invention is a graft for osteocartilaginous reconstruction, characterized in that it consists of the association of a collagen matrix of porous structure impregnated with a slow setting fibrin glue , the proportions, by volume, of the fibrin glue relative to the collagen matrix being at least 1/4.
  • the subject of the invention is also a process for preparing such a graft, characterized in that it consists in taking a block of collagen in spongy form, in depositing on this block slow-setting fibrin glue, in the form viscous, at the rate of at least one part, by volume, of fibrin glue for four parts, by volume, of collagen, and to dry the whole until elimination of practically all the evaporable water.
  • the material thus obtained is directly usable as a graft. It is in the form of a rigid structure which can be cut and shaped at will to constitute a graft easily put in place.
  • a collagen matrix for example the product sold by the company BRAUN under the trade name "OSTEOVIT", which is a cut sponge block consisting of a skeletal structure.
  • a block of collagen for example a cube of four cm3, at least 1 cm3 of a slow setting fibrin glue is deposited on the upper face.
  • This glue is obtained by the following process.
  • an assay is carried out in the known manner so as to obtain a glue for slow setting and more precisely an adhesive whose setting is obtained after a time of contact with the collagen equal to or greater than 5 minutes.
  • the mixture thus obtained is viscous. Once deposited on the bonding matrix, the fibrin glue will, by creep, gradually colonize the porous mass of collagen.
  • the operation takes place for example at room temperature and in a sterile environment and lasts the time necessary for the drying of the whole, that is to say the disappearance of practically all the evaporable water. Such drying lasts several hours and depends on the volume of the block of impregnated collagen.
  • the product obtained is a rigid, non-elastic block and remains so even if it is rewetted. It can be kept in this state as long as the starting constituents, and preferably under sterile condition.
  • the storage temperature has no particular effect on storage.
  • the operation of impregnating the block of collagen with fibrin glue can also be carried out in a non-sterile medium, in which case, after drying, a sterilization with gamma rays of the material will be carried out, before its use, which does not alter not the quality of the association of glue + collagen.
  • the collagen block can, before its impregnation with fibrin glue, be cut or shaped according to the shape of the graft to be produced.
  • the block of collagen is not previously cut or shaped, it can be after impregnation and drying, at any time before use.
  • the proportion, by volume, of fibrin glue, relative to the collagen matrix is at least one part for four parts respectively. Below this threshold, the quantity of adhesive is insufficient and the final structure is not rigid and tends to become plastic, but not elastic, if it is rewetted. On the other hand, the proportion of fibrin glue can be substantially greater than 1/4, and go as far as saturation of the porous structure of the collagen matrix.
  • the material obtained in accordance with the invention has a homogeneous structure, can be sculpted at will and allows the passage and fixation in particular of the osteoblasts which thus have, from the start, a virgin, hypoallergenic and solid frame.
  • the bone grafted in accordance with the invention is thus consolidated much faster than with usual materials which allows, from the radiological observation of consolidation, to remove any osteosynthesis material much earlier (after 3 to 4 months in general, instead of two years at least with coral or hydroxyapatite grafts).
  • the graft according to the invention permanently retains good rigidity, it is possible in certain cases to avoid associating temporary added external elements, of attachment or restraint.

Abstract

A collagen- and fibrin adhesive-based graft for osteocartilaginous reconstruction, and a preparation method therefor. The graft comprises a collagen matrix with a porous structure impregnated with a slow-setting fibrin adhesive, wherein the proportions by volume of the fibrin adhesive relative to the collagen matrix are of at least 1/4. Said graft is particularly suitable for osteocartilaginous reconstruction.

Description

GREFFON A BASE DE COLLAGENE ET DE COLLE DE FIBRINE GRAFT BASED ON COLLAGEN AND FIBRIN GLUE
POUR LA RECONSTRUCTION OSTEO-CARTILAGINEUSEFOR OSTEO-CARTILAGINOUS RECONSTRUCTION
ET SON PROCEDE DE PREPARATIONAND ITS PREPARATION PROCESS
La présente invention se rapporte à la reconstruction osseuse après traumatisme ou exérèse osseuse, tout particulièrement pour les os longs, courts ou plats, et vise à proposer un nouveau matériau de comblement d'un déficit ou 5 d'une solution de continuité dans lesdits os ou destiné à pallier une non-formation osseuse partielle dans le cas d'agénésie ou de dysplasie notamment.The present invention relates to bone reconstruction after trauma or bone resection, especially for long bones, short or flat, and aims to provide a new filling material from a deficit or 5 of a solution of continuity in the said bones or intended to compensate for partial bone non-formation in the case of agenesis or dysplasia in particular.
Pour traiter les cas ci-dessus et dans le domaine plus général de la greffe osseuse, on dispose principalement de ° deux matériaux qui sont le corail et les constituants organiques de l'os tels que l'hydroxy-apatite.To treat the above cases and in the more general field of bone grafting, there are mainly two materials which are coral and organic components of bone such as hydroxyapatite.
On demande notamment aux matériaux utilisés d'être biocompatibles, de présenter un terrain sain, propre, vascularisê, d'être suffisamment rigides, d'avoir une 5 congruence optimale avec le site receveur et d'éviter autant que possible la pose d'éléments externes de solidarisation ou contention.In particular, the materials used are asked to be biocompatible, to present a healthy, clean, vascularized terrain, to be sufficiently rigid, to have an optimal congruence with the recipient site and to avoid as far as possible the laying of elements. external solidarity or restraint.
Le corail présente ces qualités mais il est cassant, difficilement taillable et coûteux. 0 L'hydroxy-apatite, qui se présente sous la forme d'une pâte dense, ne permet pas d'avoir une forme préétablie et neCoral has these qualities but it is brittle, difficult to cut and expensive. 0 Hydroxyapatite, which is in the form of a dense paste, does not make it possible to have a predetermined shape and does not
. s'intègre à l'environnement qu'au bout d'un temps très long, de l'ordre de deux ans.. integrates into the environment only after a very long time, of the order of two years.
Une telle intégration, constatée par l'observation d'une 5 même densité osseuse radiologique sur l'os receveur et sur le greffon, est aussi longue avec le corail.Such integration, observed by the observation of the same radiological bone density on the recipient bone and on the graft, is also long with coral.
De plus, ces deux types de matériaux ne permettent pas de pallier des solutions de continuité. En effet, dans ces applications la masse du greffon est relativement importante et la perméation, nulle ou très faible, du corail ou de l'hydroxy-apatite, c'est-à-dire l'aptitude à permettre le passage des liquides ou substances relativement visqueuses, n'assure pas la colonisation du greffon et donc l'homogénéisation entre l'os receveur et le greffon. Le but de l'invention est de pallier ces inconvénients en proposant un nouveau matériau apte à constituer des greffons pour la reconstruction ostéo-cartilagineuse assurant une totale homogénéisation entre l'os receveur et le greffon et dont les qualités, en particulier mécaniques, permettent une reconstruction adaptée, facile, rapide et solide.In addition, these two types of materials do not make it possible to overcome continuity solutions. Indeed, in these applications the mass of the graft is relatively large and the permeation, zero or very low, of the coral or of the hydroxyapatite, that is to say the ability to allow the passage of liquids or substances relatively viscous, does not ensure colonization of the graft and therefore homogenization between the recipient bone and the graft. The object of the invention is to overcome these drawbacks by proposing a new material capable of constituting grafts for osteocartilaginous reconstruction ensuring total homogenization between the recipient bone and the graft and whose qualities, in particular mechanical, allow a suitable, easy, fast and solid reconstruction.
A cet effet, l'invention a pour objet un greffon pour la reconstruction ostéo-cartilagineuse, caractérisé en ce qu'il est constitué de l'association d'une matrice de collagène de structure poreuse imprégnée d'une colle de fibrine à prise lente, les proportions, en volume, de la colle de fibrine par rapport à la matrice de collagène étant d'au moins 1/4.To this end, the subject of the invention is a graft for osteocartilaginous reconstruction, characterized in that it consists of the association of a collagen matrix of porous structure impregnated with a slow setting fibrin glue , the proportions, by volume, of the fibrin glue relative to the collagen matrix being at least 1/4.
L'invention a également pour objet un procédé de préparation d'un tel greffon, caractérisé en ce qu'il consiste à prendre un bloc de collagène sous forme spongieuse, à déposer sur ce bloc de la colle de fibrine à prise lente, sous forme visqueuse, à raison d'au moins une partie, en volume, de colle de fibrine pour quatre parties, en volume, de collagène, et à faire sécher l'ensemble jusqu'à élimination de pratiquement toute l'eau évaporable. Le matériau ainsi obtenu est directement utilisable comme greffon. Il se présente sous forme d'une structure rigide qui peut être taillée et conformée à volonté pour constituer un greffon mis en place aisément.The subject of the invention is also a process for preparing such a graft, characterized in that it consists in taking a block of collagen in spongy form, in depositing on this block slow-setting fibrin glue, in the form viscous, at the rate of at least one part, by volume, of fibrin glue for four parts, by volume, of collagen, and to dry the whole until elimination of practically all the evaporable water. The material thus obtained is directly usable as a graft. It is in the form of a rigid structure which can be cut and shaped at will to constitute a graft easily put in place.
On va maintement décrire en détail, à titre d'exemple, un mode de mise en oeuvre du procédé ci-dessus.We will now describe in detail, by way of example, an embodiment of the above method.
On part d'une matrice de collagène, par exemple le produit commercialisé par la Société BRAUN sous la dénomination commerciale "OSTEOVIT", qui est un bloc spongieux taillé constitué d'une structure squelettique.We start from a collagen matrix, for example the product sold by the company BRAUN under the trade name "OSTEOVIT", which is a cut sponge block consisting of a skeletal structure.
Sur un tel bloc de collagène, par exemple un cube de quatre cm3, on dépose sur la face supérieure au moins 1 cm3 d'une colle de fibrine à prise lente. Cette colle est obtenue par le processus suivant.On such a block of collagen, for example a cube of four cm3, at least 1 cm3 of a slow setting fibrin glue is deposited on the upper face. This glue is obtained by the following process.
A partir d'un kit de lyophilisats de diverses .vitesses de coagulation, par exemple le kit commercialisé par la société autrichienne IMMUNO sous la dénomination commerciale "TISSUCOL", on effectue, à la manière connue, un dosage de façon à obtenir une colle à prise lente et plus précisément une colle dont la prise est obtenue au bout d'un temps de contact avec le collagène égal ou supérieur à 5 minutes environ.From a kit of lyophilisates of various coagulation speeds, for example the kit marketed by the Austrian company IMMUNO under the trade name "TISSUCOL", an assay is carried out in the known manner so as to obtain a glue for slow setting and more precisely an adhesive whose setting is obtained after a time of contact with the collagen equal to or greater than 5 minutes.
Le mélange ainsi obtenu est visqueux. Une fois déposée sur la matrice de collage, la colle de fibrine va, par fluage, progressivement coloniser la masse poreuse de collagène.The mixture thus obtained is viscous. Once deposited on the bonding matrix, the fibrin glue will, by creep, gradually colonize the porous mass of collagen.
L'opération se passe par exemple à la température ambiante et en milieu stérile et dure le temps nécessaire au séchage d l'ensemble, c'est-à-dire à la disparition de pratiquemen toute l'eau évaporable. Un tel séchage dure plusieurs heures et dépend du volume du bloc de collagène imprégné.The operation takes place for example at room temperature and in a sterile environment and lasts the time necessary for the drying of the whole, that is to say the disappearance of practically all the evaporable water. Such drying lasts several hours and depends on the volume of the block of impregnated collagen.
Une fois séché, le produit obtenu est un bloc rigide, non élastique et le demeure même s'il est réhumidifié. Il peu être conservé dans cet état aussi longtemps que le constituants de départ, et de préférence sous conditionnemen stérile. La température de conservation n'a pas d'incidenc particulière sur la conservation.Once dried, the product obtained is a rigid, non-elastic block and remains so even if it is rewetted. It can be kept in this state as long as the starting constituents, and preferably under sterile condition. The storage temperature has no particular effect on storage.
L'opération d'imprégnation du bloc de collagène par l colle de fibrine peut s'effectuer également en milieu no stérile, auquel cas, après séchage, on effectuera un stérilisation aux rayons gamma du matériau, avant so utilisation, ce qui n'altère pas la qualité de l'associatio colle + collagène. Le bloc de collagène peut, avant son imprégnation par l colle de fibrine, être taillé ou conformé suivant la forme d greffon à réaliser.The operation of impregnating the block of collagen with fibrin glue can also be carried out in a non-sterile medium, in which case, after drying, a sterilization with gamma rays of the material will be carried out, before its use, which does not alter not the quality of the association of glue + collagen. The collagen block can, before its impregnation with fibrin glue, be cut or shaped according to the shape of the graft to be produced.
Si le bloc de collagène n'est pas au préalable taillé o conformé, il peut l'être après imprégnation et séchage, à tou moment avant son utilisation. La taille ou conformation du collagène, avant ou après imprégnation et séchage, ne présente aucune difficulté.If the block of collagen is not previously cut or shaped, it can be after impregnation and drying, at any time before use. The size or conformation of the collagen, before or after impregnation and drying, presents no difficulty.
Il est nécessaire que la proportion, en volume, de colle de fibrine, par rapport à la matrice de collagène soit au moins d'une partie pour quatre parties respectivement. En deçà de ce seuil, la quantité de colle est insuffisante et la structure finale n'est pas rigide et a tendance à devenir plastique, mais pas élastique, si elle est réhumidifiée. Par contre, la proportion de colle de fibrine peut être sensiblement supérieure à 1/4, et aller jusqu'à la saturation de la structure poreuse de la matrice de collagène.It is necessary that the proportion, by volume, of fibrin glue, relative to the collagen matrix is at least one part for four parts respectively. Below this threshold, the quantity of adhesive is insufficient and the final structure is not rigid and tends to become plastic, but not elastic, if it is rewetted. On the other hand, the proportion of fibrin glue can be substantially greater than 1/4, and go as far as saturation of the porous structure of the collagen matrix.
Le matériau obtenu conformément à l'invention présente une structure homogène, est sculptable à volonté et permet le passage et la fixation notamment des ostéoblastes qui ont ainsi, dès le début, une trame vierge, anallergique et solide.The material obtained in accordance with the invention has a homogeneous structure, can be sculpted at will and allows the passage and fixation in particular of the osteoblasts which thus have, from the start, a virgin, hypoallergenic and solid frame.
Dans le cadre d'une étude clinique prospective on a remplacé 25 % du fût fémoral d'un lapin par un greffon selon l'invention, stabilisé par un fixateur externe.Within the framework of a prospective clinical study, 25% of the femoral barrel of a rabbit was replaced by a graft according to the invention, stabilized by an external fixator.
Au bout de dix jours on a constaté, par des coupes histologiques, la colonisation de la totalité du greffon, ce qui confirme la perméation remarquable du greffon.After ten days, the entire graft was colonized by histological sections, which confirms the remarkable permeation of the graft.
Il est à noter que quel que soit le volume du greffon, sa colonisation totale s'opère en toutes circonstances, contrairement au corail et à l'hydroxy-apatite. Au bout de trois mois on a constaté radiologiquement, non seulement l'obtention d'une même densité osseuse de la structure interne du greffon par rapport à la partie originelle, mais un alignement de la continuité osseuse corticale (partie dure et portante de l'os) . Avec le greffon selon l'invention, la reconstruction osseuse ne commence plus par une phase de "désertification" cellulaire du tissu greffé et le temps de colonisation s'en trouve diminué d'autant. D'autre part, la corticalisation du greffon et son adaptation à l'environnement tissulaire ne passe pas par un stade de remaniement osseux interne, comme c'est le cas pour les techniques de greffe osseuse avec des matériaux du type corail ou os de banque.It should be noted that whatever the volume of the graft, its total colonization takes place in all circumstances, unlike coral and hydroxyapatite. At the end of three months it was found radiologically, not only the obtaining of the same bone density of the internal structure of the graft relative to the original part, but an alignment of the cortical bone continuity (hard and bearing part of the os). With the graft according to the invention, bone reconstruction no longer begins with a phase of cellular "desertification" of the grafted tissue and the colonization time is thereby reduced accordingly. On the other hand, the corticalization of the graft and its adaptation to the tissue environment does not go through a stage of internal bone reorganization, as is the case for bone grafting techniques with materials of the coral or bank bone type. .
L'os greffé conformément à l'invention est ainsi consolidé beaucoup plus rapidement qu'avec les matériaux habituels ce qui permet, dès la constatation radiologique de la consolidation, d'enlever l'éventuel matériel d'ostéosynthèse beaucoup plus précocement (au bout de 3 à 4 mois en général, au lieu de deux ans au moins avec des greffons en corail ou hydroxy-apatite) .The bone grafted in accordance with the invention is thus consolidated much faster than with usual materials which allows, from the radiological observation of consolidation, to remove any osteosynthesis material much earlier (after 3 to 4 months in general, instead of two years at least with coral or hydroxyapatite grafts).
Du fait que le greffon selon l'invention conserve en permanence une bonne rigidité, on peut dans certains cas, éviter d'associer des éléments externes rapportés temporaires, de solidarisation ou contention.Because the graft according to the invention permanently retains good rigidity, it is possible in certain cases to avoid associating temporary added external elements, of attachment or restraint.
Enfin, l'invention n'est évidemment pas limitée aux modes de réalisation décrits ci-dessus mais en couvre au contraire toutes les variantes. Finally, the invention is obviously not limited to the embodiments described above but on the contrary covers all the variants thereof.

Claims

R E V E N D I C A T I O N S
1. Greffon pour la reconstruction ostéo-cartilagineuse, caractérisé en ce qu'il est constitué de l'association d'une matrice de collagène de structure poreuse imprégnée d'une colle de fibrine à prise lente, les proportions, en volume, de la colle de fibrine par rapport à la matrice de collagène étant d'au moins 1/4.1. Graft for osteo-cartilaginous reconstruction, characterized in that it consists of the association of a collagen matrix of porous structure impregnated with a slow setting fibrin glue, the proportions, in volume, of the fibrin glue relative to the collagen matrix being at least 1/4.
2. Procédé de préparation d'un greffon selon la revendication 1, caractérisé en ce qu'il consiste à prendre un bloc de collagène sous forme spongieuse, à déposer sur ce bloc de la colle de fibrine à prise lente, sous forme visqueuse, à raison d'au moins une partie, en volume, de colle de fibrine pour quatre parties, en volume, de collagène, et à faire sécher l'ensemble jusqu'à élimination de pratiquement toute l'eau évaporable. 2. Method for preparing a graft according to claim 1, characterized in that it consists in taking a block of collagen in spongy form, in depositing on this block of fibrin glue with slow setting, in viscous form, at least one part, by volume, of fibrin glue for four parts, by volume, of collagen, and drying the whole until almost all the evaporable water is eliminated.
3. Procédé suivant la revendication 2, caractérisé en ce que la colle de fibrine est réalisée, à partir d'un kit de lyophilisats de diverses vitesses de coagulation, par dosage, de façon à obtenir une prise au bout d'un temps de contact avec le collagène égal ou supérieur à cinq minutes environ. 3. Method according to claim 2, characterized in that the fibrin glue is produced from a kit of lyophilisates of various coagulation rates, by dosing, so as to obtain a setting after a contact time. with collagen about five minutes or more.
4. Procédé suivant la revendication 2 ou 3, caractérisé en ce que les diverses opérations s'effectuent en milieu stérile.4. Method according to claim 2 or 3, characterized in that the various operations are carried out in a sterile environment.
5. Procédé suivant la revendication 2 ou 3, caractérisé en ce que les diverses opérations s'effectuent en milieu non stérile, le produit obtenu étant, après séchage, soumis à une stérilisation aux rayons gamma. 5. Method according to claim 2 or 3, characterized in that the various operations are carried out in a non-sterile medium, the product obtained being, after drying, subjected to sterilization with gamma rays.
PCT/EP1992/000344 1992-02-19 1992-02-19 Collagen- and fibrin adhesive-based graft for osteocartilaginous reconstruction, and preparation method therefor WO1993016739A1 (en)

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PCT/EP1992/000344 WO1993016739A1 (en) 1992-02-19 1992-02-19 Collagen- and fibrin adhesive-based graft for osteocartilaginous reconstruction, and preparation method therefor

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US6110484A (en) * 1998-11-24 2000-08-29 Cohesion Technologies, Inc. Collagen-polymer matrices with differential biodegradability
WO2007106582A2 (en) * 2006-03-15 2007-09-20 Promethean Lifesciences, Inc. Preparation and storage of stable, biologically active materials
US7335508B2 (en) 2004-07-22 2008-02-26 Prochon Biotech Ltd. Porous plasma protein matrices and methods for preparation thereof
US7815926B2 (en) 2005-07-11 2010-10-19 Musculoskeletal Transplant Foundation Implant for articular cartilage repair
USRE42208E1 (en) 2003-04-29 2011-03-08 Musculoskeletal Transplant Foundation Glue for cartilage repair
US8221500B2 (en) 2003-05-16 2012-07-17 Musculoskeletal Transplant Foundation Cartilage allograft plug
US8292968B2 (en) 2004-10-12 2012-10-23 Musculoskeletal Transplant Foundation Cancellous constructs, cartilage particles and combinations of cancellous constructs and cartilage particles
US8435551B2 (en) 2007-03-06 2013-05-07 Musculoskeletal Transplant Foundation Cancellous construct with support ring for repair of osteochondral defects
US8690874B2 (en) 2000-12-22 2014-04-08 Zimmer Orthobiologics, Inc. Composition and process for bone growth and repair
US8906110B2 (en) 2007-01-24 2014-12-09 Musculoskeletal Transplant Foundation Two piece cancellous construct for cartilage repair
US9283074B2 (en) 2002-06-13 2016-03-15 Kensey Nash Bvf Technology, Llc Devices and methods for treating defects in the tissue of a living being
US9701940B2 (en) 2005-09-19 2017-07-11 Histogenics Corporation Cell-support matrix having narrowly defined uniformly vertically and non-randomly organized porosity and pore density and a method for preparation thereof
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EP1334733A3 (en) * 1995-06-07 2003-11-19 Stryker Corporation Terminally sterilized osteogenic devices and preparation thereof
US6013856A (en) * 1995-06-07 2000-01-11 Stryker Corporation Terminally sterilized osteogenic devices and preparation thereof
US6028242A (en) * 1995-06-07 2000-02-22 Stryker Corporation Terminally sterilized osteogenic devices and preparation thereof
US6504079B2 (en) 1995-06-07 2003-01-07 Stryker Corporation Terminally sterilized osteogenic devices and preparation thereof
WO1996040297A1 (en) * 1995-06-07 1996-12-19 Stryker Corporation Terminally sterilized osteogenic devices and preparation thereof
US5674292A (en) * 1995-06-07 1997-10-07 Stryker Corporation Terminally sterilized osteogenic devices and preparation thereof
EP1334733A2 (en) * 1995-06-07 2003-08-13 Stryker Corporation Terminally sterilized osteogenic devices and preparation thereof
US6110484A (en) * 1998-11-24 2000-08-29 Cohesion Technologies, Inc. Collagen-polymer matrices with differential biodegradability
US6277394B1 (en) 1998-11-24 2001-08-21 Cohesion Technologies, Inc. Collagen-polymer matrices with differential biodegradability
US8690874B2 (en) 2000-12-22 2014-04-08 Zimmer Orthobiologics, Inc. Composition and process for bone growth and repair
US9283074B2 (en) 2002-06-13 2016-03-15 Kensey Nash Bvf Technology, Llc Devices and methods for treating defects in the tissue of a living being
USRE43258E1 (en) 2003-04-29 2012-03-20 Musculoskeletal Transplant Foundation Glue for cartilage repair
USRE42208E1 (en) 2003-04-29 2011-03-08 Musculoskeletal Transplant Foundation Glue for cartilage repair
US8221500B2 (en) 2003-05-16 2012-07-17 Musculoskeletal Transplant Foundation Cartilage allograft plug
US7335508B2 (en) 2004-07-22 2008-02-26 Prochon Biotech Ltd. Porous plasma protein matrices and methods for preparation thereof
US8292968B2 (en) 2004-10-12 2012-10-23 Musculoskeletal Transplant Foundation Cancellous constructs, cartilage particles and combinations of cancellous constructs and cartilage particles
US7815926B2 (en) 2005-07-11 2010-10-19 Musculoskeletal Transplant Foundation Implant for articular cartilage repair
US9701940B2 (en) 2005-09-19 2017-07-11 Histogenics Corporation Cell-support matrix having narrowly defined uniformly vertically and non-randomly organized porosity and pore density and a method for preparation thereof
WO2007106582A3 (en) * 2006-03-15 2007-11-22 Promethean Lifesciences Inc Preparation and storage of stable, biologically active materials
WO2007106582A2 (en) * 2006-03-15 2007-09-20 Promethean Lifesciences, Inc. Preparation and storage of stable, biologically active materials
US8906110B2 (en) 2007-01-24 2014-12-09 Musculoskeletal Transplant Foundation Two piece cancellous construct for cartilage repair
US8435551B2 (en) 2007-03-06 2013-05-07 Musculoskeletal Transplant Foundation Cancellous construct with support ring for repair of osteochondral defects
US10077420B2 (en) 2014-12-02 2018-09-18 Histogenics Corporation Cell and tissue culture container
US11555172B2 (en) 2014-12-02 2023-01-17 Ocugen, Inc. Cell and tissue culture container

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