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WO1993008265A2 - Production of bone and nacre from bone-forming cells in the presence of nacre - Google Patents

Production of bone and nacre from bone-forming cells in the presence of nacre Download PDF

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Publication number
WO1993008265A2
WO1993008265A2 PCT/FR1992/001008 FR9201008W WO9308265A2 WO 1993008265 A2 WO1993008265 A2 WO 1993008265A2 FR 9201008 W FR9201008 W FR 9201008W WO 9308265 A2 WO9308265 A2 WO 9308265A2
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WIPO (PCT)
Prior art keywords
bone
mother
pearl
nacre
cells
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Application number
PCT/FR1992/001008
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French (fr)
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WO1993008265A3 (en
Inventor
Georges Camprasse
Evelyne Lopez
Serge Camprasse
Original Assignee
Georges Camprasse
Evelyne Lopez
Serge Camprasse
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Publication date
Application filed by Georges Camprasse, Evelyne Lopez, Serge Camprasse filed Critical Georges Camprasse
Publication of WO1993008265A2 publication Critical patent/WO1993008265A2/en
Publication of WO1993008265A3 publication Critical patent/WO1993008265A3/en

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    • AHUMAN NECESSITIES
    • A44HABERDASHERY; JEWELLERY
    • A44CPERSONAL ADORNMENTS, e.g. JEWELLERY; COINS
    • A44C17/00Gems or the like
    • A44C17/007Special types of gems
    • 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
    • A61L27/36Materials 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
    • A61L27/38Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/0068General culture methods using substrates
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0652Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0654Osteocytes, Osteoblasts, Odontocytes; Bones, Teeth
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2533/00Supports or coatings for cell culture, characterised by material
    • C12N2533/10Mineral substrates
    • C12N2533/18Calcium salts, e.g. apatite, Mineral components from bones, teeth, shells

Definitions

  • the present invention relates to a method for producing natural bone and mother-of-pearl from bone-forming mother-of-pearl cells from the aquatic mollusc test.
  • it has never been possible to artificially produce a sufficient quantity of bone tissue of animal or human origin intended to serve as a graft.
  • the surgical circumstances that can give rise to the need for bone grafts are numerous: orthopedic surgery, trauma or plastic repair surgery, neurosurgery, carcinology eu; ... Dan ⁇ - all cases, the grafts come from: - either from the patient itself and in this case an autograft is performed - that is, a bone bank made up of bone parts free of their organic part which can cause immune reactions sterilized by ionizing radiation and frozen.
  • the production protocols relating to the process according to the invention are as follows: A layer of cells phenotypically and biochemically recognized to be bone-forming cells (osteoblasts) is placed in an appropriate culture medium: -1) Particles of mother-of-pearl or mother-of-pearl powder
  • Bone fragments and pearl fragments In a particular situation.
  • physiological normal bone formation is observed in several places in the culture and at a distance from the fragments of mother-of-pearl.
  • second case a) An increase in volume of the explant by apposition of newly formed bone and formation of bone fragments in the immediate environment of the bone and mother-of-pearl.
  • the study by microspectroscopy showed that the mineral deposit of the newly formed mother-of-pearl is very characteristic and specific of this substance.
  • the study with the electron microscope, with the photon microscope in polarized light, by immunocytology and radiology has shown that the neo-formed bone is of the same nature as the initial bone fragment with the presence of bone-specific coUagen and mineral
  • the method according to the invention has been implemented in animals. Fragments of mother-of-pearl or mother-of-pearl powder were placed according to a specific protocol in the presence of bone cells which form bone or are supposed to be able to do so. In all cases, the formation of newly formed bone with all the characteristics and specificities of physiological bone was observed.
  • the methods according to the invention demonstrate:
  • the bone-forming cells are derived from bone fragments originating from different groups of vertebrates in particular, from human bone. Mother-of-pearl comes from the pearly test of bivalve, gastropod or cephalopod aquatic molluscs.
  • the method according to the invention can be implemented in modules of variable size and shape. These modules will serve as molds in which the method according to the invention will develop in order to obtain replicas of bone or mother-of-pearl.
  • the method according to the invention can, on the one hand, lead to the manufacture of bone pieces intended to serve as grafts in bone surgery and, on the other hand, to the production of mother-of-pearl, pearls, jewelry and mother-of-pearl objects, of variable shape and size without this being limiting.
  • mother-of-pearl, pearls, jewelry and mother-of-pearl objects of variable shape and size without this being limiting.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Cell Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Botany (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Transplantation (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Farming Of Fish And Shellfish (AREA)
  • Materials For Medical Uses (AREA)

Abstract

According to the invention the artificial fabrication method for fabricating simultaneously or separately bone and nacre is implemented by the activity of osteonacrigenic factors contained in nacre. The method according to the invention consists in using fragments of nacre or powder of nacre resulting from the test of bivalve aquatic Mollusca Gasteropoda or Cephalopoda in the 'in vitro' or 'in vivo' presence of bone cells or bone-forming cells or cells susceptible of becoming bone-forming cells, associated to one or a plurality of bone fragments. The method according to the invention may be implemented in molds of various shapes and sizes, whereafter the bone parts thus obtained may be used as grafts in bone surgery and the nacre may be used to produce pearls, jewels or objects.

Description

PRODUCTION D'OS ET DE NACRE. A PARTIR DE CELLULES FORMATRICES D'OS MISES EN PRESENCE DE NACRE -PRODUCTION OF BONE AND PEARL. FROM FORMATORY CELLS OF BONES PRESENTED OF NACRE -
La présente invention concerne un procédé de production d'os naturel et de nacre, a partir de cellules formatrices d'os et de nacre provenant du test de mollusques aquatiques. Jusqu'à ce jour, on n'a jamais pu produire de manière artificielle en quantité suffisante du tissu osseux d'origine animale ou humaine destiné a servir de greffon. Les circonstances chirurgicales pouvant donner lieu à la nécessité d'effectuer des greffes osseuses sont nombreuses : chirurgie orthopédique, chirurgie réparatrice traumatologique ou plastique, neurochirurgie, carcinologie eu;... Dan^- tous les cas, les greffons proviennent : - soit du patient lui-même et dans ce cas on pratique une autogreffe - soit d'une banque d'os constituée de pièces osseuses débarrassées de leur partie organique pouvant provoquer des réactions immunitaires stérilisées par rayonnement ionisant et congelées. Dans ce cas, on pratique une hétérogreffe. Ces pièces osseuses, une fois greffées, constituent une trame minérale dans laquelle il est supposé se développer un processus de néoformation osseuse. Les inconvénients liés aux greffes osseuses sont de plusieurs ordres, toutefois les plus importantes sont les difficultés d'approvisionnement et de stockage ainsi que les réactions immunitaires de rejet, et les risques évidents de contamination infectieuse et virale. Dans le cas d' autogreffe, l'inconvénient majeur réside notamment, dans le fait que l'on ne peut disposer de fragments osseux de volume suffisant lorsqu'il s'agit de remplacer une grande perte de substance. C'est la raison pour laquelle certains inventeurs ont proposé des pièces osseuses réalisées dans des biomatériaux naturels biologiquement compatibles, tel que le corail. Ces biomatériaux ne peuvent servir, en fait, que de réserve de calcium. Ils occupent le volume laissé vide par la perte de substance osseuse, et, peu à peu, sont remplacés par de l'os néoformé. Le problème majeur lié à ces types de biomatériaux vient du fait que le pouvoir de résorption des cellules osseuses dîtes "ostéoclastes" s'épuise, limitant de ce fait, la colonisation totale du biomatériau par les cellules formatrices d'os, en conséquence, par l 'os néoformé. D'autres inventeurs ont proposé comme substitut de pièces osseuses, des éléments usinés à partir du test nacré de certains mollusques, ce test nacré n'étant pas résorbé en position intra-osseuse. Par ailleurs, l'obtention de perles de culture par des mollusques bivalves producteurs de nacre se fait à partir de fragments de nacre que l'on introduit dans un organe spécifique du mollusque vivant- L'inclusion d'un tel fragment produit un phénomène irritatif qui luirmême induit un processus de minéralisation par apposition de nacre néoformé autour du fragment de nacre étranger. Les perles ainsi obtenues étant de diverses formes. Or, on a trouvé, et c'est ce qui fait l'objet de l'invention, un procédé simple et rapide de production simultanée ou séparée d'os et de nacre pouvant conduire à la formation de perles.The present invention relates to a method for producing natural bone and mother-of-pearl from bone-forming mother-of-pearl cells from the aquatic mollusc test. To date, it has never been possible to artificially produce a sufficient quantity of bone tissue of animal or human origin intended to serve as a graft. The surgical circumstances that can give rise to the need for bone grafts are numerous: orthopedic surgery, trauma or plastic repair surgery, neurosurgery, carcinology eu; ... Dan ^ - all cases, the grafts come from: - either from the patient itself and in this case an autograft is performed - that is, a bone bank made up of bone parts free of their organic part which can cause immune reactions sterilized by ionizing radiation and frozen. In this case, a heterograft is performed. These bone pieces, once grafted, constitute a mineral framework in which it is supposed to develop a process of new bone formation. The disadvantages associated with bone grafts are of several orders, however the most important are the difficulties of supply and storage as well as the immune reactions of rejection, and the obvious risks of infectious and viral contamination. In the case of autografting, the major drawback lies in particular in the fact that one cannot have bone fragments of sufficient volume when it comes to replacing a large loss of substance. This is the reason why certain inventors have proposed bone pieces produced in biologically compatible natural biomaterials, such as coral. These biomaterials can in fact only serve as a calcium reserve. They occupy the volume left empty by the loss of bone substance, and, little by little, are replaced by newly formed bone. The major problem associated with these types of biomaterials comes from the fact that the resorption power of the so-called "osteoclast" bone cells is exhausted, thereby limiting the total colonization of the biomaterial by the bone-forming cells, consequently, by newly formed bone. Other inventors have proposed, as bone substitute parts, elements machined from the nacreous test of certain molluscs, this nacreous test not being absorbed in the intraosseous position. Furthermore, obtaining cultured pearls by bivalve molluscs producing nacre is done from nacre fragments which are introduced into a specific organ of the living mollusc. The inclusion of such a fragment produces an irritant phenomenon r which itself induces mineralization process by affixing newly formed pearl nacre around the foreign fragment. The pearls thus obtained being of various shapes. However, we have found, and this is the subject of the invention, a simple and rapid process for the simultaneous or separate production of bone and mother-of-pearl which can lead to the formation of pearls.
L'invention sera mieux comprise à la lecture de la description de quelques exemples de réalisations.The invention will be better understood on reading the description of a few examples of embodiments.
Les protocoles de réalisation relatifs au procédé selon l'invention sont les suivants : On a mis dans un milieu de culture approprié, une couche de cellules reconnues phénotypiquement et biochimiquement pour être des cellules formatrices d'os (ostéoblastes) en présence : -1) De particules de nacre ou de poudre de nacreThe production protocols relating to the process according to the invention are as follows: A layer of cells phenotypically and biochemically recognized to be bone-forming cells (osteoblasts) is placed in an appropriate culture medium: -1) Particles of mother-of-pearl or mother-of-pearl powder
-2) De fragments d'os et de fragments de nacre.dans une situation particulière. Dans le premier cas, on observe en plusieurs endroits de la culture et à distance des fragments de nacre la formation d'os physiologiquement normal. Dans le second cas a) Une augmentation de volume de l'expiant par apposition d'os néoformé et formation de fragments d'os dans l'environnement immédiat de l'os et de la nacre. b) Une augmentation de volume du fragment de nacre par apposition de nacre néoformée et de fragment de nacre dans l'environnement immédiat de la nacre et de l'os.-2) Bone fragments and pearl fragments. In a particular situation. In the first case, physiological normal bone formation is observed in several places in the culture and at a distance from the fragments of mother-of-pearl. In the second case a) An increase in volume of the explant by apposition of newly formed bone and formation of bone fragments in the immediate environment of the bone and mother-of-pearl. b) An increase in volume of the mother-of-pearl fragment by affixing neoformed mother-of-pearl and of mother-of-pearl fragment in the immediate environment of the mother-of-pearl and the bone.
L'étude par microspectroscopie (effet RAMAN) a montré que le dépôt minéral de la nacre néoformée est bien caractéristique et spécifique de cette substance. L'étude au microscope électronique, au microscope photonique en lumière polarisée, par immunocytologie et radiologie a montré que l'os néo formé est de même nature que le fragment d'os initial avec présence de coUagène et de minéral spécifiques de l'os Selon un autre mode de réalisation, le procédé selon l'invention a été mis en oeuvre chez l'animal. Des fragments de nacre ou de la poudre de nacre ont été placés suivant un protocole particulier en présence de cellules osseuses formatrices d'os ou supposées capables de le devenir. Dans tous les cas, on a observé la formation d'os néoformé présentant toutes les caractéristiques et spécificités de l'os physiologique. Les procédés, selon l'invention, mettent en évidence :The study by microspectroscopy (RAMAN effect) showed that the mineral deposit of the newly formed mother-of-pearl is very characteristic and specific of this substance. The study with the electron microscope, with the photon microscope in polarized light, by immunocytology and radiology has shown that the neo-formed bone is of the same nature as the initial bone fragment with the presence of bone-specific coUagen and mineral According to another embodiment, the method according to the invention has been implemented in animals. Fragments of mother-of-pearl or mother-of-pearl powder were placed according to a specific protocol in the presence of bone cells which form bone or are supposed to be able to do so. In all cases, the formation of newly formed bone with all the characteristics and specificities of physiological bone was observed. The methods according to the invention demonstrate:
- La présence dans la nacre de facteurs ostéogènes, nacrigènes (ostéonacrigènes) et ou inducteurs de biominéralisation diffusibles et ayant une action à distance.- The presence in the nacre of osteogenic factors, nacrigens (osteonacrigens) and or inducers of diffusible biomineralization and having a remote action.
- La production, par les cellules osseuses formatrices d'os ou susceptibles de l'être, sous l'effet de ces facteurs, d'une matrice organique servant de support aussi bien à la formation d'os, qu'à la formation de nacre, donc contenant des substances de différents types de biominéralisations.- The production, by bone cells which form or are likely to be bone, under the effect of these factors, of an organic matrix serving as support both for bone formation and for the formation of mother-of-pearl, therefore containing substances of different types of biomineralization.
La présence, d'un ou de plusieurs de ces facteurs est indispensable à la mise en oeuvre du procédé selon l'invention. Dans ces procédés selon l'invention, les cellules formatrices d'os sont issues de fragments d'os provenant de différents groupes de vertébrés notamment, d'os humain. La nacre provient du test nacré de mollusques aquatiques bivalves, gastéropodes ou céphalopodes. Le procédé selon l'invention, peut être mis en oeuvre dans des modules de taille et forme variables. Ces modules serviront de moules dans lesquels se développera le procédé selon l'invention afin d'en obtenir les répliques en os en ou nacre. Selon un mode de réalisation préférentielle, le procédé selon l'invention, peut, d'une part, conduire à la fabrication de pièces osseuses destinées à servir de greffon en chirurgie osseuse et, d'autre part, à la production de nacre, de perles, de bijoux et d'objets en nacre, de forme et de dimensions variables sans que cela soit limitatif. Ces modes de réalisation présentés à titre d'exemple non exhaustif, il revient à l'homme de métier de mettre en présence des cellules osseuses formatrices d'os ou susceptibles de le devenir provenant de divers groupes de vertébrés, notamment, de l'homme, et des fragments de nacre ou de la poudre de nacre, issus des tests nacrés de mollusques aquatiques, toutes les fois où il aura besoin de produire artificiellement ou de l'os ou de la nacre. The presence of one or more of these factors is essential for the implementation of the method according to the invention. In these methods according to the invention, the bone-forming cells are derived from bone fragments originating from different groups of vertebrates in particular, from human bone. Mother-of-pearl comes from the pearly test of bivalve, gastropod or cephalopod aquatic molluscs. The method according to the invention can be implemented in modules of variable size and shape. These modules will serve as molds in which the method according to the invention will develop in order to obtain replicas of bone or mother-of-pearl. According to a preferred embodiment, the method according to the invention can, on the one hand, lead to the manufacture of bone pieces intended to serve as grafts in bone surgery and, on the other hand, to the production of mother-of-pearl, pearls, jewelry and mother-of-pearl objects, of variable shape and size without this being limiting. These embodiments presented by way of non-exhaustive example, it is up to the person skilled in the art to put in the presence of bone cells which form bone or are likely to become it coming from various groups of vertebrates, in particular from humans. , and fragments of mother-of-pearl or mother-of-pearl powder, obtained from pearly tests of aquatic molluscs, whenever it will need to produce artificially either bone or mother-of-pearl.

Claims

REVENDICATIONS
- 4 -- 4 -
1) Procédé de fabrication d'os ou de nacre caractérisé en ce qu'il est réalisé in vitro in vivo à partir de l'action de facteurs inducteurs de biominéralisation dits "ostéonacrigènes" libérés par des fragments de nacre placés, soit en présence de cellules osseuses formatrices d'os ou susceptibles de le devenir, soit en présence des mêmes types de cellules auxquels on ajoute des fragments d'os.1) Process for the manufacture of bone or mother-of-pearl, characterized in that it is carried out in vitro in vivo from the action of factors inducing biomineralization known as "osteonacrigens" released by fragments of mother-of-pearl placed, either in the presence of bone cells that form or are likely to become bone, either in the presence of the same types of cells to which bone fragments are added.
2) Procédé selon la revendication 1 caractérisé en ce que les fragments de nacre et la poudre de nacre proviennent du test nacré de mollusques bivalves, gastéropodes et céphalopodes.2) Method according to claim 1 characterized in that the nacre fragments and the nacre powder come from the pearly test of bivalve molluscs, gastropods and cephalopods.
3) Procédé selon les revendications 1 2, caractérisé en ce que le fragment d'os, les cellules osseuses formatrices d'os ou susceptibles de l'être sont issus de divers groupes de vertébrés incluant l'homme.3) Method according to claims 1 2, characterized in that the bone fragment, bone cells bone forming or likely to be from a variety of vertebrate groups including humans.
4) Procédé selon les revendications I, 2 et 3 caractérisé en ce que les cultures de cellules formatrices d'os ou susceptibles de l'être, sont contenues dans des moules de formes et de dimensions variables, destinés à en obtenir des répliques d'os ou de nacre.4) Method according to claims I, 2 and 3 characterized in that the cultures of bone-forming cells or likely to be, are contained in molds of varying shapes and sizes, intended to obtain replicas of bone or mother-of-pearl.
5) Utilisation de cellules osseuses formatrices d'os ou susceptibles de le devenir, et de fragments de nacre ou de poudre de nacre pour la fabrication artificielle d'os physiologiquement normal. Utilisation de cellules osseusesformatrices d'os ou susceptibles de le devenir et de fragments de nacre ou de poudre de nacre pour la fabrication artificielle de nacre. 5) Use of bone cells which form or are likely to become bone, and fragments of mother-of-pearl or mother-of-pearl powder for the artificial manufacture of physiologically normal bone. Use of bone cells that form or are likely to become bone and fragments of mother-of-pearl or mother-of-pearl powder for the artificial manufacture of mother-of-pearl.
PCT/FR1992/001008 1991-10-23 1992-10-23 Production of bone and nacre from bone-forming cells in the presence of nacre WO1993008265A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR9113083A FR2682965A1 (en) 1991-10-23 1991-10-23 PRODUCTION OF BONE AND PEARL FROM CULTURE OF BONE FORMING CELLS.
FR91/13083 1991-10-23

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WO1993008265A2 true WO1993008265A2 (en) 1993-04-29
WO1993008265A3 WO1993008265A3 (en) 1993-09-16

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WO1989002919A1 (en) * 1987-09-28 1989-04-06 Lee Dosuk Method for culturing pearls
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WO1990014111A1 (en) * 1989-05-23 1990-11-29 Serge Camprasse Prosthetic bones and dental roots made from mother of pearl

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WO1989002919A1 (en) * 1987-09-28 1989-04-06 Lee Dosuk Method for culturing pearls
DE3810803A1 (en) * 1988-03-30 1989-10-12 Battelle Institut E V Process for the production of a synthetic bone material with properties intrinsic to the body
WO1990014111A1 (en) * 1989-05-23 1990-11-29 Serge Camprasse Prosthetic bones and dental roots made from mother of pearl

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CALCIFIED TISSUE INTERNATIONAL vol. 51, no. 5, Novembre 1992, BERLIN pages 363 - 369 SILVE C; LOPEZ E; VIDAL B; SMITH D C; CAMPRASSE S; CAMPRASSE G; COULY G 'NACRE INITIATES BIOMINERALIZATION BY HUMAN OSTEOBLASTS MAINTAINED IN-VITRO' *
CALCIFIED TISSUE INTERNATIONAL, SUPPL. vol. 48, 1991, BERLIN page A49 SILVE C; LOPEZ E; VIDAL B; CAMPRASSE S; CAMPRASSE G 'MOTHER OF PEARL INITIATES BONE GROWTH AND MATRIX MINERALISATION BY HUMAN BONE CELLS IN-VITRO IN THE ABSENCE OF CHEMICAL INDUCERS' *
COMPTES RENDUS DE L'ACADEMIE DES SCIENCES vol. 309, no. 6, 1989, PARIS pages 203 - 210 Lopez E; Gill GA; Camprasse G; Camprasse S; Lallier F 'Soudure sans transition (osteoassimilation) entre l'os maxillaire humain et un implant dentaire compact en calcite naturelle d'invertebres marins.' *
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TISSUE & CELL vol. 24, no. 5, Septembre 1992, HARLOW GB pages 667 - 679 LOPEZ E; VIDAL B; BERLAND S; CAMPRASSE S; CAMPRASSE G; SILVE C 'DEMONSTRATION ON THE CAPACITY OF NACRE TO INDUCE BONE FORMATION BY HUMAN OSTEOBLASTS MAINTAINED IN-VITRO' *

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5807554A (en) * 1997-04-11 1998-09-15 Yng-Wong; Quing Non Herbal formulations with nacre

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AU2948792A (en) 1993-05-21
WO1993008265A3 (en) 1993-09-16

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