DE3719177A1 - Material for a bionic cornea - Google Patents

Material for a bionic cornea

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Publication number
DE3719177A1
DE3719177A1 DE19873719177 DE3719177A DE3719177A1 DE 3719177 A1 DE3719177 A1 DE 3719177A1 DE 19873719177 DE19873719177 DE 19873719177 DE 3719177 A DE3719177 A DE 3719177A DE 3719177 A1 DE3719177 A1 DE 3719177A1
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Germany
Prior art keywords
bionic
corneal endothelial
endothelial cells
cornea
proteins
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Legal status (The legal status 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 status listed.)
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Application number
DE19873719177
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German (de)
Inventor
Rolf Dr Siegel
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Individual
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Individual
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Priority to DE19873719177 priority Critical patent/DE3719177A1/en
Publication of DE3719177A1 publication Critical patent/DE3719177A1/en
Withdrawn legal-status Critical Current

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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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • 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
    • A61F2/14Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
    • 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
    • A61F2/14Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
    • A61F2/142Cornea, e.g. artificial corneae, keratoprostheses or corneal implants for repair of defective corneal tissue
    • 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
    • A61L27/54Biologically active materials, e.g. therapeutic substances
    • 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/21Acids
    • A61L2300/214Amino acids
    • 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23Carbohydrates
    • 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/25Peptides having up to 20 amino acids in a defined sequence
    • 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/252Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Transplantation (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Molecular Biology (AREA)
  • Materials For Medical Uses (AREA)

Abstract

The material for a bionic cornea comprises starting materials known per se on whose surface various biologically active carbohydrate group chains and/or proteins which promote corneal endothelial cell adhesion and cellular proliferation are covalently bonded or adsorbed. It is sutured in after performing a keratotomy which leaves a peripheral ring of corneal endothelial cells and, by reason of the carbohydrate group chains and/or proteins present on the surface, permits adherent and proliferative growth, which then covers the surface of the material, of the remaining corneal endothelial cells.

Description

Die Erfindung betrifft ein Material, welches Anwendung in der operativen Augenheilkunde findet. Ausgangspunkt ist die Tatsache, daß Hornhauttransplantationen, welche nach Traumata, z.B. Ver­ ätzungen bzw. bei Hornhauttrübungen notwendig sind, durch den Mangel an humanen Spenderhornhäuten limitiert sind.The invention relates to a material which application in the operative ophthalmology takes place. Starting point is the fact that corneal transplants, which after trauma, e.g. Ver etching or corneal opacity are necessary due to the Lack of human donor corneas are limited.

Aufgabe der Erfindung ist die Schaffung eines Materials für eine bionische Hornhaut. Der Begriff bionisch (eine Zusammenziehung aus den Begriffen biologisch und technisch) resultiert daher, daß als technischer Anteil des erfindungsgemäßen Materials es sich zunächst um bekannte Materialien handelt, die aber erst nach einer biologischen Oberflächenmodifikation bestimmungsgemäß als Ersatz für die bisher verwendeten humanen Spenderhornhäute ver­ wendet werden können.The object of the invention is to create a material for a bionic cornea. The term bionic (a contraction from the terms biological and technical) it follows that as a technical part of the material according to the invention initially known materials, but only after a biological surface modification as intended Replacement for the previously used human donor corneas ver can be applied.

Dies bedeutet, daß nach einer Keratotomie, die unter Belassung eines peripheren Corneaendothelzellrings durchgeführt wurde, der iatrogen gesetzte Defekt mit diesem bionischen Material gedeckt wird, wo dann im weiteren Verlauf, die verbliebenen Corneaendo­ thelzellen des Patienten auf der Materialoberfläche fest haftend, diese geordnet bedeckend wachsen. Das bionische Material dient also als Unterlage (Substrat, "support") für regenerationsfähige, metabolisch aktive Corneaendothelzellen. This means that after a keratotomy that is left under of a peripheral corneal endothelial cell ring, which iatrogenic defect covered with this bionic material where, in the further course, the remaining Corneaendo patient's cell cells firmly adhering to the material surface, these grow orderly covering. The bionic material serves So as a base (substrate, "support") for regenerative, metabolically active corneal endothelial cells.  

Der technische Anteil des bionischen Materials besteht darin, daß das Ausgangsmaterial folgende Eigenschaften aufweisen muß: es muß durchsichtig, UV-beständig, zur Ernährung für die Corneaendothel­ zellen für Ionen und Nährstoffe permeabel, flexibel, immunologisch inert, nähbar und im µm-Bereich dünn ist. Diese Materialien sind als sysnthetische oder natürliche Polymere bekannt. Als Beispiele seien niedermolekulares Polystyrol, Polyäthylen und Polypropylen niederer Dichte, Teflon (R), Polycarbonate etc., ebenso wie Materialien aus (chemisch modifizierter) Cellulose oder auch (vernetztem) Protein genannt.The technical part of the bionic material is that the starting material must have the following properties: it must be transparent, UV-resistant, permeable to ions and nutrients for nutrition for the corneal endothelial cells, flexible, immunologically inert, sewable and thin in the µm range . These materials are known as synthetic or natural polymers. Examples include low molecular weight polystyrene, low density polyethylene and polypropylene, Teflon ( R ), polycarbonates etc., as well as materials made from (chemically modified) cellulose or (crosslinked) protein.

Die erfindungsgemäße biologische Oberflächenmodifikation o.g. Materialien mit biologisch aktiven Substanzen hat zum Ziel, daß, wenn nach Operation dieses bionische Material den iatrogen ge­ setzten Defekt deckt, dieses Material eine Unterlage darstellt, auf der die verbliebenen Corneaendothelzellen fest haftend und sich vermehrend geordnet wachsen.The biological surface modification according to the invention mentioned above. The aim of materials with biologically active substances is that if after surgery this bionic material passes the iatrogen covers defect, this material is a base, on which the remaining corneal endothelial cells adhere firmly and grow in orderly order.

Hierzu ist es notwendig, daß die unmittelbare Materialoberfläche Kohlenhydratgruppenketten und/oder Proteine aufweist, die für die Corneaendothelzellen "Ankermöglichkeiten" darstellen, (siehe auch H. Rauvala, Trends in Biochemistry Science, 7, 323-325 (1983), woraus hervorgeht, daß Interaktionen von lektinähnlichen Prote­ inen, Glykosidasen und Glykosyltransferasen auf der Zellmembran­ oberfläche mit bestimmten Kohlenhydratgruppenketten und/oder Proteinen Interaktionen eingehen, die Voraussetzung für Zell­ adhärenz und Zelldifferenzierung sind).For this it is necessary that the immediate surface of the material Has carbohydrate group chains and / or proteins for the Represent corneal endothelial cells "anchor options" (see also H. Rauvala, Trends in Biochemistry Science, 7, 323-325 (1983), which indicates that interactions of lectin-like protein in, glycosidases and glycosyltransferases on the cell membrane surface with certain carbohydrate group chains and / or  Proteins interact, the prerequisite for cells adherence and cell differentiation are).

Derartige Kohlenhydratgruppenketten, die zur erfindungsgemäßen biologischen Oberflächenmodifikation eingsetzt werden, finden sich beispielsweise als die polaren Molekülanteile von Glycerin­ phosphatiden, Spingolip(o)iden, Glykosphingolip(o)iden oder Lipo­ proteinen und sind beispielsweise als Lip(o)id-Extrakt leicht erhältlich und umfassen je nach Aufarbeitung und Ausgangsmaterial unterschiedliche Mengen an (acetylierten und/oder aminierten) verzweigten oder unverzweigten Kohlenhydraten wie Fucose, Man­ nose, Galaktose, sowie N-Acetylgalactosamin, N-Acylneuraminsäure als Reinsubstanzen oder Mischungen. Weiterhin werden Heteropoly­ saccharide, Glykosaminglykanen eingesetzt, die bekanntermaßen für die fibronectin-vermittelte Zelladhärenz auf Oberflächen ver­ antwortlich sind. - Es versteht sich, daß der prozentuale Anteil der einzelnen bei der biologischen Oberflächenmodifikation eingesetzten biologisch aktiven Substanzen, also der einzelnen Kohlenhydrate bzw. Kohlenhydratgruppenketten und/oder Proteine, Peptide bzw. auch Aminosäuren, jeweils frei variierbar ist und den in vivo Erfordernissen optimal angepasst wird.Such carbohydrate group chains for the invention biological surface modification are used for example as the polar moiety of glycerin phosphatiden, Spingolip (o) iden, Glykosphingolip (o) iden or Lipo proteins and are light, for example, as lip (o) id extract available and include depending on the processing and starting material different amounts of (acetylated and / or aminated) branched or unbranched carbohydrates such as fucose, Man nose, galactose, and N-acetylgalactosamine, N-acylneuraminic acid as pure substances or mixtures. Furthermore, heteropoly saccharide, glycosaminoglycans, which are known for the fibronectin-mediated cell adherence on surfaces ver are answerable. - It is understood that the percentage of the individual in the biological surface modification used biologically active substances, i.e. the individual Carbohydrates or carbohydrate group chains and / or proteins, Peptides or amino acids, each is freely variable and is optimally adapted to the in vivo requirements.

Die o.g. biologisch aktiven Substanzen werden auf die Material­ oberflächen entweder adsorptiv oder kovalent gebunden. Verfahren hierzu sind bekannt: durch Lösen von amphiphilen Substanzen, wie sie die oben erwähnten Lip(o)ide darstellen, in einem im wesent­ lichen unpolaren Lösungsmittel (gemisch) und anschließendem in­ innigen-Kontakt-bringen mit einem Material, welches die auf Seite 2 beschriebenen Voraussetzungen erfüllt, beispielsweise Teflon (R), und danach völligem Entfernen des Lösungsmittel (gemisches), lagern sich die amphiphilen Substanzen mit ihrem hydrophoben Molekülanteil über van der Waals′sche und hydrophobe Kräfte fest an die Materialoberfläche an, wobei der hydrophile aus Kohlen­ hydratgruppenketten und/oder Proteinen bestehende Molekülanteil nunmehr die unmittelbare Materialoberfläche darstellt und die oben erwähnten "Ankermöglichkeiten" für die Corenaendothelzellen bietet.The above biologically active substances are either adsorptively or covalently bound to the material surfaces. Methods for this are known: by dissolving amphiphilic substances, such as those represented by the lip (o) ide mentioned above, in an essentially non-polar solvent (mixture) and then bringing them into intimate contact with a material which corresponds to that on page 2 fulfills the described conditions, for example Teflon ( R ), and then completely remove the solvent (mixture), the amphiphilic substances with their hydrophobic molecular component are firmly attached to the surface of the material via van der Waals'sche and hydrophobic forces, the hydrophilic group consisting of carbohydrates and / or proteins present in the molecule now represents the immediate surface of the material and offers the above-mentioned "anchor options" for the corenaendothelial cells.

Die kovalente Bindung der biologisch aktiven Substanzen auf die Materialoberfläche setzt voraus, daß die Oberfläche des Ausgangs­ materials genügend reaktive, funktionelle Gruppen, z.B. Hydroxi­ gruppen bei der Verwendung des Cellulosederivats Cellophan (R), aufweist. Diese Gruppen könnten, falls erforderlich, beispiels­ weise durch CnBr, noch aktiviert werden, so daß eine stabile kovalente Bindung zwischen Materialoberfläche und den einge­ setzten biologisch aktiven Substanzen entsteht.The covalent bonding of the biologically active substances to the material surface presupposes that the surface of the starting material has sufficient reactive, functional groups, for example hydroxyl groups, when using the cellulose derivative Cellophan ( R ). These groups could, if necessary, be activated by CnBr, for example, so that a stable covalent bond between the material surface and the biologically active substances used is formed.

Die derart biologisch oberflächenmodifizierten Materialien sind leicht und somit preiswert herstellbar, sie können auf den be­ nötigten Durchmesser zurecht geschnitten werden, da sie nach erfolgter Keratotomie sofort eingenäht werden, schützen sie nach Implantation sofort den hinteren Teil des Auges, eine Gefäßproli­ feration, wie sie bei der Implantation von Spenderhornhäuten häufig eintritt, wird wegen der unmittelbar nach Implantation noch fehlenden Corneaendothelzellschicht nicht eintreten, dafür bietet dieses Material aber den vorhandenen Corneaendothelzellen die Möglichkeit, sich fest haftend und geordnet auf dieser bio­ nischen Materialoberfläche anzusiedeln.The biologically surface-modified materials are easy and therefore inexpensive to manufacture, you can on the be required diameter can be cut to size as they are  If the keratotomy is sewn in immediately, protect it afterwards Immediately implant the posterior part of the eye, a vascular prolapse feration, as in the implantation of donor corneas occurs frequently because of immediately after implantation do not enter the missing corneal endothelial cell layer, instead but offers this material to the existing corneal endothelial cells the opportunity to stick firmly and orderly on this bio niche material surface.

Beispielexample

Als Ausgangsmaterial wird 5 µm starkes, durchsichtiges Teflon (R) eingesetzt. Dieses Material wird kurz in einen Chloroform/Me­ thanol (2 : 1 v/v) Gesamtlip(o)id-Extrakt aus EDTA-Vollblut des Patienten getaucht und wieder herausgezogen (9 Teile Lösungs­ mittelgemisch : 1 Teil EDTA-Blut). Das derart lip(o)id­ beschichtete Teflon (R)-Material wird getrocknet, dann gründlich mit Ringerlösung gewaschen und in Ringerlösung dampfsterilisert und kann danach implantiert werden.5 µm thick, transparent Teflon ( R ) is used as the starting material. This material is briefly immersed in a chloroform / methanol (2: 1 v / v) total lip (o) id extract from the patient's EDTA whole blood and withdrawn again (9 parts of solvent mixture: 1 part of EDTA blood). The Teflon ( R ) material coated with lip (o) id in this way is dried, then washed thoroughly with Ringer's solution and steam-sterilized in Ringer's solution and can then be implanted.

Claims (1)

Material für eine bionische Hornhaut bestehend aus einem scheibenförmigen, klaren, flexiblen, UV-beständigen, im µm- Bereich dünnen, zur Ernährung von Corneaendothelzellen für Ionen und Nährstoffe permeablen und chirurgisch nähbaren Material, welches nach partieller Keratotomie in bekannter Art und Weise eingenäht wird, dadurch gekennzeichnet, daß auf die Oberfläche dieses Materials synthetische oder natürliche, biologisch aktive Kohlenhydrate und/oder Kohlenhydratgruppenketten und/oder Amino­ säuren und/oder Peptide und/oder Proteine, die die Corneaendo­ thelzelladhärenz und deren geordnetes Wachstum auf Oberflächen fördern, als Reinsubstanzen oder mengenmäßig definierte Mischungen adsorptiv oder kovalent gebunden sind.Material for a bionic cornea consisting of a disc-shaped, clear, flexible, UV-resistant, thin in the µm range, which is permeable to surgery and suturally sewable for the nutrition of cornea endothelial cells for ions and nutrients, which is sutured in after the partial keratotomy in a known manner, characterized in that on the surface of this material synthetic or natural, biologically active carbohydrates and / or carbohydrate group chains and / or amino acids and / or peptides and / or proteins that promote Corneaendel cell adherence and their orderly growth on surfaces, as pure substances or in quantitative terms defined mixtures are adsorptively or covalently bound.
DE19873719177 1987-06-09 1987-06-09 Material for a bionic cornea Withdrawn DE3719177A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DE19873719177 DE3719177A1 (en) 1987-06-09 1987-06-09 Material for a bionic cornea

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DE19873719177 DE3719177A1 (en) 1987-06-09 1987-06-09 Material for a bionic cornea

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3939648A1 (en) * 1989-11-30 1991-06-06 Adatomed Pharma & Med Intra=ocular lens of silicone rubber - with surface coated with protein with affinity to inner side of natural lens casing
WO2005037144A2 (en) * 2003-10-10 2005-04-28 Cellular Bioengineering, Inc. Methods and compositions for growing corneal endothelial and related cells on biopolymers and creation of artifical corneal transplants

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3939648A1 (en) * 1989-11-30 1991-06-06 Adatomed Pharma & Med Intra=ocular lens of silicone rubber - with surface coated with protein with affinity to inner side of natural lens casing
WO2005037144A2 (en) * 2003-10-10 2005-04-28 Cellular Bioengineering, Inc. Methods and compositions for growing corneal endothelial and related cells on biopolymers and creation of artifical corneal transplants
WO2005037144A3 (en) * 2003-10-10 2005-07-14 Ge Ming Liu Methods and compositions for growing corneal endothelial and related cells on biopolymers and creation of artifical corneal transplants

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