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WO1993001843A1 - Preparing grafts for implantation - Google Patents

Preparing grafts for implantation Download PDF

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Publication number
WO1993001843A1
WO1993001843A1 PCT/GB1992/001364 GB9201364W WO9301843A1 WO 1993001843 A1 WO1993001843 A1 WO 1993001843A1 GB 9201364 W GB9201364 W GB 9201364W WO 9301843 A1 WO9301843 A1 WO 9301843A1
Authority
WO
WIPO (PCT)
Prior art keywords
graft
cells
implantation
suspension
chamber
Prior art date
Application number
PCT/GB1992/001364
Other languages
French (fr)
Inventor
Robert Leonard Chamberlain
Original Assignee
University Of Leicester
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 University Of Leicester filed Critical University Of Leicester
Publication of WO1993001843A1 publication Critical patent/WO1993001843A1/en

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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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses

Definitions

  • This invention relates to methods and apparatus for preparing grafts, for example synthetic or biological vascular grafts, for implantation into human or animal patients.
  • Synthetic vascular grafts which may be made for example of polytetrafluoroethylene (PTFE) are implanted when the patient's own tissue is not available though animal, e.g. bovine, grafts can also be used.
  • PTFE polytetrafluoroethylene
  • non-thrombogenic grafts it is desirable that the PTFE be covered by the patient's own or other non-rejectable endothelial cells. While endothelial cell growth occurs to bare PTFE implants after implantation, this takes place only to a limited extent near the suturing positions.
  • Endothelial cell seeding has been attempted, but high cell losses occur on implantation once the implant is subjected to blood flow stresses.
  • the present invention provides methods and apparatus which overcome this problem.
  • the invention comprises a method for preparing a graft for implantation by lining with endothelial cells, comprising placing a cell suspension in a culture medium in contact with the graft and incubating the cells whilst maintaining a small shear stress at the medium/graft boundary whereby to cause the cells to become confluent and flatten thus enhancing their attachment to the graft surface.
  • the graft may be a vascular graft in the form of a flexible tube.
  • the flexible tube may be held extended substantially horizontally and rotated about its axis to maintain the said shear stress. Or it may be held vertically or in any other orientation, as may any non-tubular graft, in a slow fluid current.
  • a tubular graft may be coated internally; successive charges of suspension may be introduced into the graft lumen with the graft oriented in different positions about its substantially horizontal axis.
  • the graft may also be coated externally and may be rotated in a cell suspension in a culture medium.
  • the incubation may be carried on overnight.
  • the shear stress may be applied by relative movement of the graft and the suspension at a rate of
  • the invention also comprises apparatus for preparing a graft for implantation by lining with endothelial cells, comprising a chamber in which the graft can be contained and means for flowing a cell suspension in culture medium over a surface of the graft so as to create and maintain a small shear stress at the medium/graft boundary.
  • Apparatus according to the invention for lining a vascular graft with endothelial cells may comprise a chamber with provision for cannulae on which the ends of the graft are placed and between which the graft is extended whereby cell suspension can be introduced into and removed from the graft lumen.
  • a cylindrical chamber being adapted for rotation about its axis, so as to bring about the necessary small shear effect.
  • the chamber can be arranged vertically or in any other orientation and the medium with suspended cells flowed through the graft.
  • the chamber may be adapted for rotation about its axis by end closures doubling as support means for use on a roller table or by tyres at or intermediate its ends.
  • End closures may comprise inlet and outlet apertures for a suspension of cells contacting the exterior surface of the graft.
  • the apparatus may be supplied with a graft mounted therein ready for preparation for implantation, the whole being already sterilized, if desired, for example by gamma irradiation.
  • Figure 1 is a lengthwise section of a vascular graft showing internal and external cell coatings
  • Figure 2 is a lengthwise section of a chamber for preparing a vascular graft, with a graft in place;
  • FIG. 1 illustrate methods and apparatus for preparing a synthetic vascular graft 11 for implantation by lining with endothelial cells 12 , Figure 1.
  • the endothelial cells may be harvested from the patient, where this is possible, or from umbilical veins
  • S UBSTITUTESHEET otherwise.
  • An umbilical vein is cannulated at either end and flushed with 10 ml minimum essential medium (MEM) to remove old blood.
  • the vein is then distended with 5 ml 0.1% collagenase solution prewarmed to 37°C and the whole cord incubated for 15 min at 37°C. After incubation the vein is flushed through with 20 ml MEM to remove dislodged endothelial cells and the resulting cell suspension centrifuged for 7 min at 200 g and 4°C.
  • the resulting cell pellet is resuspended in 5 ml complete medium with 20 ug/ml endothelial growth supplement and 90 ug/ml heparin and the cells placed on
  • the resulting cell suspension is centrifuged for 7 min at 200 g and 4°C and the cell pellet resuspended in 8 ml complete medium at a concentration of 1.25 x 10 cells/ml.
  • Figures 2 and 3 illustrate a cylindrical treatment chamber 21 having removable end closures 22,23 with apertures for cannulae 24,25 of which cannula 24 is somewhat longer than cannula 25.
  • One end of the ⁇ graft 11 is placed on cannula 24 which is pushed through the closure 22 so that some length of it projects into the chamber 21 when the closure 22 is fitted to it.
  • the length of the chamber is suited to the length of the graft (the longest graft normally required for human patients being one metre, other grafts being of different shorter lengths so that a range of cylinder lengths will be required) so that the other end of the graft 11 projects some distance beyond the other end of the chamber 21 so as to facilitate its cannulation by cannula 25.
  • the closure 23 is then fitted to the cylinder 21 and canula 24 drawn back out of the cylinder 21 to tighten the graft 11 and extend it between the two cannulae.
  • the cannulae 24,25 are sealed and secured in position in the end closures 22,23 by screw clamps 26.
  • Inlet and outlet apertures 27,28 are provided in the end closures 22,23 for introducing a support maxim so that the graft is at neutral buoyancy during the procedure -
  • the support medium can be simply a cell culture medium that can infuse into the graft and asisst in the growth of cells on the inner wall or may include suspension of endothelial cells to coat the exterior surface of the graft 11.
  • this optional measure is adopted, rather more than the 8 ml aforementioned of cell suspension will be required.
  • 2 ml of the suspension is introduced into the graft lumen from a syringe via the end cannula.
  • the chamber 21 is laid horizontally in an incubator at 37°C for 20 min, after which the medium containing any unattached endothelial cells is removed.
  • the chamber is then rotated 90° about its axis and a further 2 ml of cell suspension introduced as before, and the chamber incubated a further 20 min.
  • the procedure is repeated twice more until all 8 ml of suspension has been used, the final aliquot being left in the graft lumen and the chamber placed on a roller table and rotated at 10 rph during overnight incubation.
  • the final aliquot is removed from the graft lumen.
  • the exterior surface of the graft can be coated in the same way at the same time.
  • the end caps 24,25 are profiled to act as supports for the chamber on the roller table (not shown) .
  • the chamber 21 may be made of durable, autoclavable materials for repeated use, it is possible to realise them as disposable items pre-loaded with graft so that the graft-mounting operation may be effected under factory conditions and with factory quality assurance rather than using hospital resources.
  • a pre-pack may be sterilized by gamma irradiation before or after packaging.
  • the coating procedure will be carried out in the hospital because it is not desirable that the coated graft is left for long before implantation.
  • the rotational speed may be different from the 10 rph quoted - speeds as high as 2 rpm have been used effectively.
  • suspension may be flowed over or through the graft by pumping or by convection, and this will in general be more useful for non-tubular grafts.

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  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Vascular Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Biomedical Technology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pulmonology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Prostheses (AREA)
  • Materials For Medical Uses (AREA)

Abstract

Method and apparatus for preparing a synthetic graft, e.g. a vascular graft, for implantation by lining it with endothelial cells, in which a cell suspension in culture medium is in contact with the graft and the cells incubated whilst maintaining a small shear stress at the medium/graft boundary whereby to cause the cells to become confluent and flatten thus enhancing their attachment to the graft surface. The graft can be placed in a cylindrical chamber rotated to effect the shear force.

Description

PREPARING GRAFTS FOR IMPLANTATION
This invention relates to methods and apparatus for preparing grafts, for example synthetic or biological vascular grafts, for implantation into human or animal patients.
Synthetic vascular grafts, which may be made for example of polytetrafluoroethylene (PTFE) are implanted when the patient's own tissue is not available though animal, e.g. bovine, grafts can also be used. For non-thrombogenic grafts it is desirable that the PTFE be covered by the patient's own or other non-rejectable endothelial cells. While endothelial cell growth occurs to bare PTFE implants after implantation, this takes place only to a limited extent near the suturing positions.
Endothelial cell seeding has been attempted, but high cell losses occur on implantation once the implant is subjected to blood flow stresses.
The present invention provides methods and apparatus which overcome this problem.
The invention comprises a method for preparing a graft for implantation by lining with endothelial cells, comprising placing a cell suspension in a culture medium in contact with the graft and incubating the cells whilst maintaining a small shear stress at the medium/graft boundary whereby to cause the cells to become confluent and flatten thus enhancing their attachment to the graft surface.
The graft may be a vascular graft in the form of a flexible tube. The flexible tube may be held extended substantially horizontally and rotated about its axis to maintain the said shear stress. Or it may be held vertically or in any other orientation, as may any non-tubular graft, in a slow fluid current.
A tubular graft may be coated internally; successive charges of suspension may be introduced into the graft lumen with the graft oriented in different positions about its substantially horizontal axis. The graft may also be coated externally and may be rotated in a cell suspension in a culture medium.
The incubation may be carried on overnight.
The shear stress may be applied by relative movement of the graft and the suspension at a rate of
10 -5 to 10-4 ms-1. This corresponds, with a horizontally extended tube, to a rotation about its axis of the order of 10 rph.
SUBSTITUTESHEET The invention also comprises apparatus for preparing a graft for implantation by lining with endothelial cells, comprising a chamber in which the graft can be contained and means for flowing a cell suspension in culture medium over a surface of the graft so as to create and maintain a small shear stress at the medium/graft boundary.
Apparatus according to the invention for lining a vascular graft with endothelial cells may comprise a chamber with provision for cannulae on which the ends of the graft are placed and between which the graft is extended whereby cell suspension can be introduced into and removed from the graft lumen. A cylindrical chamber being adapted for rotation about its axis, so as to bring about the necessary small shear effect. However, the chamber can be arranged vertically or in any other orientation and the medium with suspended cells flowed through the graft.
The chamber may be adapted for rotation about its axis by end closures doubling as support means for use on a roller table or by tyres at or intermediate its ends.
End closures may comprise inlet and outlet apertures for a suspension of cells contacting the exterior surface of the graft.
SUBSTITUTESHEET The apparatus may be supplied with a graft mounted therein ready for preparation for implantation, the whole being already sterilized, if desired, for example by gamma irradiation.
Methods and apparatus for preparing synthetic grafts for implantation according to the invention will now be described with reference to the accompanying drawings, in which :-
Figure 1 is a lengthwise section of a vascular graft showing internal and external cell coatings;
Figure 2 is a lengthwise section of a chamber for preparing a vascular graft, with a graft in place;
and Figure 3 is a cross-section on the line
III-III of Figure 2.
The drawings illustrate methods and apparatus for preparing a synthetic vascular graft 11 for implantation by lining with endothelial cells 12 , Figure 1.
The endothelial cells may be harvested from the patient, where this is possible, or from umbilical veins
SUBSTITUTESHEET otherwise. An umbilical vein is cannulated at either end and flushed with 10 ml minimum essential medium (MEM) to remove old blood. The vein is then distended with 5 ml 0.1% collagenase solution prewarmed to 37°C and the whole cord incubated for 15 min at 37°C. After incubation the vein is flushed through with 20 ml MEM to remove dislodged endothelial cells and the resulting cell suspension centrifuged for 7 min at 200 g and 4°C. The resulting cell pellet is resuspended in 5 ml complete medium with 20 ug/ml endothelial growth supplement and 90 ug/ml heparin and the cells placed on
2 to a 25 cm tissue culture flask and incubated at 37°C in 95% air/5% C02 for 3-7 days until they reach confluence. Once at confluence they are harvested with
0.1% trypsin/0.02% ethylene diaminetetracetic acid at
37°C. The trypsin is then inhibited by adding excess
MEM containing 20% fetal calf serum. The resulting cell suspension is centrifuged for 7 min at 200 g and 4°C and the cell pellet resuspended in 8 ml complete medium at a concentration of 1.25 x 10 cells/ml.
Figures 2 and 3 illustrate a cylindrical treatment chamber 21 having removable end closures 22,23 with apertures for cannulae 24,25 of which cannula 24 is somewhat longer than cannula 25. One end of the ■graft 11 is placed on cannula 24 which is pushed through the closure 22 so that some length of it projects into the chamber 21 when the closure 22 is fitted to it. The length of the chamber is suited to the length of the graft (the longest graft normally required for human patients being one metre, other grafts being of different shorter lengths so that a range of cylinder lengths will be required) so that the other end of the graft 11 projects some distance beyond the other end of the chamber 21 so as to facilitate its cannulation by cannula 25. The closure 23 is then fitted to the cylinder 21 and canula 24 drawn back out of the cylinder 21 to tighten the graft 11 and extend it between the two cannulae.
The cannulae 24,25 are sealed and secured in position in the end closures 22,23 by screw clamps 26.
Inlet and outlet apertures 27,28 are provided in the end closures 22,23 for introducing a support mediu so that the graft is at neutral buoyancy during the procedure - the support medium can be simply a cell culture medium that can infuse into the graft and asisst in the growth of cells on the inner wall or may include suspension of endothelial cells to coat the exterior surface of the graft 11. Obviously where this optional measure is adopted, rather more than the 8 ml aforementioned of cell suspension will be required. For coating the interior of the graft, assuming a 4 mm internal diameter graft 15 cm long, 2 ml of the suspension is introduced into the graft lumen from a syringe via the end cannula. The chamber 21 is laid horizontally in an incubator at 37°C for 20 min, after which the medium containing any unattached endothelial cells is removed. The chamber is then rotated 90° about its axis and a further 2 ml of cell suspension introduced as before, and the chamber incubated a further 20 min. The procedure is repeated twice more until all 8 ml of suspension has been used, the final aliquot being left in the graft lumen and the chamber placed on a roller table and rotated at 10 rph during overnight incubation.
Before implantation, the final aliquot is removed from the graft lumen.
Clearly, if desired, the exterior surface of the graft can be coated in the same way at the same time.
The end caps 24,25 are profiled to act as supports for the chamber on the roller table (not shown) .
Whilst the chamber 21 may be made of durable, autoclavable materials for repeated use, it is possible to realise them as disposable items pre-loaded with graft so that the graft-mounting operation may be effected under factory conditions and with factory quality assurance rather than using hospital resources. A pre-pack may be sterilized by gamma irradiation before or after packaging.
Of course, the coating procedure will be carried out in the hospital because it is not desirable that the coated graft is left for long before implantation.
The 10 rph rotation during incubation applies a small shear stress to the endothelial cell layer and this, together with the incubation, gives a flattened, confluent lining which resists detachment of cells under - blood flow conditions. Some cell detachment is observed in trials, but better than 80% of cells are retained.
Where time is short, the overnight incubation and rotation can be omitted. The procedure to that stage is effective at coating the graft, but substantially higher rates of detachment are experienced.
The rotational speed may be different from the 10 rph quoted - speeds as high as 2 rpm have been used effectively.
Various modifications can be made to the means for carrying out the lining according to the invention. SUBSTITUTESHEET Instead of relying on a rotation-induced shear stress, suspension may be flowed over or through the graft by pumping or by convection, and this will in general be more useful for non-tubular grafts.

Claims

1. A method for preparing a graft for implantation by lining with endothelial cells, comprising placing a cell suspension in a culture medium in contact with the graft and incubating the cells whilst maintaining a small shear stress at the medium/graft boundary whereby to cause the cells to become confluent and flatten thus enhancing their attachment to the graft surface.
2. A method according to claim 1, in which the graft is a vascular graft in the form of a flexible tube.
3. A method according to claim 2, in which the flexible tube is held extended substantially horizontally and rotated about its axis to maintain the said shear stress.
4. A method according to claim 2 or claim 3, in which the graft is coated internally.
5. A method according to claim 4, in which successive charges of suspension are introduced into the graft lumen with the graft oriented in different positions about its substantially horizontal axis.
6. A method according to any one of claims 2 to 5, in which the graft is coated externally.
SUBSTITUTESHEET
7. A method according to claim 6, in which the graft is rotated in a cell suspension in a culture medium.
8. A method according to any one of claims 1 to 7, in which the incubation is carried on overnight.
9. A method according to any one of claims 1 to 8, in which the shear stress is applied by relative movement of the graft and the suspension at a rate of
-ζ -4 -1
10 -10 /ms .
10. A method according to claim 9, in which the graft is a horizontally extended tube maintained in rotation at about 10 rph.
11. Apparatus for preparing a graft for implantation by lining with endothelial cells comprising a chamber in which the graft can be contained and means for flowing a cell suspension in culture medium over a surface of the graft so as to create and maintain a small shear stress at the medium/graft boundary.
12. Apparatus according to claim 11 for filing a vascular graft with endothelial cells, comprising a chamber with provision for cannulae on which the ends of the graft are placed and between which the graft is extended whereby cell suspension can be introduced into and removed from the graft lumen.
13. Apparatus according to claim 11, in which the chamber is cylindrical and adapted for rotation about its axis so as to bring about the necessary small shear effect.
14. Apparatus according to claim 13, having end closures with apertures for cannulae.
15. Apparatus according to claim 14, the end closures doubling as support means for use on a roller table.
16. Apparatus according to any one of claims 12 to
15, comprising inlet and outlet apertures for a suspension of cells contacting the exterior surface of the graft.
17. Apparatus according to any one of claims 11 to
16, with a graft mounted therein, ready for preparation for implantation.
18. Apparatus according to claim 17, sterilized.
19. Apparatus according to claim 18, gamma- irradiated.
PCT/GB1992/001364 1991-07-25 1992-07-23 Preparing grafts for implantation WO1993001843A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9116036.6 1991-07-25
GB919116036A GB9116036D0 (en) 1991-07-25 1991-07-25 Preparing grafts for implantation

Publications (1)

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WO1993001843A1 true WO1993001843A1 (en) 1993-02-04

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AU (1) AU2361792A (en)
GB (1) GB9116036D0 (en)
IE (1) IE922327A1 (en)
WO (1) WO1993001843A1 (en)

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997049799A1 (en) * 1996-06-27 1997-12-31 Advanced Tissue Sciences, Inc. Apparatus and method for sterilizing, seeding, culturing, storing, shipping and testing tissue, synthetic or native, vascular grafts
WO1998022573A1 (en) * 1996-11-20 1998-05-28 Advanced Tissue Sciences, Inc. Application of shear flow stress to chondrocytes
US5763267A (en) * 1996-04-16 1998-06-09 Advanced Tissue Sciences Apparatus for the large scale growth and packaging of cell suspensions and three-dimensional tissue cultures
EP0847238A1 (en) * 1995-06-07 1998-06-17 Advanced Tissue Sciences, Inc. Seeding heart valves
US5843766A (en) * 1995-06-07 1998-12-01 Advanced Tissue Sciences, Inc. Apparatus for the growth and packaging of three dimensional tissue cultures
AU703117B2 (en) * 1995-04-27 1999-03-18 Advanced Tissue Sciences, Inc. Apparatus and method for sterilizing, seeding, culturing, storing, shipping and testing tissue, synthetic or native vascular grafts
WO1999066965A1 (en) * 1998-06-25 1999-12-29 Vascular Biotech Gmbh Autologous epithelialisation or endothelialisation of hollow organs or vessels
DE19834396A1 (en) * 1998-07-30 2000-02-03 Daimlerchrysler Aerospace Ag Heart valve prosthesis coated prior to implantation by agitation within a cell culture container rotated simultaneously through two axes at right angles to each other, minimizing probability of rejection
US6060306A (en) * 1995-06-07 2000-05-09 Advanced Tissue Sciences, Inc. Apparatus and method for sterilizing, seeding, culturing, storing, shipping and testing replacement cartilage tissue constructs
WO2000037123A1 (en) * 1998-12-21 2000-06-29 Cell-Lining Gesellschaft Für Zellkultivierung Mbh Cardiovascular protheses with a stable endothelial cell surface
WO2000041648A1 (en) * 1999-01-14 2000-07-20 Advanced Tissue Sciences, Inc. Apparatus and method for sterilizing, seeding, culturing, storing, shipping and testing tissue, synthetic, or native vascular grafts
WO2000050106A2 (en) * 1999-02-26 2000-08-31 Michael Hoffmann Hemocompatible surfaces and method for producing same
US6121042A (en) * 1995-04-27 2000-09-19 Advanced Tissue Sciences, Inc. Apparatus and method for simulating in vivo conditions while seeding and culturing three-dimensional tissue constructs
WO2000059618A1 (en) * 1999-04-07 2000-10-12 Augustinus Bader Method for populating substrates with biological cells and populating devices that can be used therefor
WO2000064569A1 (en) * 1999-04-23 2000-11-02 Vascular Biotech Gmbh Tissue culture system for the epithelialization or entothelialization and for functionally testing and supplying natural or artificial hollow organs or vessels under controlled sterile conditions for the purpose of surgical implantations
WO2001091817A2 (en) * 2000-06-02 2001-12-06 Cell-Lining-Gesellschaft Für Zellkultivierung Mbh Method for the determination of the confluence of a cell layer on porous biomaterials
US6416995B1 (en) * 1999-11-22 2002-07-09 Bio Science Consultants, L.L.C. Bioreactor mediated recellularization of natural and tissue engineered vascular grafts
AU766234B2 (en) * 1999-11-24 2003-10-09 Co.Don Ag Method of surface coating medical implants
CN100340220C (en) * 2004-02-19 2007-10-03 重庆大学 Method for planting esoderma/endothelial cell on inner surface of artificial blood vessel
EP1579827A3 (en) * 2003-10-24 2007-12-12 DEUTSCHE INSTITUTE FÜR TEXTIL- UND FASERFORSCHUNG STUTTGART Stiftung des öffentlichen Rechts Cardiovascular implant and method and device for manufacturing thereof
EP2275153A1 (en) * 1999-11-22 2011-01-19 Cytograft Tissue Engineering, Inc. System for the manufacture of tissue engineered blood vessels
DE102011107400B3 (en) * 2011-07-07 2012-10-04 Hugo Sachs Elektronik - Harvard Apparatus GmbH bioreactor
WO2013091865A1 (en) * 2011-12-23 2013-06-27 Medizinische Hochschule Hannover Method and device for producing a bioartifical tissue construct

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EP0348969A1 (en) * 1988-07-01 1990-01-03 Becton, Dickinson and Company Method for rapid adherence of endothelial cells onto a surface and surfaces prepared thereby
WO1991016009A1 (en) * 1990-04-17 1991-10-31 Curative Technologies, Inc. Coating prosthetic surfaces with mammalian cells

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EP0348969A1 (en) * 1988-07-01 1990-01-03 Becton, Dickinson and Company Method for rapid adherence of endothelial cells onto a surface and surfaces prepared thereby
WO1991016009A1 (en) * 1990-04-17 1991-10-31 Curative Technologies, Inc. Coating prosthetic surfaces with mammalian cells

Cited By (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5792603A (en) * 1995-04-27 1998-08-11 Advanced Tissue Sciences, Inc. Apparatus and method for sterilizing, seeding, culturing, storing, shipping and testing tissue, synthetic or native, vascular grafts
US6121042A (en) * 1995-04-27 2000-09-19 Advanced Tissue Sciences, Inc. Apparatus and method for simulating in vivo conditions while seeding and culturing three-dimensional tissue constructs
AU703117B2 (en) * 1995-04-27 1999-03-18 Advanced Tissue Sciences, Inc. Apparatus and method for sterilizing, seeding, culturing, storing, shipping and testing tissue, synthetic or native vascular grafts
EP0847238A4 (en) * 1995-06-07 2000-04-19 Advanced Tissue Sciences Inc Seeding heart valves
US5843766A (en) * 1995-06-07 1998-12-01 Advanced Tissue Sciences, Inc. Apparatus for the growth and packaging of three dimensional tissue cultures
US5846828A (en) * 1995-06-07 1998-12-08 Advanced Tissue Sciences Apparatus and method for sterilizing, seeding, culturing, storing, shipping, and testing tissue, synthetic, or mechanical heart valves orvalve segments
EP0847238A1 (en) * 1995-06-07 1998-06-17 Advanced Tissue Sciences, Inc. Seeding heart valves
US6060306A (en) * 1995-06-07 2000-05-09 Advanced Tissue Sciences, Inc. Apparatus and method for sterilizing, seeding, culturing, storing, shipping and testing replacement cartilage tissue constructs
US5763267A (en) * 1996-04-16 1998-06-09 Advanced Tissue Sciences Apparatus for the large scale growth and packaging of cell suspensions and three-dimensional tissue cultures
WO1997049799A1 (en) * 1996-06-27 1997-12-31 Advanced Tissue Sciences, Inc. Apparatus and method for sterilizing, seeding, culturing, storing, shipping and testing tissue, synthetic or native, vascular grafts
AU744686B2 (en) * 1996-11-20 2002-02-28 T. J. Smith & Nephew Limited Application of shear flow stress to chondrocytes
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