Chemistry: molecular biology and microbiology – Spore forming or isolating process
Patent
1989-07-17
1991-12-31
Stone, Jacqueline
Chemistry: molecular biology and microbiology
Spore forming or isolating process
424423, 435240243, 623 1, 623 11, 623 12, C12N 500, A61F 202, A61F 204, A61F 206
Patent
active
050772155
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to the use of a copolymer of perfluoro-3,6-dioxa-4-methyl-7-octene sulphonyl fluoride and a monomer as a surface for the attachment and growth of adherent animal cells. The invention has particular application to the manufacture and use of prosthetic vascular grafts, connective tissue replacements and soft tissue replacements that incorporate such a copolymer.
BACKGROUND ART
The design or selection of materials useful in vascular prostheses requires an understanding of the characteristics necessary for irreversible endothelialisation of a surface and for inhibition of undesirable platelet interactions. An approach to the development of vascular prostheses that has been taken has been guided by the object of circumventing the acute problems of platelet activation, adhesion and thrombogenesis. This approach involves designing a blood interface which disallows thrombogenesis by preventing platelet activation directly, and may be achieved either by the selective incorporation or adsorption of platelet binding inhibitors, such as serum albumin or heparin, or by providing a surface which directly repels or inactivates platelets electrostatically. However these modifications might also suppress the attachment and growth of endothelial cells on the luminal surface of the prosthesis. Grafts prepared using this approach may therefore be regarded as unhealed and a physiological and anatomical state comparable to the normal luminal structure is not achieved.
It is generally known that surfaces which support endothelial cell growth comparable to that seen on glow discharged polystyrene also tend to be thrombogenic. However it is also known that sulphonated polystyrenes have antithrombogenic activity which is reported to be a feature of the negative charge of sulphonate groups. The present invention has been developed by following this line of investigation.
In a recent study, McAuslan and Johnson [(1987) J. Biomedical Materials Research 21.921-935] showed that the hydroxyl rich surface of poly(hydroxyl ethyl methacrylate)(pHEMA) hydrogel can be converted from a non-cell adhesive to a highly cell adhesive state by either hydrolytic surface etching or by copolymerization with methacrylic acid. Thus cell adhesion appeared to correlate with the introduction of surface COOH groups although this alone was not a sufficient condition. This has raised the question of whether other negatively charged moieties would be just as effective at promoting cell attachment.
A fluorocarbon polymer with pendant sulphonic groups is the chemically inert, non-crosslinked cation-exchange resin known by the trade mark NAFION. NAFION is chemically identified as a copolymer of tetrafluoroethylene and perfluoro-3,6-dioxa-4-methyl-7-octene sulphonyl fluoride. The mechanical and chemical stability of this perfluorosulphonate ionomer and its selective permeability to charged ions had made it useful for industrial electrochemical separating processes. It can be prepared as films or tubes and is hydrophilic, which is in contrast to polytetrafluoroethylene (PTFE, which is known by the trade mark TEFLON) or expanded PTFE (which is known by the trade mark GORE-TEX), a material which is in wide use as a vascular graft.
We have now found that any copolymer of perfluoro-3,6-dioxa-4-methyl-7-octene sulphonyl fluoride and a monomer, and particularly NAFION, may, when in a neutralised form, be used as a surface for the attachment and growth of adherent animal cells from different tissue sources, including endothelial cells. In this specification and claims, reference to being in a neutralised form means within one pH unit of pH 7.0.
DISCLOSURE OF THE INVENTION
It is an object of the present invention to provide a material useful in vascular prostheses and other implantables having improved biocompatibility arising from enhanced endothelial cell attachment properties and anti-thrombogenicity which will substantially overcome the disadvantages of the prior art.
In accordance with one aspect of the present inven
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Johnson Graham
McAuslan Brian R.
Norris William
Steele John G.
Commonwealth Scientific and Industrial Research Organisation
Elliott George C.
Stone Jacqueline
Telectronics Pty. Limited
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