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Title:
SKIN EQUIVALENT CULTURE
Document Type and Number:
WIPO Patent Application WO2006097701
Kind Code:
A3
Abstract:
Methods of forming soft connective tissue compositions such as skin equivalents, compositions made by the methods and their uses. In particular, a method of forming a connective tissue equivalent, comprising the steps of: (i) incubating collagen-producing cells in or on a support matrix; (ii) inducing and/or enhancing collagen production by the collagen-producing cells to form a collagenous construct and degradation and replacement of the support matrix; (iii) freeze-drying the construct; and (iv) re-populating the freeze-dried construct with collagen-producing cells and/or epithelial cells and/or endothelial cells and/or mesenchymal cells, thereby forming a connective tissue equivalent, wherein: (a) the collagen-producing cells are substantially fibroblasts; for example human neonatal dermal fibroblasts; (b) the support matrix is a provisional support matrix in which the support matrix is a fibrin matrix, for example formed by thrombin-mediated polymerisation of fibrinogen; and (c) as a result of the collagen production by the collagen-producing cells the provisional fibrin support matrix is digested by the cells and is replaced by collagen, thereby essentially replacing the provisional fibrin matrix with a collagen matrix synthesised in situ by the cells.

Inventors:
KEMP PAUL (GB)
SHERING DAVID (GB)
JOHNSON PENNY (GB)
MARSHALL DAMIAN (GB)
Application Number:
PCT/GB2006/000890
Publication Date:
October 26, 2006
Filing Date:
March 14, 2006
Export Citation:
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Assignee:
INTERCYTEX LTD (GB)
KEMP PAUL (GB)
SHERING DAVID (GB)
JOHNSON PENNY (GB)
MARSHALL DAMIAN (GB)
International Classes:
A61L27/38; A61L27/60; C12N5/071
Domestic Patent References:
WO2003041568A22003-05-22
Other References:
MEANA A ET AL: "Large surface of cultured human epithelium obtained on a dermal matrix based on live fibroblast-containing fibrin gels", BURNS, BUTTERWORTH HEINEMANN, GB, vol. 24, no. 7, November 1998 (1998-11-01), pages 621 - 630, XP002204017, ISSN: 0305-4179
NEIDERT M R ET AL: "Enhanced fibrin remodeling in vitro with TGF-beta1, insulin and plasmin for improved tissue-equivalents", BIOMATERIALS, ELSEVIER SCIENCE PUBLISHERS BV., BARKING, GB, vol. 23, no. 17, September 2002 (2002-09-01), pages 3717 - 3731, XP004361334, ISSN: 0142-9612
HANSBROUGH ET AL: "Composite grafts of human keratinocytes", JOURNAL OF BURN CARE AND REHABILITATION, MOSBY- YEARBOOK INC., ST LOUI, MO, US, vol. 14, 1993, pages 485 - 494, XP002097653, ISSN: 0273-8481
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