公开(公告)号：US08114670B2

公开(公告)日：2012-02-14

申请号：US11886113

申请日：2006-03-14

申请人： Paul Kemp ,  David Shering ,  Andrew Shering, legal representative ,  Penny Johnson ,  Damian Marshall

发明人： Paul Kemp ,  David Shering ,  Penny Johnson ,  Damian Marshall

IPC分类号： C12N5/00 ,  G01N33/53 ,  A01N63/00 ,  A61K9/14

CPC分类号： C12N5/0698 ,  A61L27/20 ,  A61L27/225 ,  A61L27/24 ,  A61L27/3687 ,  A61L27/3691 ,  A61L27/3804 ,  A61L27/3839 ,  A61L27/3886 ,  A61L27/3895 ,  A61L27/54 ,  A61L27/60 ,  C12N2500/25 ,  C12N2500/30 ,  C12N2500/32 ,  C12N2501/11 ,  C12N2501/15 ,  C12N2502/094 ,  C12N2502/1323 ,  C12N2533/56

摘要： 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.

摘要翻译： 形成软结缔组织组合物如皮肤当量的方法，通过方法制备的组合物及其用途。 特别地，形成结缔组织当量的方法，包括以下步骤：（i）在载体基质中或载体上孵育胶原产生细胞; （ii）诱导和/或增强胶原产生细胞的胶原产生以形成胶原构建物并降解和置换支持基质; （iii）冷冻干燥该构造体; 和（iv）用胶原产生细胞和/或上皮细胞和/或内皮细胞和/或间充质细胞重新填充冷冻干燥的构建体，从而形成结缔组织当量，其中：（a）胶原产生细胞 基本上是成纤维细胞; 例如人类新生儿真皮成纤维细胞; （b）载体基质是临时支持基质，其中载体基质是纤维蛋白基质，例如通过凝血酶介导的纤维蛋白原聚合形成; 和（c）作为胶原蛋白产生细胞产生胶原的结果，临床纤维蛋白载体基质被细胞消化并被胶原替代，从而基本上用由细胞原位合成的胶原基质代替临时纤维蛋白基质 。