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    • 2. 发明申请
    • SKIN EQUIVALENT CULTURE
    • 皮肤等效培养
    • WO2006097701A2
    • 2006-09-21
    • PCT/GB2006/000890
    • 2006-03-14
    • INTERCYTEX LIMITEDKEMP, PaulSHERING, DavidJOHNSON, PennyMARSHALL, Damian
    • KEMP, PaulSHERING, DavidJOHNSON, PennyMARSHALL, Damian
    • C12N5/06A61L27/60
    • C12N5/0698A61L27/20A61L27/225A61L27/24A61L27/3687A61L27/3691A61L27/3804A61L27/3839A61L27/3886A61L27/3895A61L27/54A61L27/60C12N2500/25C12N2500/30C12N2500/32C12N2501/11C12N2501/15C12N2502/094C12N2502/1323C12N2533/56
    • 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.
    • 形成软结缔组织组合物例如皮肤等同物的方法,通过所述方法及其用途制备的组合物。 具体而言,一种形成结缔组织等效物的方法,包括以下步骤:(i)将产生胶原蛋白的细胞孵育在支持基质中或上; (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体并降解和置换支持基质; (iii)冷冻干燥该构建体; 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,由此形成结缔组织等效物,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)支撑基质是临时支撑基质,其中支撑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; (c)作为胶原产生细胞产生胶原蛋白的结果,临时纤维蛋白载体基质被细胞消化并被胶原代替,从而基本上用细胞原位合成的胶原基质代替临时纤维蛋白基质