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1. 发明申请

US20050136510A1 Methods of preparing crosslinked materials and bioprosthetic devices 有权
标题翻译：制备交联材料和生物假体装置的方法
公开(公告)号：US20050136510A1
公开(公告)日：2005-06-23
申请号：US10974206
申请日：2004-10-27
申请人： Marc Hendriks , Frank Everaerts , Mirian Gillissen , Michel Verhoeven , Mark Torrianni
发明人： Marc Hendriks , Frank Everaerts , Mirian Gillissen , Michel Verhoeven , Mark Torrianni
IPC分类号： A61L27/24 , A61L27/36 , C12P21/06 , C08G63/48
CPC分类号： A61L27/3687 , A61L27/24
摘要： Methods for making crosslinked material, such as collagen-based material, and bioprosthetic devices. The crosslinked material includes hydroxyl groups, carboxyl groups, and amine groups prior to crosslinking. The methods include removing at least a portion of the zero-length ester crosslinks in a crosslinked material and/or blocking at least a portion of the amine groups that are reactive with carboxyl groups and form zero-length crosslinks.
摘要翻译：用于制造交联材料的方法，例如胶原基材料和生物假体装置。交联材料在交联之前包括羟基，羧基和胺基。所述方法包括去除交联材料中的零长度酯交联的至少一部分和/或阻断与羧基反应并形成零长度交联的至少一部分胺基。

2. 发明申请

US20050020506A1 Crosslinked compositions comprising collagen and demineralized bone matrix, methods of making and methods of use 审中-公开
标题翻译：包含胶原和脱矿质骨基质的交联组合物，制备方法和使用方法
公开(公告)号：US20050020506A1
公开(公告)日：2005-01-27
申请号：US10626571
申请日：2003-07-25
申请人： Susan Drapeau , Mark Torrianni , Frank Everaerts , William McKay
发明人： Susan Drapeau , Mark Torrianni , Frank Everaerts , William McKay
IPC分类号： A61L24/00 , A61L24/10 , A61L27/22 , A61L27/36 , A61K38/39 , A61K38/18
CPC分类号： A61L27/3687 , A61L24/0005 , A61L24/102 , A61L27/227 , A61L27/3608 , A61L27/3645 , A61L2430/02
摘要： A composition comprising a collagen protein and demineralized bone matrix is described wherein the composition is chemically cross-linked with a carbodiimide such as N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC). The crosslinking reaction can be conducted in the presence of N-hydroxysuccinimide (NHS). The collagen can be in a porous matrix or scaffolding. The DBM can be in the form of particles dispersed in the collagen. A method of making the composition is also described wherein a collagen slurry is cast into the desired shape, freeze dried to form a porous scaffolding and infitrated with a solution comprising the cross-linking agent. The composition can be used as an implant for tissue (e.g., soft tissue or bone) engineering.
摘要翻译：描述了包含胶原蛋白和软化骨基质的组合物，其中组合物与碳二亚胺如N-（3-二甲基氨基丙基）-N-乙基碳二亚胺盐酸盐（EDC）化学交联。交联反应可以在N-羟基琥珀酰亚胺（NHS）的存在下进行。胶原蛋白可以在多孔基质或脚手架中。 DBM可以是分散在胶原中的颗粒的形式。还描述了制备组合物的方法，其中将胶原浆液浇铸成所需形状，冷冻干燥以形成多孔脚手架，并用包含交联剂的溶液进行渗透。组合物可以用作组织（例如，软组织或骨）工程的植入物。

3. 发明申请

US20070020248A1 Process for biological tissue 有权
标题翻译：生物组织过程
公开(公告)号：US20070020248A1
公开(公告)日：2007-01-25
申请号：US11365401
申请日：2006-03-01
申请人： Frank Everaerts , Mark Torrianni , Frans Everaerts , Paul Trescony , Wilfred Hartog
发明人： Frank Everaerts , Mark Torrianni , Frans Everaerts , Paul Trescony , Wilfred Hartog
IPC分类号： A61K48/00 , C12N15/87
CPC分类号： A61K35/34 , A61L27/3604 , A61L27/3625 , A61L27/3683
摘要： The present invention provides an electrophoretic system, apparatus, and method of use thereof for the preparation of a tissue-derived bioprosthesis.
摘要翻译：本发明提供了一种用于制备组织衍生生物假体的电泳系统，装置及其使用方法。

4. 发明申请

US20050266390A1 Processes for removing cells and cell debris from tissue and tissue constructs used in transplantation and tissue reconstruction 审中-公开
标题翻译：从用于移植和组织重建的组织和组织构建体中去除细胞和细胞碎片的方法
公开(公告)号：US20050266390A1
公开(公告)日：2005-12-01
申请号：US10858174
申请日：2004-06-01
申请人： Yuichiro Ueda , Mark Torrianni
发明人： Yuichiro Ueda , Mark Torrianni
IPC分类号： A01N1/02 , A61F2/06 , A61F2/24
CPC分类号： A61F2/062
摘要： Methods for decellularizing mammalian tissue for use in transplantation and tissue engineering. The invention includes methods for simultaneous application of an ionic detergent and a nonionic detergent for a long time period, which may exceed five days. One method utilizes SDS as the ionic detergent and Triton-X 100 as the nonionic detergent. A long rinse step follows, which may also exceed five days in length. This long duration, simultaneous extraction with two detergents produced tissue showing stress-strain curves and DSC data similar to that of fresh, unprocessed tissue. The processed tissue is largely devoid of cells, has the underlying structure essentially intact, and also shows a significantly improved inflammatory response relative to fresh tissue, even without glutaraldehyde fixation. Significantly reduced in situ calcification has also been demonstrated relative to glutaraldehyde fixed tissue. Applicants believe the ionic and non-ionic detergents may act synergistically to bind protein to the ionic detergent and may remove an ionic detergent-protein complex from the tissue using the non-ionic detergent. The present methods find one exemplary use in decellularizing porcine heart valve leaflet and wall tissue for use in transplantation.
摘要翻译：用于移植和组织工程的哺乳动物组织脱细胞的方法。本发明包括长时间同时施用离子型洗涤剂和非离子洗涤剂的方法，其可能超过5天。一种方法使用SDS作为离子型洗涤剂，Triton-X 100作为非离子洗涤剂。长时间冲洗步骤，长度也可能超过5天。这种长时间的同时萃取与两种洗涤剂产生的组织显示应力 - 应变曲线和DSC数据类似于新鲜的，未加工的组织。经处理的组织大部分没有细胞，具有基本完整的基础结构，并且相对于新鲜组织也显示出明显改善的炎症反应，即使没有戊二醛固定。与戊二醛固定组织相比，原位钙化明显降低。申请人认为，离子和非离子洗涤剂可以协同作用以将蛋白质结合到离子洗涤剂上，并且可以使用非离子洗涤剂从组织中除去离子洗涤剂 - 蛋白质复合物。本发明方法在猪心脏瓣膜小叶和壁组织脱细胞用于移植中发现一个示例性用途。

5. 发明申请

US20070123700A1 Processes for removing cells and cell debris from tissue and tissue constructs used in transplantation and tissue reconstruction 审中-公开
标题翻译：从用于移植和组织重建的组织和组织构建体中去除细胞和细胞碎片的方法
公开(公告)号：US20070123700A1
公开(公告)日：2007-05-31
申请号：US11698818
申请日：2007-01-26
申请人： Yuichiro Ueda , Mark Torrianni
发明人： Yuichiro Ueda , Mark Torrianni
IPC分类号： C07K1/10
CPC分类号： A61F2/062
摘要： Methods for decellularizing mammalian tissue for use in transplantation and tissue engineering. The invention includes methods for simultaneous application of an ionic detergent and a nonionic detergent for a long time period, which may exceed five days. One method utilizes SDS as the ionic detergent and Triton-X 100 as the nonionic detergent. A long rinse step follows, which may also exceed five days in length. This long duration, simultaneous extraction with two detergents produced tissue showing stress-strain curves and DSC data similar to that of fresh, unprocessed tissue. The processed tissue is largely devoid of cells, has the underlying structure essentially intact, and also shows a significantly improved inflammatory response relative to fresh tissue, even without glutaraldehyde fixation. Significantly reduced in situ calcification has also been demonstrated relative to glutaraldehyde fixed tissue. Applicants believe the ionic and non-ionic detergents may act synergistically to bind protein to the ionic detergent and may remove an ionic detergent-protein complex from the tissue using the non-ionic detergent. The present methods find one exemplary use in decellularizing porcine heart valve leaflet and wall tissue for use in transplantation.
摘要翻译：用于移植和组织工程的哺乳动物组织脱细胞的方法。本发明包括长时间同时施用离子型洗涤剂和非离子洗涤剂的方法，其可能超过5天。一种方法使用SDS作为离子型洗涤剂，Triton-X 100作为非离子洗涤剂。长时间冲洗步骤，长度也可能超过5天。这种长时间的同时萃取与两种洗涤剂产生的组织显示应力 - 应变曲线和DSC数据类似于新鲜的，未加工的组织。经处理的组织大部分没有细胞，具有基本完整的基础结构，并且相对于新鲜组织也显示出明显改善的炎症反应，即使没有戊二醛固定。与戊二醛固定组织相比，原位钙化明显降低。申请人认为，离子和非离子洗涤剂可以协同作用以将蛋白质结合到离子洗涤剂上，并且可以使用非离子洗涤剂从组织中除去离子洗涤剂 - 蛋白质复合物。本发明方法在猪心脏瓣膜小叶和墙壁组织脱细胞用于移植中发现了一个示例性用途。

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