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公开(公告)号：US20170241991A1
公开(公告)日：2017-08-24
申请号：US15440888
申请日：2017-02-23
CPC分类号： G01N33/5088 , A61L27/18 , A61L27/38 , A61L27/507 , A61L27/56 , B01L3/5027 , B01L3/502707 , B01L2200/027 , B01L2300/0681 , C12M21/08 , C12M23/34 , C12M25/02 , C12M35/08 , G09B23/28 , C08L69/00
摘要： The present invention provides an in vitro blood vessel model for investigation of drug induced vascular injury and other vascular pathologies. The in vitro blood vessel model provides two channels separated by a porous membrane that is coated on one side by an endothelial cell layer and is coated on the other side by a smooth muscle cell layer, wherein said model is susceptible to the extravasation of red blood cells across said porous membrane due to drug induced vascular injury.
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公开(公告)号：US20100234678A1
公开(公告)日：2010-09-16
申请号：US12576826
申请日：2009-10-09
CPC分类号： A61F2/06 , A61F2/022 , A61F2/04 , A61F2/062 , A61F2002/068 , G01N33/5008 , G06F19/00
摘要： The invention provides method of fabricating a scaffold comprising a fluidic network, including the steps of: (a) generating an initial vascular layer for enclosing the chamber and providing fluid to the cells, the initial vascular layer having a network of channels for fluid; (b) translating the initial vascular layer into a model for fluid dynamics analysis; (c) analyzing the initial vascular layer based on desired parameters selected from the group consisting of a characteristic of a specific fluid, an input pressure, an output pressure, an overall flow rate and combinations thereof to determine sheer stress and velocity within the network of channels; (d) measuring the sheer stress and the velocity and comparing the obtained values to predetermined values; (e) determining if either of the shear stress or the velocity are greater than or less than the predetermined values, and (f) optionally modifying the initial vascular layer and repeating steps (b)-(e). The invention also provides compositions comprising a vascular layer for use in tissue lamina as well as a medical devices having a vascular layer and kits.
摘要翻译： 本发明提供了制造包括流体网络的支架的方法，包括以下步骤：（a）产生用于封闭腔室并向细胞提供流体的初始血管层，初始血管层具有用于流体的通道网络; （b）将初始血管层转化为用于流体动力学分析的模型; （c）基于从由特定流体的特性，输入压力，输出压力，总体流速及其组合组成的组中选择的期望参数来分析初始血管层，以确定网络内的纯粹的应力和速度 渠道; （d）测量纯应力和速度，并将获得的值与预定值进行比较; （e）确定剪切应力或速度是否大于或小于预定值，和（f）任选地修饰初始血管层并重复步骤（b） - （e）。 本发明还提供包含用于组织层的血管层的组合物以及具有血管层和试剂盒的医疗装置。
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公开(公告)号：US20150366651A1
公开(公告)日：2015-12-24
申请号：US14615646
申请日：2015-02-06
CPC分类号： A61F2/06 , A61F2/022 , A61F2/04 , A61F2/062 , A61F2002/068 , G01N33/5008
摘要： The invention provides method of fabricating a scaffold comprising a fluidic network, including the steps of: (a) generating an initial vascular layer for enclosing the chamber and providing fluid to the cells, the initial vascular layer having a network of channels for fluid; (b) translating the initial vascular layer into a model for fluid dynamics analysis; (c) analyzing the initial vascular layer based on desired parameters selected from the group consisting of a characteristic of a specific fluid, an input pressure, an output pressure, an overall flow rate and combinations thereof to determine sheer stress and velocity within the network of channels; (d) measuring the sheer stress and the velocity and comparing the obtained values to predetermined values; (e) determining if either of the shear stress or the velocity are greater than or less than the predetermined values, and (f) optionally modifying the initial vascular layer and repeating steps (b)-(e). The invention also provides compositions comprising a vascular layer for use in tissue lamina as well as a medical devices having a vascular layer and kits.
摘要翻译： 本发明提供了制造包括流体网络的支架的方法，包括以下步骤：（a）产生用于封闭腔室并向细胞提供流体的初始血管层，初始血管层具有用于流体的通道网络; （b）将初始血管层转化为用于流体动力学分析的模型; （c）基于从由特定流体的特性，输入压力，输出压力，总体流速及其组合组成的组中选择的期望参数来分析初始血管层，以确定网络内的纯粹的应力和速度 渠道; （d）测量纯应力和速度，并将获得的值与预定值进行比较; （e）确定剪切应力或速度是否大于或小于预定值，和（f）任选地修饰初始血管层并重复步骤（b） - （e）。 本发明还提供包含用于组织层的血管层的组合物以及具有血管层和试剂盒的医疗装置。
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24.发明申请Nanotopographic Compositions and Methods for Cellular Organization in Tissue Engineered Structures 有权组织工程结构中的细胞组织的纳米形成组合物和方法公开(公告)号：US20080026464A1
公开(公告)日：2008-01-31
申请号：US10568574
申请日：2004-08-18
CPC分类号： A61L27/3886 , A61L27/50 , B33Y80/00 , C12N5/0075 , C12N5/067 , C12N2535/10
摘要： The present invention relates to tissue engineered compositions and methods comprising nanotopographic surface topography (“nanotopography”) for use in modulating the organization and/or function of multiple cell types.
摘要翻译： 本发明涉及包含用于调节多种细胞类型的组织和/或功能的纳米形态表面形貌（“纳米形貌”）的组织工程化组合物和方法。
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25.发明授权公开(公告)号：US08147562B2
公开(公告)日：2012-04-03
申请号：US10528737
申请日：2003-09-23
IPC分类号： A61F2/02
CPC分类号： C12N5/0062 , B01L3/5027 , B33Y80/00 , C12M25/14 , G06F19/00 , G16H50/50 , Y10T137/206 , Y10T137/212
摘要： The present invention relates to methods for the design and fabrication of biological constructs, such as organ simulants or organ replacements, which contain complex microfluidic architecture. Designs of the present invention provide increased space in the lateral dimension, enabling a large number of small channels for small vessels.
摘要翻译： 本发明涉及用于设计和制造包含复杂微流体结构的生物构建体如器官模拟物或器官替代物的方法。 本发明的设计在横向尺寸上提供了增加的空间，使得能够为小型容器提供大量的小通道。
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公开(公告)号：USRE42479E1
公开(公告)日：2011-06-21
申请号：US10782750
申请日：2004-02-19
IPC分类号： A61F2/24
CPC分类号： A61L27/3886 , A61F2/2415 , A61L27/18 , A61L27/3633 , A61L27/3645 , A61L27/3804 , A61L27/3843 , A61L27/507 , A61L27/58 , C08L67/04
摘要： It has been discovered that improved yields of engineered tissue following implantation, and engineered tissue having enhanced mechanical strength and flexibility or pliability, can be obtained by implantation, preferably subcutaneously, of a fibrous polymeric matrix for a period of time sufficient to obtain ingrowth of fibrous tissue and/or blood vessels, which is the removed for subsequent implantation at the site where the implant is desired. The matrix is optionally seeded prior to the first implantation, after ingrowth of the fibrous tissue, or at the time of reimplantation. The time required for fibrous ingrowth typically ranges from days to weeks. The method is particularly useful in making valves and tubular structures, especially heart valves and blood vessels.
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27.发明申请公开(公告)号：US20110008765A1
公开(公告)日：2011-01-13
申请号：US12707469
申请日：2010-02-17
申请人： Joseph P. Vacanti , Robert Rubin , Wing Cheung
发明人： Joseph P. Vacanti , Robert Rubin , Wing Cheung
CPC分类号： C12Q1/48 , B33Y80/00 , C12Q1/00 , C12Q1/18 , C12Q1/26 , C12Q1/34 , C12Q1/42 , C12Q1/44 , G01N33/5038 , G01N33/5088
摘要： The present invention generally relates to a combination of the fields of tissue engineering, drug discovery and drug development. It more specifically provides new methods and materials for testing the efficacy and safety of experimental drugs, defining the metabolic pathways of experimental drugs and characterizing the properties (e.g., side effects, new uses) of existing drugs. Preferably, evaluation is carried out in three-dimensional tissue-engineered systems, wherein drug toxicity, metabolism, interaction and/or efficacy can be determined.
摘要翻译： 本发明一般涉及组织工程，药物发现和药物开发领域的组合。 它更具体地提供了用于测试实验药物的功效和安全性，定义实验药物的代谢途径和表征现有药物的性质（例如副作用，新用途）的新方法和材料。 优选地，在三维组织工程系统中进行评价，其中可以确定药物毒性，代谢，相互作用和/或功效。
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公开(公告)号：US07462471B2
公开(公告)日：2008-12-09
申请号：US10775768
申请日：2004-02-10
申请人： Antonios G. Mikos , Joseph P. Vacanti , Robert S. Langer , Linda G. Griffith , Georgios Sarakinos
发明人： Antonios G. Mikos , Joseph P. Vacanti , Robert S. Langer , Linda G. Griffith , Georgios Sarakinos
CPC分类号： G02B27/0031 , A61L27/18 , A61L27/56 , A61L2400/06 , G03F7/40 , H01L21/0273 , H01L21/32139 , C08L67/04
摘要： Polymeric materials are used to make a pliable, non-toxic, injectable porous template for vascular ingrowth. The pore size, usually between approximately 100 and 300 microns, allows vascular and connective tissue ingrowth throughout approximately 10 to 90% of the matrix following implantation, and the injection of cells uniformly throughout the implanted matrix without damage to the cells or patient. The introduced cells attach to the connective tissue within the matrix and are fed by the blood vessels. The preferred material for forming the matrix or support structure is a biocompatible synthetic polymer which degrades in a controlled manner by hydrolysis into harmless metabolites, for example, polyglycolic acid, polylactic acid, polyorthoester, polyanhydride, or copolymers thereof. The rate of tissue ingrowth increases as the porosity and/or the pore size of the implanted devices increases. The time required for the tissue to fill the device depends on the polymer crystallinity and is less for amorphous polymers versus semicrystalline polymers. The vascularity of the advancing tissue is consistent with time and independent of the biomaterial composition and morphology.
摘要翻译： 聚合材料用于制造一种柔韧，无毒，可注射的多孔模板，用于血管向内生长。 通常在约100和300微米之间的孔径允许血管和结缔组织在植入后约10至90％的基质向内生长，并且在整个植入的基质中均匀注射细胞而不损伤细胞或患者。 引入的细胞附着到基质内的结缔组织，并由血管进食。 用于形成基质或支撑结构的优选材料是生物相容的合成聚合物，其通过水解以受控的方式降解成无害的代谢物，例如聚乙醇酸，聚乳酸，聚原酸酯，聚酐或其共聚物。 随着植入装置的孔隙率和/或孔径增加，组织向内生长的速率增加。 组织填充装置所需的时间取决于聚合物的结晶度，对于无定形聚合物与半结晶聚合物相比较少。 前进组织的血管分布与时间一致，与生物材料组成和形态无关。
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公开(公告)号：US07078032B2
公开(公告)日：2006-07-18
申请号：US10690077
申请日：2003-10-21
CPC分类号： C12N5/0656 , A61K38/22 , A61K48/00 , B33Y10/00 , B33Y30/00 , B33Y70/00 , B33Y80/00 , C12N2510/02
摘要： Normal cells, such as fibroblasts or other tissue or organ cell types, are genetically engineered to express biologically active, therapeutic agents, such as proteins that are normally produced in small amounts, for example, MIS, or other members of the TGF-beta family Herceptin™, interferons, and anti-angiogenic factors. These cells are seeded into a matrix for implantation into the patient to be treated. Cells may also be engineered to include a lethal gene, so that implanted cells can be destroyed once treatment is completed. Cells can be implanted in a variety of different matrices. In a preferred embodiment, these matrices are implantable and biodegradable over a period of time equal to or less than the expected period of treatment, when cells engraft to form a functional tissue producing the desired biologically active agent. Implantation may be ectopic or in some cases orthotopic. Representative cell types include tissue specific cells, progenitor cells, and stem cells. Matrices can be formed of synthetic or natural materials, by chemical coupling at the time of implantation, using standard techniques for formation of fibrous matrices from polymeric fibers, and using micromachining or microfabrication techniques. These devices and strategies are used as delivery systems via standard or minimally invasive implantation techniques for any number of parenterally deliverable recombinant proteins, particularly those that are difficult to produce in large amounts and/or active forms using conventional methods of purification, for the treatment of a variety of conditions.
摘要翻译： 正常细胞如成纤维细胞或其它组织或器官细胞类型被遗传工程化以表达生物活性的治疗剂，例如通常少量产生的蛋白质，例如MIS或TGF-β家族的其他成员 赫赛汀（Herceptin TM），干扰素和抗血管生成因子。 将这些细胞接种到基质中以便植入待治疗的患者中。 细胞还可以被设计成包括致死基因，使得植入的细胞一旦完成就可以被破坏。 细胞可以植入各种不同的基质中。 在优选的实施方案中，当细胞移植以形成产生所需生物活性剂的功能组织时，这些基质可植入和生物降解的时间等于或小于预期的治疗期。 植入可能是异位的或在某些情况下是原位的。 代表性的细胞类型包括组织特异性细胞，祖细胞和干细胞。 矩阵可以由合成或天然材料形成，通过植入时的化学偶联，使用从聚合物纤维形成纤维基质的标准技术，以及使用微加工或微细加工技术。 这些装置和策略通过标准或微创植入技术用于任何数量的肠胃外可输送的重组蛋白质，特别是使用常规的纯化方法难以大量和/或活性形式生产的装置和策略，用于治疗 各种条件。
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公开(公告)号：US06692738B2
公开(公告)日：2004-02-17
申请号：US09770339
申请日：2001-01-26
IPC分类号： A61K4800
CPC分类号： C12N5/0656 , A61K38/22 , A61K48/00 , B33Y10/00 , B33Y30/00 , B33Y70/00 , B33Y80/00 , C12N2510/02
摘要： Normal cells, such as fibroblasts or other tissue or organ cell types, are genetically engineered to express biologically active, therapeutic agents, such as proteins that are normally produced in small amounts, for example, MIS, or other members of the TGF-beta family Herceptin™, interferons, andanti-angiogenic factors. These cells are seeded into a matrix for implantation into the patient to be treated. Cells may also be engineered to include a lethal gene, so that implanted cells can be destroyed once treatment is completed. Cells can be implanted in a variety of different matrices. In a preferred embodiment, these matrices are implantable and biodegradable over a period of time equal to or less than the expected period of treatment, when cells engraft to form a functional tissue producing the desired biologically active agent. Implantation may be ectopic or in some cases orthotopic. Representative cell types include tissue specific cells, progenitor cells, and stem cells. Matrices can be formed of synthetic or natural materials, by chemical coupling at the time of implantation, using standard techniques for formation of fibrous matrices from polymeric fibers, and using micromachining or microfabrication techniques. These devices and strategies are used as delivery systems via standard or minimally invasive implantation techniques for any number of parenterally deliverable recombinant proteins, particularly those that are difficult to produce in large amounts and/or active forms using conventional methods of purification, for the treatment of a variety of conditions that produce abnormal growth, including treatment of malignant and benign neoplasias, vascular malformations (hemangiomas), inflammatory conditions, keloid formation, abdominal or plural adhesions, endometriosis, congenital or endocrine abnormalities, and other conditions that can produce abnormal growth such as infection. Efficacy of treatment with the therapeutic biologicals is detected by determining specific criteria, for example, cessation of cell proliferation, regression of abnormal tissue, or cell death, or expression of genes or proteins reflecting the above.
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