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1. 发明公开

EP3600668A2 MODULAR ORGAN MICROPHYSIOLOGICAL SYSTEM WITH MICROBIOME 有权
公开(公告)号：EP3600668A2
公开(公告)日：2020-02-05
申请号：EP18732169.0
申请日：2018-03-20
申请人： Massachusetts Institute of Technology
发明人： GRIFFITH, Linda, G. , TRUMPER, David, L. , EDINGTON, Collin , ROHATGI, Gaurav , FREAKE, Duncan , SOENKSEN, Luis , KASSIS, Timothy , BHUSHAN, Brij, Mohan
IPC分类号： B01L3/00 , C12M1/32 , C12M1/12 , C12M1/00 , F04B19/00 , F04B23/06 , F04B43/04 , G01F23/00

3. 发明公开

EP2346526A2 COMPOSITIONS OF AND METHODS OF USING LIGAND DIMERS 审中-公开
标题翻译：组合物及其使用配体二聚体的方法
公开(公告)号：EP2346526A2
公开(公告)日：2011-07-27
申请号：EP09789353.1
申请日：2009-09-22
申请人： Massachusetts Institute of Technology , The Brigham and Women's Hospital, Inc.
发明人： ALVAREZ, Luis, M. , GRIFFITH, Linda, G. , LEE, Richard, T.
IPC分类号： A61K38/18 , A61P35/00 , A61P25/00 , A61P17/02 , C12N15/62
CPC分类号： A61K38/1808 , A61K38/1841 , C07K14/475 , C07K14/78 , C07K2319/70 , C07K2319/73 , C07K2319/74
摘要： Provided herein are ligand dimers, compositions thereof, as well as methods of their use. The ligand dimers provided can comprise at least one ligand to a Her receptor and can be used to force dimerization of specific receptor pairs. The forced dimerization of specific receptor pairs can be used to control (e.g., promote or inhibit) signaling, and, therefore, the ligand dimers provided can also be used in various forms of treatment in which such signaling control is beneficial to a subject. It follows that methods for controlling signaling are provided as are various methods of treatment.

4. 发明公开

EP1121072A1 COMPOSITES FOR TISSUE REGENERATION AND METHODS OF MANUFACTURE THEREOF 审中-公开
标题翻译：维尔德维尔·弗吉尼亚州赫尔辛基
公开(公告)号：EP1121072A1
公开(公告)日：2001-08-08
申请号：EP99951941.6
申请日：1999-10-12
申请人： Therics, Inc. , MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： SHERWOOD, Jill, K. , GRIFFITH, Linda, G. , BROWN, Scott
IPC分类号： A61F2/28 , A61F2/30 , A61L27/00
CPC分类号： A61L27/46 , A61F2/28 , A61F2/30756 , A61F2/3094 , A61F2/468 , A61F2002/0086 , A61F2002/2817 , A61F2002/2835 , A61F2002/30004 , A61F2002/30011 , A61F2002/30062 , A61F2002/30199 , A61F2002/30301 , A61F2002/30678 , A61F2002/30762 , A61F2002/30766 , A61F2002/3093 , A61F2002/30952 , A61F2002/30962 , A61F2002/30968 , A61F2002/3097 , A61F2002/30971 , A61F2002/4648 , A61F2210/0004 , A61F2230/0063 , A61F2230/0095 , A61F2240/001 , A61F2250/0014 , A61F2250/0023 , A61F2310/00179 , A61F2310/00203 , A61F2310/00293 , A61F2310/00365 , A61L27/56 , B29C64/165 , B29L2031/7532 , B33Y70/00 , B33Y80/00 , A61L27/58 , A61L27/54
摘要： Composite devices for tissue engineering are provided having a gradient of one or more of the following: materials, macroarchitecture, microarchitecture, or mechanical properties, which can be used to select or promote attachment of specific cell types on and in the devices prior to and/or after implantation. In various embodiments, the gradient forms a transition zone in the device from a region composed of materials or having properties best suited for one type of tissue to a region composed of materials or having properties suited for a different type of tissue. The devices are made in a continuous process that imparts structural integrity as well as a unique gradient of materials in the architecture. The gradient may relate to the materials, the macroarchitecture, the microarchitecture, the mechanical properties of the device, or several of these together. The devices disclosed herein typically are made using solid free form processes, especially three-dimensional printing process (3DPTM). The device can be manufactured in a single continuous process such that the transition from one form of tissue regeneration scaffold and the other form of tissue regeneration scaffold have no 'seams' and are not subject to differential swelling along an axis once the device is implanted into physiological fluid.
摘要翻译：提供用于组织工程的复合装置，其具有下列一种或多种的梯度：材料，微结构，微结构或机械性质，其可用于选择或促进特定细胞类型附着在装置之前和/ 或植入后。在各种实施方案中，梯度在由材料构成的区域或具有最适合于一种类型的组织的特征的区域中形成过渡区域到由材料构成的区域或具有适于不同类型的组织的性质的区域。这些设备是在连续的过程中制造的，在架构中赋予结构完整性以及唯一的材料梯度。梯度可能与材料，宏建筑结构，微架构，设备的机械性能或其中几种有关。本文公开的装置通常使用固体自由形式工艺，特别是三维印刷工艺（3DP TM）制成。该装置可以在单个连续过程中制造，使得来自组织再生支架的一种形式的过渡和组织再生支架的另一种形式没有“接缝”，并且一旦将该装置植入，就不会沿轴线发生不同的肿胀生理液体。

5. 发明公开

EP1064353A2 VASCULARIZED PERFUSED MICROTISSUE/MICRO-ORGAN ARRAYS 无效
标题翻译：血管灌注安排微结构和微器官
公开(公告)号：EP1064353A2
公开(公告)日：2001-01-03
申请号：EP99913967.8
申请日：1999-03-18
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： GRIFFITH, Linda, G. , TANNENBAUM, Steven, R. , POWERS, Mark, J. , DOMANSKY, Karel , THOMPSON, Charles, D.
IPC分类号： C12M3/04 , C12M1/34
CPC分类号： G01N33/5038 , B01J19/0046 , B01J2219/00286 , B01J2219/00308 , B01J2219/00313 , B01J2219/00317 , B01J2219/00319 , B01J2219/00351 , B01J2219/00376 , B01J2219/00416 , B01J2219/00585 , B01J2219/00659 , B01J2219/0072 , B33Y10/00 , B33Y80/00 , B82Y30/00 , C12M21/08 , C12M23/12 , C12M41/46 , C40B60/14 , G01N33/5008 , G01N33/502 , G01N33/5058 , G01N33/5064 , G01N33/5073
摘要： Systems including (1) a micromatrix and perfusion assembly suitable for seeding and attachment of cells within the matrix and for morphogenesis of seeded cells into complex, hierarchical tissue or organ structures, wherein the matrix includes channels or vessels through which culture medium, oxygen, or other nutrient or body fluids can be perfused while controlling gradients of nutrients and exogenous metabolites throughout the perfusion path independently of perfusion rate, and (2) sensor means for detecting changes in either cells within the matrix or in materials exposed to the cells, have been developed. Methods for making the micromatrices include micromachining, micromolding, embossing, laser drilling, and electro deposition machining. Cells can be of one or more types, either differentiated or undifferentiated. In a preferred embodiment, the matrix is seeded with a mixture of cells including endothelial cells which will line the channels to form 'blood vessels', and at least one type of parenchymal cells, such as hepatocytes, pancreatic cells, or other organ cells. The system can be used to screen materials for an effect on the cells, for an effect of the cells on the materials (for example, in a manner equivalent to tissue metabolism of a drug), or to test a material on a biological that must first infect cells or tissues, such as viruses. The apparatus also can be used to provide a physiological environment for expansion of stem cells, or for enabling gene therapy in vitro.

6. 发明公开

EP2648740A2 TRICALCIUM PHOSPHATE BINDING PEPTIDES AND USES THEREOF 有权转让
标题翻译： TRAILCIUMPHOSPHAT-BINDENDE PEPTIDE UND IHRE VERWENDUNG
公开(公告)号：EP2648740A2
公开(公告)日：2013-10-16
申请号：EP11811206.9
申请日：2011-12-06
申请人： Massachusetts Institute Of Technology
发明人： ALVAREZ, Luis , GRIFFITH, Linda, G. , GUERRERO, Yadir , STOCKDALE, Linda , RIVERA, Jaime
IPC分类号： A61K35/28
CPC分类号： C07K7/08 , A61K35/28 , A61K38/10 , A61K38/1808 , A61L27/12 , A61L27/3834 , A61L27/3847 , A61L27/54 , A61L27/56 , A61L2300/25 , A61L2300/252 , A61L2300/414 , A61L2400/08 , A61L2400/18 , A61L2430/02 , C07K14/485 , C12N5/0662 , A61K2300/00
摘要： The invention is directed to a composition comprising all or a portion of a beta-tricalcium phosphate (beta-TCP) bound to all or a portion of a beta-TCP binding peptide and methods of use thereof.
摘要翻译：本发明涉及包含与β-TCP结合肽的全部或一部分结合的全部或部分β-磷酸三钙（β-TCP）的组合物及其使用方法。

7. 发明授权

EP1071467B1 COMB COPOLYMERS FOR REGULATING CELL-SURFACE INTERACTIONS 有权
标题翻译：梳状聚合物，用于调节细胞表面相互作用
公开(公告)号：EP1071467B1
公开(公告)日：2004-09-15
申请号：EP99917442.8
申请日：1999-04-13
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： MAYES, Anne, M. , GRIFFITH, Linda, G. , IRVINE, Darrell J. , BANERJEE, Pallab , JOHNSON, Terry D.
IPC分类号： A61K47/48
CPC分类号： A61K47/48 , A61K47/50 , A61K47/56 , A61K47/641 , C08G81/00 , C08G81/024 , C08J5/24
摘要： Synthetic comb copolymers which elicit controlled cellular response, methods of applying these polymers to various surfaces, and methods of using the polymers for modifying biomaterial surfaces, in tissue engineering applications and as drug delivery devices are provided. The comb copolymers are comprised of hydrophobic polymer backbones and hydrophilic, non-cell binding side chains which can be end-capped with cell-signaling ligands that guide cellular response. By mixing non-cell binding combs with ligand-bearing combs, the surface concentration and spatial distribution of one or more types of ligands, including adhesion peptides and growth factors, can be tuned on a surface to achieve desired cellular response. In one embodiment, the combs are used as stabilizing agents for dispersion polymerization of latexes. The comb-stabilized latexes can be applied to substrates by standard coating operations to create a bioregulating surface, or used as drug delivery agents. In another embodiment, the combs can be blended in small quantities to a hydrophobic matrix polymer and processed to affect the surface segregation of the comb.

8. 发明授权

EP1064353B1 VASCULARIZED PERFUSED MICROTISSUE/MICRO-ORGAN ARRAYS 无效
标题翻译：密克罗尼西亚的VASKULARISIERTE PERFUNDIERTE ANORDNUNGENFÜRMIKROGEWEBE
公开(公告)号：EP1064353B1
公开(公告)日：2002-11-06
申请号：EP99913967.8
申请日：1999-03-18
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： GRIFFITH, Linda, G. , TANNENBAUM, Steven, R. , POWERS, Mark, J. , DOMANSKY, Karel , THOMPSON, Charles, D.
IPC分类号： C12M3/04 , C12M1/34
CPC分类号： G01N33/5038 , B01J19/0046 , B01J2219/00286 , B01J2219/00308 , B01J2219/00313 , B01J2219/00317 , B01J2219/00319 , B01J2219/00351 , B01J2219/00376 , B01J2219/00416 , B01J2219/00585 , B01J2219/00659 , B01J2219/0072 , B33Y10/00 , B33Y80/00 , B82Y30/00 , C12M21/08 , C12M23/12 , C12M41/46 , C40B60/14 , G01N33/5008 , G01N33/502 , G01N33/5058 , G01N33/5064 , G01N33/5073
摘要： Systems including (1) a micromatrix and perfusion assembly suitable for seeding and attachment of cells within the matrix and for morphogenesis of seeded cells into complex, hierarchical tissue or organ structures, wherein the matrix includes channels or vessels through which culture medium, oxygen, or other nutrient or body fluids can be perfused while controlling gradients of nutrients and exogenous metabolites throughout the perfusion path independently of perfusion rate, and (2) sensor means for detecting changes in either cells within the matrix or in materials exposed to the cells, have been developed. Methods for making the micromatrices include micromachining, micromolding, embossing, laser drilling, and electro deposition machining. Cells can be of one or more types, either differentiated or undifferentiated. In a preferred embodiment, the matrix is seeded with a mixture of cells including endothelial cells which will line the channels to form 'blood vessels', and at least one type of parenchymal cells, such as hepatocytes, pancreatic cells, or other organ cells. The system can be used to screen materials for an effect on the cells, for an effect of the cells on the materials (for example, in a manner equivalent to tissue metabolism of a drug), or to test a material on a biological that must first infect cells or tissues, such as viruses. The apparatus also can be used to provide a physiological environment for expansion of stem cells, or for enabling gene therapy in vitro.
摘要翻译：系统包括（1）微阵列和灌注组件，其适用于将基质内的细胞接种和附着，并将种子细胞的形态发生转化为复杂的分层组织或器官结构，其中所述基质包括通道或血管，培养基，氧气或可以灌注其他营养液或体液，同时控制整个灌注路径中的营养物质和外源性代谢物的梯度，与灌注速率无关，和（2）用于检测基质内或细胞暴露的材料中任一细胞的变化的传感器装置，发达。制造微阵列的方法包括微加工，微胶印，压花，激光钻孔和电沉积加工。细胞可以是一种或多种，分化或未分化。在一个优选的实施方案中，用包含内皮细胞的细胞混合物接种基质，所述内皮细胞将通道形成“血管”，以及至少一种类型的实质细胞，例如肝细胞，胰腺细胞或其它器官细胞。该系统可用于筛选对细胞的影响的材料，用于细胞对材料的影响（例如，以等同于药物的组织代谢的方式），或用于测试必需的生物学上的材料首先感染细胞或组织，如病毒。该装置还可用于提供用于扩大干细胞的生理环境，或用于在体外实现基因治疗。

9. 发明授权

EP0836453B1 VASCULARIZED TISSUE REGENERATION MATRICES FORMED BY SOLID FREE-FORM FABRICATION METHODS 失效
标题翻译：制造方法，制作了矩阵免费FRAMED固定结构的手段血管化组织再生
公开(公告)号：EP0836453B1
公开(公告)日：2002-10-09
申请号：EP96918272.4
申请日：1996-06-05
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , CHILDREN'S MEDICAL CENTER CORPORATION
发明人： VACANTI, Joseph, P. , GRIFFITH, Linda, G. , CIMA, Michael, J.
IPC分类号： A61F2/10 , A61L27/00
CPC分类号： A61F2/105 , A61F2/022 , A61F2/28 , A61F2/30756 , A61F2/3094 , A61F2002/0086 , A61F2002/009 , A61F2002/30011 , A61F2002/30032 , A61F2002/30034 , A61F2002/30062 , A61F2002/30199 , A61F2002/3028 , A61F2002/30677 , A61F2002/3093 , A61F2002/30932 , A61F2002/30962 , A61F2210/0004 , A61F2230/0063 , A61F2240/001 , A61F2250/0023 , A61F2250/003 , A61F2250/0031 , A61F2250/0067 , A61L27/3808 , A61L27/40 , A61L27/56 , A61L27/60 , B29C64/135 , B29C64/165 , B29K2995/0064 , B33Y10/00 , B33Y30/00 , B33Y80/00 , Y10S623/901 , A61L27/38
摘要： Solid free-form fabrication (SFF) methods are used to manufacture devices for allowing tissue regeneration and for seeding and implanting cells to form organ and structural components, which can additionally provide controlled release of bioactive agents, wherein the matrix is characterized by a network of lumens functionally equivalent to the naturally occurring vasculature of the tissue formed by the implanted cells, and which can be lined with endothelial cells and coupled to blood vessels at the time of implantation to form a vascular network throughout the matrix. The SFF methods can be adapted for use with a variety of polymeric, inorganic and composite materials to create structures with defined compositions, strengths, and densities, using computer aided design (CAD). Examples of SFF methods include stereo-lithography (SLA), selective laser sintering (SLS), ballistic particle manufacturing (BPM), fusion deposition modeling (FDM), and three-dimensional printing (3DP).
摘要翻译：固体形式自由的制造（SFF）方法被用来制造用于使组织再生和用于接种和植入细胞形成器官和结构部件的设备，其可以附加地提供生物活性剂的受控释放，worin矩阵是由一网络特征的流明功能上等价于由植入的细胞形成的组织的天然存在的脉管系统，并且能够与内皮细胞内衬和耦合到血管在植入时以形成血管网在整个基质中。所述SFF方法可以适于与多种聚合物，无机和复合材料以产生具有所定义的组合物，强度和密度的结构的使用，使用计算机辅助设计（CAD）的SFF方法.Examples包括立体光刻（SLA）选择性激光烧结（SLS），弹道粒子制造（BPM），融合沉积建模（FDM），和三维印刷（3DP）。

10. 发明公开

EP1071467A1 COMB COPOLYMERS FOR REGULATING CELL-SURFACE INTERACTIONS 有权
标题翻译： KAMM-POLYMERE ZUR REGELUNG DERZELLOBERFLÄCHENWECHSELWIRKUNG
公开(公告)号：EP1071467A1
公开(公告)日：2001-01-31
申请号：EP99917442.8
申请日：1999-04-13
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： MAYES, Anne, M. , GRIFFITH, Linda, G. , IRVINE, Darrell J. , BANERJEE, Pallab , JOHNSON, Terry D.
IPC分类号： A61K47/48
CPC分类号： A61K47/48 , A61K47/50 , A61K47/56 , A61K47/641 , C08G81/00 , C08G81/024 , C08J5/24
摘要： Synthetic comb copolymers which elicit controlled cellular response, methods of applying these polymers to various surfaces, and methods of using the polymers for modifying biomaterial surfaces, in tissue engineering applications and as drug delivery devices are provided. The comb copolymers are comprised of hydrophobic polymer backbones and hydrophilic, non-cell binding side chains which can be end-capped with cell-signaling ligands that guide cellular response. By mixing non-cell binding combs with ligand-bearing combs, the surface concentration and spatial distribution of one or more types of ligands, including adhesion peptides and growth factors, can be tuned on a surface to achieve desired cellular response. In one embodiment, the combs are used as stabilizing agents for dispersion polymerization of latexes. The comb-stabilized latexes can be applied to substrates by standard coating operations to create a bioregulating surface, or used as drug delivery agents. In another embodiment, the combs can be blended in small quantities to a hydrophobic matrix polymer and processed to affect the surface segregation of the comb.
摘要翻译：提供引起受控细胞反应的合成梳状共聚物，将这些聚合物应用于各种表面的方法，以及使用该聚合物改性生物材料表面的方法，在组织工程应用中以及作为药物递送装置。梳状共聚物由疏水性聚合物主链和亲水的非细胞结合侧链组成，其可以用引导细胞反应的细胞信号传导配体封端。通过将非细胞结合梳与含配体的梳子混合，可以在表面上调节一种或多种类型的配体（包括粘附肽和生长因子）的表面浓度和空间分布，以实现所需的细胞反应。在一个实施方案中，梳子用作胶乳分散聚合的稳定剂。梳状稳定的胶乳可以通过标准涂布操作施加到基底上以产生生物调节表面，或用作药物递送剂。在另一个实施方案中，梳子可以少量混合到疏水性基质聚合物中并进行加工以影响梳子的表面分离。梳状共聚物在一个实施方案中通过提供包括反应性基团的可生物降解的聚酯主链，并使主链中的反应性基团与低分子量亲水聚合物上的反应性链端端反应形成。在另一个实施方案中，通过自由基合成疏水性单体和亲水性大分子单体形成不可生物降解的梳状共聚物。在所有上述实施方案中，一部分亲水性聚合物侧链可共价偶联至细胞信号传导配体如粘附肽或生长因子以控制细胞反应。

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