公开(公告)号：US06875442B2

公开(公告)日：2005-04-05

申请号：US10216877

申请日：2002-08-13

申请人： Chantal E. Holy ,  Molly S. Shoichet ,  John E. Davies

发明人： Chantal E. Holy ,  Molly S. Shoichet ,  John E. Davies

IPC分类号： A61F2/00 ,  C12N5/02 ,  C12N5/06 ,  C12N5/08 ,  C12N11/08

CPC分类号： C12N5/0068 ,  A61L27/18 ,  A61L27/3821 ,  A61L27/3847 ,  A61L27/56 ,  C12N11/08 ,  C12N2533/40 ,  C08L67/04

摘要： A polymer scaffold is provided comprising an extensively interconnected macroporous network. The polymer scaffold embodies macropores having a diameter in a range of 0.5-3.5 mm, and preferably in a range of about 1.0-2.0 mm. The polymer scaffold is prepared using a novel process which advantageously combines the techniques of particulate leaching and phase inversion to render a process that provides amplified means by which to control the morphology of the resulting polymer scaffold. The polymer scaffold has utility in the area of tissue engineering, particularly as a scaffold for both in vitro and in vivo cell growth.

摘要翻译： 提供了一种聚合物支架，其包括广泛互连的大孔网络。 聚合物支架体现了直径在0.5-3.5mm范围内，优选在约1.0-2.0mm范围内的大孔。 聚合物支架使用新颖的方法制备，其有利地结合了颗粒浸出和相转化的技术，以提供提供扩增的方法来控制所得聚合物支架的形态的方法。 聚合物支架在组织工程领域具有实用性，特别是作为体外和体内细胞生长的支架。

公开(公告)号：US09205046B2

公开(公告)日：2015-12-08

申请号：US12778879

申请日：2010-05-12

申请人： Molly S. Shoichet ,  M. Douglas Baumann ,  Catherine Elizabeth Kang

发明人： Molly S. Shoichet ,  M. Douglas Baumann ,  Catherine Elizabeth Kang

IPC分类号： A61K31/717 ,  A61K9/10 ,  A61K9/127 ,  A61P25/00 ,  A61P41/00 ,  A61K9/00 ,  A61K38/18 ,  A61K47/36 ,  A61K47/38

CPC分类号： A61K9/0024 ,  A61K9/0095 ,  A61K38/1825 ,  A61K38/1858 ,  A61K38/1866 ,  A61K38/1891 ,  A61K47/36 ,  A61K47/38

摘要： The present invention relates to a composite hydrogel comprising a blend of an aqueous solution of an anionic polysaccharide or a derivative thereof, such as hyaluronan (also commonly referred to as hyaluronic acid) or a derivative thereof and an aqueous solution of methylcellulose or another water soluble cellulose derivative thereof, having dispersed polymeric particles, such as polymeric hydrophobic particles therein selected from micro particles and nanoparticles, and wherein the stability of the hydrogel is enhanced relative to the stability of the hydrogel alone. The polymeric particles may contain at least one therapeutic agent, in which case each therapeutic agent exhibits a linear sustained release rate that can be tuned or altered by selecting the appropriate polymer formulation of the micro particles and/or nanoparticles. The composite may be injectable, and in the absence of a therapeutic agent may be used as a bulking agent for reconstructive and cosmetic surgery or may act as a platform for subsequent delivery of therapeutic agents.

摘要翻译： 本发明涉及一种复合水凝胶，其包含阴离子多糖或其衍生物的水溶液如透明质酸（也通常称为透明质酸）或其衍生物和甲基纤维素水溶液或其它水溶性的共混物 纤维素衍生物，其具有分散的聚合物颗粒，例如其中选自微粒和纳米颗粒的聚合疏水颗粒，并且其中相对于单独的水凝胶的稳定性，水凝胶的稳定性得到增强。 聚合物颗粒可以含有至少一种治疗剂，在这种情况下，每种治疗剂都显示线性缓释速率，可通过选择微粒和/或纳米颗粒的合适的聚合物配方来调节或改变。 复合材料可以是可注射的，并且在没有治疗剂的情况下可以用作用于重建和整容手术的填充剂，或者可以用作随后递送治疗剂的平台。

公开(公告)号：US20100285113A1

公开(公告)日：2010-11-11

申请号：US12778879

申请日：2010-05-12

申请人： Molly S. Shoichet ,  M. Douglas Baumann ,  Catherine Elizabeth Kang

发明人： Molly S. Shoichet ,  M. Douglas Baumann ,  Catherine Elizabeth Kang

IPC分类号： A61K31/717 ,  A61K9/10 ,  A61K9/127 ,  A61P25/00 ,  A61P41/00 ,  A61K38/18 ,  A61K31/7088 ,  A23L1/0534

CPC分类号： A61K9/0024 ,  A61K9/0095 ,  A61K38/1825 ,  A61K38/1858 ,  A61K38/1866 ,  A61K38/1891 ,  A61K47/36 ,  A61K47/38

摘要： The present invention relates to a composite hydrogel comprising a blend of an aqueous solution of an anionic polysaccharide or a derivative thereof, such as hyaluronan (also commonly referred to as hyaluronic acid) or a derivative thereof and an aqueous solution of methylcellulose or another water soluble cellulose derivative thereof, having dispersed polymeric particles, such as polymeric hydrophobic particles therein selected from micro particles and nanoparticles, and wherein the stability of the hydrogel is enhanced relative to the stability of the hydrogel alone. The polymeric particles may contain at least one therapeutic agent, in which case each therapeutic agent exhibits a linear sustained release rate that can be tuned or altered by selecting the appropriate polymer formulation of the micro particles and/or nanoparticles. The composite may be injectable, and in the absence of a therapeutic agent may be used as a bulking agent for reconstructive and cosmetic surgery or may act as a platform for subsequent delivery of therapeutic agents.

摘要翻译： 本发明涉及一种复合水凝胶，其包含阴离子多糖或其衍生物的水溶液如透明质酸（也通常称为透明质酸）或其衍生物和甲基纤维素水溶液或其它水溶性的共混物 纤维素衍生物，其具有分散的聚合物颗粒，例如其中选自微粒和纳米颗粒的聚合疏水颗粒，并且其中相对于单独的水凝胶的稳定性，水凝胶的稳定性得到增强。 聚合物颗粒可以含有至少一种治疗剂，在这种情况下，每种治疗剂都显示线性缓释速率，可通过选择微粒和/或纳米颗粒的合适的聚合物配方来调节或改变。 复合材料可以是可注射的，并且在没有治疗剂的情况下可以用作用于重建和整容手术的填充剂，或者可以用作随后递送治疗剂的平台。

公开(公告)号：US20090297609A1

公开(公告)日：2009-12-03

申请号：US11988207

申请日：2006-07-06

申请人： Molly S. Shoichet ,  Yumin Yuan ,  Meng Shi ,  Jordan Wosnick

发明人： Molly S. Shoichet ,  Yumin Yuan ,  Meng Shi ,  Jordan Wosnick

IPC分类号： A61K9/14 ,  A61K39/395 ,  A61K35/12 ,  A61K35/76 ,  A61K38/43 ,  A61K38/00 ,  A61K31/7088 ,  C08F18/24 ,  C08F24/00 ,  C08F116/02 ,  C08F20/58 ,  C07C43/00

CPC分类号： C08G63/912 ,  A61K47/48907 ,  A61K47/6935 ,  C08G63/64 ,  C08G64/0241 ,  C08G64/42

摘要： The present invention provides a method for the covalent immobilization of biomolecules on polymers for delivery of the biomolecules, which has the advantage of being simple, highly efficient, environmentally friendly and free of side products relative to traditional immobilization techniques. The invention provides a modified micro/nanoparticle system, which uses a functionalized polymer formed into micro or nanoparticles to bind a molecule to the particles using uses facile chemistry, the Diels-Alder cycloaddition between a diene and a dienophile with the polymer being functionalized with one of them and the molecule with the other, or the Huisgen 1,3-dipolar cycloaddition between a terminal alkyne and an azide to bind the molecule to the particle. The molecules and/or other therapeutic agents may be encapsulated within the polymer particles for intravenous therapeutic delivery. The invention also provides a novel synthetic biodegradable polymer, a furan/alkyne-functionalized poly(trimethylene carbonate) (PTMC)-based polymer, whose composition can be designed to meet the defined physical and chemical property requirements. In one example, the particle system self-aggregates from functionalized PTMC-based copolymers containing poly(ethylene glycol) (PEG) segments. The composition of the copolymers can be designed to meet various particle system requirements, including size, thermodynamic stability, surface PEG density, drug encapsulation capacity and biomolecule immobilization capacity.

摘要翻译： 本发明提供了生物分子共价固定在聚合物上用于递送生物分子的方法，其具有相对于传统固定技术简单，高效，环保且无副产物的优点。 本发明提供了一种修饰的微/纳米颗粒体系，其使用形成微米或纳米颗粒的官能化聚合物使用易于使用的化学方法将分子与颗粒结合，二烯与亲双烯体之间的Diels-Alder环加成与聚合物被一个官能化 的分子和另一个分子，或者在末端炔烃和叠氮化物之间的Huisgen 1,3-偶极环加成以将分子结合到颗粒。 分子和/或其它治疗剂可以包封在聚合物颗粒内用于静脉内治疗递送。 本发明还提供了一种新型的合成可生物降解聚合物，呋喃/炔官能化的聚（碳酸亚丙基酯）（PTMC）（PTMC））聚合物，其组合物可以被设计成满足规定的物理和化学性质要求。 在一个实例中，颗粒系统自聚集于含有聚（乙二醇）（PEG）链段的官能化的基于PTMC的共聚物。 共聚物的组成可以设计成满足各种颗粒系统的要求，包括尺寸，热力学稳定性，表面PEG密度，药物包封能力和生物分子固定能力。

公开(公告)号：US06379962B1

公开(公告)日：2002-04-30

申请号：US09191107

申请日：1998-11-13

申请人： Chantal E. Holy ,  Molly S. Shoichet ,  John E. Davies

发明人： Chantal E. Holy ,  Molly S. Shoichet ,  John E. Davies

IPC分类号： C12N506

CPC分类号： A61L27/56 ,  A61L27/18 ,  A61L27/3821 ,  A61L27/3847 ,  C08L67/04

摘要： A polymer scaffold is provided having an extensively interconnected macroporous network with macropores having microporous struts as walls. Macropore diameter ranges from about 0.5 to about 3.5 mm. The polymer may be a biocompatible, biodegradable polymer such as poly(lactide-co-glycolide) containing 75% polylactide and 25% polyglycolide. The polymer scaffold is prepared by mixing a liquid polymer with particles, precipitating the liquid polymer with a non-solvent for the liquid polymer and dissolving the particles with a solvent to form the macroporous polymer scaffold which preferably has porosity greater than 50%. The surface of the polymer scaffold may be modified by acid or base treatment, or by collagen or calcium phosphate deposition. The polymer scaffold has utility for tissue engineering, particularly as a scaffold for in vitro and in vivo cell growth.

摘要翻译： 提供了具有广泛互连的大孔网络的聚合物支架，其中具有作为壁的微孔支柱的大孔。 大孔直径为约0.5至约3.5mm。 聚合物可以是生物相容的可生物降解聚合物，例如含有75％聚丙交酯和25％聚乙交酯的聚（丙交酯 - 共 - 乙交酯）。 通过将液体聚合物与颗粒混合制备聚合物支架，用液体聚合物的非溶剂沉淀液体聚合物并用溶剂溶解颗粒以形成孔隙率大于50％的大孔聚合物支架。 聚合物支架的表面可以通过酸或碱处理，或通过胶原或磷酸钙沉积进行改性。 聚合物支架可用于组织工程，特别是作为体外和体内细胞生长的支架。

公开(公告)号：US5853717A

公开(公告)日：1998-12-29

申请号：US447356

申请日：1995-05-23

申请人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

发明人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

IPC分类号： A01K67/027 ,  A61K48/00 ,  A61L27/00 ,  A61L27/18 ,  A61L27/22 ,  A61L27/38 ,  C07K14/82 ,  C12N5/00 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12 ,  A01N63/00

CPC分类号： C12N5/0068 ,  A61L27/18 ,  A61L27/227 ,  A61L27/383 ,  A61L27/3834 ,  A61L27/3839 ,  A61L27/3895 ,  C07K14/82 ,  A61K48/00 ,  C12N2510/00 ,  C12N2510/04 ,  C12N2533/30 ,  C12N2533/54 ,  C12N2533/74

摘要： This invention relates to methods and compositions of controlling cell distribution within a bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the BAO with ECM molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination.

公开(公告)号：US07022522B2

公开(公告)日：2006-04-04

申请号：US10134652

申请日：2002-04-30

申请人： Limin Guan ,  Chantal E. Holy ,  Molly S. Shoichet ,  John E. Davies

发明人： Limin Guan ,  Chantal E. Holy ,  Molly S. Shoichet ,  John E. Davies

IPC分类号： C12N5/06 ,  C12N5/08 ,  C12N11/08 ,  A61F2/00

CPC分类号： C12N5/0654 ,  A61L27/18 ,  A61L27/46 ,  A61L27/56 ,  C12N5/0068 ,  C12N2533/18 ,  C12N2533/40 ,  C08L67/04

摘要： A polymer scaffold is provided comprising an extensively interconnected macroporous network. The polymer scaffold embodies macropores having a diameter in a range of 0.5-3.5 mm, and preferably in a range of about 1.0-2.0 mm. The polymer scaffold is prepared using a novel process which advantageously combines the techniques of particulate leaching and phase inversion to render a process that provides amplified means by which to control the morphology of the resulting polymer scaffold. The polymer scaffold has utility in the area of tissue engineering, particularly as a scaffold for both in vitro and in vivo cell growth. The polymer scaffold may be produced using pure polymer or alternatively a composite material may be formed consisting of a macroporous polymer scaffold and osteoclast-resorbable calcium phosphate particles with a binding agent binding the calcium phosphate particles to the polymer scaffold.

摘要翻译： 提供了一种聚合物支架，其包括广泛互连的大孔网络。 聚合物支架体现了直径在0.5-3.5mm范围内，优选在约1.0-2.0mm范围内的大孔。 聚合物支架使用新颖的方法制备，其有利地结合了颗粒浸出和相转化的技术，以提供提供扩增的方法来控制所得聚合物支架的形态的方法。 聚合物支架在组织工程领域具有实用性，特别是作为体外和体内细胞生长的支架。 聚合物支架可以使用纯聚合物制备，或者可以由复合材料形成，其由大孔聚合物支架和破骨细胞可吸收的磷酸钙颗粒与具有将磷酸钙颗粒结合到聚合物支架的结合剂组成。

公开(公告)号：US06787090B2

公开(公告)日：2004-09-07

申请号：US10169948

申请日：2002-07-11

申请人： Paul D. Dalton ,  Molly S. Shoichet

发明人： Paul D. Dalton ,  Molly S. Shoichet

IPC分类号： B29C3908

CPC分类号： A61K9/0092 ,  A61B17/1128 ,  B29C37/006 ,  B29C39/006 ,  B29C39/08 ,  B29C41/042 ,  B29C41/50 ,  B29K2105/0014 ,  B29K2105/04 ,  B29L2023/00 ,  B29L2031/753 ,  Y10T428/1352 ,  Y10T428/139

摘要： Hollow polymeric structures with unique morphologies are manufactured with a rotational spinning technique wherein phase separation of soluble solutions is induced within a filled mold as it is rotated. As phase-separation occurs, an increase in density of one phase results in sediment at a periphery under centrifugal forces and after or during sedimentation, gelation of phase-separated particles fixes a tube morphology. By controlling the rotational speed and the formulation chemistry, the tube dimensions and wall morphology can be manipulated. The method requires small quantities of starting material, permits multi-layering of tubes, is applicable to diverse polymers and results in highly diffusive hollow structures while maintaining good mechanical strength.

摘要翻译： 使用旋转纺丝技术制造具有独特形态的中空聚合物结构，其中在填充的模具中旋转时，可溶性溶液的相分离被诱导。 当相分离发生时，一相的密度增加导致离心力周围的沉积物，并且在沉淀之后或沉淀期间，相分离的颗粒的凝胶化固定管形态。 通过控制旋转速度和配方化学性质，可以操纵管尺寸和壁形态。 该方法需要少量的起始材料，允许多层管，适用于多种聚合物，并导致高度扩散的中空结构，同时保持良好的机械强度。

公开(公告)号：US06472210B1

公开(公告)日：2002-10-29

申请号：US09578718

申请日：2000-05-26

申请人： Chantal E. Holy ,  Molly S. Shoichet ,  John E. Davies

发明人： Chantal E. Holy ,  Molly S. Shoichet ,  John E. Davies

IPC分类号： C12N506

CPC分类号： C12N5/0068 ,  A61L27/18 ,  A61L27/3821 ,  A61L27/3847 ,  A61L27/56 ,  C12N11/08 ,  C12N2533/40 ,  C08L67/04

摘要： A polymer scaffold is provided having an extensively interconnected macroporous network with macropores having microporous struts as walls. Macropore diameter ranges from about 0.5 to about 3.5 mm. The polymer may be a biocompatible, biodegradable polymer such as poly(lactide-co-glycolide) containing 75% polylactide and 25% polyglycolide. The polymer scaffold is prepared by mixing a liquid polymer with particles, precipitating the liquid polymer with a non-solvent for the liquid polymer and dissolving the particles with a solvent to form the macroporous polymer scaffold which preferably has porosity greater than 50%. The surface of the polymer scaffold may be modified by acid or base treatment, or by collagen or calcium phosphate deposition. The polymer scaffold has utility for tissue engineering, particularly as a scaffold for in vitro and in vivo cell growth.

公开(公告)号：US5935849A

公开(公告)日：1999-08-10

申请号：US279773

申请日：1994-07-20

申请人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

发明人： Malcolm Schinstine ,  Molly S. Shoichet ,  Frank T. Gentile ,  Joseph P. Hammang ,  Laura M. Holland ,  Brian M. Cain ,  Edward J. Doherty ,  Shelley R. Winn ,  Patrick Aebischer

IPC分类号： A01K67/027 ,  A61K48/00 ,  A61L27/00 ,  A61L27/18 ,  A61L27/22 ,  A61L27/38 ,  C07K14/82 ,  C12N5/00 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12

CPC分类号： A61L27/3839 ,  A61L27/18 ,  A61L27/227 ,  C07K14/82 ,  C12N5/0012 ,  C12N5/0068 ,  A61K48/00 ,  C12N2510/00 ,  C12N2510/04 ,  C12N2533/30 ,  C12N2533/54 ,  C12N2533/74

摘要： This invention relates to methods and compositions of controlling cell distribution within a bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the BAO with ECM molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination.

摘要翻译： 本发明涉及通过将细胞暴露于抑制细胞增殖，促进细胞分化或影响细胞附着于生物人造器官内的生长表面的处理来控制生物人造器官内的细胞分布的方法和组合物。 这样的处理包括（1）遗传操纵细胞，（2）将细胞暴露于增殖抑制化合物或分化诱导化合物，或除去细胞暴露于增殖刺激化合物或分化抑制化合物; 使细胞暴露于照射，和（3）用ECM分子修饰BAO的生长表面，影响细胞增殖或粘附的分子，或惰性支架或其组合。 这些处理可以组合使用。