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1. 发明授权

US06287340B1 Bioengineered anterior cruciate ligament 有权
公开(公告)号：US06287340B1
公开(公告)日：2001-09-11
申请号：US09312203
申请日：1999-05-14
申请人： Gregory Altman , David Kaplan , Gordana Vunjak-Novakovic , Ivan Martin
发明人： Gregory Altman , David Kaplan , Gordana Vunjak-Novakovic , Ivan Martin
IPC分类号： A61F208
CPC分类号： C12M35/04 , A61F2/08 , A61L27/3604 , A61L27/3691 , A61L27/38 , A61L2430/10 , C12M21/08 , C12M25/14 , Y10S623/901
摘要： The present invention provides a method for producing an anterior cruciate ligament ex vivo. The method comprises seeding pluripotent stem cells in a three dimensional matrix, anchoring the seeded matrix by attachment to two anchors, and culturing the cells within the matrix under conditions appropriate for cell growth and regeneration, while subjecting the matrix to one or more mechanical forces via movement of one or both of the attached anchors. Bone marrow stromal cells are preferably used as the pluripotent cells in the method. Suitable matrix materials are materials to which cells can adhere, such as a gel made from collagen type I. Suitable anchor materials are materials to which the matrix can attach, such as Goinopra coral and also demineralized bone. Optimally, the mechanical forces to which the matrix is subjected mimic mechanical stimuli experienced by an anterior cruciate ligament in vivo. This is accomplished by delivering the appropriate combination of tension, compression, torsion, and shear, to the matrix. The bioengineered ligament which is produced by this method is characterized by a cellular orientation and/or matrix crimp pattern in the direction of the applied mechanical forces, and also by the production of collagen type I, collagen type III, and fibronectin proteins along the axis of mechanical load produced by the mechanical forces. Optimally, the ligament produced has fiber bundles which are arranged into a helical organization. The method for producing an anterior cruciate ligament can be adapted to produce a wide range of tissue types ex vivo by adapting the anchor size and attachment sites to reflect the size of the specific type of tissue to be produced, and also adapting the specific combination of forces applied, to mimic the mechanical stimuli experienced in vivo by the specific type of tissue to be produced. The methods of the present invention can be further modified to incorporate other stimuli experienced in vivo by the particular developing tissue, some examples of the stimuli being chemical stimuli, and electro-magnetic stimuli. Some examples of tissue which can be produced include other ligaments in the body (hand, wrist, elbow, knee), tendon, cartilage, bone, muscle, and blood vessels.

2. 发明申请

US20070212730A1 Covalently immobilized protein gradients in three-dimensional porous scaffolds 有权
标题翻译：在三维多孔支架中共价固定的蛋白质梯度
公开(公告)号：US20070212730A1
公开(公告)日：2007-09-13
申请号：US11407373
申请日：2006-04-19
申请人： Charu Vepari , David Kaplan , Gordana Vunjak-Novakovic
发明人： Charu Vepari , David Kaplan , Gordana Vunjak-Novakovic
IPC分类号： G01N33/53 , C12M1/34
CPC分类号： C07K17/02 , C07K17/04 , C12N11/02 , C12N11/04 , C12N11/06 , C12N11/10
摘要： The invention provides a method for forming an immobilized agent gradient within a 3-dimensional porous scaffold. A 3-dimensional scaffold formed from a biocompatible material is provided. The surface of the scaffold and/ or the agent is activated so as to allow binding of the agent to the scaffold. The activated scaffold is contacted with a solution containing the agent. Contact with the solution is maintained for a sufficient period of time to allow diffusion of the solution through a portion of the scaffold, thereby forming a desired gradient of the agent through the 3-dimensional scaffold.
摘要翻译：本发明提供了在三维多孔支架内形成固定化剂梯度的方法。提供由生物相容性材料形成的3维支架。支架和/或试剂的表面被活化，以允许试剂与支架结合。活化的支架与含有该试剂的溶液接触。保持与溶液接触足够的时间以允许溶液扩散通过支架的一部分，从而通过3维支架形成所需试剂的梯度。

3. 发明申请

US20060273279A1 Electrospun pharmaceutical compositions 有权
标题翻译： Electrospun药物组合物
公开(公告)号：US20060273279A1
公开(公告)日：2006-12-07
申请号：US10541182
申请日：2004-01-07
申请人： David Kaplan , Rina Nazarov , Gordana Vunjak-Novakovic , Lorenz Meinel
发明人： David Kaplan , Rina Nazarov , Gordana Vunjak-Novakovic , Lorenz Meinel
IPC分类号： A23J7/00
CPC分类号： A61K38/1825 , A61K38/1841 , A61K47/42 , A61L27/227 , A61L27/26 , A61L27/3604 , A61L27/3847 , A61L27/3852 , A61L27/3895 , A61L27/56 , D01D5/00 , D01F4/02 , Y10T428/29 , C08L89/00
摘要： The present invention provides processes for producing porous silk fibroin scaffold material. The porous silk fibroin scaffold can be used for tissue engineering. The porosity of the silk fibroin scaffolds described herein can be adjusted to mimic the gradient of densities found in natural tissue. Accordingly, methods for engineering of 3-dimensional tissue, e.g. bone and cartilage, using the silk fibroin scaffold material are also provided.
摘要翻译：本发明提供生产多孔丝素蛋白支架材料的方法。多孔丝素蛋白支架可用于组织工程。可以调节本文所述的丝素蛋白支架的孔隙率以模拟在天然组织中发现的密度梯度。因此，用于三维组织工程的方法，例如，还提供使用丝素蛋白骨架材料的骨和软骨。

4. 发明授权

US06582960B1 Use of fibroblast growth factor 2 for expansion of chondrocytes and tissue engineering 失效
标题翻译：使用成纤维细胞生长因子2扩展软骨细胞和组织工程
公开(公告)号：US06582960B1
公开(公告)日：2003-06-24
申请号：US09397417
申请日：1999-09-17
申请人： Ivan Martin , Lisa E. Freed , Robert Langer , Gordana Vunjak-Novakovic
发明人： Ivan Martin , Lisa E. Freed , Robert Langer , Gordana Vunjak-Novakovic
IPC分类号： C12N500
CPC分类号： C12N5/0655 , A61K35/12 , C12N2500/25 , C12N2501/11 , C12N2501/115 , C12N2501/135 , C12N2501/15 , C12N2501/33 , C12N2510/00
摘要： The present invention provides an improved method for expanding cells for use in tissue engineering. In particular the method provides specific biochemical factors to supplement cell culture medium during the expansion process in order to reproduce events occurring during embryonic development with the goal of regenerating tissue equivalents that resemble natural tissues both structurally and functionally. These specific biochemical factors improve proliferation of the cells and are capable of de-differentiation mature cells isolated from tissue so that the differentiation potential of the cells is preserved. The bioactive molecules also maintain the responsiveness of the cells to other bioactive molecules. Specifically, the invention provides methods for expanding chondrocytes in the presence of fibroblast growth factor 2 for use in regeneration of cartilage tissue.
摘要翻译：本发明提供了用于组织工程中用于扩张细胞的改进方法。特别地，该方法提供特定的生物化学因子以在扩增过程中补充细胞培养基，以便再现胚胎发育期间发生的事件，目的是在结构和功能上再生类似于天然组织的组织等同物。这些具体的生物化学因素改善了细胞的增殖，并且能够使从组织中分离的成熟细胞去分化，从而保持了细胞的分化潜能。生物活性分子还保持细胞对其他生物活性分子的反应性。具体地说，本发明提供了在成纤维细胞生长因子2存在下扩展软骨细胞用于软骨组织再生的方法。

5. 发明授权

US07842780B2 Silk fibroin materials and use thereof 有权
标题翻译：丝素蛋白材料及其用途
公开(公告)号：US07842780B2
公开(公告)日：2010-11-30
申请号：US10541182
申请日：2004-01-07
申请人： David L. Kaplan , Rina Nazarov , Gordana Vunjak-Novakovic , Lorenz Meinel
发明人： David L. Kaplan , Rina Nazarov , Gordana Vunjak-Novakovic , Lorenz Meinel
IPC分类号： A23J7/00 , A61K38/08 , A61K38/39 , C07K7/06 , C07K7/08
CPC分类号： A61K38/1825 , A61K38/1841 , A61K47/42 , A61L27/227 , A61L27/26 , A61L27/3604 , A61L27/3847 , A61L27/3852 , A61L27/3895 , A61L27/56 , D01D5/00 , D01F4/02 , Y10T428/29 , C08L89/00
摘要： The present invention provides processes for producing porous silk fibroin scaffold material. The porous silk fibroin scaffold can be used for tissue engineering. The porosity of the silk fibroin scaffolds described herein can be adjusted as to mimic the gradient of densities found in natural tissue. Accordingly, methods for engineering of 3-dimensional tissue, e.g. bone and cartilage, using the silk fibroin scaffold material are also provided.
摘要翻译：本发明提供生产多孔丝素蛋白支架材料的方法。多孔丝素蛋白支架可用于组织工程。可以调节本文所述的丝素蛋白支架的孔隙率以模拟在天然组织中发现的密度梯度。因此，用于三维组织工程的方法，例如，还提供使用丝素蛋白骨架材料的骨和软骨。

6. 发明申请

US20080274157A1 Cartilage implant plug with fibrin glue and method for implantation 审中-公开
标题翻译：具有纤维蛋白胶的软骨植入物塞和植入方法
公开(公告)号：US20080274157A1
公开(公告)日：2008-11-06
申请号：US12079629
申请日：2008-03-26
申请人： Gordana Vunjak-Novakovic , Katherine G. Truncale , Moon Hae Sunwoo , Arthur A. Gertzman
发明人： Gordana Vunjak-Novakovic , Katherine G. Truncale , Moon Hae Sunwoo , Arthur A. Gertzman
IPC分类号： A61K35/32 , A61F2/00 , A61P19/00
CPC分类号： A61K35/32 , A61B17/00491 , A61F2/30744 , A61F2/30756 , A61F2/3859 , A61F2002/2817 , A61F2002/2839 , A61F2002/2867 , A61F2002/30062 , A61F2002/30224 , A61F2002/30225 , A61F2002/30759 , A61F2210/0004 , A61F2230/0069 , A61F2310/00365 , A61F2310/00383 , A61K38/00 , A61K38/363 , A61K38/4833 , A61L24/0005 , A61L24/0015 , A61L27/3608 , A61L27/3612 , A61L27/3654 , A61L27/3687 , A61L27/38 , A61L27/48 , A61L27/54 , A61L27/56 , A61L2300/414 , A61L2300/43 , A61L2300/64 , A61L2430/06 , A61K2300/00
摘要： The invention is directed toward a cartilage repair assembly comprising a shaped structure of subchondral bone with an integral overlying cartilage cap which is treated to remove cellular debris and proteoglycans and milled cartilage in a bioabsorbable carrier. The shaped structure is dimensioned to fit in a drilled bore in a cartilage defect area so that said shaped bone and cartilage cap when centered in the bore does not engage the side wall of the bore and is positioned from the side wall of the bone a distance ranging from 10 microns to 1000 microns and is surrounded by milled cartilage and a fibrin thrombin glue. A method for inserting the assembly into a cartilage defect area is disclosed.
摘要翻译：本发明涉及一种软骨修复组件，其包括具有整体上覆软骨帽的软骨下骨的成形结构，其被处理以除去生物可吸收载体中的细胞碎片和蛋白聚糖和研磨的软骨。该成形结构的尺寸适于装配在软骨缺损区域中的钻孔中，使得当在孔中心定位时所述成形的骨和软骨帽不接合孔的侧壁并且从骨的侧壁定位一定距离范围从10微米到1000微米，被碾磨的软骨和纤维蛋白凝血酶胶包围。公开了一种将组件插入软骨缺损区域的方法。

7. 发明授权

US09808557B2 Tubular silk compositions and methods of use thereof 有权
公开(公告)号：US09808557B2
公开(公告)日：2017-11-07
申请号：US12672521
申请日：2008-08-11
申请人： Michael L. Lovett , Xianyan Wang , Christopher M. Cannizzaro , Gordana Vunjak-Novakovic , David L. Kaplan
发明人： Michael L. Lovett , Xianyan Wang , Christopher M. Cannizzaro , Gordana Vunjak-Novakovic , David L. Kaplan
IPC分类号： A61F2/06 , A61L27/36 , A61L27/22 , A61F2/08 , A61L27/26 , A61F2/07 , A61F2/82
CPC分类号： A61L27/227 , A61F2/07 , A61F2/08 , A61F2/82 , A61L27/26 , A61L27/3604 , D10B2211/22 , Y10T428/13 , C08L89/00
摘要： Described are tubular silk fibroin compositions and methods for their manufacture and use. Tubular compositions as described herein can be produced in a range of high burst strengths, can easily be made in a range of inner diameters, can be derivatized with functional moieties, and can be produced in a range of permeabilities suitable for particularized uses. In one aspect, the tubular compositions can be used in the repair or replacement of damaged or diseased blood vessels, including, but not limited to vessels smaller than about 6 mm.

8. 发明申请

US20110076384A1 SYSTEM AND METHOD FOR MAKING BIOMATERIAL STRUCTURES 有权
标题翻译：制备生物体结构的系统和方法
公开(公告)号：US20110076384A1
公开(公告)日：2011-03-31
申请号：US12934666
申请日：2009-04-08
申请人： Christopher Cannizzaro , Michael L. Lovett , Gordana Vunjak-Novakovic , David L. Kaplan
发明人： Christopher Cannizzaro , Michael L. Lovett , Gordana Vunjak-Novakovic , David L. Kaplan
IPC分类号： B05C11/00 , A61L33/00
CPC分类号： D01F4/02 , D01D5/04 , D01D5/06 , D01D5/18 , D01D7/00
摘要： A system and method for making a biomaterial device includes a support structure providing a shape for a biomaterial device. At least one applicator has a supply of biomaterial solution and is positioned along the support structure. The at least one applicator forms a biomaterial fiber by applying shear force to the biomaterial solution and delivering the biomaterial fiber to the support structure. A controller causes relative movement between the support structure and the at least one applicator, and the biomaterial fiber is arranged on the support structure according to the relative movement to form the biomaterial device. The biomaterial may be silk fibroin which may be wound onto a reciprocating and rotating mandrel. Control over the properties of the biomaterial device is achieved through appropriate selection of material processing, winding strategy, and post-winding processing.
摘要翻译：用于制造生物材料装置的系统和方法包括为生物材料装置提供形状的支撑结构。至少一个施用器具有生物材料溶液的供应并且沿着支撑结构定位。所述至少一个施用器通过向所述生物材料溶液施加剪切力并将所述生物材料纤维递送到所述支撑结构来形成生物材料纤维。控制器引起支撑结构和至少一个施加器之间的相对运动，并且根据相对运动将生物材料纤维布置在支撑结构上以形成生物材料装置。生物材料可以是可以卷绕到往复和旋转的心轴上的丝素蛋白。通过适当选择材料加工，卷绕策略和后卷绕处理，可以控制生物材料装置的性能。

9. 发明申请

US20050074477A1 Method for the treatment of diseased, degenerated, or damaged tissue using three dimensional tissue produced in vitro in combination with tissue cells and/or exogenic factors 审中-公开
标题翻译：使用体外结合组织细胞和/或外源因子产生的三维组织治疗患病，退化或损伤的组织的方法
公开(公告)号：US20050074477A1
公开(公告)日：2005-04-07
申请号：US10501520
申请日：2003-11-07
申请人： Olivera Josimovic-Alasevic , Jeannette Libera , Hans-Peter Wiesmann , Ulrich Joos , Gordana Vunjak-Novakovic
发明人： Olivera Josimovic-Alasevic , Jeannette Libera , Hans-Peter Wiesmann , Ulrich Joos , Gordana Vunjak-Novakovic
IPC分类号： A61K35/12 , C12N5/077 , C12N13/00 , C12N5/08 , A61F2/00
CPC分类号： C12N5/0655 , A61K35/12 , C12N13/00
摘要： The invention relates to a tissue replacement structure comprising (a) a preformed three-dimensional tissue which can be produced by obtaining cells from a human or animal organism and culturing them in a stationary fashion as a suspension culture in cell culture vessels with hydrophobic surface and tapering bottom until a cell aggregate is formed which has differentiated cells embedded therein and has an outer region wherein cells capable of proliferation and migration are present; (b) (i) an autologous cell suspension which can be produced from endogenous cells, with endogenous serum being added, with no addition of growth-promoting compounds, (ii) implants or support materials and/or (iii) growth factors; and/or (c) can be obtained by exposure of the tissue according to (a) to electromagnetic fields, mechanical stimulation and/or ultrasound.
摘要翻译：本发明涉及一种组织置换结构，其包括（a）预先形成的三维组织，其可以通过从人或动物生物获得细胞并以静止方式将其作为悬浮培养物在具有疏水性表面的细胞培养容器中培养而制备，逐渐变细的底部，直到形成细胞聚集体，其具有嵌入其中的分化细胞，并且具有其中存在能够增殖和迁移的细胞的外部区域; （b）（i）可以从内源细胞产生的自体细胞悬浮液，加入内源血清，不加生长促进化合物，（ii）植入物或支持材料和/或（iii）生长因子; 和/或（c）可以通过根据（a）将组织暴露于电磁场，机械刺激和/或超声波来获得。

10. 发明授权

US09958436B2 Determination of cell chirality 有权
公开(公告)号：US09958436B2
公开(公告)日：2018-05-01
申请号：US14126902
申请日：2012-06-15
申请人： Gordana Vunjak-Novakovic , Leo Qun Wan
发明人： Gordana Vunjak-Novakovic , Leo Qun Wan
IPC分类号： G01N33/50 , C12N5/00
CPC分类号： G01N33/5091 , C12N5/0068 , C12N2503/00 , C12N2535/10
摘要： Methods for determining cell chirality using micropatterned substrates are disclosed. Also provided are methods for diagnosing diseases such as genetic diseases or cancer by comparing the chirality of sample cells from a subject with normal cells, and determining a difference in chirality between the sample cells and normal cells.

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