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1. 发明授权

US08202725B2 Cell sodding method and apparatus 有权
标题翻译：细胞浸渍法和装置
公开(公告)号：US08202725B2
公开(公告)日：2012-06-19
申请号：US11314281
申请日：2005-12-22
申请人： Paul E. Kosnik , Christopher T. England , Robert G. Dennis , Stuart K. Williams
发明人： Paul E. Kosnik , Christopher T. England , Robert G. Dennis , Stuart K. Williams
IPC分类号： C12N5/00
CPC分类号： C12N5/0697 , C12M21/08 , C12M25/10 , C12M25/14 , C12M27/10 , C12M29/10 , C12N2533/30
摘要： Tissue engineering methods and biochamber apparatus are provided for making tissue grafts for implantation into a patient. The methods include applying a sustained low magnitude pressure gradient transmurally across a permeable scaffold material using a media containing cells, preferably microvascular epithelial cells, to be deposited on the scaffold for the production of tissue grafts, preferably vascular grafts, to promote accelerated adhesion and maturation of cells on the scaffold material. Biochambers for preparing tubular tissue grafts are provided which contain connectors for holding a graft substrate, proximal and distal tubing for connection to an optional perfusion system, and structure for switching between transmural flow of a cell suspension across the graft substrate and translumenal flow through the lumen of the graft.
摘要翻译：提供组织工程方法和生物处理设备用于制造植入患者体内的组织移植物。所述方法包括使用包含细胞（优选微血管上皮细胞）的培养基透过可渗透的支架材料跨度施加持续的低幅度压力梯度，以沉积在支架上用于生产组织移植物，优选血管移植物，以促进加速粘附和成熟的细胞在脚手架材料上。提供了用于制备管状组织移植物的生物体，其包含用于保持移植物基质的连接器，用于连接到任选的灌注系统的近端和远端管，以及用于在穿过移植物基质的细胞悬浮液的跨壁流和通过内腔的经血流之间切换的结构的移植物。

2. 发明申请

US20080160085A1 Cell delivery matrices 审中-公开
标题翻译：细胞递送矩阵
公开(公告)号：US20080160085A1
公开(公告)日：2008-07-03
申请号：US11901138
申请日：2007-09-13
申请人： Eugene D. Boland , Stuart K. Williams , Paul E. Kosnik
发明人： Eugene D. Boland , Stuart K. Williams , Paul E. Kosnik
IPC分类号： A61K9/00 , A61K35/12
CPC分类号： A61K9/4808 , A61K9/0019 , A61K35/36 , A61K35/44 , A61K47/42 , A61L27/16 , A61L27/18 , A61L27/225 , A61L27/24 , A61M25/104 , C12N5/0653 , C08L27/18 , C08L67/02
摘要： Cell delivery matrices and methods for facilitating local delivery of adipose derived endothelial cells to a target tissue, body cavity, or joint are described. The cell delivery matrix may be a three-dimensional matrix scaffold comprising fibrin derived from the patient's own body. The cell delivery matrix may be biocompatible and semi-permeable. The cell delivery matrix used in the methods of the invention may be comprised of any degradable, bioabsorbable or non-degradable, biocompatible polymer. Regenerative therapies comprising implanting in the subject cell delivery matrices localizing adipose derived endothelial cells are described. The cell delivery matrices maintain the adipose derived endothelial cells at the target for a therapeutically effective amount of time. The adipose derived endothelial cells can be allogenic or syngenic to the subject. The endothelial cells may be delivered alone or in combination with other therapeutic agents.
摘要翻译：描述了用于促进将脂肪来源的内皮细胞局部递送至靶组织，体腔或关节的细胞递送基质和方法。细胞递送基质可以是包含衍生自患者本身的纤维蛋白的三维基质支架。细胞递送基质可以是生物相容性的和半渗透性的。用于本发明方法的细胞递送基质可以由任何可降解的，生物可吸收的或不可降解的生物相容性聚合物组成。描述了包含植入本发明的细胞递送基质定位脂肪来源的内皮细胞的再生疗法。细胞递送基质将靶向脂肪来源的内皮细胞维持在治疗有效的时间量。脂肪来源的内皮细胞可以是同种异体的或与受试者同源的。内皮细胞可以单独递送或与其它治疗剂组合递送。

3. 发明申请

US20090192454A1 CATHETER FOR CELL DELIVERY 审中-公开
标题翻译：电池输送管
公开(公告)号：US20090192454A1
公开(公告)日：2009-07-30
申请号：US12418551
申请日：2009-04-03
申请人： Eugene Boland , Stuart K. Williams , Paul E. Kosnik
发明人： Eugene Boland , Stuart K. Williams , Paul E. Kosnik
IPC分类号： A61M25/10 , A61M25/00 , A61M5/178
CPC分类号： A61M25/10182 , A61M25/007 , A61M25/10184 , A61M2025/0057 , A61M2025/105 , A61M2025/1075
摘要： A cell delivery system and method for delivering cells locally to a tissue, body cavity, or joint is described. The cell delivery system comprises a catheter configured to deliver stem cells in a pressure controlled manner. The catheter may comprise an inner bladder and an outer perforated bladder. The inner bladder may be expanded through the use of a pressure conduit in order to deploy a stent. Cells, such as endothelial cells derived from adipose tissue, may be introduced between the inner and outer bladder. The inner bladder may be further expanded in order to exert pressure on the outer perforated bladder to advance the stems cells though the apertures of the outer bladder. The inner bladder may remain pressurized to hold the outer bladder against the vessel wall, thereby directing the stem cells to specific target sites. The system may be used to deliver stem cells with or without other therapeutic agents. The system may be used with or without a stent. The system may further comprise a pressure gauge that permits measurement and regulation of pressure within the catheter.
摘要翻译：描述了将细胞局部递送至组织，体腔或关节的细胞递送系统和方法。细胞递送系统包括配置成以压力控制的方式递送干细胞的导管。导管可以包括内囊和外穿孔囊。可以通过使用压力导管来扩张内囊，以便展开支架。可以在内囊和外囊之间引入细胞，例如源自脂肪组织的内皮细胞。内囊可以进一步膨胀以便在外部穿孔的膀胱上施加压力，以通过外囊的孔推进杆细胞。内囊可以保持加压以将外囊保持抵靠血管壁，从而将干细胞引导到特定的靶位点。该系统可用于递送具有或不具有其它治疗剂的干细胞。该系统可以在有或没有支架的情况下使用。该系统还可以包括允许测量和调节导管内的压力的压力计。

4. 发明授权

US07052829B2 Prevascularized constructs for implantation to provide blood perfusion 有权
公开(公告)号：US07052829B2
公开(公告)日：2006-05-30
申请号：US10134939
申请日：2002-04-29
申请人： Stuart K. Williams , James B. Hoying , Benjamin R. Shepherd
发明人： Stuart K. Williams , James B. Hoying , Benjamin R. Shepherd
IPC分类号： A01N1/00 , A01N63/00 , C12N5/02 , C12N5/00
CPC分类号： C12N5/0691 , A61K35/12 , A61K48/00 , C12N5/0697 , C12N2501/20 , C12N2502/28 , C12N2510/00 , C12N2533/54 , C12N2533/56
摘要： This application discloses methods and materials for preparing functional microvascular beds in the laboratory. These prevascularized constructs can be used to vascularize engineered tissue constructs or to revascularize damaged or diseased tissues or organs following implantation. The prevascularized constructs may also deliver genetically engineered gene products to the bloodstream.

5. 发明授权

US07029838B2 Prevascularized contructs for implantation to provide blood perfusion 有权
标题翻译：用于植入以提供血液灌注的血管再造
公开(公告)号：US07029838B2
公开(公告)日：2006-04-18
申请号：US10112461
申请日：2002-03-29
申请人： Stuart K. Williams , James B. Hoying , Benjamin R. Shepherd
发明人： Stuart K. Williams , James B. Hoying , Benjamin R. Shepherd
IPC分类号： A01N1/00 , A01N65/00 , C12N5/02 , C12N5/00
CPC分类号： C12N5/0697 , A61K35/12 , A61K48/00 , C12N5/0691 , C12N2501/20 , C12N2502/28 , C12N2510/00 , C12N2533/54 , C12N2533/56
摘要： This application discloses methods and materials for preparing functional microvascular beds in the laboratory. These prevascularized constructs can be used to vascularize engineered tissue constructs or to revascularize damaged or diseased tissues or organs following implantation. The prevascularized constructs may also deliver genetically engineered gene products to the bloodstream.
摘要翻译：本申请公开了在实验室中制备功能性微血管床的方法和材料。这些血浆前构建体可用于血管化工程化组织构建体或植入后损伤或患病组织或器官的血运重建。先血管形成的构建体还可以将基因工程的基因产物递送到血流。

6. 发明授权

US5230693A Implantable prosthetic device for implantation into a human patient having a surface treated with microvascular endothelial cells 失效
标题翻译：植入式假体装置用于植入具有用微血管内皮细胞处理的表面的人类患者
公开(公告)号：US5230693A
公开(公告)日：1993-07-27
申请号：US725950
申请日：1991-06-27
申请人： Stuart K. Williams , Bruce E. Jarrell
发明人： Stuart K. Williams , Bruce E. Jarrell
IPC分类号： A61L27/34 , A61L27/38 , A61L27/50
CPC分类号： A61L27/507 , A61L27/34 , A61L27/38
摘要： The present invention provides a synthetic or naturally occurring implant, such as a vascular graft, for implantation into a human patient. Uncultured, microvascular endothelial cells, isolated from microvascular endothelial cell rich tissue are disposed on at least one surface of the implant to provide at least about 50% confluence of the cells on the surface of the implant prior to implantation. In a preferred embodiment, the microvascular endothelial cells are obtained from fat tissue. Because of the large number of fresh microvascular endothelial cells that may be obtained from such tissue, sufficient cells may be placed on the implant so that they attach to provide at least 50% confluent coverage of the implant surface prior to the time of implantation.
摘要翻译：本发明提供了用于植入人类患者的合成或天然存在的植入物，例如血管移植物。从微血管内皮细胞富集组织分离的未培养的微血管内皮细胞设置在植入物的至少一个表面上，以在植入之前提供至少约50％的细胞在植入物表面上的汇合。在优选的实施方案中，微血管内皮细胞从脂肪组织获得。由于可以从这样的组织获得大量新鲜的微血管内皮细胞，可以将足够的细胞放置在植入物上，使得它们附着以在植入之前提供植入物表面的至少50％汇合覆盖。

7. 发明授权

US09506040B2 Prevascularized constructs for implantation to provide blood perfusion 有权
公开(公告)号：US09506040B2
公开(公告)日：2016-11-29
申请号：US12464041
申请日：2009-05-11
申请人： Stuart K. Williams , James B. Hoying , Benjamin R. Shepherd
发明人： Stuart K. Williams , James B. Hoying , Benjamin R. Shepherd
IPC分类号： A01N63/00 , C12N5/071 , A61K35/12 , A61K48/00
CPC分类号： C12N5/0697 , A61K35/12 , A61K48/00 , C12N5/0691 , C12N2501/20 , C12N2502/28 , C12N2510/00 , C12N2533/54 , C12N2533/56
摘要： This application discloses methods and materials for preparing functional microvascular beds in the laboratory. These prevascularized constructs can be used to vascularize engineered tissue constructs or to revascularize damaged or diseased tissues or organs following implantation. The prevascularized constructs may also deliver genetically engineered gene products to the bloodstream.

8. 发明授权

US09226494B2 Bioreactors, systems, and methods for vascularizing tissue constructs 有权
标题翻译：用于血管化组织构建体的生物反应器，系统和方法
公开(公告)号：US09226494B2
公开(公告)日：2016-01-05
申请号：US12562832
申请日：2009-09-18
申请人： Carlos C. Chang , James B. Hoying , Stuart K. Williams
发明人： Carlos C. Chang , James B. Hoying , Stuart K. Williams
IPC分类号： A01N1/02 , A01N1/00 , C12M1/00 , C12M3/00 , C12M1/12
CPC分类号： A01N1/0247 , C12M21/08 , C12M23/38 , C12M23/44 , C12M25/14 , C12M29/10
摘要： A modular bioreactor is provided that includes an upper biochamber; a lower biochamber; and an intermediate biochamber that is positioned between the upper biochamber and the lower biochamber. Each biochamber of the bioreactor is in fluid communication with each other biochamber of the bioreactor and includes an interior wall, which defines a centrally-disposed cavity for each biochamber, and an inflow port and an outflow port that are in fluid communication with each centrally disposed cavity. Systems and methods for vascularizing a tissue construct are also provided.
摘要翻译：提供了一种模块化生物反应器，其包括上部生物室; 一个较低的生物室; 以及位于上部生物室和下部生物室之间的中间生物室。生物反应器的每个生物室与生物反应器的每个生物室流体连通，并且包括内壁，其限定每个生物室的居中设置的空腔，以及与每个中心设置的流体连通的流入端口和流出端口腔。还提供用于血管化组织构建体的系统和方法。

9. 发明授权

US09144583B2 Cell separation apparatus and methods of use 有权
标题翻译：细胞分离装置及使用方法
公开(公告)号：US09144583B2
公开(公告)日：2015-09-29
申请号：US11789188
申请日：2007-04-23
申请人： Gregory D. Ariff , Thomas Cannon , Jennifer L. Case , Christian L. Haller , Paul Kosnik , Charles P. Luddy , Craig A. Mauch , Erik Vossman , Stuart K. Williams
发明人： Gregory D. Ariff , Thomas Cannon , Jennifer L. Case , Christian L. Haller , Paul Kosnik , Charles P. Luddy , Craig A. Mauch , Erik Vossman , Stuart K. Williams
IPC分类号： A01N1/00 , A61K35/00 , A61P43/00 , C12M1/00 , A61K35/12
CPC分类号： C12M47/04 , A61K35/12 , C12M45/05 , C12M45/06 , C12M45/09
摘要： The present invention provides automated devices for use in supporting various cell therapies and tissue engineering methods. The present invention provides an automated cell separation apparatus capable of separating cells from a tissue sample for use in cell therapies and/or tissue engineering. The cell separation apparatus can be used in combination with complementary devices such as cell collection device and/or a sodding apparatus to support various therapies. The automated apparatus includes media and tissue dissociating chemical reservoirs, filters, a cell separator and a perfusion flow loop through a graft chamber which supports a graft substrate or other endovascular device. The present invention further provides methods for using the tissue grafts and cell samples prepared by the devices described herein in a multitude of therapies including revascularization, regeneration and reconstruction of tissues and organs, as well as treatment and prevention of diseases.
摘要翻译：本发明提供了用于支持各种细胞疗法和组织工程方法的自动化装置。本发明提供了一种能够从用于细胞疗法和/或组织工程的组织样品中分离细胞的自动细胞分离装置。细胞分离装置可以与诸如细胞收集装置和/或Sodding装置的补充装置组合使用以支持各种疗法。自动化装置包括介质和组织解离化学储存器，过滤器，细胞分离器和通过支撑移植物基质或其它血管内装置的移植室的灌注流动回路。本发明还提供了使用本文所述装置制备的组织移植物和细胞样品在包括血管重建，组织和器官的再血管重建和重建以及治疗和预防疾病的多种疗法中的方法。

10. 发明申请

US20110218396A1 METHODS AND COMPOSITIONS TO SUPPORT TISSUE INTEGRATION AND INOSCULATION OF TRANSPLANTED TISSUE AND TRANSPLANTED ENGINEERED PENILE TISSUE WITH ADIPOSE STROMAL CELLS 有权
标题翻译：支持组织整合的方法和组合物和移植组织和移植的工程化骨组织与ADIPOSE STROMAL CELL
公开(公告)号：US20110218396A1
公开(公告)日：2011-09-08
申请号：US12718805
申请日：2010-03-05
申请人： Stuart K. Williams , Hyun Joon Paek , Erik Vossman
发明人： Stuart K. Williams , Hyun Joon Paek , Erik Vossman
IPC分类号： A61F2/26
CPC分类号： A61F2/26
摘要： The present invention generally relates to methods, compositions and uses thereof for enhancing vascularization of a tissue or cell transplant for transplantation into a subject. In particular, one aspect of the present invention provides methods and compositions comprising the use of a population of stromal vascular fraction (SVF) cells to encapsulate or surround a tissue or cell transplant to enhance vascularization of the tissue or cell transplant. Another aspect of the present invention provides methods and compositions for enhancing vascularization of a tissue or cell transplant by combining a population of SVF cells with a tissue or cell transplant to form a transplant mixed with SVF cells. Another aspect provides a composition comprising an engineered corpus cavernosum tissue comprising SVF cells and corpus cavernosum cells, wherein the SVF cells can be mixed with or encasing the corpus cavernosum cells, and methods of uses thereof, for example in method for the treatment of impotence and erectile dysfunction and/or enhance or construct a penis. In some embodiments, the SVF cells can be generically engineered to secrete therapeutic proteins or pro-angiogenic factors.
摘要翻译：本发明总体上涉及用于增强移植到受试者中的组织或细胞移植物的血管形成的方法，组合物和用途。特别地，本发明的一个方面提供方法和组合物，其包括使用群体的基质血管部分（SVF）细胞来包封或包围组织或细胞移植物以增强组织或细胞移植物的血管形成。本发明的另一方面提供了通过将一组SVF细胞与组织或细胞移植物组合以形成与SVF细胞混合的移植物来增强组织或细胞移植物血管形成的方法和组合物。另一方面提供一种组合物，其包含工程化的海绵体组织，其包含SVF细胞和海绵体细胞，其中所述SVF细胞可与海绵体细胞混合或包裹，以及其使用方法，例如用于治疗阳in的方法，以及勃起功能障碍和/或增强或构建阴茎。在一些实施方案中，SVF细胞可被普遍设计以分泌治疗性蛋白质或促血管生成因子。

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