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1.发明授权Three-dimensional bioprinting of biosynthetic cellulose (BC) implants and scaffolds for tissue engineering 有权生物合成纤维素（BC）植入物和组织工程支架的三维生物印迹公开(公告)号：US08691974B2
公开(公告)日：2014-04-08
申请号：US13498657
申请日：2010-09-28
IPC分类号： C08B1/00 , A61K31/717 , C12P1/04 , C12N11/12
CPC分类号： C08B1/00 , A61L27/20 , A61L27/38 , A61L27/56 , A61L2400/12 , C12N5/0062 , C12N11/12 , C12N2533/78 , C12P19/04 , C08L1/02
摘要： A novel BC fermentation technique for controlling 3D shape, thickness and architecture of the entangled cellulose nano-fibril network is presented. The resultant nano-cellulose based structures are useful as biomedical implants and devices, are useful for tissue engineering and regenerative medicine, and for health care products. More particularly, embodiments of the present invention relate to systems and methods for the production and control of 3-D architecture and morphology of nano-cellulose biomaterials produced by bacteria using any biofabrication process, including the novel 3-D Bioprinting processes disclosed. Representative processes according to the invention involve control of the rate of production of biomaterial by bacteria achieved by meticulous control of the addition of fermentation media using a microfluidic system. In exemplary embodiments, the bacteria gradually grew up along the printed alginate structure that had been placed into the culture, incorporating it. After culture, the printed alginate structure was successfully removed revealing porosity where the alginate had been placed. Porosity and interconnectivity of pores in the resultant 3-D architecture can be achieved by porogen introduction using, e.g., ink-jet printer technology.
摘要翻译： 提出了一种用于控制缠结纤维素纳米纤维网络的3D形状，厚度和结构的新型BC发酵技术。 所得的纳米纤维素基结构可用作生物医学植入物和装置，可用于组织工程和再生医学以及保健产品。 更具体地说，本发明的实施方案涉及使用任何生物制造方法生产和控制由细菌生产的纳米纤维素生物材料的三维结构和形态的系统和方法，包括所公开的新型3-D生物印迹方法。 根据本发明的代表性方法涉及通过细微控制使用微流体系统添加发酵培养基来控制细菌生物材料的生产速率。 在示例性实施方案中，细菌沿已经放入培养物中的印刷的藻酸盐结构逐渐长大，并入其中。 培养后，成功去除了印刷的藻酸盐结构，显示了藻酸盐放置的孔隙度。 所得3-D结构中孔隙的孔隙率和互连性可以通过使用例如喷墨打印机技术的致孔剂引入来实现。
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2.发明申请THREE-DIMENSIONAL BIOPRINTING OF BIOSYNTHETIC CELLULOSE (BC) IMPLANTS AND SCAFFOLDS FOR TISSUE ENGINEERING 有权生物塑料纤维素（BC）植物和组织的组织工程三维生物学公开(公告)号：US20120190078A1
公开(公告)日：2012-07-26
申请号：US13498657
申请日：2010-09-28
CPC分类号： C08B1/00 , A61L27/20 , A61L27/38 , A61L27/56 , A61L2400/12 , C12N5/0062 , C12N11/12 , C12N2533/78 , C12P19/04 , C08L1/02
摘要： A novel BC fermentation technique for controlling 3D shape, thickness and architecture of the entangled cellulose nano-fibril network is presented. The resultant nano-cellulose based structures are useful as biomedical implants and devices, are useful for tissue engineering and regenerative medicine, and for health care products. More particularly, embodiments of the present invention relate to systems and methods for the production and control of 3-D architecture and morphology of nano-cellulose biomaterials produced by bacteria using any biofabrication process, including the novel 3-D Bioprinting processes disclosed. Representative processes according to the invention involve control of the rate of production of biomaterial by bacteria achieved by meticulous control of the addition of fermentation media using a microfluidic system. In exemplary embodiments, the bacteria gradually grew up along the printed alginate structure that had been placed into the culture, incorporating it. After culture, the printed alginate structure was successfully removed revealing porosity where the alginate had been placed. Porosity and interconnectivity of pores in the resultant 3-D architecture can be achieved by porogen introduction using, e.g., ink-jet printer technology.
摘要翻译： 提出了一种用于控制缠结纤维素纳米纤维网络的3D形状，厚度和结构的新型BC发酵技术。 所得的纳米纤维素基结构可用作生物医学植入物和装置，可用于组织工程和再生医学以及保健产品。 更具体地说，本发明的实施方案涉及使用任何生物制造方法生产和控制由细菌生产的纳米纤维素生物材料的三维结构和形态的系统和方法，包括所公开的新型3-D生物印迹方法。 根据本发明的代表性方法涉及通过细微控制使用微流体系统添加发酵培养基来控制细菌生物材料的生产速率。 在示例性实施方案中，细菌沿已经放入培养物中的印刷的藻酸盐结构逐渐长大，并入其中。 培养后，成功去除了印刷的藻酸盐结构，显示了藻酸盐放置的孔隙度。 所得3-D结构中孔隙的孔隙率和互连性可以通过使用例如喷墨打印机技术的致孔剂引入来实现。
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3.发明申请ELECTROMAGNETIC CONTROLLED BIOFABRICATION FOR MANUFACTURING OF MIMETIC BIOCOMPATIBLE MATERIALS 审中-公开用于生产化学生物材料的电磁控制生物制品公开(公告)号：US20110076665A1
公开(公告)日：2011-03-31
申请号：US12996412
申请日：2009-06-05
CPC分类号： A01N1/00 , A61F2/00 , C08B1/00 , C12N1/066 , C12N5/0068 , C12N13/00 , C12N2529/00 , C12N2533/78 , C12N2535/10 , C12P1/04 , Y10T428/31986
摘要： The precise application of an electromagnetic field controls cell motion to guide extrusion and deposition of biopolymers produced by the cells. This controlled biofabrication process is used to fabricate two- and three-dimensional networks of biocompatible nanofibrils (such as cellulose) for use as biomaterials, tissue scaffolds to be used in regenerative medicine, coatings for biomedical devices, and other health care products.
摘要翻译： 电磁场的精确应用控制细胞运动以引导由细胞产生的生物聚合物的挤出和沉积。 这种受控的生物制造过程用于制造用作生物材料的生物相容纳米原纤维（例如纤维素）的二维和三维网络，用于再生医学的组织支架，用于生物医学装置的涂层和其他保健产品。
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公开(公告)号：US10471254B2
公开(公告)日：2019-11-12
申请号：US15310114
申请日：2015-05-12
申请人： Virginia Tech Intellectual Properties, Inc. , Michael B. Sano , Christopher B. Arena , Scott S. Verbridge , Rafael V. Davalos
IPC分类号： A61B18/14 , A61N1/32 , A61N1/40 , A61B90/00 , A61B18/12 , A61N1/06 , A61N1/08 , A61B18/00 , A61B17/00
摘要： A system and method for selectively treating aberrant cells such as cancer cells through administration of a train of electrical pulses is described. The pulse length and delay between successive pulses is optimized to produce effects on intracellular membrane potentials. Therapies based on the system and method produce two treatment zones: an ablation zone surrounding the electrodes within which aberrant cells are non-selectively killed and a selective treatment zone surrounding the ablation zone within which target cells are selectively killed through effects on intracellular membrane potentials. As a result, infiltrating tumor cells within a tumor margin can be effectively treated while sparing healthy tissue. The system and method are useful for treating various cancers in which solid tumors form and have a chance of recurrence from microscopic disease surrounding the tumor.
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5.发明申请IRREVERSIBLE ELECTROPORATION USING TISSUE VASCULATURE TO TREAT ABERRANT CELL MASSES OR CREATE TISSUE SCAFFOLDS 有权不可逆电气使用组织血管来治疗细胞质量或产生组织病变公开(公告)号：US20130253415A1
公开(公告)日：2013-09-26
申请号：US13989175
申请日：2011-11-23
CPC分类号： A61B18/14 , A61B18/1492 , A61B2018/00613 , A61B2018/1472 , A61B2218/002 , A61K48/0075 , A61M5/00 , A61N1/327
摘要： The present invention relates to the field of medical treatment of diseases and disorders, as well as the field of biomedical engineering. Embodiments of the invention relate to the delivery of Irreversible Electroporation (IRE) through the vasculature of organs to treat tumors embedded deep within the tissue or organ, or to decellularize organs to produce a scaffold from existing animal tissue with the existing vasculature intact. In particular, methods of administering non-thermal irreversible electroporation (IRE) in vivo are provided for the treatment of tumors located in vascularized tissues and organs. Embodiments of the invention further provide scaffolds and tissues from natural sources created using IRE ex vivo to remove cellular debris, maximize recellularization potential, and minimize foreign body immune response. The engineered tissues can be used in methods of treating subjects, such as those in need of tissue replacement or augmentation.
摘要翻译： 本发明涉及疾病和病症的医疗领域以及生物医学工程领域。 本发明的实施方案涉及通过器官脉管系统递送不可逆电穿孔（IRE）以治疗深入组织或器官内的肿瘤，或者使现有动物组织脱细胞从而使现有的脉管系统完整地产生支架。 特别地，提供了在体内施用非热不可逆电穿孔（IRE）的方法用于治疗位于血管化组织和器官中的肿瘤。 本发明的实施方案进一步提供了使用IRE离体产生的来自天然来源的支架和组织，以去除细胞碎片，最大限度地获得细胞结合潜能，并使异物免疫应答最小化。 工程组织可用于治疗受试者的方法，例如需要组织置换或增生的方法。
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公开(公告)号：US09867652B2
公开(公告)日：2018-01-16
申请号：US13989175
申请日：2011-11-23
CPC分类号： A61B18/14 , A61B18/1492 , A61B2018/00613 , A61B2018/1472 , A61B2218/002 , A61K48/0075 , A61M5/00 , A61N1/327
摘要： The present invention relates to the field of medical treatment of diseases and disorders, as well as the field of biomedical engineering. Embodiments of the invention relate to the delivery of Irreversible Electroporation (IRE) through the vasculature of organs to treat tumors embedded deep within the tissue or organ, or to decellularize organs to produce a scaffold from existing animal tissue with the existing vasculature intact. In particular, methods of administering non-thermal irreversible electroporation (IRE) in vivo are provided for the treatment of tumors located in vascularized tissues and organs. Embodiments of the invention further provide scaffolds and tissues from natural sources created using IRE ex vivo to remove cellular debris, maximize recellularization potential, and minimize foreign body immune response. The engineered tissues can be used in methods of treating subjects, such as those in need of tissue replacement or augmentation.
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公开(公告)号：US20120085649A1
公开(公告)日：2012-04-12
申请号：US13269286
申请日：2011-10-07
IPC分类号： G01N27/453
CPC分类号： B03C5/005 , B03C5/026 , B03C2201/26
摘要： Devices and methods for performing dielectrophoresis are described. The devices contain a sample channel which is separated by physical barriers from electrode channels which receive electrodes. The devices and methods may be used for the separation and analysis of particles in solution, including the separation and isolation of cells of a specific type. As the electrodes do not make contact with the sample, electrode fouling is avoided and sample integrity is better maintained.
摘要翻译： 描述了用于进行介电电泳的装置和方法。 这些器件包含一个样品通道，该通道由接收电极的电极通道的物理屏障分开。 该装置和方法可用于分离和分析溶液中的颗粒，包括分离和分离特定类型的细胞。 由于电极不与样品接触，避免了电极结垢，更好地保持了样品的完整性。
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8.发明授权Devices and methods for contactless dielectrophoresis for cell or particle manipulation 有权用于细胞或颗粒操作的无接触介电电泳的装置和方法公开(公告)号：US08968542B2
公开(公告)日：2015-03-03
申请号：US12720406
申请日：2010-03-09
CPC分类号： G01N27/44791 , B01D57/02 , B03C5/005 , B03C5/022 , B03C5/026 , B03C2201/26
摘要： Devices and methods for performing dielectrophoresis are described. The devices contain sample channel which is separated by physical barriers from electrode channels which receive electrodes. The devices and methods may be used for the separation and analysis of particles in solution, including the separation and isolation of cells of a specific type. As the electrodes do not make contact with the sample, electrode fouling is avoided and sample integrity is better maintained.
摘要翻译： 描述了用于进行介电电泳的装置和方法。 这些器件包含由接收电极的电极通道的物理屏障分离的样品通道。 该装置和方法可用于分离和分析溶液中的颗粒，包括分离和分离特定类型的细胞。 由于电极不与样品接触，避免了电极结垢，更好地保持了样品的完整性。
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公开(公告)号：US10448989B2
公开(公告)日：2019-10-22
申请号：US13332133
申请日：2011-12-20
摘要： The present invention relates to the field of biomedical engineering and medical treatment of diseases and disorders. Methods, devices, and systems for in vivo treatment of cell proliferative disorders are provided. In embodiments, the methods comprise the delivery of high-frequency bursts of bipolar pulses to achieve the desired modality of cell death. More specifically, embodiments of the invention relate to a device and method for destroying aberrant cells, including tumor tissues, using high-frequency, bipolar electrical pulses having a burst width on the order of microseconds and duration of single polarity on the microsecond to nanosecond scale. In embodiments, the methods rely on conventional electroporation with adjuvant drugs or irreversible electroporation to cause cell death in treated tumors. The invention can be used to treat solid tumors, such as brain tumors.
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公开(公告)号：US20170266438A1
公开(公告)日：2017-09-21
申请号：US15310114
申请日：2015-05-12
申请人： Michael B. SANO , Christopher B. ARENA , Scott S. VERBRIDGE , Rafael V. DAVALOS , Virginia Tech Intellectual Properties, Inc.
摘要： A system and method for selectively treating aberrant cells such as cancer cells through administration of a train of electrical pulses is described. The pulse length and delay between successive pulses is optimized to produce effects on intracellular membrane potentials. Therapies based on the system and method produce two treatment zones: an ablation zone surrounding the electrodes within which aberrant cells are non-selectively killed and a selective treatment zone surrounding the ablation zone within which target cells are selectively killed through effects on intracellular membrane potentials. As a result, infiltrating tumor cells within a tumor margin can be effectively treated while sparing healthy tissue. The system and method are useful for treating various cancers in which solid tumors form and have a chance of recurrence from microscopic disease surrounding the tumor.
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