公开(公告)号：US10426872B2

公开(公告)日：2019-10-01

申请号：US15765981

申请日：2016-10-07

申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ,  THE UNITED STATES OF AMERICA AS REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS

发明人： Jeffrey S. Sakamoto ,  Dena Shahriari ,  Mark H. Tuszynski ,  Wendy Campana ,  Yacov Koffler

IPC分类号： A61L27/56 ,  A61L27/58 ,  A61L27/18 ,  A61L27/34 ,  A61L27/54

摘要： Tissue scaffolds for neural tissue growth have a plurality of microchannels disposed within a sheath. Each microchannel comprises a porous wall having a thickness of ≤about 100 μm that is formed from a biocompatible and biodegradable material comprising a polyester polymer. The polyester polymer may be polycaprolactone, poly(lactic-co-glycolic acid) polymer, and combinations thereof. The tissue scaffolds have high open volume % enabling superior (linear and high fidelity) neural tissue growth, while minimizing inflammation near the site of implantation in vivo. In other aspects, methods of making such tissue scaffolds are provided. Such a method may include mixing a reduced particle size porogen with a polymeric precursor solution. The material is cast onto a template and then can be processed, including assembly in a sheath and removal of the porogen, to form a tissue scaffold having a plurality of porous microchannels.

公开(公告)号：US11110207B2

公开(公告)日：2021-09-07

申请号：US16545855

申请日：2019-08-20

申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ,  THE UNITED STATES OF AMERICA AS REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS

发明人： Jeffrey S. Sakamoto ,  Dena Shahriari ,  Mark H. Tuszynski ,  Wendy Campana ,  Yacov Koffler

IPC分类号： A61L27/56 ,  A61L27/18 ,  A61L27/34 ,  A61L27/58 ,  A61L27/54

摘要： Tissue scaffolds for neural tissue growth have a plurality of microchannels disposed within a sheath. Each microchannel comprises a porous wall having a thickness of ≤about 100 μm that is formed from a biocompatible and biodegradable material comprising a polyester polymer. The polyester polymer may be polycaprolactone, poly(lactic-co-glycolic acid) polymer, and combinations thereof. The tissue scaffolds have high open volume % enabling superior (linear and high fidelity) neural tissue growth, while minimizing inflammation near the site of implantation in vivo. In other aspects, methods of making such tissue scaffolds are provided. Such a method may include mixing a reduced particle size porogen with a polymeric precursor solution. The material is cast onto a template and then can be processed, including assembly in a sheath and removal of the porogen, to form a tissue scaffold having a plurality of porous microchannels.

公开(公告)号：US20230323050A1

公开(公告)日：2023-10-12

申请号：US18126230

申请日：2023-03-24

申请人： The Regents of the University of California ,  The Regents of the University of Michigan

发明人： Mark H. Tuszynski ,  Jeffrey S. Sakamoto ,  Kendell M. Pawelec ,  Yacov Koffler ,  Michael Sailor ,  Jonathan Zuidema

IPC分类号： C08J5/18 ,  A61F2/02 ,  A61M31/00 ,  C08K3/36

CPC分类号： C08J5/18 ,  A61F2/02 ,  A61M31/002 ,  C08K3/36 ,  C08K3/042

摘要： Provided herein is technology relating to materials having microscale and/or nanoscale features and particularly, but not exclusively, to porous materials comprising microscale features, methods for producing porous materials comprising microscale features, drug delivery vehicles, and related kits, systems, and uses.

公开(公告)号：US11680143B2

公开(公告)日：2023-06-20

申请号：US16738872

申请日：2020-01-09

申请人： The Regents of the University of Michigan ,  The Regents of the University of California

发明人： Mark H. Tuszynski ,  Jeffrey S. Sakamoto ,  Kendell M. Pawelec ,  Yacov M. Koffler ,  Michael Sailor ,  Jonathan Zuidema

IPC分类号： C08J5/18 ,  A61F2/02 ,  A61M31/00 ,  C08K3/36 ,  C08K3/04 ,  C08K3/32 ,  A61F2/30

CPC分类号： C08J5/18 ,  A61F2/02 ,  A61M31/002 ,  C08K3/36 ,  A61F2002/30316 ,  C08J2367/04 ,  C08K3/042 ,  C08K2003/325 ,  C08K2201/011

摘要： Provided herein is technology relating to materials having microscale and/or nanoscale features and particularly, but not exclusively, to porous materials comprising microscale features, methods for producing porous materials comprising microscale features, drug delivery vehicles, and related kits, systems, and uses.

公开(公告)号：US20140308256A1

公开(公告)日：2014-10-16

申请号：US14362891

申请日：2012-12-12

申请人： The Regents of the University of California

发明人： Paul Lu ,  Mark H. Tuszynski

IPC分类号： A61K38/18 ,  A61K35/30

CPC分类号： A61K38/185 ,  A61K35/30 ,  A61K38/18 ,  A61K2300/00

摘要： Methods for inducing non-embryonic lesioned central nervous system neurons to survive, integrate, extend axons over long distances, induce intra-lesion ingrowth of neurons into the lesion from host tissue and form synapses in vivo. Pluripotent neural stem cells are grafted into the lesioned CNS tissue within a tissue adhesive suspension, optionally in the presence of growth factors. No modification of the neuronal regenerative inhibitory environment of the CNS is necessary.

摘要翻译： 诱导非胚胎损伤的中枢神经系统神经元生存，整合，长距离延伸的轴突的方法，诱导神经元内的病变向内生长进入宿主组织的病变，并在体内形成突触。 多能神经干细胞可任选地在生长因子存在下移植到组织粘附性悬浮液内的病变CNS组织中。 不需要对CNS的神经元再生抑制环境进行修饰。

公开(公告)号：US20220167988A1

公开(公告)日：2022-06-02

申请号：US17602727

申请日：2020-04-10

申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

发明人： Mark H. Tuszynski ,  Yacov Koffler ,  Isac Lazarovits

IPC分类号： A61B17/11

摘要： Biomimetic scaffolds for neural tissue growth are disclosed herein which have a plurality of microchannels disposed within a sheath. Each microchannel comprises a porous wall that is formed from a biocompatible and biodegradable material. The biocompatible and biodegradable material may be polyethylene glycol) diacrylate, methacrylated gelatin, methacrylated collagen, or polycaprolactone, and combinations thereof. The biomimetic scaffolds have high open volume % enabling superior (linear and high fidelity) neural tissue growth, while minimizing inflammation near the site of implantation in vivo.

公开(公告)号：US09649358B2

公开(公告)日：2017-05-16

申请号：US14362891

申请日：2012-12-10

申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

发明人： Paul Lu ,  Mark H. Tuszynski

IPC分类号： A61K38/18 ,  A61K35/30

CPC分类号： A61K38/185 ,  A61K35/30 ,  A61K38/18 ,  A61K2300/00

摘要： Methods for inducing non-embryonic lesioned central nervous system neurons to survive, integrate, extend axons over long distances, induce intra-lesion ingrowth of neurons into the lesion from host tissue and form synapses in vivo. Pluripotent neural stem cells are grafted into the lesioned CNS tissue within a tissue adhesive suspension, optionally in the presence of growth factors. No modification of the neuronal regenerative inhibitory environment of the CNS is necessary.

公开(公告)号：US08859520B2

公开(公告)日：2014-10-14

申请号：US14071572

申请日：2013-11-04

申请人： The Regents of the University of California

发明人： Mark H. Tuszynski

IPC分类号： A01N43/04 ,  C12N15/00 ,  C12N15/63 ,  A01N63/00 ,  C07H21/04 ,  A61K48/00 ,  C12N15/867 ,  A61K38/18 ,  C07K14/475 ,  C12N15/86

CPC分类号： A61K48/005 ,  A61K38/185 ,  A61K48/00 ,  A61K48/0075 ,  A61K48/0083 ,  C07K14/475 ,  C12N15/86 ,  C12N15/867 ,  C12N2740/16043 ,  C12N2799/021 ,  C12N2799/027

摘要： A specific clinical protocol for use toward therapy of defective, diseased and damaged neurons in the mammalian brain by delivering a definite concentration of recombinant neurotrophin, into a targeted region of the brain using a lentiviral expression vector. The neurotrophin is delivered to, or within close proximity of, identified defective, diseased or damaged brain cells. Growth of targeted neurons, and reversal of functional deficits associated with the neurodegenerative disease being treated is provided.

摘要翻译： 一种用于通过使用慢病毒表达载体将确定浓度的重组神经营养蛋白递送至脑的靶区域来用于治疗哺乳动物脑中有缺陷，患病和受损神经元的特定临床方案。 神经营养蛋白被递送到或者在非常接近的识别的有缺陷的，患病的或受损的脑细胞中。 提供靶向神经元的生长以及与正在治疗的神经变性疾病相关的功能缺陷的逆转。

公开(公告)号：US20140057974A1

公开(公告)日：2014-02-27

申请号：US14071572

申请日：2013-11-04

申请人： The Regents of the University of California

发明人： Mark H. Tuszynski

IPC分类号： A61K48/00

CPC分类号： A61K48/005 ,  A61K38/185 ,  A61K48/00 ,  A61K48/0075 ,  A61K48/0083 ,  C07K14/475 ,  C12N15/86 ,  C12N15/867 ,  C12N2740/16043 ,  C12N2799/021 ,  C12N2799/027

摘要： A specific clinical protocol for use toward therapy of defective, diseased and damaged neurons in the mammalian brain, of particular usefulness for treatment of neurodegenerative conditions such as Parkinson's disease and Alzheimer's disease. The protocol is practiced by delivering a definite concentration of recombinant neurotrophin, such as glial cell-derived neurotrophic factor), into a targeted region of the brain (such as the substantia nigra) using a lentiviral expression vector. The neurotrophin is delivered to, or within close proximity of, identified defective, diseased or damaged brain cells. The concentration of neurotrophin delivered as part of a neurotrophic composition varies from 1010 to 1015 neurotrophin encoding viral particles/ml of composition fluid. Each delivery site receives from 2.5 μl to 25 μl of neurotrophic composition, delivered slowly, as in over a period of time ranging upwards of 10 minutes/delivery site. Each delivery site is at, or within 500 μm of, a targeted cell, and no more than about 10 mm from another delivery site. The method stimulates growth of targeted neurons, and reversal of functional deficits associated with the neurodegenerative disease being treated.

摘要翻译： 用于治疗哺乳动物脑中有缺陷，患病和受损神经元的特定临床方案，对于治疗神经变性疾病如帕金森病和阿尔茨海默氏病尤其有用。 通过使用慢病毒表达载体将确定浓度的重组神经营养因子（例如神经胶质细胞衍生的神经营养因子）递送至脑的靶向区域（例如黑质）来实施该方案。 神经营养蛋白被递送到或者在非常接近的识别的有缺陷的，患病的或受损的脑细胞中。 作为神经营养组合物的一部分递送的神经营养因子的浓度在编码病毒颗粒/ ml组合物流体的1010至1015个神经营养因子中变化。 每个送货站点从2.5毫升到25毫升的神经营养组合物，缓慢递送，如超过10分钟/送货地点的一段时间。 每个递送部位在目标细胞的500μm以下，距离另一个递送部位不超过约10mm。 该方法刺激靶向神经元的生长，并与正在治疗的神经变性疾病相关的功能性逆转逆转。