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    Bone matrix compositions and methods
    21.
    发明授权
    Bone matrix compositions and methods 有权
    骨基质组成和方法

    公开(公告)号：US09034358B2

    公开(公告)日：2015-05-19

    申请号：US13008460

    申请日：2011-01-18

    申请人： Keyvan Behnam ,  Christopher Cioffi

    发明人： Keyvan Behnam ,  Christopher Cioffi

    IPC分类号： A61L27/36 ,  A61L27/38 ,  A61L27/22 ,  A61L27/54

    CPC分类号： A61K38/01 ,  A61L27/227 ,  A61L27/3608 ,  A61L27/365 ,  A61L27/3654 ,  A61L27/3683 ,  A61L27/3687 ,  A61L27/3847 ,  A61L27/3852 ,  A61L27/54 ,  A61L2300/254 ,  A61L2300/412 ,  A61L2300/432 ,  A61L2430/02 ,  A61L2430/06 ,  Y10S623/901

    摘要： The present invention provides methods of improving the osteogenic and/or chondrogenic activity of a bone matrix, e.g., a dermineralized bone matrix (DBM), by exposing the bone matrix to one or more treatments or conditions. In preferred embodiments the bone matrix is derived from human bone. The treatment or condition may alter the structure of the bone matrix and/or cleave one or more specific proteins. Cleavage may generate peptides or protein fragments that have osteoinductive, osteogenic, or chondrogenic activity. Preferred treatments include collagenase and various other proteases. The invention further provides improved bone and cartilage matrix compositions that have been prepared according to the inventive methods and methods of treatment using the compositions. The invention further provides methods of preparing, testing, and using the improved bone matrix compositions. On a assay comprises exposing relatively undifferentiated mesenchymal cells to a bone matrix composition and measuring expression of a marker characteristic of osteoblast or chondrocyte lineage(s). Increased expression of the marker relative to the level of the marker in cells that have been exposed to a control matrix (e.g., an inactivated or untreated matrix) indicates that the treatment or condition increased the osteogenic and/or chondrogenic activity of the bone matrix. Suitable cells include C2C12 cells. A suitable marker is alkaline phosphatase. The inventive methods increase the osteogenic and/or chondrogenic activity of human DBM when tested using this assay system.

    摘要翻译： 本发明提供通过将骨基质暴露于一种或多种治疗或病症来改善骨基质例如脱矿骨基质（DBM）的成骨和/或软骨形成活性的方法。 在优选实施方案中，骨基质衍生自人骨。 治疗或病症可改变骨基质的结构和/或切割一种或多种特异性蛋白质。 切割可能产生具有骨诱导，成骨或软骨形成活性的肽或蛋白质片段。 优选的治疗包括胶原酶和各种其它蛋白酶。 本发明还提供了根据本发明的方法和使用该组合物的治疗方法制备的改进的骨和软骨基质组合物。 本发明还提供了制备，测试和使用改进的骨基质组合物的方法。 在测定中包括将相对未分化的间充质细胞暴露于骨基质组合物并测量成骨细胞或软骨细胞谱系特征性标志物的表达。 已经暴露于对照基质（例如，灭活或未经处理的基质）的细胞中标志物相对于标记物水平的增加表明该治疗或病症增加了骨基质的成骨和/或软骨形成的活性。 合适的细胞包括C2C12细胞。 合适的标记是碱性磷酸酶。 当使用该测定系统测试时，本发明的方法增加人DBM的成骨和/或软骨形成活性。

    Osteoinductive demineralized cancellous bone
    22.
    发明授权
    Osteoinductive demineralized cancellous bone 有权
    骨诱导软骨松质骨

    公开(公告)号：US08734525B2

    公开(公告)日：2014-05-27

    申请号：US12140025

    申请日：2008-06-16

    申请人： Keyvan Behnam ,  Nanette Forsyth ,  James Russell ,  John Winterbottom ,  Todd Boyce

    发明人： Keyvan Behnam ,  Nanette Forsyth ,  James Russell ,  John Winterbottom ,  Todd Boyce

    IPC分类号： A61K35/32

    CPC分类号： A61K35/32 ,  A61F2/28 ,  A61F2002/2817 ,  A61F2002/30059 ,  A61F2310/00359 ,  A61L27/3608 ,  A61L27/3641 ,  A61L27/3645 ,  A61L27/3683 ,  A61L27/3687 ,  A61L27/3691 ,  A61L27/3695 ,  A61L27/3878 ,  A61L2430/02

    摘要： An osteoinductive demineralized bone matrix, corresponding osteoimplants, and methods for making the osteoinductive demineralized bone matrix are disclosed. The osteoinductive demineralized bone matrix may be prepared by providing demineralized bone and altering the collagenous structure of the bone. The osteoinductive demineralized bone matrix may also be prepared by providing demineralized bone and compacting the bone, for example via mechanical compaction, grinding into a particulate, or treatment with a chemical. Additives such as growth factors or bioactive agents may be added to the osteoinductive demineralized bone matrix. The osteoinductive demineralized bone matrix may form an osteogenic osteoimplant. The osteoimplant, when implanted in a mammalian body, may induce at the locus of the implant the full developmental cascade of endochondral bone formation including vascularization, mineralization, and bone marrow differentiation. The osteoinductive demineralized bone matrix may also be used as a delivery device to administer bioactive agents.

    摘要翻译： 公开了一种骨诱导的软骨骨架，相应的骨关节植入物以及用于制造骨诱导性软骨骨架的方法。 可以通过提供软化骨和改变骨的胶原结构来制备骨诱导的软骨骨架。 还可以通过提供脱矿质骨和压实骨，例如通过机械压实，研磨成颗粒或用化学品处理来制备骨诱导的软化骨基质。 添加剂如生长因子或生物活性剂可以加入到骨诱导的软化骨基质中。 骨诱导的骨质疏松骨质可形成成骨植骨。 当植入植入哺乳动物体内的植骨植入物可能在植入物的位置诱导软骨内骨形成的完全发育级联，包括血管化，矿化和骨髓分化。 骨诱导的软化骨基质也可以用作施用生物活性剂的递送装置。

    OSTEOINDUCTIVE DEMINERALIZED CANCELLOUS BONE
    26.
    发明申请
    OSTEOINDUCTIVE DEMINERALIZED CANCELLOUS BONE 有权

    公开(公告)号：US20090155378A1

    公开(公告)日：2009-06-18

    申请号：US12140025

    申请日：2008-06-16

    申请人： Keyvan Behnam ,  Nanette Forsyth ,  James Russell ,  John M. Winterbottom ,  Todd M. Boyce

    发明人： Keyvan Behnam ,  Nanette Forsyth ,  James Russell ,  John M. Winterbottom ,  Todd M. Boyce

    IPC分类号： A61K35/32

    CPC分类号： A61K35/32 ,  A61F2/28 ,  A61F2002/2817 ,  A61F2002/30059 ,  A61F2310/00359 ,  A61L27/3608 ,  A61L27/3641 ,  A61L27/3645 ,  A61L27/3683 ,  A61L27/3687 ,  A61L27/3691 ,  A61L27/3695 ,  A61L27/3878 ,  A61L2430/02

    摘要： An osteoinductive demineralized bone matrix, corresponding osteoimplants, and methods for making the osteoinductive demineralized bone matrix are disclosed. The osteoinductive demineralized bone matrix may be prepared by providing demineralized bone and altering the collagenous structure of the bone. The osteoinductive demineralized bone matrix may also be prepared by providing demineralized bone and compacting the bone, for example via mechanical compaction, grinding into a particulate, or treatment with a chemical. Additives such as growth factors or bioactive agents may be added to the osteoinductive demineralized bone matrix. The osteoinductive demineralized bone matrix may form an osteogenic osteoimplant. The osteoimplant, when implanted in a mammalian body, may induce at the locus of the implant the full developmental cascade of endochondral bone formation including vascularization, mineralization, and bone marrow differentiation. The osteoinductive demineralized bone matrix may also be used as a delivery device to administer bioactive agents.

    摘要翻译： 公开了一种骨诱导的软骨骨架，相应的骨关节植入物以及用于制造骨诱导性软骨骨架的方法。 可以通过提供软化骨和改变骨的胶原结构来制备骨诱导的软骨骨架。 还可以通过提供脱矿质骨和压实骨，例如通过机械压实，研磨成颗粒或用化学品处理来制备骨诱导的软化骨基质。 添加剂如生长因子或生物活性剂可以加入到骨诱导的软化骨基质中。 骨诱导的骨质疏松骨质可形成成骨植骨。 当植入植入哺乳动物体内的植骨植入物可能在植入物的位置诱导软骨内骨形成的完全发育级联，包括血管化，矿化和骨髓分化。 骨诱导的软化骨基质也可以用作施用生物活性剂的递送装置。

    BONE MATRIX COMPOSITIONS AND METHODS
    27.
    发明申请
    BONE MATRIX COMPOSITIONS AND METHODS 有权
    骨基质组合物和方法

    公开(公告)号：US20090130173A1

    公开(公告)日：2009-05-21

    申请号：US12140044

    申请日：2008-06-16

    申请人： Keyvan Behnam ,  Guobao Wei ,  Nanette Forsyth

    发明人： Keyvan Behnam ,  Guobao Wei ,  Nanette Forsyth

    IPC分类号： A61F2/00 ,  A61K9/10 ,  A61K35/12 ,  A61K35/32

    CPC分类号： A61K35/00 ,  A61F2/28 ,  A61F2002/30059 ,  A61F2310/00359 ,  A61K35/32 ,  A61L27/3604 ,  A61L27/3608 ,  A61L27/3683 ,  A61L27/3695 ,  A61L27/3834 ,  A61L27/54 ,  A61L2430/02 ,  A61L2430/40

    摘要： Osteoinductive compositions and implants having increased biological activities, and methods for their production, are provided. The biological activities that may be increased include, but are not limited to, bone forming; bone healing; osteoinductive activity, osteogenic activity, chondrogenic activity, wound healing activity, neurogenic activity, contraction-inducing activity, mitosisinducing activity, differentiation-inducing activity, chemotactic activity, angiogenic or vasculogenic activity, and exocytosis or endocytosis-inducing activity. In one embodiment, a method for producing an osteoinductive composition comprises providing partially demineralized bone, treating the partially demineralized bone to disrupt the collagen structure of the bone, and optionally providing a tissue-derived extract and adding the tissue-derived extract to the partially demineralized bone. In another embodiment, an implantable osteoinductive and osteoconductive composition comprises partially demineralized bone, wherein the collagen structure of the bone has been disrupted, and, optionally, a tissue-derived extract.

    摘要翻译： 提供具有增加的生物活性的骨诱导组合物和植入物及其生产方法。 可能增加的生物活性包括但不限于骨形成; 骨愈合; 骨诱导活性，成骨活性，软骨形成活性，伤口愈合活性，神经源性活性，收缩诱导活性，有丝分裂诱导活性，分化诱导活性，趋化活性，血管生成或血管发生活性，以及​​胞吐作用或内吞诱导活性。 在一个实施方案中，用于产生骨诱导性组合物的方法包括提供部分去矿物质的骨，处理所述部分去矿物质的骨以破坏所述骨的胶原结构，以及任选地提供组织衍生的提取物，并将所述组织衍生的提取物加入到部分去矿物质 骨。 在另一个实施方案中，可植入的骨诱导和骨传导性组合物包含部分脱矿质骨，其中所述骨的胶原结构已被破坏，并且任选地包含组织衍生的提取物。

    Activating Extraction Of Demineralized Bone Matrix
    28.
    发明申请
    Activating Extraction Of Demineralized Bone Matrix 有权
    激活脱钙骨基质提取

    公开(公告)号：US20080268012A1

    公开(公告)日：2008-10-30

    申请号：US11791940

    申请日：2005-11-29

    申请人： Keyvan Behnam ,  Elsa J. Brochmann-Murray ,  Samuel S. Murray

    发明人： Keyvan Behnam ,  Elsa J. Brochmann-Murray ,  Samuel S. Murray

    IPC分类号： A61K35/32 ,  A61K38/00 ,  A61P19/00 ,  A61K38/29 ,  A61K38/30 ,  A61K38/18 ,  A61K33/06 ,  A61K38/23 ,  A61K33/16 ,  A61F2/00 ,  A61F2/02

    CPC分类号： A61K35/32 ,  A61K38/1841 ,  A61K38/1875 ,  A61K38/23 ,  A61K38/29 ,  A61K38/30 ,  A61K45/06 ,  A61K2300/00 ,  A61K33/06

    摘要： Demineralized bone matric (DBM) and native bone morphogenetic protein (nBMP) are complex mixtures of non-collagenous bone proteins. These mixtures contain many of the BMPs that are available as recombinant molecules. Information regarding the presence in these materials of molecules that may affect the availability and activity of the BMPs is very limited. A chemical extraction of DBM, such as using alkali-urea produces a water soluble extractate which inhibits the osteogenic activity of DBM. Noggin, an extracellular BMP ligand antagonist is found in the water soluble extractate from DBM. Differential chemical extraction is a useful means of removing non-osteogenic, or osteogenic inhibitory molecules from DBM and nBMP.

    摘要翻译： 脱矿骨质（DBM）和天然骨形态发生蛋白（nBMP）是非胶原性骨蛋白的复杂混合物。 这些混合物含有许多可用作重组分子的BMP。 关于可能影响BMP的可用性和活性的这些分子材料的存在的信息非常有限。 DBM的化学提取，例如使用碱 - 尿素，产生一种抑制DBM成骨活性的水溶性提取物。 在DBM的水溶性提取物中发现Noggin是细胞外BMP配体拮抗剂。 差异化学提取是从DBM和nBMP中去除非成骨或成骨抑制分子的有用手段。

    Bone matrix compositions and methods
    29.
    发明申请
    Bone matrix compositions and methods 有权
    骨基质组成和方法

    公开(公告)号：US20070154563A1

    公开(公告)日：2007-07-05

    申请号：US10584981

    申请日：2004-12-31

    申请人： Keyvan Behnam ,  Christopher Cioffi

    发明人： Keyvan Behnam ,  Christopher Cioffi

    IPC分类号： A61K35/32

    CPC分类号： A61K38/01 ,  A61L27/227 ,  A61L27/3608 ,  A61L27/365 ,  A61L27/3654 ,  A61L27/3683 ,  A61L27/3687 ,  A61L27/3847 ,  A61L27/3852 ,  A61L27/54 ,  A61L2300/254 ,  A61L2300/412 ,  A61L2300/432 ,  A61L2430/02 ,  A61L2430/06 ,  Y10S623/901

    摘要： The present invention provides methods of improving the osteogenic and/or chondrogenic activity of a bone matrix, e.g., a dermineralized bone matrix (DBM), by exposing the bone matrix to one or more treatments or conditions. In preferred embodiments the bone matrix is derived from human bone. The treatment or condition may alter the structure of the bone matrix and/or cleave one or more specific proteins. Cleavage may generate peptides or protein fragments that have osteoinductive, osteogenic, or chondrogenic activity. Preferred treatments include collagenase and various other proteases. The invention further provides improved bone and cartilage matrix compositions that have been prepared according to the inventive methods and methods of treatment using the compositions. The invention further provides methods of preparing, testing, and using the improved bone matrix compositions. Ona assay comprises exposing relatively undifferentiated mesenchymal cells to a bone matrix composition and measuring expression of a marker characteristic of osteoblast or chondrocyte lineage(s). Increased expression of the marker relative to the level of the marker in cells that have been exposed to a control matrix (e.g., an inactivated or untreated matrix) indicates that the treatment or condition increased the osteogenic and/or chondrogenic activity of the bone matrix. Suitable cells include C2C12 cells. A suitable marker is alkaline phosphatase. The inventive methods increase the osteogenic and/or chondrogenic activity of human DBM when tested using this assay system.

    摘要翻译： 本发明提供通过将骨基质暴露于一种或多种治疗或病症来改善骨基质例如脱矿骨基质（DBM）的成骨和/或软骨形成活性的方法。 在优选实施方案中，骨基质衍生自人骨。 治疗或病症可改变骨基质的结构和/或切割一种或多种特异性蛋白质。 切割可能产生具有骨诱导，成骨或软骨形成活性的肽或蛋白质片段。 优选的治疗包括胶原酶和各种其它蛋白酶。 本发明还提供了根据本发明的方法和使用该组合物的治疗方法制备的改进的骨和软骨基质组合物。 本发明还提供了制备，测试和使用改进的骨基质组合物的方法。 Ona测定包括将相对未分化的间充质细胞暴露于骨基质组合物并测量成骨细胞或软骨细胞谱系特征性标志物的表达。 已经暴露于对照基质（例如，灭活或未经处理的基质）的细胞中标志物相对于标记物水平的增加表明该治疗或病症增加了骨基质的成骨和/或软骨形成的活性。 合适的细胞包括C2C12细胞。 合适的标记是碱性磷酸酶。 当使用该测定系统测试时，本发明的方法增加人DBM的成骨和/或软骨形成活性。