CN101505722A - 流动性载体基质 - Google Patents

流动性载体基质 Download PDF

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CN101505722A
CN101505722A CNA2007800305046A CN200780030504A CN101505722A CN 101505722 A CN101505722 A CN 101505722A CN A2007800305046 A CNA2007800305046 A CN A2007800305046A CN 200780030504 A CN200780030504 A CN 200780030504A CN 101505722 A CN101505722 A CN 101505722A
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bmp
carrier matrix
medical kit
collagen
kit according
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N·B·比尔斯
J·L·Ph·D·赛弗特
S·D·伯登
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Warsaw Orthopedic Inc
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Abstract

载体基质可以以最小的侵入方式，通过首先将胶原海绵片切割成多个相对小的片，而被输送到患者体内的靶向位点。这些片大小适合，以致于它们被湿润时，能够流动穿过套管和/或直径缩小的注射器顶端。该片被放置到注射器中且被湿润，比方说由形态发生溶液湿润，且可任选地与膨胀材料混合，其被相似地设计成大小适合穿过套管。完全混合的和湿润的产物形成了粘性聚集体，其可以随后被注入到患者的靶向位点。

Description

流动性载体基质
发明领域
本发明涉及用于与骨有关疾病的可以移植医用装置。更具体地，本发明公开了用于提供流动性载体基质的方法和有关的试剂盒，该流动载体基质可以被注入到靶位点。
发明背景
使用载体基质以促进病人体内点的骨生长是众所周知的，并且目前在市场上有相关的产品，例如由Medtronic Sofamor Danek(Memphis，TN)提供的
Figure A200780030504D00051
 Matrix。这些基质典型地是相对大的、软的胶原蛋白海绵形式。在被插入到靶向点之前，该海绵要被湿润，通常使用从患者体内吸出的骨髓，以体积计，大约1：1比率进行。骨髓被允许浸泡到由海绵提供的骨架内，且该海绵随后用手挤压，因此得到挠性一致性，其可以随后被轻轻地挤压到靶向点内。在海绵内的胶原提供了具有延展性的非水可溶的载体，其允许在移植点上精确的放置和保留生物学因子。
因为该海绵必须是手挤压，所以外科医生需要在患者体内做出切入
口，以达到靶向点处的围绕骨。因此，整个方法是相对侵入性的和有疼痛的。如果有将以胶原为基础的载体基质输送到靶向位置的更少侵入性方式将是有益的。
发明简述
本发明的一个方面提供了将载体基质输送到靶向点的方法，其包括用流体湿润多个载体基质成分，以创造出粘性聚集体，随后将该粘性聚集体注入到靶向点。该载体基质成分包括胶原，且在一个具体的实施方式中，由胶原海绵形成，其尺寸范围为从1.0mm到10mm。在一些实施方式中，该流体包括成形素。在其他实施方式中，该载体基质成分用成形素预先浸渍。而且，膨胀材料可以被加入到粘性聚集体。
另一方面提供了用于实践上述方法的医用试剂盒。该医用试剂盒包括多个载体基质成分，输送系统和成形素。在一些实施方式中，该载体基质成分由胶原海绵形成，且尺寸上不大于10mm，也不小于1.0mm。该试剂盒可以进一步包括膨胀材料。该试剂盒还可以包括流体转换管，其用于将两个注射器连接到一起，以提供将在试剂盒内的多种成分混合到一起。在另一个实施方式中，该输送系统包括输送套管，其适合于帮助将粘性聚集体注入到靶向点。
附图简述
图1描述了第一实施方式试剂盒。
图2到4示例了图1中显示的试剂盒之使用，以产生流动载体基质。
图.5和6示例了将粘性聚集体注入到靶向点。
图7描述了第二实施方式试剂盒。
发明详述
在下面，应该理解术语，例如“包括”或“包含”，意味着指明含有，而不是唯一的项目列表。没有指出的项目可以进一步包含在这样的列表中。因此，除非指明其他方式，化合物或者装置的代表性列表将不被认为是限定性的；相反，应该理解这样的列表允许加入没有明确指明的合适的项目。
参考如图1所画，其描述了第一实施方式试剂盒10。该试剂盒10包括第一注射器20，流体转换管30，输送套管40和第二注射器50，所有都用消毒容器12密封。在试剂盒10中的成分是消毒的，且在容器12中被包装，直到需要使用。在本领域中熟知的适合的消毒和包装方法，可以被用于制备试剂盒10。该试剂盒10进一步包括多个干燥的、包括胶原的载体基质成分22。这些成分22可以被包装在它们自己的容器内，或正如在试剂盒10的具体实施方式中所显示，第一注射器20可以装载有载体基质成分22。第一注射器20的远端24可以用任意熟知的方式盖住，以预防：在处理该试剂盒10期间，基质成分22的损失。尽管没有显示，该试剂盒10还包括指明试剂盒10正确用途的介绍单或表。注射器20、50，和输送套管40一起，形成输送系统，其可以被用于将本发明的流动载体基质注射到靶向点。
下面，术语“载体基质”指代用于骨科移植市场的包括胶原的生物材料；当被放入到骨缺损内时，其提供骨架，围绕该骨架，患者的新骨生长，随着靶向点愈合，逐渐地替代载体基质。适合的载体基质实施例可以包括，但不限于由Medtronic Sofamor Danek，Inc.，Memphis，TN生的
Figure A200780030504D00071
 Matrix；Medtronic Sofamor Danek，Inc.，Memphis，TN生产的
Figure A200780030504D00072
 Putty；Integra LifeSciences Corporation，Plainsboro，N.J生产的可吸收胶原海绵Absorbable Collagen Sponge(“ACS”)；用羟磷灰石涂层的牛皮肤胶原纤维，例如，由Johnson &Johnson，USA投入市场的 胶原海绵，例如Coletica SA，France上市的
Figure A200780030504D00074
或例如Integra LifeSciences Inc.，USA投入市场的
Figure A200780030504D00075
以及Zimmer Holdings，Inc.，Warsaw，IN.生产的
Figure A200780030504D00076
Bone Graft Matrix。
该载体基质成分22是小的，以适度地被改变大小适合于任意的适合的包含胶原的载体基质；当它被湿润时，由于它的光滑的、柔软的、相互粘结的特征，该胶原海绵是成分22的优选载体基质。因为该载体基质成分22是随后通过套管44被注入到靶向点，成分22的尺寸必须足够小，以允许流体状的流体穿过该套管44。因此，希望任何载体基质成分22的尺寸沿任意轴不能超出10mm，更小的尺度被用于更小标准(即更窄)的套管44。也就是，载体基质22的尺度取决于套管44的标准，其随后被用于将它们注入到靶向点内；反过来，这可能取决于靶向点的形态学和病理学特征。
例如，在试剂盒10内，载体基质成分22可以是片状干燥胶原海绵22的形式，每个尺寸大约为5×5×2mm，其适合于通过至少16-21号的套管44进行后来的注入。应该理解载体基质22的具体形状没有沿它们任意轴的实际尺度更重要；也就是，载体基质成分22可以是任意形状，矩形、圆形、球形、不规则形或者类似形状。但是，进一步希望载体基质成分22不应该太小，以至于如果在最小的压力下被放置，它们可能从靶向点流走。认为载体基质成分22在尺寸上理想的是至少1.0mm。因此，在载体基质成分22尺寸上存在操作限制，其中尺寸由输送系统所决定，例如输送套管44的规格，和/或手术空间的限定；例如，后外侧脊柱可能需要更大的、更粘附团聚的载体基质成分22，以抵抗软组织的压力，而更密封的、保护负载的空间可以允许有效地使用更小尺寸成分22的粘性聚集体基质。
在一些有利的实施方式中，该组成物的成分22将是随意地或规则形状的海绵片。这些海绵片可以被制备为独立的片，或分裂为一种或多种更大的海面结构。该海绵片每个可以表现出具有孔状结构，且每个可以表现出具有完全的或部分形状记忆的可压缩或其他变形特征。以这种方式，有益的空间填充性质可以被赋予给整个粘性聚集体；一旦移植，则其可以变形和/或发生扩大，以占据骨生长所希望的体积。而且，该海绵片可以是可化学交联的材料，例如，与醛交联剂交联，例如甲醛或戊二醛，或另外一种其他适合的化学交联剂，例如碳化二亚胺交联，或采用其他技术，例如干热交联或辐射诱导交联。这样的交联可以被用于提供骨生长的支架材料，其相对于对应的非交联材料，在移植位置增加耐久性。
尽管具体的实施方式试剂盒10描述了作为输送系统一部分的独立输送套管40的使用，但是将可以意识到注射器20的远端24可以简单地被扩大，以提供适合于本发明的输送系统。因此，可以理解到：用于穿过而将载体基质成分22的粘性聚集体注入到靶向点内的套管44，可以或者以熟知的方式被可分开地连接到注射器20上，或者可以简单地作为注射器20的一个完整部分。
试剂盒10进一步包括成形素。通常，该成形素是干燥的形式，是存在在它自己的容器内或第二注射器50内，用于如本领域所熟知的后续重构。可替代地，成形素可以是液体的形式，且被存储在第二注射器50内或在它自己的瓶内；或，正如在试剂盒10的具体实施方式中那样，载体基质成分22可以用成形素预先浸渍而被包装。术语“成形素”指代刺激或诱导骨生长的任何因子。代表性的成形素包括但不限于：骨形成蛋白(Bone Morphogenetic Proteins(BMPs))，包括BMP-1、BMP-2、BMP-3、BMP-4、BMP-5、BMP-6、BMP-7、BMP-8、BMP-9、BMP-10、BMP-11、BMP-12、BMP-13、BMP-15、BMP-16、BMP-17和BMP-18；血管内皮生长因子(Vascular Endothelial Growth Factors(VEGFs))，包括VEGF-A、VEGF-B、VEGF-C、VEGF-D和VEGF-E；结缔组织生长因子(ConnectiveTissue Growth Factors(CTGFs))，包括CTGF-1、CTGF-2和CTGF-3；骨保护素(Osteoprotegerin)；转化生长因子-β超家族(Transforming GrowthFactor betas(TGF-βs))，包括TGF-β-1、TGF-β-2和TGF-β-3以及用于肿瘤骨疽因素(例如，抗-TNFα)的抑制剂。成形素还可以包括血小板源性生长因子(Platelet Derived Growth Factors(PDGFs))，包括PDGF-A、PDGF-B、PDGF-C、PDGF-D和GDF-5；rhGDF-5和LIM矿化蛋白，胰岛索相关的生长因子-I(IGF-I)，胰岛素相关的生长因子-II(IGF-II)，成纤维细胞生长因子(FGF)和β-2-微球蛋白(BDGF II)，如美国专利第.6,630,153号所公开，在此并入以作参考。编码这些物质的多核苷酸，也可以被作为基因治疗剂予以施用。优选的成形素是重组型的人骨形态发生蛋白(recombinant human bone morphogenetic proteins(rhBMPs))，因为它们可以以相对不受限制的供应量获得，且不会传递感染性疾病。更优选地，骨形态发生蛋白是rhBMP-2，rhBMP-4，rhBMP-7，或其异源二聚体。BMPs可以从Wyeth，Madison，NJ获得；且，也可以由本领域的技术人员制备，如在授予Wozney等的美国专利第5,366,875号，Wang等的第4,877,864号，Wang等的第5,108,922号；Wang等的第5,116,738号，Wang等的第5,013,649号；Wozney等的第5,106,748号；和Wozne等的PCT专利第WO93/00432号；Celeste等的第WO94/26893号和Celeste等的第WO94/26892号。
试剂盒10可以进一步包括一种或多种其他生物活性剂。这些生物活性剂可以与成形素混合，其中成形素被单独提供、浸渍在载体基质成分22中或类似状态。该种生物活性剂或多种试剂可以包括但不限于：抗菌剂、抗生素、抗分支杆菌、抗真菌、抗病毒、抗肿瘤剂、抗癌剂、影响免疫反应的制剂、血钙调节剂、用于葡萄糖调节的制剂、抗凝剂、抗栓剂、抗高血脂剂、心脏药、抗甲状腺和拟甲状腺药、肾上腺素、抗高血压药、胆碱能药、抗胆碱药、抗痉挛药、抗溃疡药、骨骼和平滑肌松弛约、前列腺素、变态反应抑制剂、抗组胺剂、局部麻醉剂、镇痛剂、麻醉药品拮抗剂、镇咳药、镇静催眠药、抗惊厥药、抗精神病药、抗焦虑约、抗抑郁药、anorexigenlcs、非固醇类抗炎药、固醇类抗炎药，抗氧化剂、血管活性药、骨活性药、成骨因子、骨生成诱导因子、痛风药和诊断试剂
膨胀材料23也可以在试剂盒10中被提供。这种膨胀材料23可以在它自己的容器中被提供，其可在注射器20，50中或混合或浸渍在载体基质成分22中。该膨胀材料23是可以被加入到载体基质成分22中的材料，以便向粘性聚集体提供的载体基质提供有限抗压力和硬度。该膨胀材料23具有足够小的颗粒尺寸以流动穿过输送套管44。代表性的膨胀材料包括胶原/陶瓷组合产物；同种异体移植物；和提供用于骨生长支架的生物相容性陶瓷或矿物质。该陶瓷或矿物质可以是天然的或合成的，并且可以包括例如：骨颗粒、
Figure A200780030504D00101
磷酸三钙、双相磷酸钙、羟基磷灰石或珊瑚羟基磷灰石。双相磷酸钙是特别希望在试剂盒10中使用的合成陶瓷。
该试剂盒10提供了许多允许外科医生实践本发明方法所需的工具。本发明方法包括用流体湿润多种载体基质成分，因此形成粘性聚集体，随后将产生的粘性聚集体注入到靶向位点。该粘性聚集体是流动的材料，因此，形成流动的载体基质。如图2所示，到这时，第一注射器20和第二注射器50可从包装12去除并且第二注射器50可以用适量的适合流体52所装填，适合流体52如蒸馏水、析出的骨髓或类似物。用于第二注射器5的流体52数量将相应于第一注射器20提供的载体基质22数量；载体基质与流体的体积比典型地为大约1:1。因此，例如如果该载体基质成分22形成6cc总胶原海绵，则大约6ml的流体52应被装填到第二注射器50中。但是应意识到，使用实际比率将取决于使用的载体基质22的具体类型，其可能是具有更大和更小的比率。应进一步意识到：用于湿润载体基质成分22的流体52不限于上面列出的那些。相反可以应用的溶液包含一种或多种任意数量的成分，例如盐、糖、镇痛剂、消炎药、抗生素、或任意其他生物活性物质、防腐剂、X射线标记物或主治医师认为需要的赋形剂、包括上面列出的生物活性剂。如果该成形素没有预先浸渍在载体基质成分22中，这是特别真实的。那么在这种情况下，该流体52将含有成形素，其可由医师重组或在试剂盒10中以液体形式提供。
如果希望膨胀材料且其不存在于载体基质成分22中，那么随后该膨胀材料23将被加入到载体基质成分22中，例如载体基质成分22在第一注射器20中。随后，该第一注射器20和第二注射器50将通过流体转移管30的方式流动地彼此连接。该流体转换管30简单地是一个管，其具有两端32，适合于连接注射器20，50的远端24，54。任何普遍用于注射器的标准装配排列可以被使用，例如Luer-locks。当然，该注射器20，50可被设计成彼此直接装配，因此避免了对流体转移管30的需要。如图3所示，一旦被连接到第一注射器20，第二注射器50的活塞56可以被压下以将流体52注入到第一注射器20中。因此，该流体52湿润了大部分载体基质成分22。该流体52可被允许浸泡至载体基质成分22一些时间，典型地大约1到3分钟；在此之间该载体基质成分22变得柔软而光滑，并且吸收了流体52中的任意生物活性成分，例如成形素或生物活性剂，如果存在的话。该载体基质成分22随后可以与流体52，以及与任选的膨胀材料23完全地混合在一起，其通过反复操作活塞26和56以驱动混合物在注射器20，50之间前后运动。如图4所示，结果是在注射器20，50其中之一内，粘性聚集体60与成形素和任选的膨胀材料和生物活性剂浸泡，其随后被注入到患者的靶向位点。
在下文中，术语“注入”表明在靶向位点处材料的放置，通过从套管、管、孔或类似物的远端挤出这种材料。如果，例如：该粘性聚集体60留在第一注射器20中；随后如图5所示，该输送套管40可以被连接到注射器20，以提供将粘性聚集体60注入到患者的靶向位点70。当使用流体转换管30时，该输送套管40含有在其近端上适合的装配元件42，其允许输送套管40与注射器20远端的物理和流体连接。如前所述，独立的输送套管40不是输送系统所必需的。例如：注射器20的远端24可以简单地被扩大，以提供适合的注射装置；实际上，在一定的条件下，标准的套管顶部甚至可以被用作注射装置。通过在活塞26上应用压力，粘性聚集体60流动穿过套管44，或相当的装置，以便从远端46挤压到靶向位点70。该靶向位点70是典型的区域，其中在周围骨架系统72中的结构支撑是不需要的；且可以包括例如：开放和密闭的长骨骨折，以及骨架(脊柱融合术)或口腔颌面应用，例如嵴增高术。输送套管40的长度、直径和远端46都可以适应于靶向位点70和粘性聚集体60的具体特征和需求。可选地，该试剂盒10可以提供具有多种不同类型的输送套管元件40，每个被设计成具有其具体的应用；随后外科医生可根据具体的情形，使用不同类型的输送套管元件40。
本发明的组成物的使用可以采用例如微创脊柱融合方式，其包括那些涉及前部手术的方法，例如使用腹腔镜；和包括那些涉及后部手术的方法，例如使用置入器套管。用于这些类型程序的适合的Minimal AccessSpinal Technology(MAST)产品——包括例如METRxTM X-TubeTM收缩系统——可以从例如Medtronic Sofamor Danek，Inc.(Memphis，Tennessee)获得。
通常在微创方法中，提供穿过管状装置(例如腹腔镜或套管)进入到体内空间的外科进入方法。在一个具体的实施例中，微创后部进入的提供可通过包括在患者软组织内放置管状的装置——例如X-TubeTM——的方法，例如在插入和通过一系列尺寸增加的组织扩张器后，产生用于管状装置的开口。通常进行椎板切除术，其中至少一部分椎板将从上述将被进入的椎间盘空间上发生的椎骨中切除。潜在地，该方法还包括作为外科手术进入必需的去除至少关节小面的一部分(椎骨关节面切除术)或其他骨结构。在进入到椎间盘空间之后，患者椎间盘组织可以被去除；该椎骨底板可以被去皮，因此其使用微创仪器和一种或多种承载移植物，例如支架或骨间隔器，可以任选地穿过套管状装置被引入。依据于此描述的一些实施方式，使用注射器或其他管状的装置，结合有骨原物质的流动载体基质可以被引入到椎间盘空间。
在一些方面，本文所描述的骨原组成物还被输送到其他外科手术位点，具体地是在希望骨生长的位置。这包括例如：颅骨缺损修复、髂骨嵴后填、髋臼缺损以及在胫骨平台和长骨缺损的修复。这样的方法可以用于处理例如由外伤(包括开放的和密闭的骨折)、疾病或先天性缺陷所产生的在这些或其他骨内的主要或次要缺损。
如图6所示，当粘性聚集体60被注入到靶向位点70中时，该粘性聚集体60粘附到它自己和靶向位点70周围的骨72，因此在靶向位点70填充骨72中的空间。如本领域所熟知，该粘性聚集体60作为骨细胞的支架，其生长进入且吸收粘性聚集体60提供的基质，替代具有天然骨72的基质。在粘性聚集体60中的成形素和膨胀材料的存在有助于实现这个过程。因为套管44用于将粘性聚集体60注入到靶向点70内，所以可能没有或至少降低了对切口或类似物的需求得以进入到靶向点70。因此本发明注入方法提供微创技术用于将粘性聚集体60输送到靶向位点70。本领域普通技术人员应容易意识到：因为该注入技术是微创的，因此可希望的是在粘性聚集体60内提供辐射标记物用于辅助注射过程的成像。如果存在的情况下，粘性聚集体内的陶瓷成分可以提供一定量的辐射不透过；但是可加入附加的不透射线材料，例如钡念珠。该不透射线材料可以包括在试剂盒10之中。
可选的试剂盒100在图7中显示。该试剂盒100不是提供多种载体基质成分，而是提供单片的含有胶原的载体基质，且意味着将该片切割成多个载体基质成分。代表性的试剂盒100包括：第一注射器120、流体转换管130、输送套管140、第二注射器150、含胶原的载体基质片160、成形素170、膨胀材料180和切割方法190，其所有都被密封在消毒的容器112中。成形素170可以是干燥的形式以便当需要的时候随后被重组，或可以是液体的形式；该成形素170还可以保持在注射器120，150其中之一内。相似地，该膨胀材料180可以存储在注射器120，150其中之一内，而不是包装在自己的容器中。该载体基质片160可以是任何适合的以胶原为基础的载体基质，例如胶原海绵。提供的切割方法190使外科医师能够将载体基质片160切割成多个小片作为载体基质成分，其大小是适合于穿过输送套管140可注入的。该切割方法190可以是任意适合的切割装置，例如解剖刀、剪子或类似物。一旦切成适当大小的片，例如尺寸上小于10mm的片，该载体基质160的切割片可以被放入注射器120中，用成形素170制备的溶液湿润，随后使用第二注射器150和流体输送管130，按如上所述与膨胀材料混合，以形成粘性聚集体。随后使用输送套管140将产生的粘性聚集体注入到靶向点。
尽管本发明于此已经参照具体实施方式被描述，但是可以理解的是这些实施方式仅仅是本发明的示例性的原则和应用。因此，可以理解的是对示例性实施方式做出的众多修改和其他排列可以被认为不脱离下述权利要求所限定的本发明的精神和范围。

Claims (16)

1.医用试剂盒，其包括：
多种载体基质成分，所述载体基质成分包括胶原；
成形素；和
输送系统，用于将所述载体基质成分和所述成形素混合之后产生的粘性聚集体注入到位点。
2.根据权利要求1所述的医用试剂盒，其中所述成形素选自：BMP-1、BMP-2、BMP-3、BMP-4、BMP-5、BMP-6、BMP-7、BMP-8、BMP-9、BMP-10、BMP-11、BMP-12、BMP-13、BMP-15、BMP-16、BMP-17、BMP-18、VEGF-A、VEGF-B、VEGF-C、VEGF-D、VEGF-E、CTGF-1、CTGF-2、CTGF-3、骨保护素(Osteoprotegerin)、TGF-β-1、TGF-β-2、TGF-β-3、抗-TNFα、PDGF-A、PDGF-B、PDGF-C、PDGF-D、GDF-5、LIM矿物化蛋白、IGF-I、IGF-II、FGF、BDGF II、其重组形式和其异源二聚体。
3.根据权利要求1所述的医用试剂盒，其进一步包括生物活性剂，其选自抗菌剂、抗生素、抗分支杆菌、抗真菌、抗病毒、抗肿瘤剂、抗癌剂、影响免疫反应的制剂、血钙调节剂、用于葡萄糖调节的制剂、抗凝剂、抗栓剂、抗高血脂剂、心脏药、抗甲状腺和拟甲状腺药、肾上腺素、抗高血压药、胆碱能药、抗胆碱药、抗痉挛药、抗溃疡药、骨骼和平滑肌松弛药、前列腺素、变态反应抑制剂、抗组胺剂、局部麻醉剂、镇痛剂、麻醉药品拮抗剂、镇咳药、镇静催眠药、抗惊厥药、抗精神病药、抗焦虑药、抗抑郁药、anorexigenlcs、非固醇类抗炎药、固醇类抗炎药，抗氧化剂、血管活性药、骨活性药、成骨因子、骨生成诱导因子、痛风药和诊断试剂。
4.根据权利要求1所述的医用试剂盒，其进一步包括膨胀材料，其选自胶原-陶瓷复合材料、同种异体移植和提供骨生长支架的生物相容性陶瓷或矿物质。
5.根据权利要求1所述的医用试剂盒，其进一步包括流体输送管，其用于流动地将至少两个注射器连接在一起。
6.根据权利要求1所述的医用试剂盒，其中所述输送系统包括两个注射器，其是可以流动地彼此连接的。
7.根据权利要求1所述的医用试剂盒，其中所述输送系统包括至少一个输送套管，其将粘性聚集体输送到所述位点。
8.根据权利要求1所述的医用试剂盒，其中所述载体基质成分是由胶原海绵形成的。
9.根据权利要求1所述的医用试剂盒，其中所述载体基质成分的大小适合以允许其穿过输送装置的流体状流动，其被用于将粘性聚集体注入到所述靶向位点。
10.根据权利要求9所述的医用试剂盒，其中所述载体基质成分的尺寸在大约1.0mm和10mm之间。
11.医用试剂盒，其包括：
载体基质片，其包括胶原；
切割器械，其用于将载体基质片切割成多个载体基质成分；和成形素。
12.根据权利要求11所述的医用试剂盒，其中所述成形素选自：BMP-1、BMP-2、BMP-3、BMP-4、BMP-5、BMP-6、BMP-7、BMP-8、BMP-9、BMP-10、BMP-11、BMP-12、BMP-13、BMP-15、BMP-16、BMP-17、BMP-18、VEGF-A、VEGF-B、VEGF-C、VEGF-D、VEGF-E、CTGF-1、CTGF-2、CTGF-3、骨保护素(Osteoprotegerin)、TGF-β-1、TGF-β-2、TGF-β-3、抗-TNFα、PDGF-A、PDGF-B、PDGF-C、PDGF-D、GDF-5、LIM矿物化蛋白、IGF-I、IGF-II、FGF、BDGF II、其重组形式和其异源二聚体。
13.根据权利要求11所述的医用试剂盒，其进一步包括膨胀材料，其选自胶原-陶瓷复合材料、同种异体移植以及用于提供骨生长支架的生物相容性陶瓷或矿物质。
14.根据权利要求11所述的医用试剂盒，其中所述载体基质片是由胶原海绵组成。
15.一种装置，其用于促进目标体内靶向位点处的骨生长，所述装置包括：
注射器，其具有与出口孔连接的注射器管并且具有将注射器管中的材料推动穿过出口孔的活塞；和
骨原性组合物，其被接受在注射器管内，所述组合物包括并入到骨原性制剂中的多个海绵元件。
16.根据权利要求15所述的装置，其中所述出口孔具有比所述注射器管更小的横截面积，以及，其中骨原性组合物是可充分被压缩的和光滑的，用于通过活塞手动操作从出口孔的输送。
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US20120003315A1 (en) 2012-01-05
US8148326B2 (en) 2012-04-03
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US8293232B2 (en) 2012-10-23
JP2010500904A (ja) 2010-01-14

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