CN1267201A - 生物材料的化学清洗 - Google Patents
生物材料的化学清洗 Download PDFInfo
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Abstract
本发明涉及胶原组织,该胶原组织已进行过处理,以除去非胶原成分如细胞、细胞碎片和其它细胞外基质成分,如通常见于天然组织中的蛋白聚糖和葡糖胺聚糖。用碱、螯合剂、酸和盐处理组织,从胶原组织基质中除去非胶原成分,而同时控制膨胀量和溶解度,使用所得的胶原基质保留其结构组织、完整性和可生物改造性能。此方法不需要使用损害性地影响胶原基质的细胞相容性、强度和可生物改造性的洗涤剂和酶。该胶原组织基质用于植入、修补,或用在哺乳动物宿主中。
Description
发明领域
本发明属于组织工程领域。本发明涉及胶原组织,该胶原组织已进行过处理,除去非胶原成分如细胞、细胞碎片和其它细胞外基质成分,如通常见于天然组织中的蛋白聚糖和葡糖胺聚糖。用碱、螯合剂、酸和盐处理组织,从胶原组织基质中除去非胶原成分,而同时控制膨胀量和溶解度,使所得的胶原基质保留其结构组织、完整性和可生物改造性能。此方法不需要使用损害性地影响胶原基质的细胞相容性、强度和可生物改造性的洗涤剂和酶。该胶原组织基质用于植入、修补,或用在哺乳动物宿主中。
发明背景简述
组织工程领域将工程方法与生命科学的原理结合,以了解正常和病理哺乳动物组织间中结构和功能的关系。组织工程的目标是开发和最终应用生物替代物来恢复、保持或改善组织功能。(Skalak,R.和Fox,C.F.,“组织工程”,Alan R.Liss Inc.N.Y.(1988))。
胶原是体内的主要结构蛋白,其构成总的体内蛋白的大约三分之一。它包括皮肤、腱、骨和牙中的大部分有机物质,且作为纤维状包含物出现在许多其它身体结构物中。胶原的一部分性能是其高拉张强度;其离子交换能力,这点部分是由于电解质、代谢物和药物的结合;其低的抗原性,这点是由于通过螺旋结构遮盖蛋白抗原的决定体,和其低的伸长性、半渗透性和溶解性。再者,胶原是细胞粘合的天然物质。这些性能以及其它的性能使胶原适合作为可植入生物替代物和可生物改造假体的组织工程和生产的材料。
由于胶原是这些生物替代物中占大多数的成分,因此需要一种方法来获得质量稳定的充分量的胶原。目前需要一种改进的方法来除去非胶原成分如细胞、细胞碎片和其它细胞外基质成分,如通常见于天然组织中的蛋白聚糖和葡糖胺聚糖,以产生基本上纯的天然胶原基质。一般认为,这些非胶原结构物中有一些是抗原,当植入宿主中时,将诱发慢性炎症反应。现有技术有许多清洗这些胶原组织的方法,然而,这些方法导致胶原成(composition)带有不同的特性。所用的方法应当是可保持适用于组织工程中的胶原和胶原组织的生物和物理性能的一种方法。
在处理胶原组织,产生基本上是胶原基质的现有技术中,常规地使用洗涤剂和表面活性剂,将细胞和脂质体从组织中萃取出来。洗涤剂,如十二烷基硫酸钠(SDS),是两亲分子,其中疏水区结合到蛋白上,并相信增加了此蛋白的负电荷。当植入时,由于电荷的增加导致由于有更多的水被此分子的亲水区结合而产生的组织膨胀和破坏氢键结合而产生的胶原的热稳定性降低。膨胀一则使胶原分子的结构打开,使之对细胞酶如胶原酶敏感,二则使胶原基质不稳定,造成构建(construction)弱化。(Courtman等,生物医学材料研究杂志,28:655-666,1994)。再者,人们认为,SDS残留物仍结合在胶原上,并阻止细胞迁移入植入物中。(Wilson,G.J等,Ann Thorac Surg,60:S353-8,1995;Bodnar E等,“Damage of aortic valvetissue caused by the surfactant sodium dodecyl sulfate,”Thorac cardixvascSurg,34:82-85,1986)。由于用在化学清洗方法中的洗涤剂可以不良地结合上并改变在处理的组织中的胶原的可生物改造性,因此本发明者开发出一种不需要洗涤剂的方法。
用酶如胰蛋白酶、胃蛋白酶和胶原酶化学清洗组织是本领域中已知的,但它的应用将导致天然胶原分子改性,并将不利地影响构建的结构完整性。胶原组织的酶处理在现有技术中已知用来除去和/或修饰与细胞外基质有关的蛋白。蛋白酶如胃蛋白酶、胰蛋白酶、分散酶或嗜热菌蛋白酶在除去胶原端肽中使用,产生非端肽胶原。胶原端肽是胶原分子的非三螺旋部分,被某些研究者认为是弱抗原性的,而另一些研究人员则认为其与胶原的强机械性能有关。胶原组织的有限消化将除去端肽,而不将组织的胶原基质解离,而长时间的消化将解离胶原原纤维成非端肽胶原单体。现有技术中同样已知,使用酶(它分别通过使用RNA酶和DNA酶来消化内源RNA和DNA)修饰和除去基质中的核酸。由于用酶处理可以影响胶原的结构完整性,本发明的方法包括它们的使用。
从外植哺乳动物组织获得胶原组织和组织结构物的方法,和由此组织构建假体的工艺,已广泛用于外科修复或组织和器官的更换中。将此组织一般性地处理,除去有潜在细胞毒性作用的细胞成分和非胶原成分,留下天然组织基质。也进行过对进一步处理的研究,所述处理如交联、消毒或形成形状。处理胶原组织,从组织化的组织基质中除去组织成分的现有方法采用洗涤剂、酶或促进基质的无控制的膨胀。Jaffe等的WO 95/28183公开了降低或防止生物假体心脏瓣膜供给矿质后植入方法。此公开的方法提供由控制自溶的非细胞制成的生物材料。自溶是在预选的pH下,使用至少一种缓冲溶液控制进行的,使存在于组织中的自溶酶降解细胞结构成分。Stone的USP 5,007,934,以及Li等的USP 5,263,984均公开了化学清洗韧带组织的多步骤方法。该方法利用洗涤剂除去与细胞膜或胶原组织有关联的类脂。Janzen等的USP 5,523,291公开了一种粉碎的可注射植入物组合物,用于从项韧带得到的软组织增加。此韧带用氢氧化钠强碱性溶液,接着是盐酸溶液,之后是碳酸氢钠进行了一系列浸泡处理。Eckmayer等的USP 5,028,695公开了胶原膜的生产工艺,其中胶原组织是用强碱,随后用强酸处理一段时间来重复处理,之后再用无机盐处理来收缩该膜,之后用溶剂来干燥之。
发明概述
本发明公开了可生物改造的胶原组织基质和化学清洗天然组织产生此组织基质的方法。
本发明克服了获得基本上是胶原的可生物改造的组织基质的困难。本发明提供可以用作假体用具或用在修复、增加或替代损害和有病的组织与器官的材料的组织基质。
本发明的化学清洗方法使生物材料如天然组织和组织结构物基本上无细胞和基本上无非胶原成分,而同时保持胶原组织基质的结构完整性。由于在化学清洗过程中不用洗涤剂,因此不存在通常会结合于组织基质的洗涤剂残留物。由于不使用酶,胶原端肽仍留在胶原分子上。该方法包含将正常的细胞天然组织在碱性pH下与螯合物剂接触,将此组织在酸性pH下与盐溶液接触,并将此组织在生理pH下与盐溶液接触,最后淋洗所得的化学清洗后的组织基质。
本发明涉及化学清洗后的由天然的正常细胞组织得到的组织基质。清洗的组织基质是基本上是完好无损地归还的胶原,它基本上无糖蛋白、糖胺聚糖、蛋白聚糖、类脂、非胶原蛋白和核酸如DNA和RNA。重要的是,由于没有对胶原可生物改造性有不利影响的结合着的洗涤剂残留物,从而保留了组织基质的可生物改造性。再者,由于在清洗过程中胶原未经受用酶处理或修饰,胶原分子的端肽区完好无损,因此胶原是端肽胶原。
胶原材料通常保持组织得到时的总体形状,但它可能叠层和结合在一起,形成多层片、管或复杂的成形假体。本发明的结合的胶原层是结构上稳定、柔韧、半透和可缝合的。当此基质材料植入哺乳动物宿主时,经受生物降解,并伴随着足够的活细胞替代或新组织形成,这样原植入的材料最终被改造并由宿主产生的组织和细胞替代。
因此,本发明的目的是提供一种清洗天然组织,产生不表现出与许多现有技术方法有关的许多缺点的组织基质。本发明方法不用洗涤剂或酶而有效地除去天然组织的非胶原成分,产生包含基本上是胶原的组织基质。
另一目的是提供一种可生物改造的组织基质材料,它将允许和利于在植入位点上的组织内生长和/或器官再生。由此材料制成的假体,当移植到受体宿主或患者中时,同时进行可控制的生物改造和充分的活细胞替代,这样,原植入假体被患者的活细胞改造,形成再生的器官或组织。
本发明的再一目的是提供一种在自移植、异体移植和异种移植适应征(indication)中使用新颖的多目的可生物改造基质材料的方法。
另一目的是提供可以使用常规外科技术植入的新颖的组织基质材料。
发明详述
本发明提供一种处理用于移植的天然胶原组织的方法。本处理方法设计来产生一种可植入、可移植的胶原生物组织材料—一种包含胶原的细胞外基质,它作为可以由宿主在体内或通过体外的培养物中的活细胞改造的框架(scaffold)。
本发明还涉及一种由处理的天然胶原组织形成的组织工程假体,当植入哺乳动物宿主时,它可以作为功能修补、增加或替代身体部分或组织结构,和经受宿主细胞改造之同时出现的控制的生物降解。该组织材料可以用作假体,用于自移植、异体移植和异种移植适应征。本发明的假体,在其种种实施方案中,具有双重性能:首先,它用作身体部分替代品,第二,在仍作为身体部分替代品的同时,作为用于宿主细胞向内生长的改造模板。虽然假体将通过各种用具和构建物的结构进行说明,但本发明并不仅限于这些。应当理解,在其材料、形状和厚度方面进行的用具设计是根据结构物的最终适应征来选择的。
本发明的化学清洗方法使生物材料,如天然组织和组织结构物,基本上无细胞和基本上无非胶原成分,而同时保持了胶原组织基质的结构完整性。弹性蛋白有时少量存在于天然组织中,并不被化学清洗方法除去。弹性蛋白的存在在某些应用中是需要的。如本文中所用的,术语“基本上无细胞”是指比天然态的生物材料少至少95%的天然细胞和细胞结构物。“细胞和细胞结构物”是指细胞(活或不活)、细胞存留物、细胞膜和膜结构物。使用主语“基本上无非胶原成分”是指糖蛋白、糖胺聚糖、蛋白聚糖、类脂、非胶原蛋白和核酸如DNA和RNA占在所得的组织基质干重的不到5%。由于在本化学清洗过程中不使用洗涤剂,因此不存在通常会结合到组织基质上的洗涤剂残留物。由于不使用酶,因而胶原端肽保留在胶原分子上。再者,当使用灭菌设备、溶液和无菌技术处理时,本化学清洗方法可使生物材料无菌和无内毒素。
术语“结构完整性”是指化学清洗的胶原组织基质承受拉张、压缩和支撑的能力。即使在化学处理期间会出现一定的膨胀,但由于化学处理步骤中的膨胀被最小化,因此生物材料的结构完整性仍得到保留。不进行控制或过度的膨胀一方面打开了胶原分子的结构,使之对细胞酶如胶原蛋白酶敏感,另一方面又使胶原不稳定,造成构造弱化。当膨胀影响胶原分子的分子内结构时,其通过破坏胶原分子间的天然交联,在分子内水平上影响材料的总体结构。胶原分子的结构和胶原分子间的交联一起为材料提供结构完整性。
保持大多数其天然结构完整性的组织基质材料是有用的,例如,当用作假体用具或用作构建多层或复杂用具时。如果材料用于执行负载承受功能如体壁支持物、血管用具或牙科用具,则材料的完整性是很重要的。涉及结构完整性时,术语“可缝合”是指材料的机械性能包括在将假体缝合至天然组织时(一种被称作吻合术的方法),允许针和缝合材料穿过假体材料的缝合保持。在缝合时,这些假体不会因缝合所带来的张力而撕裂,且当缝合打结时,它们也不会被撕裂。假体材料的可缝合性,即,假体缝合时的抗撕裂能力,与假体材料的固有机械强度、移植物的厚度、施加于缝合物的张力和拉紧节的速率有关。
本发明中所定义的生物材料包括但不限于来源于人、牛、猪、狗、羊、猫和马的采集的哺乳动物组织及其结构物。组织结构物如真皮、动脉、静脉、心包、心脏瓣膜、硬脑脊膜、腱、肠和筋膜是优选的组织结构,其可以通过本发明方法清洗,产生基本上无细胞和基本上无非胶原成分的组织基质。
哺乳动物组织的优选来源是从小肠,最优选是从猪小肠得的被膜粘膜下层(tunica submucosa)。在天然的小肠中,被膜粘膜下层是器官的连接组织层,且包括淋巴和血管细胞。获得被膜粘膜下层的方法公开在WO96/31157中,该文被本文引用。为获得猪被膜粘膜下层(也被称为“粘膜下层”),将猪小肠收集,并机械剥离,优选使用肠清洗机械(Bitterling,诺丁汉,英国)。肠清洗机械通过机械作用和水洗涤作用,强行除去脂肪、肌肉和粘膜层。机械作用可以描述为一系列的滚辊(roller),当无损的肠在其间移动时,滚辊压紧并将接续的层剥离被膜粘膜下层。由于小肠的被膜粘膜下层比周围的组织相对而言要更坚硬,因此来自粘膜下层的较软的成分从被膜粘膜下层除去。机械清洗的结果是,将来自被膜粘膜下层管腔(ablumen)的肠系膜组织、被膜绒膜和被膜肌肉以及来自被膜粘膜下层腔的被膜粘膜层从被膜粘膜下层除去,这样只留下肠的被膜粘膜下层。被膜粘膜下层的化学清洗的组织基质也称作“肠胶原层”或“ICL”。值得说明的是,在一些动物来源中,如食肉动物和杂食动物中,小肠包括致密层,这一层大部分通过此机械清洗步骤除去。
机械剥离小肠不同层的其它方法是本领域已知的,如Badylak的USP4,902,508中描述的,该文被本文引用。此专利公开的方法包括柔和地磨擦肠组织,除去管腔层(包括被膜绒膜和被膜肌肉)和至少由被膜粘膜的腔部分组成的内层。余下的层是被膜粘膜下层及由粘膜肌层和(如果最初存在于所采集的哺乳动物组织中的)致密层组成的附着基础层。用任一种方法获得的肠材料均可以通过许多方法,包括缝合、订合、粘合组合物、化学结合和热结合,植入或预形成人体壁或血管用具中。
与某些操作参数有关的术语如量、时间和温度是针对全文和实施例定义的,这些术语可以有所变化,而不偏离本发明的精神与范围。在本文中,“有效量”是指获得所需效果而需要的组合物的体积与浓度。优选组织进行化学清洗的有效量是溶液与组织之比为100∶1v/v,但是体积的多或少可以由普通技术人员通过考虑意欲清洗的组织的形状、外形体积、厚度、密度和细胞构成性来确定。当考虑到意欲清洗的组织的细胞构成性、基质密度和厚度时,本领域普通技术人员会清楚有效的化学步骤所需的时间。较大、较厚或较密的材料需要较长的时间以使溶液渗透入组织并在其中平衡。环境温度和用于本发明的溶液温度优选是常温,大约为25℃,但可以在高于所用溶液的冰点温度以上至低于意欲处理的组织材料的变性温度之间。大约47℃至大约45℃间的温度足以进行有效的化学处理。搅拌是指机械震动或机械混合,用来改善化学成分向组织中的渗透作用,并减少有效地化学处理所需的时间。术语“缓冲溶液”是指一种含水溶液,其含有至少一种可保持溶液的氢离子浓度或pH的试剂。
在优选的方法中,采集的组织可能需要手工清洗,如通过粗解剖,和/或机械清洗多余的组织如脂肪和肌肉。在加工或进行最有效地化学处理期间,为了操作的可处理性,对于一些组织可能会需要手工清洗。
组织先通过将组织与有效量的螯合剂,优选是碱接触,以可控制地限制组织基质的膨胀。螯合剂通过降低二价阳离子浓度,提高将细胞、细胞碎片和基础膜结构物从基质中除去的作用。碱处理将糖蛋白和糖胺聚糖与胶原组织解离,并皂化类脂。本领域已知的可以使用的螯合剂包括,但不限于,乙二胺四乙酸(EDTA)和亚乙基双(氧乙烯次氮基)四乙酸(ethylenebis(oxyethylenitrilo)tetraacetic acid,EGTA)。EDTA是优选的螯合剂,且可以通过加入氢氧化钠(NaOH)、氢氧化钙(Ca(OH)2)、碳酸钠或过氧化钠而变得更碱性。EDTA或EGTA浓度优选介于大约1至大约200mM间;更优选介于大约50至大约150mM间;最优选在大约100mM左右。NaOH浓度优选介于大约0.001至大约1M间;更优选介于大约0.01至大约0.10M间;最优选在大约0.01M左右。其它碱或碱性试剂可以由本领域普通技术人员确定,使螯合溶液的pH在有效碱性pH范围内。碱性螯合溶液的最终pH应优选介于大约8至大约12之间,但更优选介于大约11.1至大约11.8之间。在最优选的实施方案中,组织与100mM EDTA/10mMNaOH的水溶液接触。组织优选是通过浸入碱性螯合剂中来接触的,而更有效的处理是通过将组织与溶液一起搅拌一段对处理步骤而言有效的时间来获得。
之后组织与有效量的酸性溶液,优选含有盐的溶液接触。酸处理同样起除去糖蛋白和糖胺聚糖以及除去非胶原蛋白和核酸如DNA和RNA的作用。盐处理在酸处理期间控制胶原组织基质的膨胀,并涉及将一些糖蛋白和蛋白聚糖从胶原基质中除去。本领域已知可以使用的酸溶液包括但不限于盐酸(HCl)、乙酸(CH3COOH)和硫酸(H2SO4)。优选的酸是盐酸,其浓度优选介于大约0.5至大约2M,更优选介于大约0.75至大约1.25M;最优选在大约1M左右。酸/盐溶液的最终pH优选介于大约0至大约1,更优选介于大约0至0.75,且最优选介于大约0.1至大约0.5之间。盐酸和其它强酸对于破坏核酸分子而言是最有效的,弱酸却不那么有效。可以使用的盐优选是无机盐,包括但不限于氯化物盐如氯化钠(NaCl)、氯化钙(CaCl2)和氯化钾(KCl),而其它有效的盐可以由本领域技术人员确定。优选的氯化物盐的使用浓度优选介于大约0.1至大约2M;更优选介于大约0.75至大约1.25M;最优选在1M左右。优选用于此方法的氯化物盐是氯化钠(NaCl)。在最优选的实施方案中,组织与1M HCl/1M NaCl的水溶液接触。组织优选浸入酸/盐溶液中,通过将组织与溶液一起搅拌一段对处理步骤而言有效的时间来获得有效的处理。
之后将组织与有效量的盐溶液,优选与缓冲到大约生理pH的溶液接触。缓冲的盐溶液中和该材料,同时降低膨胀。可以使用的盐优选是无机盐且包括但不限于氯化物盐如氯化钠(NaCl)、氯化钙(CaCl2)和氯化钾(KCl);和含氮盐如硫酸铵(NH3SO4),其它有效的盐可以由本领域技术人员确定。优选的氯化物盐的使用浓度优选介于大约0.1至大约2M之间;更优选介于大约0.75至大约1.25M之间;最优选在大约1M左右。优选的用在本方法中的氯化物盐是氯化钠(NaCl)。缓冲剂是本领域已知的且包括但不限于磷酸盐和硼酸盐溶液,其它的缓冲剂可由本领域普通技术人员针对本方法确定。一种优选的缓冲盐溶液的方法是优选加入磷酸盐缓冲的盐水(PBS),其中对于盐溶液来说,磷酸盐浓度是大约0.001至大约0.02M且盐浓度是大约0.07至大约大约0.3M。此溶液的pH优选介于大约5至大约9,更优选介于大约7至大约8,最优选介于大约7.4至大约7.6之间。在最优选的实施方案中,组织与pH介于大约7.0至大约7.6的1M氯化钠(NaCl)/10mM磷酸盐缓冲的盐水(PBS)接触。该组织优选通过浸入在缓冲的盐水溶液中接触,通过将组织与溶液一起搅拌一段对处理步骤而言有效的时间来获得有效的处理。
在化学清洗处理后,优选通过将组织与有效量的淋洗剂接触,淋洗至无化学清洗剂。可以使用的试剂如水、等渗盐溶液和生理pH缓冲的溶液,其与组织接触一段足以除去清洗剂的时间。优选的淋洗溶液是生理pH缓冲盐水如磷酸盐缓冲的盐水(PBS)。淋洗带有化学清洗剂的组织的其它方式可以由本领域技术人员确定。将组织与碱性螯合剂接触和将组织与含有盐的酸溶液接触的清洗步骤可以任一种顺序实施,获得基本上相同的清洗效果。然而,不可将溶液组合而只进行一步处理。
本发明的优选组成(composition)是由天然正常细胞组织得到的化学清洗过的组织基质。清洗过的组织基质基本上是大约93%干重的无细胞端肽胶原与低于大约5%干重的糖蛋白、糖胺聚糖、蛋白聚糖、类脂、非胶原蛋白和核酸如DNA和RNA。重要的是,由于组织中没有对胶原可生物改造性有不利影响的结合着的洗涤剂残留物,因此组织基质的可生物改造性得到保留。此外,由于在清洗过程中,组织未经酶处理,因此胶原分子的端肽区保留下来。
组织基质是从真皮、动脉、静脉、心包、心脏瓣膜、硬脑脊膜、腱、肠和筋膜得到的。最优选的组成是由小肠得到的化学清洗过的肠胶原层。适合的小肠来源是哺乳动物有机体如人、牛、猪、羊、狗、山羊和马,其中猪小肠是优选的来源。在一优选的实施方案中,胶原层包括得自猪小肠的被膜粘膜下层。另一实施方案中,胶原层包括小肠的被膜粘膜下层和基底层。基底层由层粘膜肌层和致密层(如果它存在于天然组织中)组成。
最优选的本发明组成是肠胶原层,用本发明化学清洗方法清洗过,它基本上是胶原,主要是I型胶原,与少于大约5%干重的糖蛋白、糖胺聚糖、蛋白聚糖、类脂、非胶原蛋白和核酸如DNA和RNA。胶原层中没有对胶原的可生物改造性有不利影响的结合着的洗涤剂残留物。胶原层基本上没有细胞和细胞碎片,包括内源核酸如DNA和RNA和类脂。再者,当使用灭菌设备、溶液和无菌技术处理时,肠胶原层是无菌且无内毒素的。
一旦胶原组织基质提供了基本上无细胞和基本上无非胶原外细胞基质成分,则可将其用于生产植入或移植的假体。胶原层可以通过使用任一种本领域已知的技术来缝合或结合在一起。用于结合所述层的方法可以采用粘合剂如凝血酶、纤维蛋白或合成材料如氰基异丁烯酸酯或化学交联剂。其它方法可以采用由激光、光或微波产生的热。也可以采用对流炉或加热液体浴。
胶原层的热焊接是将本发明的胶原层结合在一起的优选方法。胶原的热焊接方法描述于WO 95/22301、WO 96/31157和USP 5,571,216,本发明引入这些技术作为参考。ICL(肠胶原层)先是被沿纵向切开,平放在固体平板上。之后将一或多个连续的层一一加上,优选改成垂直方向。第二个固体平板放置在层的上方,并将二个板紧紧夹在一起。之后将完成的装置,夹着的板和胶原层,在足以进行胶原层结合的条件下加热一段时间。施加的热量应当足够的高,以使胶原结合,但不应高到造成胶原不可逆的变性。加热和结合的时间将取决于所用的胶原材料层类型、材料的水分和厚度和所施加的热。加热的典型范围是大约50℃至大约75℃,更典型的是60℃至65℃,且最典型的是62℃。时间的典型范围是大约7分钟至大约24小时,典型的是大约一小时。加热程度和加热的时间长短易于通过变化热和时间参数,用常规实验确定。结合步骤可以在常规烘箱中完成,但也可以采用其它的装置和加热器具,它们包括但不限于水浴、激光能或电热传导进行。紧接着加热和结合之后,将胶原层用空气或水浴在20℃至1℃间的室温范围内用空气或水浴冷却。需要用快速冷却,术语称作骤冷,结束加热作用,并产生胶原层间的有效结合。为完成此步骤,胶原层可以典型的在水浴中冷却,所用的温度优选是大约1℃至大约10℃,最优选的是4℃。虽然低于1℃的冷却温度也可使用,但需要小心,不使胶原层冷冻,冷冻会造成结构损害。此外,高于10℃的温度可以在骤冷中使用,但如果骤冷温度太高,则冷却速率太慢,胶原层相互间的固定不充分。
在优选的实施方案中,胶原材料被交联。交联赋予形成的假体构建物增加的强度和结构完整性,同时在此构建物植入患体时,通过细胞调节胶原的可生物改造性。胶原交联剂包括戊二醛、甲醛、碳化二亚胺、六亚甲基二异氰酸酯、二亚氨酸酯(bisimidate)、乙二醛、己二酰氯、二醛淀粉、和某些聚环氧化合物如乙二醇二缩水甘油醚、聚醇聚缩水甘油醚和二羧酸二缩水甘油酯。也可以使用脱氢热、UV照射和/或糖介导法。胶原也可以在室温下老化而自然交联。然而,交联剂不限于这些,也可以采用其它本领域技术人员已知的交联剂和方法。应当选择交联剂,以产生能被宿主细胞改造的生物相容材料。优选的交联剂是1-乙基-3-(3-二甲基氨基丙基)碳化二亚胺盐酸盐(EDC)。含有EDC和水的交联溶液也可以含有丙酮。用EDC交联业已描述于国际专利申请公开WO 95/22301和WO 96/31157中。
在一些实施方案中,额外的胶原层可以在交联前或后,加到结合的胶原层的外或内表面上。在管状构建物中,如在血管构建物中,可以将致密原纤维胶原加到腔表面,产生平滑流动表面,用于其最终应用,如在国际专利申请公开WO 95/22301中描述的那样,该文被本文引用作为参考。此平滑胶原层同样促进宿主细胞连接,如在新内膜形成时,它有利于构建物的向内生长和生物改造。如在国际专利申请公开WO 95/22301中描述的,平滑胶原层可以由酸提取的原纤维或非原纤维胶原制成,它主要是I型胶原,但也可以包括其它类型的胶原。所用的胶原可以由任一种哺乳动物源,典型的是牛、猪或羊皮肤或腱得到。胶原优选用酸提取处理,得到高纯度的原纤维分散体或凝胶。胶原可以是由胶原源使用弱酸,如乙酸、柠檬酸或甲酸酸提取而得。一旦提取入溶液,胶原可以使用氯化钠进行盐沉淀,然后回收,使用标准的技术如离心或过滤。由牛腱中酸提取的胶原的详情描述于例如USP 5106949中,该文被本文引用作为参考。
肝素可以通过各种已熟知的技术施加到假体上。例如,肝素可以用下列三种方式加入假体。其一,可以通过将假体浸蘸苯甲烃铵肝素(benzalkonium heparin,BA-Hep)溶液,之后风干之,将BA-Hep溶液施加到假体上。此步骤用离子结合的BA-Hep配合物处理胶原。其二,EDC可以用来活化肝素,之后将肝素共价结合至胶原纤维上。其三,可以用EDC来活化胶原,之后共价结合鱼精蛋白至胶原上,之后离子结合肝素至鱼精蛋白上。许多本领域已知的其它涂敷、结合和连接步骤同样也可以使用。
组织基质材料的处理也可以用药剂如生长因子或药物与肝素一起或替代肝素来完成。例如,药剂可以包括例如,促进血管形成和上皮形成的生长因子,如由生长因子衍生的巨噬细胞(MDFG),由生长因子衍生的血小板(PDGF),由生长因子衍生的血管内皮细胞(VEGF);抗任何来自外科植入潜在感染的抗生素;或当假体用作神经再生的导管时引入内部胶原层的神经生长因子。构建物中还可以包括与药剂一起的或用于替代药剂的基质成分如蛋白聚糖或糖蛋白或糖胺聚糖。
由此形成的胶原假体可以用中性pH的稀过乙酸溶液灭菌。将胶原灭菌的方法描述于USP 5,460,962中,该文被本文引用作为参考。在优选的方法中,胶原用中性pH的稀过乙酸溶液消毒。过乙酸的浓度优选是大约0.01至0.3v/v%水溶液,中和后的pH介于大约pH6至8之间。另一种选择是,用咖玛照射灭菌,典型的是用2.5Mrad的强度,或也可以使用气体等离子体灭菌。也可以使用本领域已知的其它方法来将胶原灭菌。
提供下列实施例旨在对本发明的实施作更好的阐述,不应被理解为以任何方式限制本发明的范围。本领域技术人员知道,对于在此描述的方法可以有各种修改,但并不偏离本发明的精神与范围。
实施例
实施例1:机械剥离的猪小肠的化学清洗
采集猪小肠,并机械剥离,使用Bitterling肠清洗机(英国诺丁汉),该清洗机械使用机械作用和水洗涤作用,强制性地从被膜粘膜下层除去脂肪、肌肉和粘膜层。机械作用可以描述为一系列的滚辊,当无损的肠在滚辊间通过时,滚辊压制并从被膜粘膜下层剥离接续的层。由于小肠的被膜粘膜下层比周围的组织相对而言要更硬和挺,因此来自粘膜下层的较软的成分被滚辊从被膜粘膜下层压出。机械清洗的结果是只留下肠的被膜粘膜下层。余下步骤是在无菌和在室温下进行的。化学溶液均在室温下使用。之后将肠纵向切下腔,之后切成15cm的段。将材料称重,并以大约100∶1v/v的溶液与肠材料的比放置于容器中。
A.向每一装有肠的容器中加入大约1L的0.22mm(微米)过滤纸(filter)灭菌的100mM乙二胺四乙酸四钠盐(EDTA)/10mM氢氧化钠(NaOH)溶液。之后将容器放置于转速为大约200rmp的震荡器台上震荡大约18小时。震荡之后,将EDTA/NaOH溶液从每一容器中除去。
B.向每一容器中加入大约1L的0.22mm滤纸灭菌的1M盐酸(HCl)/1M氯化钠(NaCl)溶液。之后将容器放置于转速为大约200rmp的震荡器台上震荡大约6至8小时。震荡之后,将HCl/NaCl溶液从每一容器中除去。
C.向每一容器中加入大约1L的0.22mm滤纸灭菌的1M氯化钠(NaCl)/10mM磷酸盐缓冲的盐水(PBS)。之后将容器放置于转速为大约200rmp的震荡器台上震荡大约18小时。震荡之后,将NaCl/PBS溶液从每一容器中除去。
D.向每一容器中加入大约1L的0.22mm滤纸灭菌的10mM PBS。之后将容器放置于转速为大约200rmp的震荡器台上震荡大约2小时。震荡之后,将磷酸盐缓冲的盐水从每一容器中除去。
E.最后,向每一容器中加入大约1L的0.22mm滤纸灭菌的水。之后将容器放置于转速为大约200rmp的震荡器台上震荡大约一小时。震荡之后,将水从每一容器中除去。
将处理后的样品切割、固定,用于组织分析。在对照和处理的组织的横断和纵断样品上进行Hemotoxylin与eosin(H & E)和Masson三色染色。处理的组织样品表现为无细胞和细胞碎片,而对照样品表现正常并如所预期的有非常多的细胞。
实施例2:猪心脏瓣膜的化学清洗
从1磅小猪获得猪心,并用搁在冰上的生理pH盐水装运。4小时内,使用解剖刀和镊子将心脏瓣膜从心脏中取出。进行一些进一步的粗解剖,从心瓣周围除去多余的组织。一只瓣膜作为对照,切下样品块并固定,用于各种组织分析,另一瓣膜经受化学清洗过程。余下的步骤在无菌条件和在室温下进行。化学溶液均在室温下使用。
将心瓣(valve)置于100mM EDTA/10mM NaOH的1L溶液中大约18小时,同时在震荡器平台上搅拌。之后将此心瓣置入1L的1M HCl/1M NaCl中并搅拌8小时。接着将此心瓣置入1L的1M HCl/10mM磷酸盐缓冲的盐水(PBS)中并搅拌约18小时。之后过搅拌,边将心瓣用PBS淋洗大约2-4小时,最后用无菌水淋洗大约1小时。将处理的样品块切开并固定,用于各种组织分析。
在对照和处理的心瓣的横断和纵断样品上进行Hemotoxylin与eosin(H & E)和Masson三色染色。处理的心瓣样品表现为无细胞和细胞碎片,而对照样品表现正常并如所预期的有非常多的细胞。
实施例3:猪动脉、心包和筋膜的化学清洗
从450磅的大母猪中获得股动脉、整个心包和筋膜的片断。这些组织用搁在冰上的生理pH盐水装运。将这些进一步解剖,除去多余的组织。每一组织的样品不经清洗,作为对照样品,并固定,用于各种组织分析,而此组织余下的部分经受化学清洗过程。余下的程序在无菌条件和在室温下进行。化学溶液均在室温下使用。
将组织分别置于100mM EDTA/10mM NaOH的1L溶液中并在震荡器平台上搅拌大约18小时。之后将组织各自分别置入1L的1M HCl/1M NaCl中并搅拌8小时。接下来,将组织分别置入1L的1M HCl/10mM磷酸盐缓冲的盐水(PBS)中并搅拌18小时。之后过搅拌,边将组织分别用PBS淋洗大约2-4小时,最后用灭菌水淋洗大约1小时。将处理的样品块切开并固定,用于各种组织分析。
在对照和处理的心瓣的横断和纵断样品上进行Hemotoxylin与eosin(H & E)和Masson三色染色。处理的组织样品表现为无细胞和细胞碎片,而对照样品表现正常并如所预期的有非常多的细胞。
实施例4:不同顺序的化学清洗
本方法在无菌条件和在室温下进行。化学溶液均在室温下使用。
机械剥离的猪肠如实施例1中所述切成五个15cm的段。
向每一容器中加入大约1L的0.22mm滤纸灭菌的1M盐酸(HCl)/1M氯化钠(NaCl)溶液。之后将容器放置于转速为大约200rmp的震荡器台上震荡大约8小时。震荡之后,将HCl/NaCl溶液从每一容器中除去。
向每一容器中加入大约1L的0.22mm(微米)过滤纸灭菌的100mM乙二胺四乙酸四钠盐(EDTA)/10mM氢氧化钠(NaOH)溶液。之后将容器放置于转速为大约200rmp的震荡器台上震荡大约18小时。震荡之后,将EDTA/NaOH溶液从每一容器中除去。
向每一容器中加入大约1L的0.22mm滤纸灭菌的1M盐酸(HCl)/10mM磷酸盐缓冲的盐水(PBS)。之后将容器放置于转速为大约200rmp的震荡器台上震荡大约18小时。震荡之后,将NaCl/PBS溶液从每一容器中除去。
向每一容器中加入大约1L的0.22mm滤纸灭菌的10mM PBS。之后将容器放置于转速为大约200rmp的震荡器台上震荡大约1小时。震荡之后,将此磷酸盐缓冲的盐水从每一容器中除去。
最后,向每一容器中加入大约1L的0.22mm滤纸灭菌的水。之后将容器放置于转速为大约200rmp的震荡器台上震荡大约一小时。震荡之后,将水从每一容器中除去。
切下处理的样品块并固定,用于组织分析。在对照和处理的组织的横断和纵断样品上进行Hemotoxylin与eosin(H & E)和Masson三色染色。处理的组织样品表现为无细胞和细胞碎片,而对照样品表现正常并如所预期的有非常多的细胞。
实施例5:不同的碱和螯合剂
根据实施例1中所描述的方法清洗机械剥离的猪肠粘膜下层。本方法在无菌条件和在室温下进行。化学溶液均在室温下使用。按照实施例1的化学清洗程序,但用其它的类似性质的碱螯合剂来替代其步骤A中的碱螯合剂
A.向每一装有肠的容器中加入大约1L的0.22mm(微米)过滤纸灭菌的或者是100mM亚乙基双(氧乙烯次氮基)四乙酸(EGTA)/10mM氢氧化钠(NaOH)溶液;100mM EDTA/10mM氢氧化钙(Ca(OH)2)溶液;或者是100mM EDTA/10mM碳酸钾(K2CO3)溶液。之后将容器放置于转速为大约200rmp的震荡器台上震荡大约18小时。震荡之后,将碱性螯合剂溶液从每一容器中除去。
B.向每一容器中加入大约1L的0.22mm滤纸灭菌的1M盐酸(HCl)/1M氯化钠(NaCl)溶液。之后将容器放置于转速为大约200rmp的震荡器台上震荡大约6至8小时。震荡之后,将HCl/NaCl溶液从每一容器中除去。
C.向每一容器中加入大约1L的0.22mm滤纸灭菌的1M氯化钠(NaCl)/10mM磷酸盐缓冲的盐水(PBS)。之后将容器放置于转速为大约200rmp的震荡器台上大约18小时。震荡之后,将NaCl/PBS溶液从每一容器中除去。
D.向每一容器中加入大约1L的0.22mm滤纸灭菌的10mM PBS溶液。之后将容器放置于转速为大约200rmp的震荡器台上大约1小时。震荡之后,将此磷酸盐缓冲的盐水从每一容器中除去。
E.最后,向每一容器中加入大约1L的0.22mm滤纸灭菌的水。之后将容器放置于转速为大约200rmp的震荡器台上大约一小时。震荡之后,将水从每一容器中除去。
将样品固定,用于组织分析。在对照和处理的组织的横断和纵断样品上进行Hemotoxylin与eosin(H & E)和Masson三色染色。处理的组织样品表现为无细胞和细胞碎片,而对照样品表现正常并如所预期的有非常多的细胞。
实施例6:不同的酸和盐试剂
根据实施例1中所描述的方法清洗机械剥离的猪肠粘膜下层,在步骤B中使用替代的酸试剂或替代的盐试剂进行化学清洗。本方法在无菌条件和在室温下进行。化学溶液均在室温下使用。
A.向每一装有肠的容器中加入大约1L的0.22mm(微米)过滤纸灭菌的100mM乙二胺四乙酸四钠盐(EDTA)/10mM氢氧化钠(NaOH)溶液。之后将容器放置于转速为大约200rmp的震荡器台上大约18小时。震荡之后,将EDTA/NaOH溶液从每一容器中除去。
B.向每一容器中加入大约1L的0.22mm滤纸灭菌的或者是1M乙酸(CH3COOH)/1M氯化钠(NaCl)溶液;或者是1M H2SO4/1M NaCl溶液。之后将容器放置于转速为大约200rmp的震荡器台上大约6至8小时。震荡之后,将溶液从每一容器中除去。
C.向每一容器中加入大约1L的0.22mm滤纸灭菌的1M氯化钠(NaCl)/10mM磷酸盐缓冲的盐水(PBS)。之后将容器放置于转速为大约200rmp的震荡器台上大约18小时。震荡之后,将NaCl/PBS溶液从每一容器中除去。
D.向每一容器中加入大约1L的0.22mm滤纸灭菌的10mM PBS。之后将容器放置于转速为大约200rmp的震荡器台上大约1小时。震荡之后,将此磷酸盐缓冲的盐水从每一容器中除去。
E.最后,向每一容器中加入大约1L的0.22mm滤纸灭菌的水。之后将容器放置于转速为大约200rmp的震荡器台上大约一小时。震荡之后,将水从每一容器中除去。
切下处理后的样品块并固定,用于组织分析。在对照和处理的组织的横断和纵断样品上进行Hemotoxylin与eosin(H & E)和Masson三色染色。处理的组织样品表现为无细胞和细胞碎片,而对照样品表现正常并如所预期的有非常多的细胞。
实施例7:用乙酸纤维素凝胶电泳和Alcian蓝分析测定ICL(肠胶原层)的糖胺聚糖(GAG)含量
为确定ICL的GAG含量,用化学清洗的ICL的提取液进行乙酸纤维素电泳,随后进行Alcian蓝染色。
将经过概述于实施例1中的化学清洗方式的ICL样品切成0.125cm2的片,并放置入微量离心管中。为消化样品,向每一管中加入100μl木瓜蛋白酶(在0.1M磷酸钠中的0.1mg/ml木瓜蛋白酶、0.1M氯化钠、0.005MEDTA、0.9mg/ml半胱氨酸中,pH5.8),并将之在60℃下温育大约18小时。平行制备含有已知量GAG(肝素)的标准。之后加入Dowex(0.4g HCl形式)和3ml水。在旋转除去Dowex树脂后,取出1ml并冻干。之后将样品于100μl纯化水中再水合,并离心大约5分钟。
使用Newton等人(1974)的方法,将样品分到乙酸纤维素板(sheet)上。将乙酸纤维素板浸泡于0.1M氯化锂/EDTA缓冲液(pH5.8)中,轻轻渗开。将样品(各5μl)涂在板的阴极端,并在5mA下电泳30分钟。
电泳之后,将板即刻浸入Alcian蓝染色溶液(0.2%Alcian蓝8GX,0.05M氯化镁、0.025M乙酸钠缓冲液(pH5.8)的50%乙烯(ethylene alcohol)醇溶液)并在室温下放置于震荡器平台上大约30分钟。之后将板用至少三次脱色溶液(0.05M氯化镁、0.025M乙酸钠缓冲液(pH5.8)的50%乙烯醇溶液)在震荡器平台上总计脱色大约30分钟。用肝素消化的ICL未观察到GAG染色,并且只可查出低到0.005微克的肝素标准。
这些结果显示,留在化学清洗过的ICL的GAG的总量低于1%(干重)。
实施例8:用二氯甲烷提取测定的ICL类脂含量
将ICL平放在塑料平板上,并风干2小时。一旦变干,就将ICL切成大约1cm2的小块,其中,将1.100g转移到索格利特套管(soxhlet thimble)中。
向Kontes牌圆底烧瓶24/40中加入90ml二氯甲烷。将索格利特安装在通风橱中,烧瓶底置于热水浴中,并且冰邻却的水流过蒸馏器。
提取四小时,之后将索格利特卸下,将含有溶剂和提取物的圆底烧瓶留在热水浴中,直到二氯甲烷蒸发到只剩5ml。之后将此二氯甲烷转移到11×13玻璃培养试管中,沸腾蒸出余下的溶剂。向试管中加入2ml二氯甲烷,并将试管即刻塞好,并试管置于-20℃冰箱中。
之后测定提取物的重量。将上述玻璃试管置于冰浴中。在微量天平(Spectrum Supermicro)上平衡Ludiag 1.12ml铝质称量皿的重量。向此称量杯皿加入10μl再悬浮的提取物,并将称量皿放置在热板上45秒钟,蒸除溶剂。让称量皿冷却大约190秒,并放置在微量天平上。之后对20μl和30μl提取物体积重复上述过程。
结果表明,类脂的百分率为干的化学清洗过的ICL重量的不到大约0.7%。相反,非化学清洗的ICL含有较高部分的类脂;为干的未用本发明方法清洗过的ICL重量中的至少大约1.5%。
实施例9:ICL的氨基酸分析
胶原是特征在于其三螺旋区的蛋白,它具有三组重复的氨基酸甘氨酸-X-Y,其中X通常是脯氨酸,而Y经常是羟基脯氨酸。羟基脯氨酸通常用作将胶原定性与定量的氨基酸(Udenfriend,《科学》,152:1335-1340,1966)。
为测定完整的ICL氨基酸分析,用机械清洗(不是化学清洗的)猪ICL和化学清洗的ICL进行PICO-TAG HPLC。对二种材料的羟基脯氨酸含量进行测定和比较。
使用CEM AVC80烘箱(CEM Corp.;Matthews,NC),对来源于每一条件下的重量为大约0.31至大约0.36g的ICL样品块进行进一步干燥。由这些干燥的ICL块上切出重量为大约9.5至大约13.1mg的更小的样品。将样品放入螺旋盖培养试管中,之后将样品在1%苯酚的6M HCl溶液中在110℃水解(每一条件,n=3)大约16小时。ICL水解物之后用0.1M HCl稀释以标准化材料浓度至1mg/ml。对于标定的玻璃试管(6×55),20ml水解物和8ml 1.25mmol/ml L-正亮氨酸作为内标。之后将样品冷冻并冰干。通过向试管中加入20ml的2∶2∶1的乙醇∶水∶三乙胺来再干燥,冷冻和冰干。之后将样品在室温下通过加入20ml试剂(7∶1∶1∶1乙醇∶水∶三乙胺∶PITC)衍生20分钟,接着冰冻和冰干。最后将样品悬浮于200mlPICO-TAG样品稀释剂中,并等分成小份入HPLC管。
氨基酸标准物用下列方式制备:将0.1ml氨基酸标准物(产品#:A-9531,Sigma)加入到1.9ml 0.1M HCl中。使用0.1M HCl以1∶1的比率制成五种系列稀释液。体积为100ml的每种系列稀释液和8ml的1.25mmol/ml L-正亮氨酸一起加入玻璃试管(6×55)中,之后用与ICL样品同样的方式制备。
将样品和标准物上3.9×150mm PICO-TAG氨基酸柱(Part#88131;Waters Corp.;Miford,MA,美国)。分析时,样品注射量为10ml,标准物注射量为20ml,每一处理重复三次。
结果表明,对于化学清洗的ICL材料而言,在材料中的主要胶原氨基酸的含量接近纯化的胶原制剂。使用羟基脯氨酸衡量胶原含量,计算出ICL中的胶原按重量计的百分率为胶原干重的至少93%。相反,非化学清洗的ICL含有高含量的非胶原氨基酸;介于ICL干重大约11至25%的是非胶原材料。
虽然在上文中,为了清楚和理解的目的,采用例解说明和实施例的方式对发明作了一定程度的详细描述,但对于本领域技术人员而言,在本发明权利要求书的范围内可以进行某些变化和修改,这点是不言自明的。
Claims (27)
1.一种从天然哺乳动物组织中除去非胶原成分以产生基本上是胶原组织基质的无洗涤剂和无酶的方法,包含
(a)将组织与有效量的螯合剂的碱性溶液接触;
(b)将组织与有效量的含有盐的酸性溶液接触;
(c)将组织与有效量的缓冲到大致生理pH的盐溶液接触;和
(d)将组织与有效量的淋洗剂接触。
2.权利要求1的方法,其中,步骤(a)的螯合剂选自:乙二胺四乙酸(EDTA)和亚乙基双(氧乙烯次氮基)四乙酸(EGTA)。
3.权利要求2的方法,其中,螯合剂的浓度介于大约1至大约200mM之间。
4.权利要求2的方法,其中,螯合剂的浓度介于大约50至大约150mM之间。
5.权利要求1的方法,其中,步骤(a)的碱性试剂选自:氢氧化钠、氢氧化钙、碳酸钠或过氧化钠。
6.权利要求5的方法,其中,碱性试剂的浓度介于大约0.001至大约1M之间。
7.权利要求1的方法,其中,步骤(b)的酸性溶液选自:盐酸、乙酸和硫酸。
8.权利要求7的方法,其中,酸性溶液的浓度介于大约0.5至2M之间。
9.权利要求7的方法,其中,酸性溶液的浓度介于大约0.95至1.25M之间。
10.权利要求7的方法,其中,酸性溶液的浓度为1M左右。
11.权利要求1的方法,其中,酸-盐溶液的pH介于0至大约1之间。
12.权利要求1的方法,其中,酸-盐溶液的pH介于0至大约0.75之间。
13.权利要求1的方法,其中,酸-盐溶液的pH介于0.1至大约0.5之间。
14.权利要求1的方法,其中,步骤(b)或(c)之一的盐是无机盐。
15.权利要求1的方法,其中,步骤(b)或(c)之一的盐选自:氯化钠、氯化钙、氯化钾和硫酸铵。
16.权利要求1的方法,其中,步骤(b)或(c)之一的盐浓度为大约0.1至大约2M。
17.权利要求1的方法,其中,步骤(b)或(c)之一的盐浓度为大约0.75至大约1.25M。
18.权利要求1的方法,其中,步骤(b)或(c)之一的盐浓度为1M左右。
19.权利要求1的方法,其中,所述的组织选自:真皮、动脉、静脉、心包、心脏瓣膜、硬脑脊膜、骨、软骨、腱、筋膜和肠。
20.权利要求19的方法,其中,所述的肠组织包括小肠的被膜粘膜下层。
21.权利要求19的方法,其中,所述的组织来源于人、牛、猪、羊、狗、猫或马。
22.权利要求1的方法,其中淋洗剂选自水或生理缓中盐水。
23.权利要求1的方法,其中,步骤(b)的方法是在步骤(a)前进行的。
24.一种从天然哺乳动物组织中除去非胶原成分以产生基本上是胶原组织基质的无洗涤剂和无酶的方法,包含
(a)将组织与pH介于大约8至大约12的乙二胺四乙酸的碱性溶
液接触;
(b)将组织与pH介于大约0至大约1的氯化钠的酸性溶液接触;
(c)将组织与pH介于大约5至大约9的氯化钠溶液接触;和
(d)淋洗组织。
25.权利要求1至24的任一种方法获得的可生物改造胶原组织基质。
26.一种从天然哺乳动物组织得到的可生物改造的胶原组织基质组成,它基本上没有在所述天然组织中见到的非胶原和非弹性蛋白成分,其无洗涤剂残留物和酶修饰,用于修复或替代损害的或有病的包含胶原和弹性蛋白的身体部分的移植中。
27.一种从小肠的天然被膜粘膜下层得到的无洗涤剂残留物的可生物改造的胶原组织基质组成,其中组织基质包含:
端肽胶原;
弹性蛋白,其中弹性蛋白低于总组成的10%;和
非胶原和非弹性蛋白组分,其中所述的组分低于总组成的5%。
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---|---|---|---|---|
WO2007071168A1 (en) * | 2005-12-20 | 2007-06-28 | Summit (Gd) Biotech Co., Ltd | Biological wound dressing and method of making |
US7674289B2 (en) | 2005-07-29 | 2010-03-09 | Grandhope Biotech Co., Ltd. | Biological artificial ligament and method of making |
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US8100970B2 (en) | 2005-12-20 | 2012-01-24 | Grandhope Biotech Co., Ltd. | Biological surgical patch and method of making |
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Families Citing this family (349)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6334872B1 (en) * | 1994-02-18 | 2002-01-01 | Organogenesis Inc. | Method for treating diseased or damaged organs |
US20020095218A1 (en) * | 1996-03-12 | 2002-07-18 | Carr Robert M. | Tissue repair fabric |
US6666892B2 (en) * | 1996-08-23 | 2003-12-23 | Cook Biotech Incorporated | Multi-formed collagenous biomaterial medical device |
ES2208974T3 (es) | 1996-08-23 | 2004-06-16 | Cook Biotech, Inc. | Protesis de injertos, materiales y metodos. |
US8716227B2 (en) | 1996-08-23 | 2014-05-06 | Cook Biotech Incorporated | Graft prosthesis, materials and methods |
US20060025786A1 (en) * | 1996-08-30 | 2006-02-02 | Verigen Transplantation Service International (Vtsi) Ag | Method for autologous transplantation |
US20020173806A1 (en) * | 1996-08-30 | 2002-11-21 | Verigen Transplantation Service International (Vtsi) Ag | Method for autologous transplantation |
TW510803B (en) * | 1996-11-20 | 2002-11-21 | Yasuhiko Shimizu | Man-made esophagus and its manufacturing method |
US5993844A (en) * | 1997-05-08 | 1999-11-30 | Organogenesis, Inc. | Chemical treatment, without detergents or enzymes, of tissue to form an acellular, collagenous matrix |
US6482584B1 (en) * | 1998-11-13 | 2002-11-19 | Regeneration Technologies, Inc. | Cyclic implant perfusion cleaning and passivation process |
US20010031254A1 (en) * | 1998-11-13 | 2001-10-18 | Bianchi John R. | Assembled implant |
US6652818B1 (en) | 1998-11-13 | 2003-11-25 | Regeneration Technologies, Inc. | Implant sterilization apparatus |
US6613278B1 (en) | 1998-11-13 | 2003-09-02 | Regeneration Technologies, Inc. | Tissue pooling process |
US6371992B1 (en) * | 1997-12-19 | 2002-04-16 | The Regents Of The University Of California | Acellular matrix grafts: preparation and use |
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US8563232B2 (en) * | 2000-09-12 | 2013-10-22 | Lifenet Health | Process for devitalizing soft-tissue engineered medical implants, and devitalized soft-tissue medical implants produced |
US7063726B2 (en) * | 1998-06-30 | 2006-06-20 | Lifenet | Plasticized bone grafts and methods of making and using same |
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US6743574B1 (en) | 2000-09-12 | 2004-06-01 | Lifenet | Process for devitalizing soft-tissue engineered medical implants, and devitalized soft-tissue medical implants produced |
US6734018B2 (en) | 1999-06-07 | 2004-05-11 | Lifenet | Process for decellularizing soft-tissue engineered medical implants, and decellularized soft-tissue medical implants produced |
US20030217415A1 (en) * | 1998-06-30 | 2003-11-27 | Katrina Crouch | Plasticized bone grafts and methods of making and using same |
US6214054B1 (en) | 1998-09-21 | 2001-04-10 | Edwards Lifesciences Corporation | Method for fixation of biological tissues having mitigated propensity for post-implantation calcification and thrombosis and bioprosthetic devices prepared thereby |
US8882850B2 (en) | 1998-12-01 | 2014-11-11 | Cook Biotech Incorporated | Multi-formed collagenous biomaterial medical device |
US6611833B1 (en) * | 1999-06-23 | 2003-08-26 | Tissueinformatics, Inc. | Methods for profiling and classifying tissue using a database that includes indices representative of a tissue population |
EP1498089A1 (de) | 1999-12-15 | 2005-01-19 | Zimmer GmbH | Präparat für die Reparatur von Knorpel- oder Knorpel/Knochen-Defekten in menschlichen oder tierischen Gelenken |
US6866686B2 (en) | 2000-01-28 | 2005-03-15 | Cryolife, Inc. | Tissue graft |
DE10026482A1 (de) * | 2000-05-29 | 2001-12-13 | Augustinus Bader | Verfahren zur Herstellung eines bioartifiziellen Transplantats |
DE10026442A1 (de) * | 2000-05-29 | 2001-12-13 | Augustinus Bader | Verfahren zur Herstellung eines empfängerspezifischen Gewebe-Transplantats |
US8366787B2 (en) | 2000-08-04 | 2013-02-05 | Depuy Products, Inc. | Hybrid biologic-synthetic bioabsorbable scaffolds |
US6638312B2 (en) | 2000-08-04 | 2003-10-28 | Depuy Orthopaedics, Inc. | Reinforced small intestinal submucosa (SIS) |
US6599526B2 (en) * | 2000-08-18 | 2003-07-29 | The University Of North Texas Health Science Center At Fort Worth | Pericardial anti-adhesion patch |
WO2002017936A1 (en) * | 2000-08-28 | 2002-03-07 | Collagenesis, Inc. | Methods for processing animal tissues |
CA2422852C (en) * | 2000-09-18 | 2012-06-26 | Organogenesis Inc. | Methods for treating a patient using a bioengineered flat sheet graft prostheses |
AU2001292917A1 (en) * | 2000-09-20 | 2002-04-02 | Regeneration Technologies, Inc. | Method of preparing and processing transplant tissue |
US20030050276A1 (en) * | 2001-08-15 | 2003-03-13 | Cunanan Crystal M. | Treatment of tissue, instruments and work surfaces to remove infectious agents |
DE10064948C1 (de) * | 2000-12-20 | 2002-07-11 | Auto Tissue Gmbh | Verfahren zur Dezellularisierung von Fremdmaterial zur Herstellung von Bioprothesen und Vorrichtung zur Durchführung des Verfahrens |
US7326564B2 (en) | 2001-02-20 | 2008-02-05 | St. Jude Medical, Inc. | Flow system for medical device evaluation and production |
KR100427557B1 (ko) * | 2001-03-26 | 2004-04-27 | 주식회사 웰스킨 | 뼈의 콜라겐 지지체 |
US6444222B1 (en) * | 2001-05-08 | 2002-09-03 | Verigen Transplantation Services International Ag | Reinforced matrices |
EP1416880B1 (en) | 2001-07-16 | 2011-03-02 | DePuy Products, Inc. | Cartilage repair apparatus |
US7819918B2 (en) | 2001-07-16 | 2010-10-26 | Depuy Products, Inc. | Implantable tissue repair device |
US7201917B2 (en) | 2001-07-16 | 2007-04-10 | Depuy Products, Inc. | Porous delivery scaffold and method |
AU2002322567B2 (en) | 2001-07-16 | 2007-09-06 | Depuy Products, Inc. | Devices form naturally occurring biologically derived |
WO2003007787A2 (en) | 2001-07-16 | 2003-01-30 | Depuy Products, Inc. | Cartilage repair and regeneration device and method |
AU2002354911B2 (en) | 2001-07-16 | 2007-08-30 | Depuy Products, Inc. | Meniscus regeneration device and method |
EP1416874A4 (en) | 2001-07-16 | 2007-04-18 | Depuy Products Inc | BIOLOGICAL / SYNTHETIC POROUS EXTRACELLULAR HYBRID MATRIX SCUFF |
US8025896B2 (en) | 2001-07-16 | 2011-09-27 | Depuy Products, Inc. | Porous extracellular matrix scaffold and method |
TWI284665B (en) * | 2001-08-17 | 2007-08-01 | Univ Nat Cheng Kung | Fabrication method of the porous collagen matrix |
KR100514582B1 (ko) * | 2001-09-05 | 2005-09-13 | 한스바이오메드 주식회사 | 생체복원물질의 제조방법 |
WO2003026486A2 (en) * | 2001-09-27 | 2003-04-03 | Mayo Foundation For Medical Education And Research | Eyelet reinforcement at the tissue-suture interface |
EP1446015B1 (en) * | 2001-10-18 | 2018-03-14 | Lifecell Corporation | Remodeling of tissues and organs |
DE60225824T2 (de) * | 2001-10-26 | 2009-04-16 | Cook Biotech, Inc., West Lafayette | Medizinisches implantat mit netzartiger struktur |
WO2003053493A2 (en) | 2001-12-19 | 2003-07-03 | Nmt Medical, Inc. | Septal occluder and associated methods |
US7318833B2 (en) | 2001-12-19 | 2008-01-15 | Nmt Medical, Inc. | PFO closure device with flexible thrombogenic joint and improved dislodgement resistance |
WO2003059195A2 (en) * | 2001-12-21 | 2003-07-24 | Organogenesis Inc. | System and method for forming bioengineered tubular graft prostheses |
US6878168B2 (en) | 2002-01-03 | 2005-04-12 | Edwards Lifesciences Corporation | Treatment of bioprosthetic tissues to mitigate post implantation calcification |
WO2003059152A2 (en) | 2002-01-14 | 2003-07-24 | Nmt Medical, Inc. | Patent foramen ovale (pfo) closure method and device |
US20080086792A1 (en) | 2006-10-13 | 2008-04-17 | Thomas Charles Kuracina | Method and apparatus for diverting sweat, liquid, moisture or the like from an eye |
JP4624678B2 (ja) | 2002-02-21 | 2011-02-02 | パイオニア・サージカル・オーソバイオロジックス,インコーポレイテッド | 架橋生物活性ヒドロゲルマトリックス |
WO2003072128A2 (en) * | 2002-02-22 | 2003-09-04 | Ebi, L.P. | Methods and compositions for treating bone or cartilage defects |
WO2003082076A2 (en) | 2002-03-25 | 2003-10-09 | Nmt Medical, Inc. | Patent foramen ovale (pfo) closure clips |
US20030187515A1 (en) * | 2002-03-26 | 2003-10-02 | Hariri Robert J. | Collagen biofabric and methods of preparing and using the collagen biofabric |
DE10217779A1 (de) | 2002-04-18 | 2003-11-13 | Co Don Ag | Konservierte Gewebematrix eines Hohlorganes, insbesondere eines Blutgefäßes, Verfahren zur Herstellung und Verwendung dieser |
JP2005528162A (ja) | 2002-06-03 | 2005-09-22 | エヌエムティー メディカル インコーポレイテッド | 心臓内欠損閉塞のための生物学的組織足場を有するデバイス |
WO2003103476A2 (en) | 2002-06-05 | 2003-12-18 | Nmt Medical, Inc. | Patent foramen ovale (pfo) closure device with radial and circumferential support |
US20040072294A1 (en) * | 2002-06-19 | 2004-04-15 | Braunhut Susan J. | Tissue reconstruction and regeneration |
US7550004B2 (en) | 2002-08-20 | 2009-06-23 | Cook Biotech Incorporated | Endoluminal device with extracellular matrix material and methods |
WO2004022107A2 (en) * | 2002-09-06 | 2004-03-18 | Cook Biotech Incorporated | Tissue graft prosthesis devices containing juvenile or small diameter submucosa |
US7008763B2 (en) * | 2002-09-23 | 2006-03-07 | Cheung David T | Method to treat collagenous connective tissue for implant remodeled by host cells into living tissue |
US20040136968A1 (en) * | 2002-09-27 | 2004-07-15 | Verigen Ag | Autologous cells on a support matrix for tissue repair |
WO2004037333A1 (en) | 2002-10-25 | 2004-05-06 | Nmt Medical, Inc. | Expandable sheath tubing |
WO2004052213A1 (en) | 2002-12-09 | 2004-06-24 | Nmt Medical, Inc. | Septal closure devices |
US7658747B2 (en) | 2003-03-12 | 2010-02-09 | Nmt Medical, Inc. | Medical device for manipulation of a medical implant |
WO2004082528A2 (en) | 2003-03-17 | 2004-09-30 | Cook Incorporated | Vascular valve with removable support component |
US7871434B2 (en) * | 2003-04-01 | 2011-01-18 | Cook Incorporated | Percutaneously deployed vascular valves |
US8480706B2 (en) | 2003-07-14 | 2013-07-09 | W.L. Gore & Associates, Inc. | Tubular patent foramen ovale (PFO) closure device with catch system |
US7678123B2 (en) | 2003-07-14 | 2010-03-16 | Nmt Medical, Inc. | Tubular patent foramen ovale (PFO) closure device with catch system |
US9861346B2 (en) | 2003-07-14 | 2018-01-09 | W. L. Gore & Associates, Inc. | Patent foramen ovale (PFO) closure device with linearly elongating petals |
EP1659992B1 (en) * | 2003-07-31 | 2013-03-27 | Cook Medical Technologies LLC | Prosthetic valve devices and methods of making such devices |
DE602004017750D1 (de) | 2003-08-19 | 2008-12-24 | Nmt Medical Inc | Expandierbarer Schleusenschlauch |
GB2424586B (en) | 2003-08-25 | 2008-05-28 | Cook Biotech Inc | Graft materials containing bioactive substances, and methods for their manufacture |
AU2004270239C1 (en) * | 2003-09-04 | 2011-07-07 | Cook Biotech Incorporated | Extracellular matrix composite materials, and manufacture and use thereof |
US7645229B2 (en) * | 2003-09-26 | 2010-01-12 | Armstrong David N | Instrument and method for endoscopic visualization and treatment of anorectal fistula |
WO2005032473A2 (en) * | 2003-10-02 | 2005-04-14 | Depuy Spine, Inc. | Chemical treatment for removing cellular and nuclear material from naturally occurring extracellular matrix-based biomaterials |
US6976679B2 (en) * | 2003-11-07 | 2005-12-20 | The Boeing Company | Inter-fluid seal assembly and method therefor |
US20050273119A1 (en) | 2003-12-09 | 2005-12-08 | Nmt Medical, Inc. | Double spiral patent foramen ovale closure clamp |
WO2005063314A1 (ja) * | 2003-12-26 | 2005-07-14 | Cardio Incorporated | 脱細胞化組織およびその作成方法 |
CN1909840B (zh) * | 2004-01-21 | 2012-03-21 | 库克公司 | 用来闭合瘘管的植入式移植物 |
US20050192626A1 (en) | 2004-01-30 | 2005-09-01 | Nmt Medical, Inc. | Devices, systems, and methods for closure of cardiac openings |
WO2005079675A2 (en) | 2004-02-17 | 2005-09-01 | Cook Biotech Incorporated | Medical devices and methods for applying bolster material |
US7871419B2 (en) | 2004-03-03 | 2011-01-18 | Nmt Medical, Inc. | Delivery/recovery system for septal occluder |
US7449027B2 (en) * | 2004-03-29 | 2008-11-11 | Cook Incorporated | Modifying fluid flow in a body vessel lumen to promote intraluminal flow-sensitive processes |
CA2560876A1 (en) * | 2004-03-29 | 2005-10-13 | Cook Biotech Incorporated | Medical graft products with differing regions and methods and systems for producing the same |
US8216299B2 (en) | 2004-04-01 | 2012-07-10 | Cook Medical Technologies Llc | Method to retract a body vessel wall with remodelable material |
US20050267524A1 (en) | 2004-04-09 | 2005-12-01 | Nmt Medical, Inc. | Split ends closure device |
US7648676B2 (en) | 2004-04-20 | 2010-01-19 | Rti Biologics, Inc. | Process and apparatus for treating implants comprising soft tissue |
US8361110B2 (en) | 2004-04-26 | 2013-01-29 | W.L. Gore & Associates, Inc. | Heart-shaped PFO closure device |
US8308760B2 (en) | 2004-05-06 | 2012-11-13 | W.L. Gore & Associates, Inc. | Delivery systems and methods for PFO closure device with two anchors |
US7842053B2 (en) | 2004-05-06 | 2010-11-30 | Nmt Medical, Inc. | Double coil occluder |
JP2007535997A (ja) | 2004-05-07 | 2007-12-13 | エヌエムティー メディカル, インコーポレイティッド | 管状中隔オクルーダーの捕捉機構 |
US7704268B2 (en) | 2004-05-07 | 2010-04-27 | Nmt Medical, Inc. | Closure device with hinges |
CA2575240A1 (en) * | 2004-07-30 | 2006-02-09 | Cook Biotech Incorporated | Graft with increased resistance to enzymatic degradation |
WO2006036837A2 (en) | 2004-09-24 | 2006-04-06 | Nmt Medical, Inc. | Occluder device double securement system for delivery/recovery of such occluder device |
US7442206B2 (en) * | 2004-10-28 | 2008-10-28 | Cook Incorporated | Methods and systems for modifying vascular valves |
US7513866B2 (en) | 2004-10-29 | 2009-04-07 | Depuy Products, Inc. | Intestine processing device and associated method |
WO2006050460A1 (en) * | 2004-10-29 | 2006-05-11 | Cook Incorporated | Vascular valves having implanted and target configurations and methods of preparing the same |
US7905826B2 (en) * | 2004-11-03 | 2011-03-15 | Cook Incorporated | Methods for modifying vascular vessel walls |
US7387604B2 (en) * | 2004-11-03 | 2008-06-17 | Cook Incorporated | Methods for treating valve-associated regions of vascular vessels |
EP1827527B1 (en) * | 2004-12-06 | 2016-08-24 | Cook Incorporated | Inflatable occlusion devices, methods, and systems |
WO2006062976A2 (en) | 2004-12-07 | 2006-06-15 | Cook Incorporated | Methods for modifying vascular vessel walls |
US20060134072A1 (en) * | 2004-12-22 | 2006-06-22 | Pedrozo Hugo A | Self-assembling protein matrix prepared from natural extracellular matrices |
WO2006074060A2 (en) * | 2004-12-30 | 2006-07-13 | Cook Incorporated | Inverting occlusion devices and systems |
US20060206139A1 (en) * | 2005-01-19 | 2006-09-14 | Tekulve Kurt J | Vascular occlusion device |
US9138445B2 (en) * | 2005-03-09 | 2015-09-22 | Cook Biotech Incorporated | Medical graft materials with adherent extracellular matrix fibrous mass |
US7723108B2 (en) * | 2005-03-16 | 2010-05-25 | Musculoskeletal Transplant Foundation | Soft tissue processing |
US20100112543A1 (en) * | 2005-03-16 | 2010-05-06 | Manh-Dan Ngo | Processing soft tissue, methods and compositions related thereto |
EP1868507A1 (en) | 2005-03-18 | 2007-12-26 | NMT Medical, Inc. | Catch member for pfo occluder |
EP1863545B1 (en) * | 2005-03-19 | 2015-11-18 | Cook Biotech, Inc. | Prosthetic implants including ECM composite material |
US8197534B2 (en) | 2005-03-31 | 2012-06-12 | Cook Medical Technologies Llc | Valve device with inflatable chamber |
CA2833585C (en) * | 2005-04-29 | 2017-06-20 | Cook Biotech Incorporated | Volumetric grafts for treatment of fistulae and related methods and systems |
WO2007011443A2 (en) * | 2005-04-29 | 2007-01-25 | Cook Biotech Incorporated | Fistula graft with deformable sheet-form material |
US9788821B2 (en) * | 2005-04-29 | 2017-10-17 | Cook Biotech Incorporated | Physically modified extracellular matrix materials and uses thereof |
EP1719533A1 (en) * | 2005-05-04 | 2006-11-08 | Tecnobiomedica S.p.A. | Method of preparing acellularized, biocompatible, implantable material |
US20060251702A1 (en) * | 2005-05-05 | 2006-11-09 | Cook Biotech Incorporated | Implantable materials and methods for inhibiting tissue adhesion formation |
US8475512B2 (en) * | 2005-05-17 | 2013-07-02 | Cook Medical Technologies Llc | Prosthetic valve devices and methods of making and using such devices |
JP2008543504A (ja) | 2005-06-21 | 2008-12-04 | クック・インコーポレイテッド | 瘻孔を閉鎖する移植可能なグラフト |
EP1901789A2 (en) * | 2005-06-30 | 2008-03-26 | Anthrogenesis Corporation | Repair of tympanic membrane using placenta derived collagen biofabric |
US20070038295A1 (en) * | 2005-08-12 | 2007-02-15 | Cook Incorporated | Artificial valve prosthesis having a ring frame |
US8771340B2 (en) * | 2005-08-25 | 2014-07-08 | Cook Medical Technologies Llc | Methods and devices for the endoluminal deployment and securement of prostheses |
WO2007028052A2 (en) * | 2005-09-01 | 2007-03-08 | Cook Incorporated | Attachment of material to an implantable frame by cross-linking |
WO2007030433A2 (en) | 2005-09-06 | 2007-03-15 | Nmt Medical, Inc. | Removable intracardiac rf device |
US9259267B2 (en) | 2005-09-06 | 2016-02-16 | W.L. Gore & Associates, Inc. | Devices and methods for treating cardiac tissue |
EP1764117A1 (en) | 2005-09-20 | 2007-03-21 | Zimmer GmbH | Implant for the repair of a cartilage defect and method for manufacturing the implant |
EP1931265B1 (en) * | 2005-09-30 | 2011-12-07 | Cook Medical Technologies LLC | Coated vaso-occlusion device |
US7503928B2 (en) | 2005-10-21 | 2009-03-17 | Cook Biotech Incorporated | Artificial valve with center leaflet attachment |
US7563277B2 (en) * | 2005-10-24 | 2009-07-21 | Cook Incorporated | Removable covering for implantable frame projections |
US8778362B2 (en) | 2005-10-27 | 2014-07-15 | University Of Notre Dame | Anti-tumor/cancer heterologous acellular collagenous preparations and uses thereof |
WO2007064819A2 (en) * | 2005-12-02 | 2007-06-07 | Cook Incorporated | Devices, systems, and methods for occluding a defect |
WO2007070301A2 (en) * | 2005-12-05 | 2007-06-21 | Regeneration Technologies, Inc. | Vascular graft sterilization and decellularization |
WO2007073566A1 (en) | 2005-12-22 | 2007-06-28 | Nmt Medical, Inc. | Catch members for occluder devices |
WO2007090150A2 (en) * | 2006-01-31 | 2007-08-09 | Cook Biotech Incorporated | Fistula grafts and related methods and systems for treating fistulae |
US7648527B2 (en) * | 2006-03-01 | 2010-01-19 | Cook Incorporated | Methods of reducing retrograde flow |
US8870913B2 (en) | 2006-03-31 | 2014-10-28 | W.L. Gore & Associates, Inc. | Catch system with locking cap for patent foramen ovale (PFO) occluder |
US8551135B2 (en) | 2006-03-31 | 2013-10-08 | W.L. Gore & Associates, Inc. | Screw catch mechanism for PFO occluder and method of use |
JP2009532125A (ja) | 2006-03-31 | 2009-09-10 | エヌエムティー メディカル, インコーポレイティッド | オクルーダ装置用の変形可能なフラップキャッチ機構 |
US7829108B2 (en) | 2006-04-21 | 2010-11-09 | Wake Forest University Health Sciences | Structurally modified acellular tissue engineering scaffolds and methods of production |
US20070269478A1 (en) * | 2006-05-22 | 2007-11-22 | Tecnobiomedica S.P.A. | Method of preparing acellularized, biocompatible, implantable material |
EP2020958B1 (en) | 2006-05-30 | 2012-05-30 | Cook Medical Technologies LLC | Artificial valve prosthesis |
EP2043531B1 (en) | 2006-06-15 | 2013-01-02 | Cook Medical Technologies LLC | Systems and devices for the delivery of endoluminal prostheses |
AU2007260914B2 (en) | 2006-06-21 | 2012-11-29 | Cook Biotech Incorporated | Fistula grafts and related methods and systems useful for treating gastrointestinal fistulae |
FR2902661B1 (fr) * | 2006-06-22 | 2011-05-13 | Orthomed | Tubes de collagene |
WO2008016919A2 (en) | 2006-07-31 | 2008-02-07 | Organogenesis Inc. | Mastopexy and breast reconstruction prostheses and method |
US8105634B2 (en) * | 2006-08-15 | 2012-01-31 | Anthrogenesis Corporation | Umbilical cord biomaterial for medical use |
EP2053975A1 (en) * | 2006-08-24 | 2009-05-06 | Wilson-Cook Medical Inc. | Devices and methods for occluding a fistula |
US20080131522A1 (en) * | 2006-10-03 | 2008-06-05 | Qing Liu | Use of placental biomaterial for ocular surgery |
US8071135B2 (en) | 2006-10-04 | 2011-12-06 | Anthrogenesis Corporation | Placental tissue compositions |
CN101622007A (zh) | 2006-10-06 | 2010-01-06 | 人类起源公司 | 天然(端肽)胎盘胶原组合物 |
US8029532B2 (en) * | 2006-10-11 | 2011-10-04 | Cook Medical Technologies Llc | Closure device with biomaterial patches |
CA2666485C (en) | 2006-10-27 | 2015-10-06 | Edwards Lifesciences Corporation | Biological tissue for surgical implantation |
US7871440B2 (en) | 2006-12-11 | 2011-01-18 | Depuy Products, Inc. | Unitary surgical device and method |
US8343536B2 (en) | 2007-01-25 | 2013-01-01 | Cook Biotech Incorporated | Biofilm-inhibiting medical products |
WO2008094706A2 (en) | 2007-02-01 | 2008-08-07 | Cook Incorporated | Closure device and method of closing a bodily opening |
US8617205B2 (en) | 2007-02-01 | 2013-12-31 | Cook Medical Technologies Llc | Closure device |
WO2008094691A2 (en) * | 2007-02-01 | 2008-08-07 | Cook Incorporated | Closure device and method for occluding a bodily passageway |
CA2677308A1 (en) * | 2007-02-02 | 2008-08-14 | Manh-Dan Ngo | Processing skin from living donors |
US20080260794A1 (en) * | 2007-02-12 | 2008-10-23 | Lauritzen Nels J | Collagen products and methods for producing collagen products |
US9056151B2 (en) * | 2007-02-12 | 2015-06-16 | Warsaw Orthopedic, Inc. | Methods for collagen processing and products using processed collagen |
WO2008101083A2 (en) | 2007-02-15 | 2008-08-21 | Cook Incorporated | Artificial valve prostheses with a free leaflet portion |
DE102007009095A1 (de) * | 2007-02-24 | 2008-08-28 | Gfe Nanomedical International Ag | Verfahren zur Behandlung biologischer Gewebe tierischen oder menschlichen Ursprungs wie Schweine-, Rinderperikard- oder menschlicher Leichen-Herzklappen sowie entsprechend behandeltes biologisches Gewebe |
US9005242B2 (en) | 2007-04-05 | 2015-04-14 | W.L. Gore & Associates, Inc. | Septal closure device with centering mechanism |
WO2008124361A2 (en) * | 2007-04-06 | 2008-10-16 | Cook Biotech Incorporated | Fistula plugs having increased column strength and fistula plug delivery apparatuses and methods |
CA2684011A1 (en) * | 2007-04-16 | 2008-10-23 | Tissue Science Laboratories Plc | Decellularised collagen-containing matrix for guided tissue regeneration |
US20100179639A1 (en) * | 2007-04-16 | 2010-07-15 | Stephen Bloor | Vascular implant |
WO2008125858A2 (en) * | 2007-04-16 | 2008-10-23 | Tissue Science Laboratories Plc | Bone implant |
WO2008131167A1 (en) | 2007-04-18 | 2008-10-30 | Nmt Medical, Inc. | Flexible catheter system |
US20080294270A1 (en) * | 2007-05-24 | 2008-11-27 | Zimmer Orthobiologics, Inc. | Differentially processed tissue and processing methods thereof |
US20090142400A1 (en) * | 2007-05-31 | 2009-06-04 | Hiles Michael C | Analgesic coated medical product |
US20080306610A1 (en) * | 2007-06-07 | 2008-12-11 | Zimmer Orthobiologics, Inc. | Tissue processing for nonimmunogenic implants |
US9101691B2 (en) | 2007-06-11 | 2015-08-11 | Edwards Lifesciences Corporation | Methods for pre-stressing and capping bioprosthetic tissue |
US8932619B2 (en) * | 2007-06-27 | 2015-01-13 | Sofradim Production | Dural repair material |
US8535349B2 (en) * | 2007-07-02 | 2013-09-17 | Cook Biotech Incorporated | Fistula grafts having a deflectable graft body portion |
ES2563071T3 (es) | 2007-07-10 | 2016-03-10 | Lifecell Corporation | Composiciones acelulares de matriz tisular para reparación de tejidos |
US20090024224A1 (en) | 2007-07-16 | 2009-01-22 | Chen Silvia S | Implantation of cartilage |
US9113851B2 (en) | 2007-08-23 | 2015-08-25 | Cook Biotech Incorporated | Fistula plugs and apparatuses and methods for fistula plug delivery |
US8025495B2 (en) * | 2007-08-27 | 2011-09-27 | Cook Medical Technologies Llc | Apparatus and method for making a spider occlusion device |
US8734483B2 (en) | 2007-08-27 | 2014-05-27 | Cook Medical Technologies Llc | Spider PFO closure device |
US8308752B2 (en) * | 2007-08-27 | 2012-11-13 | Cook Medical Technologies Llc | Barrel occlusion device |
US20090068250A1 (en) | 2007-09-07 | 2009-03-12 | Philippe Gravagna | Bioresorbable and biocompatible compounds for surgical use |
US20090069843A1 (en) * | 2007-09-10 | 2009-03-12 | Agnew Charles W | Fistula plugs including a hydration resistant component |
US8029560B2 (en) | 2007-09-12 | 2011-10-04 | Cook Medical Technologies Llc | Enhanced remodelable materials for occluding bodily vessels |
US20090082816A1 (en) | 2007-09-20 | 2009-03-26 | Graham Matthew R | Remodelable orthopaedic spacer and method of using the same |
US10500309B2 (en) * | 2007-10-05 | 2019-12-10 | Cook Biotech Incorporated | Absorbable adhesives and their formulation for use in medical applications |
US20090112238A1 (en) * | 2007-10-26 | 2009-04-30 | Vance Products Inc., D/B/A Cook Urological Inc. | Fistula brush device |
JP5214223B2 (ja) * | 2007-11-15 | 2013-06-19 | 船井電機株式会社 | プロジェクタ |
US7846199B2 (en) | 2007-11-19 | 2010-12-07 | Cook Incorporated | Remodelable prosthetic valve |
US8057532B2 (en) * | 2007-11-28 | 2011-11-15 | Cook Medical Technologies Llc | Implantable frame and valve design |
US9308068B2 (en) | 2007-12-03 | 2016-04-12 | Sofradim Production | Implant for parastomal hernia |
US8257434B2 (en) | 2007-12-18 | 2012-09-04 | Cormatrix Cardiovascular, Inc. | Prosthetic tissue valve |
US8679176B2 (en) | 2007-12-18 | 2014-03-25 | Cormatrix Cardiovascular, Inc | Prosthetic tissue valve |
US8357387B2 (en) | 2007-12-21 | 2013-01-22 | Edwards Lifesciences Corporation | Capping bioprosthetic tissue to reduce calcification |
US8211165B1 (en) | 2008-01-08 | 2012-07-03 | Cook Medical Technologies Llc | Implantable device for placement in a vessel having a variable size |
KR100947553B1 (ko) * | 2008-02-14 | 2010-03-12 | 주식회사 바이오랜드 | 생체조직 이식재 및 그의 제조 방법 |
US20130165967A1 (en) | 2008-03-07 | 2013-06-27 | W.L. Gore & Associates, Inc. | Heart occlusion devices |
CN101970024B (zh) | 2008-03-14 | 2014-11-05 | 库克生物科技公司 | 移植材料和生物活性组分的分阶段传递的方法 |
US20100008965A1 (en) * | 2008-04-01 | 2010-01-14 | Pavalko Fredrick M | Biocompatible medical products having enhanced anti-thrombogenic properties |
EP2293745A1 (en) * | 2008-04-18 | 2011-03-16 | Cook Incorporated | Branched vessel prosthesis |
US8709096B2 (en) | 2008-04-29 | 2014-04-29 | Proxy Biomedical Limited | Tissue repair implant |
WO2009134949A1 (en) * | 2008-05-02 | 2009-11-05 | Cook Biotech Incorporated | Self deploying sis in needle |
WO2009146369A1 (en) | 2008-05-29 | 2009-12-03 | Cook Biotech Incorporated | Devices and methods for treating rectovaginal and other fistulae |
US9242026B2 (en) | 2008-06-27 | 2016-01-26 | Sofradim Production | Biosynthetic implant for soft tissue repair |
AU2009281937B2 (en) * | 2008-08-14 | 2015-05-07 | 3M Innovative Properties Company | Tissue scaffolds |
CA2746114C (en) | 2008-12-23 | 2016-03-22 | Cryomedix Llc | Isotherm-based tissue ablation control system and method |
WO2010078478A1 (en) | 2008-12-31 | 2010-07-08 | Cook Biotech Incorporated | Tissue adjuvants and medical products including the same |
US8469779B1 (en) | 2009-01-02 | 2013-06-25 | Lifecell Corporation | Method for debristling animal skin |
WO2010088678A2 (en) | 2009-02-02 | 2010-08-05 | Cook Biotech Incorporated | Medical bead products |
US8628572B2 (en) | 2009-02-26 | 2014-01-14 | Wake Forest University Health Sciences | Corneal endothelial scaffolds and methods of use |
US8906362B2 (en) | 2009-03-23 | 2014-12-09 | Wake Forest University Health Sciences | Tissue engineered meniscus scaffolds and methods of use |
EP2236544A1 (en) | 2009-03-24 | 2010-10-06 | Friedrich-Alexander-Universität Erlangen-Nürnberg | Collagen Implant |
AU2010234663A1 (en) * | 2009-04-06 | 2011-10-13 | Cryomedix Llc | Single phase liquid refrigerant cryoablation system with multitubular distal section and related method |
US8888768B2 (en) * | 2009-04-30 | 2014-11-18 | Cryomedix, Llc | Cryoablation system having docking station for charging cryogen containers and related method |
US9636094B2 (en) | 2009-06-22 | 2017-05-02 | W. L. Gore & Associates, Inc. | Sealing device and delivery system |
US20120029556A1 (en) | 2009-06-22 | 2012-02-02 | Masters Steven J | Sealing device and delivery system |
US7964704B2 (en) * | 2009-07-27 | 2011-06-21 | Life Fusion, Llc | Preparation of high purity collagen |
US8198408B2 (en) * | 2009-07-27 | 2012-06-12 | National Cheng Kung University | Method for preparing porous collagen matrices |
FR2949688B1 (fr) | 2009-09-04 | 2012-08-24 | Sofradim Production | Tissu avec picots revetu d'une couche microporeuse bioresorbable |
WO2011038023A1 (en) * | 2009-09-22 | 2011-03-31 | Colorado State University Research Foundation | Methods for processing biological tissues |
NZ602066A (en) | 2010-03-23 | 2013-09-27 | Edwards Lifesciences Corp | Methods of conditioning sheet bioprosthetic tissue |
US8460691B2 (en) | 2010-04-23 | 2013-06-11 | Warsaw Orthopedic, Inc. | Fenestrated wound repair scaffold |
US8790699B2 (en) | 2010-04-23 | 2014-07-29 | Warsaw Orthpedic, Inc. | Foam-formed collagen strand |
US8906601B2 (en) | 2010-06-17 | 2014-12-09 | Edwardss Lifesciences Corporation | Methods for stabilizing a bioprosthetic tissue by chemical modification of antigenic carbohydrates |
WO2012018680A1 (en) | 2010-07-31 | 2012-02-09 | Global Therapeutics Llc | Methods and systems for generating a tissue pocket in a patient |
US9101455B2 (en) | 2010-08-13 | 2015-08-11 | Cook Medical Technologies Llc | Preloaded wire for endoluminal device |
CA2747610C (en) | 2010-08-13 | 2014-09-16 | Cook Medical Technologies Llc | Precannulated fenestration |
WO2012027641A2 (en) | 2010-08-26 | 2012-03-01 | Cryomedix, Llc | Cryoablation balloon catheter and related method |
US8435305B2 (en) | 2010-08-31 | 2013-05-07 | Zimmer, Inc. | Osteochondral graft delivery device and uses thereof |
EP2621549B1 (en) | 2010-09-28 | 2015-10-21 | Cook Biotech Incorporated | Device for treating fistulae and other bodily openings and passageways |
DE112011102907T5 (de) | 2010-10-01 | 2013-06-20 | Cook Biotech Incorporated | Kits, Komponeten und Verfahren zur Geweberekonstrution |
EP2627265B8 (en) | 2010-10-15 | 2019-02-20 | Cook Medical Technologies LLC | Occlusion device for blocking fluid flow through bodily passages |
AU2011319789A1 (en) | 2010-10-27 | 2013-05-02 | Cryomedix, Llc | Cryoablation apparatus with enhanced heat exchange area and related method |
US9351829B2 (en) | 2010-11-17 | 2016-05-31 | Edwards Lifesciences Corporation | Double cross-linkage process to enhance post-implantation bioprosthetic tissue durability |
DE102011008604A1 (de) | 2011-01-14 | 2012-07-19 | Tutogen Medical Gmbh | Herstellung eines Transplantats aus tierischer Dermis mit Natriumsulfidlösung |
FR2972626B1 (fr) | 2011-03-16 | 2014-04-11 | Sofradim Production | Prothese comprenant un tricot tridimensionnel et ajoure |
KR101269618B1 (ko) * | 2011-04-12 | 2013-06-05 | 한스바이오메드 주식회사 | 포유류의 연골조직에서 유래한 생체이식재 |
AU2012262549B2 (en) * | 2011-05-27 | 2016-02-11 | Cormatrix Cardiovascular, Inc. | Extracellular matrix material valve conduit and methods of making thereof |
US9427233B2 (en) | 2011-06-06 | 2016-08-30 | Cook Medical Technologies, LLC | Vascular occlusion devices and methods |
US8915941B2 (en) | 2011-06-14 | 2014-12-23 | Cook Medical Technologies Llc | Fistula closure devices and methods |
FR2977789B1 (fr) | 2011-07-13 | 2013-07-19 | Sofradim Production | Prothese pour hernie ombilicale |
FR2977790B1 (fr) | 2011-07-13 | 2013-07-19 | Sofradim Production | Prothese pour hernie ombilicale |
EP2731561B1 (en) | 2011-07-14 | 2016-03-23 | Cook Medical Technologies LLC | A sling to be used in the treatment of obstructive sleep apnea |
US9089523B2 (en) | 2011-07-28 | 2015-07-28 | Lifecell Corporation | Natural tissue scaffolds as tissue fillers |
US9770232B2 (en) | 2011-08-12 | 2017-09-26 | W. L. Gore & Associates, Inc. | Heart occlusion devices |
WO2013033341A1 (en) | 2011-09-01 | 2013-03-07 | Cook Medical Technologies Llc | Aneurysm closure clip |
AU2012313983B2 (en) | 2011-09-30 | 2017-01-19 | Sofradim Production | Multilayer implants for delivery of therapeutic agents |
WO2013046058A2 (en) | 2011-09-30 | 2013-04-04 | Sofradim Production | Reversible stiffening of light weight mesh |
WO2013067195A1 (en) | 2011-11-02 | 2013-05-10 | Halscion, Inc. | Methods and compositions for wound treatment |
US8728148B2 (en) | 2011-11-09 | 2014-05-20 | Cook Medical Technologies Llc | Diameter reducing tie arrangement for endoluminal prosthesis |
US20130138219A1 (en) * | 2011-11-28 | 2013-05-30 | Cook Medical Technologies Llc | Biodegradable stents having one or more coverings |
US9162011B2 (en) | 2011-12-19 | 2015-10-20 | Allosource | Flowable matrix compositions and methods |
BR112014014975B1 (pt) | 2011-12-20 | 2019-06-25 | Lifecell Corporation | Produto de tecido, e método para produzir uma composição de tecido |
ES2729712T3 (es) | 2011-12-20 | 2019-11-05 | Lifecell Corp | Productos de tejido de lámina |
EP2606851B1 (en) | 2011-12-22 | 2015-11-04 | Cook Medical Technologies LLC | Preloaded wire for endoluminal device |
FR2985271B1 (fr) | 2011-12-29 | 2014-01-24 | Sofradim Production | Tricot a picots |
FR2985170B1 (fr) | 2011-12-29 | 2014-01-24 | Sofradim Production | Prothese pour hernie inguinale |
PT2798057T (pt) * | 2011-12-30 | 2018-11-29 | Vivex Biologics Inc | Matriz de tecido regenerativa |
ES2705823T3 (es) | 2012-01-24 | 2019-03-26 | Lifecell Corp | Matrices de tejidos alargadas |
WO2013116744A1 (en) * | 2012-02-01 | 2013-08-08 | Children's Medical Center Corporation | Biomaterial for articular cartilage maintenance and treatment of arthritis |
US10940167B2 (en) | 2012-02-10 | 2021-03-09 | Cvdevices, Llc | Methods and uses of biological tissues for various stent and other medical applications |
US9504458B2 (en) | 2012-02-17 | 2016-11-29 | Cook Biotech Incorporated | Methods and systems for treating complex fistulae |
US10071184B2 (en) | 2012-02-29 | 2018-09-11 | Collagen Matrix, Inc. | Collagen-coated tissue-based membranes |
ES2716993T3 (es) | 2012-03-08 | 2019-06-18 | Lifecell Corp | Matrices de colágeno y tejido activadas por enzimas |
RU2665366C2 (ru) | 2012-05-11 | 2018-08-29 | АрТиАй СЕРДЖИКАЛ, ИНК. | Ксеногенные имплантаты мягких тканей и способы изготовления и использования |
CN104684593B (zh) * | 2012-06-12 | 2016-07-06 | 昊图细胞有限公司 | 用于生产胶原蛋白膜的方法及其应用 |
US11090338B2 (en) | 2012-07-13 | 2021-08-17 | Lifecell Corporation | Methods for improved treatment of adipose tissue |
FR2994185B1 (fr) | 2012-08-02 | 2015-07-31 | Sofradim Production | Procede de preparation d’une couche poreuse a base de chitosane |
US9308107B2 (en) | 2012-08-27 | 2016-04-12 | Cook Medical Technologies Llc | Endoluminal prosthesis and delivery device |
FR2995778B1 (fr) | 2012-09-25 | 2015-06-26 | Sofradim Production | Prothese de renfort de la paroi abdominale et procede de fabrication |
FR2995788B1 (fr) | 2012-09-25 | 2014-09-26 | Sofradim Production | Patch hemostatique et procede de preparation |
FR2995779B1 (fr) | 2012-09-25 | 2015-09-25 | Sofradim Production | Prothese comprenant un treillis et un moyen de consolidation |
CA2885327A1 (en) | 2012-09-26 | 2014-04-03 | Lifecell Corporation | Processed adipose tissue |
AU2013322268B2 (en) | 2012-09-28 | 2017-08-31 | Sofradim Production | Packaging for a hernia repair device |
US20140121750A1 (en) | 2012-10-31 | 2014-05-01 | Cook Medical Technologies Llc | Fixation Process For Nesting Stents |
US10238771B2 (en) | 2012-11-08 | 2019-03-26 | Edwards Lifesciences Corporation | Methods for treating bioprosthetic tissue using a nucleophile/electrophile in a catalytic system |
US9669190B2 (en) * | 2012-11-28 | 2017-06-06 | Cook Medical Technologies Llc | Selectively positionable catheter cuff |
EP2745813A1 (en) | 2012-12-18 | 2014-06-25 | Cook Medical Technologies LLC | Preloaded wire for endoluminal device |
US9861466B2 (en) | 2012-12-31 | 2018-01-09 | Cook Medical Technologies Llc | Endoluminal prosthesis |
US10828019B2 (en) | 2013-01-18 | 2020-11-10 | W.L. Gore & Associates, Inc. | Sealing device and delivery system |
EP3798226A1 (en) * | 2013-02-01 | 2021-03-31 | Children's Medical Center Corporation | Collagen scaffolds |
EP3659633A1 (en) | 2013-02-06 | 2020-06-03 | LifeCell Corporation | Methods for localized modification of tissue products |
AU2014214700B2 (en) | 2013-02-11 | 2018-01-18 | Cook Medical Technologies Llc | Expandable support frame and medical device |
US9993330B2 (en) | 2013-03-13 | 2018-06-12 | Cook Medical Technologies Llc | Endoluminal prosthesis system |
AU2014227561C1 (en) | 2013-03-15 | 2017-12-14 | Cook Biotech Incorporated | ECM implant compositions and methods |
CA2899713C (en) | 2013-03-15 | 2022-07-19 | Allosource | Cell repopulated collagen matrix for soft tissue repair and regeneration |
CN105102009B (zh) | 2013-03-15 | 2018-06-26 | 库克医药技术有限责任公司 | 药物洗脱支架构造物和方法 |
FR3006578B1 (fr) | 2013-06-07 | 2015-05-29 | Sofradim Production | Prothese a base d’un textile pour voie laparoscopique |
FR3006581B1 (fr) | 2013-06-07 | 2016-07-22 | Sofradim Production | Prothese a base d’un textile pour voie laparoscopique |
EP3027235A1 (en) | 2013-07-30 | 2016-06-08 | Musculoskeletal Transplant Foundation | Acellular soft tissue-derived matrices and methods for preparing same |
EP3498239B1 (en) | 2013-08-01 | 2021-04-21 | Cook Medical Technologies LLC | Tissue adjustment implant |
CN103432627B (zh) * | 2013-08-26 | 2015-03-25 | 北京瑞健高科生物科技有限公司 | 一种制备动物脱细胞组织基质材料的方法及其制备的组织基质材料 |
US20150080940A1 (en) | 2013-09-13 | 2015-03-19 | Cook Medical Technologies Llc | Anti-tumor macrophage m1 morphology inducer |
US9615922B2 (en) | 2013-09-30 | 2017-04-11 | Edwards Lifesciences Corporation | Method and apparatus for preparing a contoured biological tissue |
US10959839B2 (en) | 2013-10-08 | 2021-03-30 | Edwards Lifesciences Corporation | Method for directing cellular migration patterns on a biological tissue |
CN104758089B (zh) | 2014-01-08 | 2018-03-30 | 库克医学技术有限责任公司 | 用于塞住经皮心脏瓣膜泄漏的ecm条带 |
US9808230B2 (en) | 2014-06-06 | 2017-11-07 | W. L. Gore & Associates, Inc. | Sealing device and delivery system |
US9562834B2 (en) * | 2014-08-21 | 2017-02-07 | John J. Nelson | Aqueous compositions and methods of using the same for histopathological evaluation of tissue samples |
EP3000489B1 (en) | 2014-09-24 | 2017-04-05 | Sofradim Production | Method for preparing an anti-adhesion barrier film |
EP3000433B1 (en) | 2014-09-29 | 2022-09-21 | Sofradim Production | Device for introducing a prosthesis for hernia treatment into an incision and flexible textile based prosthesis |
EP3000432B1 (en) | 2014-09-29 | 2022-05-04 | Sofradim Production | Textile-based prosthesis for treatment of inguinal hernia |
EP3029189B1 (en) | 2014-12-05 | 2021-08-11 | Sofradim Production | Prosthetic porous knit, method of making same and hernia prosthesis |
US10183152B2 (en) | 2014-12-12 | 2019-01-22 | Cook Medical Technologies Llc | Cinching peritoneal dialysis catheter |
US9238090B1 (en) | 2014-12-24 | 2016-01-19 | Fettech, Llc | Tissue-based compositions |
EP3059255B1 (en) | 2015-02-17 | 2020-05-13 | Sofradim Production | Method for preparing a chitosan-based matrix comprising a fiber reinforcement member |
EP3085337B1 (en) | 2015-04-24 | 2022-09-14 | Sofradim Production | Prosthesis for supporting a breast structure |
ES2676072T3 (es) | 2015-06-19 | 2018-07-16 | Sofradim Production | Prótesis sintética que comprende un tejido de punto y una película no porosa y método para formarla |
US10912864B2 (en) | 2015-07-24 | 2021-02-09 | Musculoskeletal Transplant Foundation | Acellular soft tissue-derived matrices and methods for preparing same |
US11052175B2 (en) | 2015-08-19 | 2021-07-06 | Musculoskeletal Transplant Foundation | Cartilage-derived implants and methods of making and using same |
US10173027B2 (en) | 2015-10-07 | 2019-01-08 | Cook Medical Technologies Llc | Methods, medical devices and kits for modifying the luminal profile of a body vessel |
CN108601862B (zh) * | 2015-12-02 | 2022-02-11 | 库克生物技术股份有限公司 | 丝状移植物植入物及它们的制造方法和用途 |
WO2017100625A2 (en) | 2015-12-10 | 2017-06-15 | Cook Biotech Incorporated | Poly(ester urea) fiber devices and related methods |
AU2016366404A1 (en) | 2015-12-11 | 2018-06-14 | Lifecell Corporation | Methods and systems for stiffening of tissue for improved processing |
EP3195830B1 (en) | 2016-01-25 | 2020-11-18 | Sofradim Production | Prosthesis for hernia repair |
WO2017210109A1 (en) | 2016-06-03 | 2017-12-07 | Lifecell Corporation | Methods for localized modification of tissue products |
US20170354500A1 (en) | 2016-06-08 | 2017-12-14 | Cook Medical Technologies Llc | Mitral prolapse valve restrictor |
AU2017292652B2 (en) | 2016-07-05 | 2022-03-24 | Lifecell Corporation | Tissue matrices incorporating multiple tissue types |
WO2018017611A1 (en) | 2016-07-18 | 2018-01-25 | Cook Biotech Incorporated | Implantable pouch with segmental lamination structure, and related methods of manufacture and use |
US20180071526A1 (en) | 2016-09-10 | 2018-03-15 | Cook Biotech Incorporated | Electrostimulative graft products, and related methods of use and manufacture |
EP3312325B1 (en) | 2016-10-21 | 2021-09-22 | Sofradim Production | Method for forming a mesh having a barbed suture attached thereto and the mesh thus obtained |
US11191632B2 (en) | 2016-11-10 | 2021-12-07 | Cook Medical Technologies Llc | Temporary diameter reduction constraint arrangement for a stent graft in combination with a stent graft |
EP3320881B1 (en) | 2016-11-10 | 2019-09-04 | Cook Medical Technologies LLC | Diameter reduction constraint arrangement for a stent graft in combination with a stent graft |
JP2020501660A (ja) | 2016-12-22 | 2020-01-23 | ライフセル コーポレーションLifeCell Corporation | 組織を凍結切削する装置および方法 |
EP3398554A1 (en) | 2017-05-02 | 2018-11-07 | Sofradim Production | Prosthesis for inguinal hernia repair |
US11357660B2 (en) | 2017-06-29 | 2022-06-14 | Cook Medical Technologies, LLC | Implantable medical devices for tissue repositioning |
JP7297739B2 (ja) | 2017-10-18 | 2023-06-26 | ライフセル コーポレーション | 脂肪組織製品および製造方法 |
US11123375B2 (en) | 2017-10-18 | 2021-09-21 | Lifecell Corporation | Methods of treating tissue voids following removal of implantable infusion ports using adipose tissue products |
US11246994B2 (en) | 2017-10-19 | 2022-02-15 | Lifecell Corporation | Methods for introduction of flowable acellular tissue matrix products into a hand |
WO2019079672A1 (en) | 2017-10-19 | 2019-04-25 | Lifecell Corporation | ACELLULAR TISSUE MATRIX PRODUCTS FLUIDS AND METHODS OF PRODUCTION |
AU2018214103B1 (en) | 2018-08-09 | 2018-10-04 | Cook Medical Technologies Llc | A stent-graft |
WO2020092205A1 (en) | 2018-11-01 | 2020-05-07 | Edwards Lifesciences Corporation | Transcatheter pulmonic regenerative valve |
EP3653171A1 (en) | 2018-11-16 | 2020-05-20 | Sofradim Production | Implants suitable for soft tissue repair |
CA3142151A1 (en) | 2019-05-30 | 2020-12-03 | Lifecell Corporation | Biologic breast implant |
WO2022027011A1 (en) | 2020-07-27 | 2022-02-03 | Cook Biotech Incorporated | System and methods for supplying surgical staple line reinforcement |
US20220023489A1 (en) | 2020-07-27 | 2022-01-27 | Cook Biotech Incorporated | Adhesive for surgical staple line reinforcement |
EP4225387A1 (en) | 2020-12-10 | 2023-08-16 | Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. | Decellularized tissue/polymer multi-component biomaterials |
KR102559788B1 (ko) * | 2022-04-21 | 2023-07-27 | 주식회사 티앤알바이오팹 | 다단계 탈세포화된 조직 매트릭스 및 이의 제조방법 |
WO2023215885A1 (en) | 2022-05-05 | 2023-11-09 | Cook Biotech Incorporated | Subtissue implant material |
WO2023215883A1 (en) | 2022-05-05 | 2023-11-09 | Cook Biotech Incorporated | Photocrosslinkable synthetic polymers |
WO2023218455A1 (en) | 2022-05-10 | 2023-11-16 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Decellularized tissue/polymer multi-component biomaterials |
Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2127903A (en) | 1936-05-05 | 1938-08-23 | Davis & Geck Inc | Tube for surgical purposes and method of preparing and using the same |
FR1358465A (fr) * | 1963-02-21 | 1964-04-17 | Procédé de traitement de tissus animaux, en particulier en vue de la séparation de polysaccharides | |
US3551560A (en) * | 1967-10-02 | 1970-12-29 | Heinrich F Thiele | Process of reconstructing tendons,cartilage,nerve sheaths,and products |
US4097234A (en) * | 1976-12-10 | 1978-06-27 | Nippi, Incorporated | Method for preparing dispersion of collagen fiber |
US4601896A (en) * | 1984-03-21 | 1986-07-22 | Mark Nugent | Pharmaceutical capsule compositions and structures for gastric sensitive materials |
GB8413319D0 (en) | 1984-05-24 | 1984-06-27 | Oliver Roy Frederick | Biological material |
US5007934A (en) * | 1987-07-20 | 1991-04-16 | Regen Corporation | Prosthetic meniscus |
US5263984A (en) * | 1987-07-20 | 1993-11-23 | Regen Biologics, Inc. | Prosthetic ligaments |
DE3850956D1 (de) * | 1988-03-11 | 1994-09-08 | Chemokol G B R Ing Buero Fuer | Verfahren zur Herstellung von Kollagenmembranen für Hämostase, Wundbehandlung und Implantate. |
US5336616A (en) * | 1990-09-12 | 1994-08-09 | Lifecell Corporation | Method for processing and preserving collagen-based tissues for transplantation |
US5523291A (en) * | 1993-09-07 | 1996-06-04 | Datascope Investment Corp. | Injectable compositions for soft tissue augmentation |
US5460962A (en) * | 1994-01-04 | 1995-10-24 | Organogenesis Inc. | Peracetic acid sterilization of collagen or collagenous tissue |
US5571216A (en) | 1994-01-19 | 1996-11-05 | The General Hospital Corporation | Methods and apparatus for joining collagen-containing materials |
WO1995022301A1 (en) | 1994-02-18 | 1995-08-24 | Organogenesis, Inc. | Bioremodelable collagen graft prosthesis |
EP0732215B1 (en) | 1994-04-15 | 1999-10-20 | Rohm Co., Ltd. | Thermal print head, driving ic used therefor, and control method of thermal print head |
US5595571A (en) * | 1994-04-18 | 1997-01-21 | Hancock Jaffe Laboratories | Biological material pre-fixation treatment |
US5733337A (en) | 1995-04-07 | 1998-03-31 | Organogenesis, Inc. | Tissue repair fabric |
ES2208974T3 (es) | 1996-08-23 | 2004-06-16 | Cook Biotech, Inc. | Protesis de injertos, materiales y metodos. |
US5993844A (en) | 1997-05-08 | 1999-11-30 | Organogenesis, Inc. | Chemical treatment, without detergents or enzymes, of tissue to form an acellular, collagenous matrix |
-
1997
- 1997-05-08 US US08/853,372 patent/US5993844A/en not_active Expired - Lifetime
-
1998
- 1998-05-08 CN CN98804844A patent/CN1267201A/zh active Pending
- 1998-05-08 JP JP54853698A patent/JP4558107B2/ja not_active Expired - Fee Related
- 1998-05-08 AT AT98920349T patent/ATE281128T1/de not_active IP Right Cessation
- 1998-05-08 EP EP04076470A patent/EP1452150B1/en not_active Expired - Lifetime
- 1998-05-08 BR BRPI9809216-2A patent/BR9809216B1/pt not_active IP Right Cessation
- 1998-05-08 PT PT98920349T patent/PT1018979E/pt unknown
- 1998-05-08 IL IL13251798A patent/IL132517A0/xx unknown
- 1998-05-08 AU AU72947/98A patent/AU736312B2/en not_active Ceased
- 1998-05-08 ES ES98920349T patent/ES2231984T3/es not_active Expired - Lifetime
- 1998-05-08 CA CA002288823A patent/CA2288823C/en not_active Expired - Fee Related
- 1998-05-08 DE DE69827402T patent/DE69827402T2/de not_active Expired - Lifetime
- 1998-05-08 ES ES04076470T patent/ES2404033T3/es not_active Expired - Lifetime
- 1998-05-08 EP EP98920349A patent/EP1018979B1/en not_active Expired - Lifetime
- 1998-05-08 KR KR1019997010239A patent/KR100587868B1/ko not_active IP Right Cessation
- 1998-05-08 WO PCT/US1998/009432 patent/WO1998049969A1/en active IP Right Grant
- 1998-05-08 DK DK98920349T patent/DK1018979T3/da active
-
1999
- 1999-11-03 NO NO995372A patent/NO995372D0/no not_active Application Discontinuation
- 1999-11-30 US US09/450,577 patent/US6599690B1/en not_active Expired - Fee Related
-
2003
- 2003-07-08 US US10/615,623 patent/US6893653B2/en not_active Expired - Fee Related
-
2005
- 2005-05-16 US US11/130,018 patent/US20060024380A1/en not_active Abandoned
Cited By (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7674289B2 (en) | 2005-07-29 | 2010-03-09 | Grandhope Biotech Co., Ltd. | Biological artificial ligament and method of making |
US7824447B2 (en) | 2005-07-29 | 2010-11-02 | Grandhope Biotech Co. Ltd. | Biological artificial ligament and method of making |
US8292799B2 (en) | 2005-07-29 | 2012-10-23 | Grandhope Biotech Co., Ltd. | Biological artificial blood vessel and method of making |
US8197500B2 (en) | 2005-08-04 | 2012-06-12 | Grandhope Biotech Co., Ltd. | Biological membrane-carrying aneurysm clip |
US8100970B2 (en) | 2005-12-20 | 2012-01-24 | Grandhope Biotech Co., Ltd. | Biological surgical patch and method of making |
WO2007071168A1 (en) * | 2005-12-20 | 2007-06-28 | Summit (Gd) Biotech Co., Ltd | Biological wound dressing and method of making |
US8366770B2 (en) | 2005-12-20 | 2013-02-05 | Grandhope Biotech Co. Ltd. | Biological artificial nerve guide and method of making |
CN106390200A (zh) * | 2006-10-23 | 2017-02-15 | 库克生物科技公司 | 组分特性增强的处理的ecm材料 |
CN104491928A (zh) * | 2008-06-20 | 2015-04-08 | 库克生物科技公司 | 可压缩/可扩张医疗移植产品以及应用止血的方法 |
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CN113332494A (zh) * | 2020-05-26 | 2021-09-03 | 山东隽秀生物科技股份有限公司 | 一种高强度细胞外基质海绵及其制备方法和应用 |
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EP1018979A1 (en) | 2000-07-19 |
JP4558107B2 (ja) | 2010-10-06 |
EP1452150B1 (en) | 2013-01-09 |
JP2002510995A (ja) | 2002-04-09 |
US20060024380A1 (en) | 2006-02-02 |
CA2288823A1 (en) | 1998-11-12 |
KR20010012287A (ko) | 2001-02-15 |
BR9809216A (pt) | 2000-06-27 |
US6599690B1 (en) | 2003-07-29 |
ATE281128T1 (de) | 2004-11-15 |
CA2288823C (en) | 2007-07-31 |
US20040005703A1 (en) | 2004-01-08 |
US6893653B2 (en) | 2005-05-17 |
BR9809216B1 (pt) | 2010-03-09 |
WO1998049969A1 (en) | 1998-11-12 |
AU736312B2 (en) | 2001-07-26 |
NO995372L (no) | 1999-11-03 |
PT1018979E (pt) | 2005-02-28 |
DK1018979T3 (da) | 2005-02-14 |
EP1452150A1 (en) | 2004-09-01 |
DE69827402D1 (de) | 2004-12-09 |
NO995372D0 (no) | 1999-11-03 |
KR100587868B1 (ko) | 2006-06-13 |
AU7294798A (en) | 1998-11-27 |
DE69827402T2 (de) | 2005-11-03 |
US5993844A (en) | 1999-11-30 |
ES2404033T3 (es) | 2013-05-23 |
EP1018979A4 (en) | 2000-08-09 |
ES2231984T3 (es) | 2005-05-16 |
EP1018979B1 (en) | 2004-11-03 |
IL132517A0 (en) | 2001-03-19 |
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