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1. 发明申请

US20050222688A1 Transmural concentric multilayer ingrowth matrix within well-defined porosity 审中-公开
标题翻译：透明同心多层向内生长矩阵在明确孔隙度内
公开(公告)号：US20050222688A1
公开(公告)日：2005-10-06
申请号：US10627114
申请日：2003-07-25
申请人： Peter Zilla , Deon Bezuidenhout , Theresa Dower
发明人： Peter Zilla , Deon Bezuidenhout , Theresa Dower
IPC分类号： A61F2/02 , A61F2/06 , A61L27/22 , A61L27/48 , A61L27/56
CPC分类号： A61L27/225 , A61F2/06 , A61L27/48 , A61L27/56 , C08L89/00
摘要： A multilayer ingrowth matrix is constructed within well-defined porosity of a prosthetic material. The matrix consists of either proteinaceous or synthetic layers or gradients, or a combination of proteinaceous and synthetic layers or gradients. Each layer within the matrix is designed to achieve a specific function, such as facilitation of ingrowth of a particular cell type or release of a particular growth factor. The well-defined porosity is in the form of either helically oriented, interconnected transmural ingrowth channels, or a porous wall structure containing uniformly shaped pores (i.e. voids) in a very narrow size range, or a combination of channels and pores. This invention allows for uninterrupted ingrowth of connective tissue into walls of a synthetic graft prosthesis made from the prosthetic material. Furthermore, this invention can produce small diameter prostheses having an internal diameter of 6 mm or less.
摘要翻译：多层向内生长基质被构造在假体材料的明确孔隙度内。基质由蛋白质或合成层或梯度组成，或蛋白质和合成层或梯度的组合。设计基质内的每个层以实现特定功能，例如促进特定细胞类型的向内生长或特定生长因子的释放。明确定义的孔隙度是螺旋取向的，互连的透壁向内生长通道或包含非常窄尺寸范围内的均匀形状的孔（即空隙）或通道和孔的组合的多孔壁结构的形式。本发明允许结缔组织向假体材料制成的合成移植假体的壁中不间断地向内延伸。此外，本发明可以制造内径为6mm以下的小直径假体。

2. 发明授权

US07955788B2 Bioprosthetic tissue preparation with synthetic hydrogels 有权
标题翻译：用合成水凝胶制备生物假体组织
公开(公告)号：US07955788B2
公开(公告)日：2011-06-07
申请号：US10967365
申请日：2004-10-18
申请人： Peter Zilla , Deon Bezuidenhout , Anel Oostheysen , Paul Human
发明人： Peter Zilla , Deon Bezuidenhout , Anel Oostheysen , Paul Human
IPC分类号： A01N1/00
CPC分类号： A61L27/52 , A61L27/3687 , A61L27/507
摘要： Methods for treating xenogenic tissue for implantation into a human body including in-situ polymerization of a hydrogel polymer in tissue, and tissue treated according to those methods, where the polymerization takes place in tissue that has not been fixed with glutaraldehyde. The polymerization may only fill the tissue, bind the polymer to the tissue, or cross-link the tissue through the polymer, depending on the embodiment. One method includes free radical polymerization of a first vinylic compound, and can include cross-linking through use of a second compound having at least two vinyl groups. Another method utilizes nucleophilic addition polymerization of two compounds, one of which can include PEG and can further include hydrolytically degradable regions. In one embodiment, applicants believe the in-situ polymerization inhibits calcification, and that the polymerization of tissue un-fixed by glutaraldehyde allows for improved penetration of the polymer. The methods find one use in the treatment of porcine heart valve tissue, intended to extend the useful life of the valves by inhibiting calcification. The incorporation of degradable hydrogel regions may initially fill the tissue and reduce any initial inflammatory response, but allow for later infiltration by cells to remodel the tissue.
摘要翻译：用于治疗异种组织用于植入人体的方法，包括组织中水凝胶聚合物的原位聚合，以及根据那些方法处理的组织，其中聚合发生在未用戊二醛固定的组织中。根据实施例，聚合可以仅填充组织，将聚合物结合到组织，或者通过聚合物交联组织。一种方法包括第一乙烯基化合物的自由基聚合，并且可以包括通过使用具有至少两个乙烯基的第二化合物的交联。另一种方法利用两种化合物的亲核加成聚合，其中一种可以包括PEG，并且还可以包括水解可降解区域。在一个实施方案中，申请人认为原位聚合抑制钙化，并且由戊二醛未固定的组织的聚合允许改善聚合物的渗透性。该方法可用于治疗猪心脏瓣膜组织，旨在通过抑制钙化来延长瓣膜的使用寿命。可降解水凝胶区域的引入可以初始地填充组织并减少任何初始炎症反应，但允许细胞稍后浸润以重塑组织。

3. 发明申请

US20060149358A1 Porous synthetic vascular grafts with oriented ingrowth channels 失效
公开(公告)号：US20060149358A1
公开(公告)日：2006-07-06
申请号：US11357670
申请日：2006-02-17
申请人： Peter Zilla , Deon Bezuidenhout
发明人： Peter Zilla , Deon Bezuidenhout
IPC分类号： A61F2/06
CPC分类号： A61F2/06 , A61F2250/0031 , A61L27/18 , A61L27/507 , B29C47/0004 , B29C47/0014 , B29C47/0023 , B29C47/20 , B29C53/587 , B29C53/665 , B29K2075/00 , B29K2105/045 , B29K2105/06 , B29K2105/101 , B29L2031/7534 , C08L75/04
摘要： A vascular prosthesis is constructed from a structure having interconnected, helically oriented channel-porosity to allow oriented ingrowth of connective tissue into a wall of the prosthesis. The prosthesis can have a small internal diameter of 6 mm or less. Several different methods can be used to produce the prosthesis, including a fiber winding and extraction technique, a melt extrusion technique, and a particle and fiber extraction technique using either a layered method or a continuous method. Furthermore, mechanical properties of the prosthesis are matched with mechanical properties of the host vessel, thereby overcoming problems of compliance mismatch.

4. 发明授权

US07727274B2 Porous synthetic vascular grafts with oriented ingrowth channels 失效
标题翻译：具有定向向内生长通道的多孔合成血管移植物
公开(公告)号：US07727274B2
公开(公告)日：2010-06-01
申请号：US11357670
申请日：2006-02-17
申请人： Peter Zilla , Deon Bezuidenhout
发明人： Peter Zilla , Deon Bezuidenhout
IPC分类号： A61F2/06 , A61M29/00
CPC分类号： A61F2/06 , A61F2250/0031 , A61L27/18 , A61L27/507 , B29C47/0004 , B29C47/0014 , B29C47/0023 , B29C47/20 , B29C53/587 , B29C53/665 , B29K2075/00 , B29K2105/045 , B29K2105/06 , B29K2105/101 , B29L2031/7534 , C08L75/04
摘要： A vascular prosthesis is constructed from a structure having interconnected, helically oriented channel-porosity to allow oriented ingrowth of connective tissue into a wall of the prosthesis. The prosthesis can have a small internal diameter of 6 mm or less. Several different methods can be used to produce the prosthesis, including a fiber winding and extraction technique, a melt extrusion technique, and a particle and fiber extraction technique using either a layered method or a continuous method. Furthermore, mechanical properties of the prosthesis are matched with mechanical properties of the host vessel, thereby overcoming problems of compliance mismatch.
摘要翻译：血管假体由具有相互连接的螺旋形取向的通道孔隙的结构构成，以允许结缔组织的定向向内生长进入假体的壁。假体可以具有6mm或更小的小内径。可以使用几种不同的方法来生产假体，包括纤维缠绕和提取技术，熔体挤出技术以及使用分层方法或连续方法的颗粒和纤维提取技术。此外，假体的机械性能与主体容器的机械性能相匹配，从而克服顺应性失配的问题。

5. 发明申请

US20050070995A1 Compliant venous graft 有权
标题翻译：合并静脉移植
公开(公告)号：US20050070995A1
公开(公告)日：2005-03-31
申请号：US10834360
申请日：2004-04-28
申请人： Peter Zilla , Nasser Rafiee , Deon Bezuidenhout , Thomas Franz , Mark Yeoman , Hellmut Bowles , Nareak Douk , Michael Wolf
发明人： Peter Zilla , Nasser Rafiee , Deon Bezuidenhout , Thomas Franz , Mark Yeoman , Hellmut Bowles , Nareak Douk , Michael Wolf
IPC分类号： A61F2/06 , A61F2/24 , A61F2/90 , A61L27/14 , A61L27/36
CPC分类号： A61F2/06 , A61F2/90 , A61L27/14 , A61L27/3625
摘要： A venous graft for replacement of a section of an artery and methods of making the graft. The graft comprises a flexible, resilient, generally tubular external support and a vein segment carried within and having an ablumenal surface in contact with and supported by the tubular support, the venous graft being capable of resilient radial expansion in a manner mimicking the radial compliance properties of an artery.
摘要翻译：用于替换动脉的一部分的静脉移植物和制造移植物的方法。移植物包括柔性的，弹性的，大体上管状的外部支撑件和承载在管状支撑件内并具有与管状支撑件接触并由其支撑的缩小表面的静脉段，静脉移植物能够以模拟径向顺应性的方式弹性径向膨胀的动脉。

6. 发明申请

US20070293932A1 Compliant blood vessel graft 有权
标题翻译：符合血管移植
公开(公告)号：US20070293932A1
公开(公告)日：2007-12-20
申请号：US11797648
申请日：2007-05-04
申请人： Peter Zilla , Nasser Rafiee , Deon Bezuidenhout , Thomas Franz , Mark Yeoman , Hellmut Bowles , Nareak Douk , Michael Wolf , Paul Human
发明人： Peter Zilla , Nasser Rafiee , Deon Bezuidenhout , Thomas Franz , Mark Yeoman , Hellmut Bowles , Nareak Douk , Michael Wolf , Paul Human
IPC分类号： A61F2/06 , A61F2/82
CPC分类号： A61B17/11 , A61B5/1076 , A61B2017/1107 , A61B2017/1132 , A61B2017/1135 , A61B2017/1139 , A61F2/06 , A61F2/07 , A61F2/82 , A61F2/856 , A61F2/90 , A61F2/95 , A61F2240/002
摘要： Stents and methods of using stents are provided. Stents of the invention provide external support structure for a blood vessel segment disposed within, wherein the stents are capable of resilient radial expansion in a manner mimicking the compliance properties of an artery. The stent may be formed of a knitted or braided mesh formed so as to provide the needed compliance properties. A venous graft with the stent and a vein segment disposed within is provided, wherein graft is capable of mimicking the compliance properties of an artery. Methods of selecting stents for downsizing and methods of using the stents of the invention in downsizing and smoothening are provided. Methods of replacing a section of an artery with a venous graft including a stent of the invention are provided. Methods of reducing intimal hyperplasia in implanted vein segment in a venous graft using stents of the invention are provided.
摘要翻译：提供支架和使用支架的方法。本发明的支架为设置在其内的血管段提供外部支撑结构，其中支架能够以模仿动脉的顺应性的方式弹性径向扩张。支架可以由形成的针织或编织网形成，以便提供所需的顺应性。提供具有支架和设置在其内的静脉段的静脉移植物，其中移植物能够模拟动脉的顺应性。提供了选择小型化支架的方法和使用本发明的支架在缩小和平滑方面的方法。提供了用包括本发明的支架的静脉移植物代替动脉的一部分的方法。提供了使用本发明的支架在静脉移植物中减少植入静脉段内膜增生的方法。

7. 发明申请

US20060223955A1 Modification of thermoplastic polymers 失效
公开(公告)号：US20060223955A1
公开(公告)日：2006-10-05
申请号：US11388317
申请日：2006-03-24
申请人： Deon Bezuidenhout , Jacobus Theron , Lawrence Higham , Peter Zilla
发明人： Deon Bezuidenhout , Jacobus Theron , Lawrence Higham , Peter Zilla
IPC分类号： C08L75/00 , B32B27/40
CPC分类号： C09D175/16 , C08G18/10 , C08G18/282 , C08G18/2825 , C08G18/7657 , C09D175/14 , C08G18/718
摘要： A method of preparing a polymer involving reacting at least one backbone carbamate (and/or optional urea) nitrogen of a thermoplastic polymer with a modification agent to form a modified polymer.

8. 发明申请

US20050131520A1 Compliant blood vessel graft 审中-公开
标题翻译：符合血管移植
公开(公告)号：US20050131520A1
公开(公告)日：2005-06-16
申请号：US10987313
申请日：2004-11-12
申请人： Peter Zilla , Nasser Rafiee , Deon Bezuidenhout , Thomas Franz , Mark Yeoman , Hellmut Bowles , Nareak Douk , Michael Wolf
发明人： Peter Zilla , Nasser Rafiee , Deon Bezuidenhout , Thomas Franz , Mark Yeoman , Hellmut Bowles , Nareak Douk , Michael Wolf
IPC分类号： A61F2/06 , A61F2/90
CPC分类号： A61F2/06 , A61F2/90 , A61L27/14 , A61L27/3625
摘要： A graft for replacement of a section of an artery and methods of making the graft. The graft comprises a flexible, resilient, generally tubular external support and a blood vessel segment, e.g., a vein segment, carried within and having an ablumenal surface in contact with and supported by the tubular support, the graft being capable of resilient radial expansion in a manner mimicking the radial compliance properties of an artery.
摘要翻译：用于替换动脉的一部分的移植物和制造移植物的方法。移植物包括柔性的，弹性的，大体上管状的外部支撑件和血管段，例如静脉段，其承载在并具有与管状支撑件接触并由其支撑的腹膜表面，所述移植物能够弹性径向膨胀模拟动脉的径向顺应性的方式。

9. 发明申请

US20050119736A1 Bioprosthetic tissue preparation with synthetic hydrogels 有权
标题翻译：用合成水凝胶制备生物假体组织
公开(公告)号：US20050119736A1
公开(公告)日：2005-06-02
申请号：US10967365
申请日：2004-10-18
申请人： Peter Zilla , Deon Bezuidenhout , Anel Oostheysen , Paul Human
发明人： Peter Zilla , Deon Bezuidenhout , Anel Oostheysen , Paul Human
IPC分类号： A61F2/24 , A61L27/26 , A61L27/52
CPC分类号： A61L27/52 , A61L27/3687 , A61L27/507
摘要： Methods for treating xenogenic tissue for implantation into a human body including in-situ polymerization of a hydrogel polymer in tissue, and tissue treated according to those methods, where the polymerization takes place in tissue that has not been fixed with glutaraldehyde. The polymerization may only fill the tissue, bind the polymer to the tissue, or cross-link the tissue through the polymer, depending on the embodiment. One method includes free radical polymerization of a first vinylic compound, and can include cross-linking through use of a second compound having at least two vinyl groups. Another method utilizes nucleophilic addition polymerization of two compounds, one of which can include PEG and can further include hydrolytically degradable regions. In one embodiment, applicants believe the in-situ polymerization inhibits calcification, and that the polymerization of tissue un-fixed by glutaraldehyde allows for improved penetration of the polymer. The methods find one use in the treatment of porcine heart valve tissue, intended to extend the useful life of the valves by inhibiting calcification. The incorporation of degradable hydrogel regions may initially fill the tissue and reduce any initial inflammatory response, but allow for later infiltration by cells to remodel the tissue.
摘要翻译：用于治疗异种组织用于植入人体的方法，包括组织中水凝胶聚合物的原位聚合，以及根据那些方法处理的组织，其中聚合发生在未用戊二醛固定的组织中。根据实施例，聚合可以仅填充组织，将聚合物结合到组织，或者通过聚合物交联组织。一种方法包括第一乙烯基化合物的自由基聚合，并且可以包括通过使用具有至少两个乙烯基的第二化合物的交联。另一种方法利用两种化合物的亲核加成聚合，其中一种可以包括PEG，并且还可以包括水解可降解区域。在一个实施方案中，申请人认为原位聚合抑制钙化，并且由戊二醛未固定的组织的聚合允许改善聚合物的渗透性。该方法可用于治疗猪心脏瓣膜组织，旨在通过抑制钙化来延长瓣膜的使用寿命。可降解水凝胶区域的引入可以初始地填充组织并减少任何初始炎症反应，但允许细胞稍后浸润以重塑组织。

10. 发明申请

US20050119762A1 Hydrogel providing cell-specific ingrowth 审中-公开
标题翻译：水凝胶提供细胞特异性向内生长
公开(公告)号：US20050119762A1
公开(公告)日：2005-06-02
申请号：US10980989
申请日：2004-11-03
申请人： Peter Zilla , Neil Davies , Terri Dower , Mona Bracher
发明人： Peter Zilla , Neil Davies , Terri Dower , Mona Bracher
IPC分类号： A61F2/02 , A61L27/34 , A61L27/44 , A61L27/52 , A61L27/54 , A61L27/58 , A61L29/08 , A61L31/10 , A61L31/14 , C12N5/08
CPC分类号： A61L31/148 , A61L27/34 , A61L27/52 , A61L27/54 , A61L27/58 , A61L31/10 , A61L2300/25 , A61L2300/604
摘要： A polymeric biomaterial that facilitates cell-specific ingrowth. The polymeric biomaterial encourages the ingrowth of cell types while reducing the ingrowth of undesirable cell types. This activity encourages proper integration of prosthetic implants or scaffolds utilizing this biomaterial by discouraging encapsulation or the accumulation of inflammatory cells such as macrophages, while encouraging infiltration by desirable cells such as endothelial or smooth muscle cells. Short peptide sequences are included in a polymeric biomaterial that result in complementary activities. Peptide sequences that are specifically cleaved by proteases found within preferred cells are used to cross-link the biomaterial and lead to degradation by those cells. Peptide sequences taken from proteins involved in cell adhesion can also be attached to the biomaterial to encourage adhesion by preferred cells. Combined use of both peptides in the polymeric biomaterial provides both specific adhesion and selective ingrowth.
摘要翻译：促进细胞特异性向内生长的聚合物生物材料。聚合物生物材料鼓励细胞类型的向内生长，同时减少不期望的细胞类型的向内生长。该活动鼓励通过阻止炎症细胞如巨噬细胞的包囊或积累，同时鼓励所需细胞如内皮细胞或平滑肌细胞的渗透，利用该生物材料适当地整合假体植入物或支架。短肽序列被包括在导致互补活性的聚合物生物材料中。使用在优选细胞内发现的蛋白酶特异性切割的肽序列用于交联生物材料并导致这些细胞的降解。从参与细胞粘附的蛋白质获取的肽序列也可附着于生物材料上以促进优选细胞的粘附。在聚合物生物材料中两种肽的组合使用提供特异性粘附和选择性向内生长。

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