CN108472140A - 人造生物组织的修复与强化 - Google Patents

人造生物组织的修复与强化 Download PDF

Info

Publication number
CN108472140A
CN108472140A CN201780004995.0A CN201780004995A CN108472140A CN 108472140 A CN108472140 A CN 108472140A CN 201780004995 A CN201780004995 A CN 201780004995A CN 108472140 A CN108472140 A CN 108472140A
Authority
CN
China
Prior art keywords
valve
artificial
tissue
adhesive
leaflet
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201780004995.0A
Other languages
English (en)
Other versions
CN108472140B (zh
Inventor
T·蒂恩
C·艾伯哈德特
K·加德
B·黄
W·王
E·霍华德
L·麦克林利
K·欧尔尼
T·温特斯
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Medtronic Vascular Inc
Original Assignee
Medtronic Vascular Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Medtronic Vascular Inc filed Critical Medtronic Vascular Inc
Publication of CN108472140A publication Critical patent/CN108472140A/zh
Application granted granted Critical
Publication of CN108472140B publication Critical patent/CN108472140B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/24—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body
    • A61F2/2412—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body with soft flexible valve members, e.g. tissue valves shaped like natural valves
    • A61F2/2415—Manufacturing methods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/24—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body
    • A61F2/2409—Support rings therefor, e.g. for connecting valves to tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/24—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body
    • A61F2/2412—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body with soft flexible valve members, e.g. tissue valves shaped like natural valves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/10—Polypeptides; Proteins
    • A61L24/108—Specific proteins or polypeptides not covered by groups A61L24/102 - A61L24/106
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/26—Mixtures of macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3625—Vascular tissue, e.g. heart valves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
    • C09J189/00—Adhesives based on proteins; Adhesives based on derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
    • C09J4/00—Adhesives based on organic non-macromolecular compounds having at least one polymerisable carbon-to-carbon unsaturated bond ; adhesives, based on monomers of macromolecular compounds of groups C09J183/00 - C09J183/16
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2220/00—Fixations or connections for prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2220/0025—Connections or couplings between prosthetic parts, e.g. between modular parts; Connecting elements
    • A61F2220/005—Connections or couplings between prosthetic parts, e.g. between modular parts; Connecting elements using adhesives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2220/00—Fixations or connections for prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2220/0025—Connections or couplings between prosthetic parts, e.g. between modular parts; Connecting elements
    • A61F2220/0075—Connections or couplings between prosthetic parts, e.g. between modular parts; Connecting elements sutured, ligatured or stitched, retained or tied with a rope, string, thread, wire or cable
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/20—Materials or treatment for tissue regeneration for reconstruction of the heart, e.g. heart valves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/40—Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Cardiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Vascular Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dermatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Surgery (AREA)
  • Organic Chemistry (AREA)
  • Manufacturing & Machinery (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Zoology (AREA)
  • Botany (AREA)
  • Prostheses (AREA)
  • Polymers & Plastics (AREA)
  • Materials For Medical Uses (AREA)

Abstract

一种强化或修复用作人造瓣膜小叶的人造生物组织的方法。该方法包括在植入患者之前对人造生物组织进行测评，鉴定所述人造生物组织中的缺陷，向所述缺陷部位的人造生物组织表面施用粘合剂。

Description

人造生物组织的修复与强化
背景技术
有多种类型和构造的人造心脏瓣膜用于置换患病的原生人心脏瓣膜。任何特定人造心脏瓣膜的实际形状和构造一定程度上取决于被置换的瓣膜(即二尖瓣、三尖瓣、主动脉瓣或肺动脉瓣)。通常，人造心脏瓣膜设计试图复制被置换瓣膜的功能，因此会包括瓣膜小叶样结构，将其与人造生物心脏瓣膜或机械心脏瓣膜假体联用。
生物假体或“组织瓣膜”通常用合适的动物组织或材料制成(例如获取的猪瓣膜小叶、牛或马心包小叶、合成材料小叶等)，这些合适的动物组织或材料能够安装到被称为“支架”的固定金属或塑料框架上。不论是否有支架，人造生物/合成心脏瓣膜通常是管状的(即，小叶“张开”时形成流体(如血液)能够从中流动通过的内部通道)，并具有缝纫或缝合环。
生物材料制成的小叶会有原生缺陷，包括小叶切割边缘上的通孔(fenestration)或穿孔。有缺陷的小叶通常会在瓣膜生产过程中被丢弃，或者，有缺陷的心脏瓣膜会在用于患者前的其他时刻被丢弃。此外，小叶的生物材料被缝线订穿，以将小叶组装到人造心脏瓣膜中。这会在生物材料中形成弱化点。
为了提高人造心脏瓣膜可用小叶的量，需要对小叶中的穿孔、开裂及其他缺陷进行修复。此外，需要对瓣膜选定区域(包括缝合线处)进行强化。
发明内容
本文的一个方面提供了一种强化或修复用作人造瓣膜小叶的人造生物组织的方法。该方法包括在植入患者之前对人造生物组织进行测评，鉴定所述人造生物组织中的缺陷，向所述缺陷部位的人造生物组织表面施用粘合剂。
另一方面提供了制造人造心脏瓣膜的方法。该方法包括固定人造生物组织，将人造生物组织切割成瓣膜小叶，对人造瓣膜小叶进行组装，这包括将所述瓣膜小叶缝合到瓣膜框架上，以及选择性地施用添加剂化合物到瓣膜小叶的缝线孔部位。
另一方面还提供了瓣膜组件，该组件包括瓣膜框架和通过安装元件组装到瓣膜框架的由人造生物组织形成的人造瓣膜小叶，人造瓣膜小叶至少其一具有施用于选定区域的粘合剂，所述区域具有小叶表面缺陷。
附图说明
图1是本文所述组织强化方法一示例的流程图。
图2是本文所述组织强化方法一示例的流程图。
图3是本文所述组织强化方法一示例的流程图。
图4A显示组织缝合部位；
图4B显示具有本文所述局部强化区域的组织缝合部位；和
图5是本文所述具有局部处理区域的人造心脏瓣膜一示例的端视图。
具体实施方式
人造生物瓣膜中所用生物组织可以具有根据需要经强化而不改变组织整体性能(例如柔性等)的选定区域。例如，组织可能具有天然缺陷，例如开口或通孔，这些不影响瓣膜的性能或功用。通孔是一种外观缺陷，原生猪主动脉根组织常因小叶中的天然通孔而被弃之不用。此外，瓣膜组装中的制造过程期间会在组织上形成缝合孔之类缺陷。在瓣膜植入患者之前，尤其在瓣膜制造过程中，对在这些特定缺陷部位进行强化或加强是有利的。另外，可能需要在组织其他选定部位聚焦式改变生物组织以提高强度或硬度。组织强化能够增加被认定为能够用于患者移植的可得组织和由该组织制造的心脏瓣膜。
图1显示制造心脏瓣膜的方法100的流程图，其中包括主动脉根组织强化。制备供心脏瓣膜小叶之用的人造生物组织的过程包括多个步骤。起始步骤102包括接收和初步清除主动脉根组织上的肌肉组织。步骤102应在由生物来源收获组织后尽快进行。对组织最初清理之后，在步骤104中对组织进行剖切并进一步清除粘附的脂肪或松散结缔组织。步骤104的剖切之后，将组织置于步骤106的全组织固定所用溶液中。组织固定引起胶原和与胶原关联的蛋白样化合物的交联，用来保存结缔组织的超结构。固定可以用戊二醛或其他合适的固定剂进行。然后，在步骤108对组织进行为了用于人造瓣膜的定尺寸和缺陷测评。在步骤102-108中任一步骤都可检测通孔或其他缺陷，尤其是步骤108。鉴定发现的通孔或凹穴缺陷以待修复。
根据本文，有通孔或其他缺陷的组织在步骤110定尺寸和测评期间或之后且持续经过瓣膜制造过程被修复。可将粘合剂或者添加剂化合物选择性地施用于发现的通孔或其他缺陷。粘合剂可以是生物来源的(含胶原)或是合成聚合物，为心包组织提供局部加强。例如，粘合剂可以由化学物质(如戊二醛)和蛋白质形成。或者，粘合剂可以是例如氰基丙烯酸酯粘合剂。也可采用生物相容且结合组织的其他粘合剂。不论如何，粘合剂选择性地施用于特定的通孔或其他缺陷区域的组织外表面，为通孔或其他缺陷增加强度或密封性。粘合剂仅施用于组织的特定区域，且能改变特定粘合剂施用区域的物理性能，但不改变柔性等组织整体性能。
实施方式之一中，将少量戊二醛/蛋白质粘合剂预装在双管注射器中，以备通孔部位的施用。粘合剂中的蛋白质和戊二醛分装在各自容器或管中，粘合剂涂布前不混合。在粘合剂涂布时，蛋白质与戊二醛按预定的蛋白质与戊二醛比混合，启动粘合剂固化进程。粘合剂可以有控制地直接施用到组织表面，或者用独立的施用器施用到组织。施用器有时能够更精准地将粘合剂施用在组织表面的所需区域。实施方式之一中，步骤110中，粘合剂用于充填组织内通孔周界形成的容积。某些实施方式中，通孔直径为0.1mm至1.0mm，对通孔进行全直径的覆盖/充填，然后让粘合剂就这样干燥。
步骤112中，组织小叶组装在一起形成人造心脏瓣膜。小叶可以沿缝合环或支持结构组装在一起形成人造心脏瓣膜。小叶采用缝合或其他合适的安装元件来组装。组装后，在步骤114中对瓣膜进行消毒，然后在116中包装，以备递送到手术场所并植入患者。
图2是瓣膜制造方法200的流程图，其中包括心包小叶的修复或强化。心包小叶常常会因为开裂或组织分层被认为不能用于心脏瓣膜而被丢弃。组织开裂通常长3mm至4mm。通常，检查中若发现组织有开裂则认为不可用而丢弃。按照组织修复方法200，原本会因生物分检过程中发现开裂而被丢弃的组织被留待修复并组装到心脏瓣膜中。
方法200包括步骤202即接收和清除心包小叶上粘附的脂肪或松散结缔组织。步骤202应在由生物来源获取心包组织后尽快进行。清理后，将组织置于步骤204全组织固定所用溶液中。固定可以用戊二醛或其他合适的固定剂进行。步骤206中，将心包小叶切成(例如激光切割或冲切)合适的大小和形状以用于人造瓣膜。在步骤202-206中的任一步中都可检测小叶组织的开裂区域，尤其是在步骤206。步骤208中，将粘合剂施用于组织中发现的开裂。将少量粘合剂(例如戊二醛/蛋白质粘合剂或氰基丙烯酸酯粘合剂)施用在开裂处将组织层粘合起来。实施方式之一中，如同前文就图1方法所述，蛋白质和戊二醛分装在各自容器中，粘合剂涂布前不混合。在粘合剂涂布时，蛋白质与戊二醛按预定的蛋白质与戊二醛比混合，启动粘合剂固化进程。或者，粘合剂可以是氰基丙烯酸酯粘合剂，无需涂布过程中的混合。粘合剂固化后，粘合剂施用区域组织内的开裂被密合。步骤210中，组装瓣膜。步骤212中，对组装好的瓣膜进行消毒，然后在步骤214中进行包装。
图3显示制造心脏瓣膜的方法300的流程图，其中包括局部组织强化。例如，所述组织可以是心包组织。在步骤302，收获组织后尽快接收组织并清除粘附的脂肪或松散结缔组织。步骤302后，将组织置于步骤304全组织固定所用溶液中。步骤304的固定可以用戊二醛或其他合适的固定剂进行。在步骤306，将组织切成适当大小和形状的小叶用于组装到所需的人造瓣膜中。实施方式之一中，步骤306采用激光切割。在步骤308，小叶可以沿缝合环或支持结构组装在一起形成人造心脏瓣膜。小叶可采用缝合或其他合适的安装元件来组装。
组装中的缝合会在组织中形成缝合孔，因此对组织造成损伤。缝合孔的大小一般为0.1mm至0.5mm。在步骤310，将粘合剂局部施用于缝合部位或缝合孔，从而强化缝合部位的组织。尤其，可在小叶上缝合部位例如缝合线处施用一层薄的高径向阻抗(radialresistance)粘合强化材料。粘合剂或添加剂化合物可以是生物来源的(含胶原)或是合成聚合物，为心包组织提供局部加强。实施方式之一中，粘合剂施用于缝合部位的厚度小于100μm。其他厚度也可能是合适的。施用的粘合剂强化材料占据一小片局部小叶表面区域，比之现有其他方式，这使得心包小叶组织能够耐受更高的缝合拉扯力。如同前文所述实施方式，对瓣膜组件进行消毒(步骤312)，然后包装(步骤314)，以备手术场所使用。
图4显示人造生物组织402的缝合部位400。图4A中的缝合部位400未经处理。箭头“A”指示缝合部位400的缝线(未显示)拉出方向。图4B显示人造生物组织402的缝合部位400具有本文所述局部强化区域404。图4B中组织402具有选择性施用以形成局部强化区域404的粘合剂。箭头“A”指示图4B缝合部位400的缝线(未显示)拉出方向。与图4A所示无处理的缝合部位组织相比，图4B所示缝合部位400处或紧邻的组织402具有局部强化粘合剂处理区域404，在破坏时获得了更高的拉伸强度和更高的负荷值。实施例之一中，无处理缝合部位组织的极限拉伸应力为1.1MPa(兆帕)，有粘合剂处理区域的缝合部位组织的极限拉伸应力大于1.6MPa。实施例之一中，无处理缝合部位组织在被破坏时的负荷约为3N(牛顿)，而局部强化粘合剂处理区域的组织在被破坏时的负荷约为6N。
图5显示一示例性人造心脏瓣膜500，其具有如本文所述局部强化处理区域502、504。图5的人造心脏瓣膜500具有支持结构506和由人造生物组织形成的人造瓣膜小叶508，瓣膜小叶508用安装元件510(例如缝线)组装到瓣膜框架506上。人造瓣膜小叶508至少其一在小叶508的表面具有选择性施用于局部强化区域502的粘合剂，局部强化区域502位于需要强化的区域512，例如通孔或其他缺陷，如前文根据图1和图2的方法所述。小叶508还可以具有粘合剂选择性施用于人造表面小叶508通孔处的局部粘合剂强化区域504，所述通孔由缝线510或其他合适的安装元件形成(如图3的方法所述)。局部处理区域502、504可以是小叶上需要通过选择性施用粘合剂或添加剂化合物来聚焦式或局部改变组织机械性能(例如提高机械硬度和强度)的任何区域。
实施方式之一中，粘合剂的施用厚度小于100μm，但局部施用粘合剂的其他厚度可能也是合适的。粘合剂通过局部改变组织性能(例如硬度或强度)来局部改变人造生物组织。粘合剂或添加剂化合物在组织表面固化，可用表面化学分析(如X光密实度扫描仪(XTS))检测到。也可采用其他合适的方法和设备来检测粘合剂。粘合剂可直接由注射器施用到组织上，然后根据需要在局部组织区域分散，或者，可将粘合剂加入施用器来施用到局部组织区域。值得注意的是，前文所述处理人造生物组织的方法可用于多种人造生物组织应用场合，而并不限用于本文所述的人造心脏瓣膜所用组织。
尽管本文是结合优选实施方式进行的描述，本领域技术人员知道，可以进行许多形式或细节上的改变而不脱离本文的精神和范围。

Claims (20)

1.一种强化用作人造瓣膜小叶的人造生物组织的方法，所述方法包括：
对生物组织进行测评；
鉴定人造生物组织中的缺陷；和
植入患者之前，将粘合剂选择性施用于缺陷部位处的人造生物组织表面。
2.如权利要求1所述的方法，其中，选择性施用步骤包括在选择性施用所述粘合剂时将蛋白质与戊二醛混合来制备所述粘合剂。
3.如权利要求2所述的方法，其中，选择性施用粘合剂之前，蛋白质和戊二醛是分装的。
4.如权利要求2所述的方法，其中，戊二醛与蛋白质按照预定比例混合。
5.如权利要求2所述的方法，其中，所述蛋白质是白蛋白。
6.如权利要求1所述的方法，其中，所述粘合剂是氰基丙烯酸酯。
7.如权利要求1所述的方法，其中，选择性施用粘合剂的步骤包括用粘合剂充填通孔，粘合剂由此延展通过通孔从而接触通孔周界的组织。
8.如权利要求1所述的方法，其中，所述缺陷是组织分层，所述选择性施用步骤将分层密合在一起。
9.如权利要求1所述的方法，其中，还包括在选择性施用粘合剂之后：
将所述组织组装到人造瓣膜中，这包括将人造生物瓣膜小叶缝合到瓣膜框架上；和
将添加剂化合物选择性施用在小叶的缝合部位。
10.一种制造人造心脏瓣膜的方法，包括：
对人造生物组织进行固定；
将所述人造生物组织切割成瓣膜小叶；
组装人造心脏瓣膜，这包括将所述瓣膜小叶缝合到瓣膜框架上；和
将添加剂化合物选择性施用在瓣膜小叶的缝合孔处。
11.如权利要求10所述的方法，其中，所述添加剂化合物包括胶原。
12.如权利要求10所述的方法，其中，所述添加剂化合物是合成的。
13.如权利要求10所述的方法，还包括：
将所述添加剂化合物选择性施用于缺陷部位处的人造生物组织表面。
14.一种瓣膜组件，其包含：
瓣膜框架；和
由人造生物组织形成的人造瓣膜小叶，其通过安装元件组装到瓣膜框架上，所述人造瓣膜小叶至少其一具有施用于该小叶表面选定区域的粘合剂，所述选定区域有缺陷。
15.如权利要求14所述的瓣膜组件，其还包含施用于所述人造瓣膜小叶选定区域的粘合剂，所述选定区域是所述安装元件形成的通孔。
16.如权利要求15所述的瓣膜组件，其中，所述粘合剂在所述通孔处的厚度小于100μm。
17.如权利要求14所述的瓣膜组件，其中，所述选定区域比小叶的无处理区域具有更高的拉伸强度。
18.如权利要求14所述的瓣膜组件，其中，所述粘合剂包含蛋白质和戊二醛。
19.如权利要求17所述的瓣膜组件，其中，所述蛋白质是白蛋白。
20.如权利要求14所述的瓣膜组件，其中，所述粘合剂是氰基丙烯酸酯。
CN201780004995.0A 2016-01-07 2017-01-05 人造生物组织的修复与强化 Active CN108472140B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662275933P 2016-01-07 2016-01-07
US62/275,933 2016-01-07
PCT/US2017/012354 WO2017120351A2 (en) 2016-01-07 2017-01-05 Biorosthetic tissue repair and reinforcement

Publications (2)

Publication Number Publication Date
CN108472140A true CN108472140A (zh) 2018-08-31
CN108472140B CN108472140B (zh) 2021-03-09

Family

ID=57861291

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201780004995.0A Active CN108472140B (zh) 2016-01-07 2017-01-05 人造生物组织的修复与强化

Country Status (5)

Country Link
US (1) US10299916B2 (zh)
EP (1) EP3399946A2 (zh)
CN (1) CN108472140B (zh)
AU (1) AU2017206009B2 (zh)
WO (1) WO2017120351A2 (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109529098A (zh) * 2018-12-03 2019-03-29 广州润虹医药科技股份有限公司 一种外科医用粘合剂
CN109793931A (zh) * 2019-03-15 2019-05-24 上海以心医疗器械有限公司 一种降低生物组织厚度的方法及其生物组织

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10299916B2 (en) * 2016-01-07 2019-05-28 Medtronic Vascular, Inc. Bioprosthetic tissue repair and reinforcement

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4818291A (en) * 1986-12-10 1989-04-04 Ajinomoto Co., Inc. Silk-fibroin and human-fibrinogen adhesive composition
US20020173770A1 (en) * 2001-05-16 2002-11-21 Flory Alan R. Adhesive delivery system
CN1471412A (zh) * 2000-06-29 2004-01-28 ����ϳɼ������ô�˾ 用于修复和再生软骨和其它组织的组合物和方法
US20070027528A1 (en) * 2005-07-29 2007-02-01 Cook Incorporated Elliptical implantable device
US20070154515A1 (en) * 2005-12-29 2007-07-05 Johnson Chad E Implantable graft material
US20100297218A1 (en) * 2006-09-20 2010-11-25 Pneumrx, Inc. Tissue adhesive compositions and methods thereof
CN102869320A (zh) * 2010-03-01 2013-01-09 科利柏心脏瓣膜有限责任公司 可经皮输送的心脏瓣膜及相关制备方法
CN103025841A (zh) * 2010-03-05 2013-04-03 泰根尼克斯有限公司 用于粘结多孔胶原基材料和无孔胶原基材料的胶原凝胶
CN104780952A (zh) * 2012-07-02 2015-07-15 波士顿科学医学有限公司 假体心脏瓣膜形成

Family Cites Families (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4378224A (en) 1980-09-19 1983-03-29 Nimni Marcel E Coating for bioprosthetic device and method of making same
US5614587A (en) * 1988-11-21 1997-03-25 Collagen Corporation Collagen-based bioadhesive compositions
US5936035A (en) * 1988-11-21 1999-08-10 Cohesion Technologies, Inc. Biocompatible adhesive compositions
US5163955A (en) * 1991-01-24 1992-11-17 Autogenics Rapid assembly, concentric mating stent, tissue heart valve with enhanced clamping and tissue alignment
US5192312A (en) 1991-03-05 1993-03-09 Colorado State University Research Foundation Treated tissue for implantation and methods of treatment and use
US5480424A (en) * 1993-11-01 1996-01-02 Cox; James L. Heart valve replacement using flexible tubes
US5713950A (en) * 1993-11-01 1998-02-03 Cox; James L. Method of replacing heart valves using flexible tubes
US5583114A (en) 1994-07-27 1996-12-10 Minnesota Mining And Manufacturing Company Adhesive sealant composition
US6475239B1 (en) * 1998-10-13 2002-11-05 Sulzer Carbomedics Inc. Method for making polymer heart valves with leaflets having uncut free edges
US6638312B2 (en) 2000-08-04 2003-10-28 Depuy Orthopaedics, Inc. Reinforced small intestinal submucosa (SIS)
US20030022146A1 (en) 2001-07-26 2003-01-30 Cunanan Crystal M. Oxidized bioprosthetic materials
US20070020620A1 (en) * 2005-07-14 2007-01-25 Finn M G Compositions and methods for coupling a plurality of compounds to a scaffold
US8470022B2 (en) * 2005-08-31 2013-06-25 Cook Biotech Incorporated Implantable valve
US7569071B2 (en) * 2005-09-21 2009-08-04 Boston Scientific Scimed, Inc. Venous valve, system, and method with sinus pocket
EP1948088A2 (en) * 2005-11-18 2008-07-30 Innovia LLC Trileaflet heart valve
US9415567B2 (en) * 2007-02-05 2016-08-16 Boston Scientific Scimed, Inc. Synthetic composite structures
US8136218B2 (en) * 2008-04-29 2012-03-20 Medtronic, Inc. Prosthetic heart valve, prosthetic heart valve assembly and method for making same
BRPI0919911A2 (pt) * 2008-10-29 2016-02-16 Symetis Sa métodos e sistemas para fabricação e montagem de válvula de stent
US9522321B2 (en) * 2010-09-09 2016-12-20 Kma Concepts Limited Toy bow and arrow system with internal bow lighting
US9554902B2 (en) * 2012-06-28 2017-01-31 St. Jude Medical, Cardiology Division, Inc. Leaflet in configuration for function in various shapes and sizes
EP2967863B1 (en) 2013-03-15 2018-01-31 Edwards Lifesciences Corporation Valved aortic conduits
US9622863B2 (en) * 2013-11-22 2017-04-18 Edwards Lifesciences Corporation Aortic insufficiency repair device and method
US10117744B2 (en) * 2015-08-26 2018-11-06 Edwards Lifesciences Cardiaq Llc Replacement heart valves and methods of delivery
US20170112619A1 (en) * 2015-10-22 2017-04-27 Medtronic Vascular, Inc. Systems and Methods of Sealing a Deployed Valve Component
US10299916B2 (en) * 2016-01-07 2019-05-28 Medtronic Vascular, Inc. Bioprosthetic tissue repair and reinforcement

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4818291A (en) * 1986-12-10 1989-04-04 Ajinomoto Co., Inc. Silk-fibroin and human-fibrinogen adhesive composition
CN1471412A (zh) * 2000-06-29 2004-01-28 ����ϳɼ������ô�˾ 用于修复和再生软骨和其它组织的组合物和方法
US20020173770A1 (en) * 2001-05-16 2002-11-21 Flory Alan R. Adhesive delivery system
US20070027528A1 (en) * 2005-07-29 2007-02-01 Cook Incorporated Elliptical implantable device
US20070154515A1 (en) * 2005-12-29 2007-07-05 Johnson Chad E Implantable graft material
US20100297218A1 (en) * 2006-09-20 2010-11-25 Pneumrx, Inc. Tissue adhesive compositions and methods thereof
CN102869320A (zh) * 2010-03-01 2013-01-09 科利柏心脏瓣膜有限责任公司 可经皮输送的心脏瓣膜及相关制备方法
CN103025841A (zh) * 2010-03-05 2013-04-03 泰根尼克斯有限公司 用于粘结多孔胶原基材料和无孔胶原基材料的胶原凝胶
CN104780952A (zh) * 2012-07-02 2015-07-15 波士顿科学医学有限公司 假体心脏瓣膜形成

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109529098A (zh) * 2018-12-03 2019-03-29 广州润虹医药科技股份有限公司 一种外科医用粘合剂
CN109793931A (zh) * 2019-03-15 2019-05-24 上海以心医疗器械有限公司 一种降低生物组织厚度的方法及其生物组织

Also Published As

Publication number Publication date
US20170196686A1 (en) 2017-07-13
CN108472140B (zh) 2021-03-09
US10299916B2 (en) 2019-05-28
WO2017120351A2 (en) 2017-07-13
WO2017120351A3 (en) 2017-08-17
AU2017206009A1 (en) 2018-07-12
EP3399946A2 (en) 2018-11-14
AU2017206009B2 (en) 2019-11-07

Similar Documents

Publication Publication Date Title
CN102869320B (zh) 可经皮输送的心脏瓣膜及相关制备方法
EP1041942B1 (en) Stentless bioprosthetic heart valve with coronary protuberances
Andreas et al. Conventional versus rapid-deployment aortic valve replacement: a single-centre comparison between the Edwards Magna valve and its rapid-deployment successor
Simon et al. Early failure of the tissue engineered porcine heart valve SYNERGRAFT® in pediatric patients
US6074419A (en) Indicia for prosthetic device
Carr et al. Aortic valve repair for aortic insufficiency in adults: a contemporary review and comparison with replacement techniques
AU718295B2 (en) Physiologic mitral valve bioprosthesis
CN104799975B (zh) 人工生物心脏瓣膜及其制作方法
CN108472140A (zh) 人造生物组织的修复与强化
Walther et al. Trans-catheter valve-in-valve implantation: in vitro hydrodynamic performance of the SAPIEN+ cloth trans-catheter heart valve in the Carpentier-Edwards Perimount valves
Amahzoune et al. Traumatic leaflet injury during the use of percutaneous valves: a comparative study of balloon-and self-expandable valved stents
Singh et al. Polymeric prosthetic heart valves: a review of current technologies and future directions
Christ et al. Long-term results after the Ross procedure with the decellularized AutoTissue Matrix P® bioprosthesis used for pulmonary valve replacement
Stanger et al. Pitfalls and premature failure of the Freedom SOLO stentless valve
Bui et al. Transcatheter heart valves: a biomaterials perspective
US5910169A (en) Total mitral heterologous bioprosthesis to be used in mitral tricuspid heart replacement
Tasca et al. Fluid-dynamic results of in vitro comparison of four pericardial bioprostheses implanted in small porcine aortic roots
Landes et al. Transcatheter valve implantation in degenerated bioprosthetic surgical valves (ViV) in aortic, mitral, and tricuspid positions: a review
Sündermann et al. Implantation of personalized, biocompatible mitral annuloplasty rings: feasibility study in an animal model
Schoen et al. Cardiac valve replacement and related interventions
Lutter et al. Transcatheter pulmonary valve replacement: a new polycarbonate urethane valve
Saisho et al. An ex vivo evaluation of two different suture techniques for the Ozaki aortic neocuspidization procedure
Goetz et al. Forces at single point attached commissures (SPAC) in pericardial aortic valve prosthesis
Hamasaki et al. Solo smart stentless bioprosthesis for redo aortic valve replacement
Pomerantzeff et al. “Less Stented” Bovine Pericardial Xenograft: A New Concept

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant