CN106163580A - 用于制造用于生物医学应用的多孔金属材料的方法和通过所述方法获得的材料 - Google Patents

用于制造用于生物医学应用的多孔金属材料的方法和通过所述方法获得的材料 Download PDF

Info

Publication number
CN106163580A
CN106163580A CN201580016476.7A CN201580016476A CN106163580A CN 106163580 A CN106163580 A CN 106163580A CN 201580016476 A CN201580016476 A CN 201580016476A CN 106163580 A CN106163580 A CN 106163580A
Authority
CN
China
Prior art keywords
microns
titanium
binding agent
parts
particle diameter
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
CN201580016476.7A
Other languages
English (en)
Other versions
CN106163580B (zh
Inventor
何塞·安东尼奥·卡莱罗马丁尼兹
弗朗西斯科·哈维尔·吉尔穆尔
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.)
Mixed Metal Stock Co
AMES Group Sintering SA
Original Assignee
Mixed Metal Stock Co
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 Mixed Metal Stock Co filed Critical Mixed Metal Stock Co
Publication of CN106163580A publication Critical patent/CN106163580A/zh
Application granted granted Critical
Publication of CN106163580B publication Critical patent/CN106163580B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A61L27/02—Inorganic materials
    • A61L27/04—Metals or alloys
    • A61L27/06—Titanium or titanium alloys
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F3/00—Manufacture of workpieces or articles from metallic powder characterised by the manner of compacting or sintering; Apparatus specially adapted therefor ; Presses and furnaces
    • B22F3/10—Sintering only
    • B22F3/11—Making porous workpieces or articles
    • 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
    • A61L27/56—Porous materials, e.g. foams or sponges
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F1/00—Metallic powder; Treatment of metallic powder, e.g. to facilitate working or to improve properties
    • B22F1/10—Metallic powder containing lubricating or binding agents; Metallic powder containing organic material
    • B22F1/102—Metallic powder coated with organic material
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F1/00—Metallic powder; Treatment of metallic powder, e.g. to facilitate working or to improve properties
    • B22F1/10—Metallic powder containing lubricating or binding agents; Metallic powder containing organic material
    • B22F1/105—Metallic powder containing lubricating or binding agents; Metallic powder containing organic material containing inorganic lubricating or binding agents, e.g. metal salts
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F3/00—Manufacture of workpieces or articles from metallic powder characterised by the manner of compacting or sintering; Apparatus specially adapted therefor ; Presses and furnaces
    • B22F3/02—Compacting only
    • B22F3/04—Compacting only by applying fluid pressure, e.g. by cold isostatic pressing [CIP]
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F3/00—Manufacture of workpieces or articles from metallic powder characterised by the manner of compacting or sintering; Apparatus specially adapted therefor ; Presses and furnaces
    • B22F3/10—Sintering only
    • B22F3/1017—Multiple heating or additional steps
    • B22F3/1021—Removal of binder or filler
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F3/00—Manufacture of workpieces or articles from metallic powder characterised by the manner of compacting or sintering; Apparatus specially adapted therefor ; Presses and furnaces
    • B22F3/10—Sintering only
    • B22F3/11—Making porous workpieces or articles
    • B22F3/1121—Making porous workpieces or articles by using decomposable, meltable or sublimatable fillers
    • B22F3/1125—Making porous workpieces or articles by using decomposable, meltable or sublimatable fillers involving a foaming process
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F3/00—Manufacture of workpieces or articles from metallic powder characterised by the manner of compacting or sintering; Apparatus specially adapted therefor ; Presses and furnaces
    • B22F3/10—Sintering only
    • B22F3/11—Making porous workpieces or articles
    • B22F3/1146—After-treatment maintaining the porosity
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F3/00—Manufacture of workpieces or articles from metallic powder characterised by the manner of compacting or sintering; Apparatus specially adapted therefor ; Presses and furnaces
    • B22F3/12—Both compacting and sintering
    • B22F3/16—Both compacting and sintering in successive or repeated steps
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F3/00—Manufacture of workpieces or articles from metallic powder characterised by the manner of compacting or sintering; Apparatus specially adapted therefor ; Presses and furnaces
    • B22F3/24—After-treatment of workpieces or articles
    • 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
    • A61F2/30—Joints
    • A61F2/44—Joints for the spine, e.g. vertebrae, spinal discs
    • A61F2/4455—Joints for the spine, e.g. vertebrae, spinal discs for the fusion of spinal bodies, e.g. intervertebral fusion of adjacent spinal bodies, e.g. fusion cages
    • 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
    • A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00005—The prosthesis being constructed from a particular material
    • A61F2310/00011—Metals or alloys
    • A61F2310/00023—Titanium or titanium-based alloys, e.g. Ti-Ni alloys
    • 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
    • A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00389—The prosthesis being coated or covered with a particular material
    • A61F2310/00592—Coating or prosthesis-covering structure made of ceramics or of ceramic-like compounds
    • A61F2310/00598—Coating or prosthesis-covering structure made of compounds based on metal oxides or hydroxides
    • 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
    • A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00389—The prosthesis being coated or covered with a particular material
    • A61F2310/00592—Coating or prosthesis-covering structure made of ceramics or of ceramic-like compounds
    • A61F2310/00598—Coating or prosthesis-covering structure made of compounds based on metal oxides or hydroxides
    • A61F2310/00616—Coating made of titanium oxide or hydroxides
    • 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
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/08—Methods for forming porous structures using a negative form which is filled and then removed by pyrolysis or dissolution
    • 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
    • A61L2430/38—Materials or treatment for tissue regeneration for reconstruction of the spine, vertebrae or intervertebral discs
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F3/00—Manufacture of workpieces or articles from metallic powder characterised by the manner of compacting or sintering; Apparatus specially adapted therefor ; Presses and furnaces
    • B22F3/24—After-treatment of workpieces or articles
    • B22F2003/241—Chemical after-treatment on the surface
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F3/00—Manufacture of workpieces or articles from metallic powder characterised by the manner of compacting or sintering; Apparatus specially adapted therefor ; Presses and furnaces
    • B22F3/24—After-treatment of workpieces or articles
    • B22F2003/247—Removing material: carving, cleaning, grinding, hobbing, honing, lapping, polishing, milling, shaving, skiving, turning the surface
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F2301/00—Metallic composition of the powder or its coating
    • B22F2301/20—Refractory metals
    • B22F2301/205—Titanium, zirconium or hafnium
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F2302/00—Metal Compound, non-Metallic compound or non-metal composition of the powder or its coating
    • B22F2302/45—Others, including non-metals
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F2303/00—Functional details of metal or compound in the powder or product
    • B22F2303/01—Main component
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B22—CASTING; POWDER METALLURGY
    • B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F2998/00—Supplementary information concerning processes or compositions relating to powder metallurgy
    • B22F2998/10—Processes characterised by the sequence of their steps

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Manufacturing & Machinery (AREA)
  • Mechanical Engineering (AREA)
  • Animal Behavior & Ethology (AREA)
  • Transplantation (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Fluid Mechanics (AREA)
  • Physics & Mathematics (AREA)
  • Materials For Medical Uses (AREA)
  • Prostheses (AREA)

Abstract

本发明涉及获得多孔钛部件的方法，其特征在于初始钛粉为纯的，具有200微米的平均粒径，93秒的流动速率和1.0g/cm3的表观密度。所述粉以34重量％钛的比例与粒径为300微米至600微米的至少50重量％的NaCl混合。由于这些参数，所得材料具有用于生物医学应用的最佳骨结合性、生物相容性和强度。

Description

用于制造用于生物医学应用的多孔金属材料的方法和通过所 述方法获得的材料
技术领域
本发明涉及用于某些生物医学应用的多孔金属材料。特别地，本发明包含用于制造和合金化具有提高的骨结合性和吸附性质的钛的方法。
背景技术
选择用于生物医学关节成形术应用的金属材料中一个主要问题是需要将例如骨结合和与人骨硬度相似的两种功能特征结合，所有这些的首要前提是形成在使用中能够承受动载荷的材料。
钛具有三个主要益处：其极佳的生物相容性、降低的刚性模量(110GPa，相比于常规卫生级钢的210GPa)以及与诊断和评估技术例如CAT扫描或MRI的相容性。所有这些使得钛或其合金成为最适合用于制造必须放入人体中的任何假体或植入物的金属材料。
当形成用于制造这些假体的金属材料时，使用机加工成由专家设计的形状的锻造材料，前述机械性质得以保持。
然而，即使这些性质优于市场中的任意钢或CrCo材料的性质，其仍不足以改善两个基本方面，即骨吸附性和骨结合性。上述方面的第一方面与骨的刚性模量(在30GPa下0.5)和金属假体的刚性模量之间的差异紧密相关。随着这两个值彼此接近，假体在功能上用作骨且骨吸收降低，提高了植入物寿命且因此提高患者的生活质量。降低模量而不改性材料的最简单的方式为提供体系的孔隙率，而生产多孔材料的最卓越的技术为粉末冶金技术。
用于假体的现有材料可能提高的第二方面为骨结合性。越来越多地使用未胶结的假体，从而不仅在多孔腔中而且在评价凝固的胶结物断裂风险中降低锚固自身的影响。未胶结假体的使用涉及锚固系统自身的开发，以及用于陶瓷或金属材料的生物相容性涂层的施用，现今最广泛使用的是使用热喷涂技术或通过小规模胶合和烧结的微球沉积。两种类型的系统均具有数个缺陷。热喷涂产生粗糙表面，但该表面粗糙度不存在实质的和深入的相互联系，因此骨组织仅“抓住”所产生的形貌的腔和峰。反过来，考虑到待烧结的所述微球具有的少量焊接点，微球沉积引起这些微球中的一些脱落的固有风险与随后的患者健康的风险。此外，在后一种情况中，已存在假体在使用中由于疲劳而破裂的多种问题。球至模具的焊接附着产生锐利边缘，其为应力增加的点。
通过粉末冶金加工钛材料和合金以获得多孔材料是现有技术中已知的。在随后生产流程的一些过程中消除了间隔剂(spacing agent)的使用是所带来的最大成功且看来很快将工业化。
间隔剂的使用限制了去除间隔剂后部件中产生的孔隙的尺寸。然而，大孔的存在不一定意味着存在尺寸与大孔相似的、用于朝向多孔材料内部的毛细血管生长的通道。
粉末冶金工艺允许将具有300微米平均粒径的钛和/或钛合金粉压制到小于25微米的尺寸。该工艺接着适当烧结使得所形成的钛材料能够获得实心体的85％至98％的密度，其归因于烧结期间可观察到的显著收缩。考虑到细晶粒结构，当部件在高真空条件下烧结时，机械性质的值与实心材料的值大致相同。
应力通过假体传递至骨，因此假体必须具有尽可能与骨相似的弹性模量，以适当地向骨传递载荷并防止由于缺少施加至骨的应力而引起骨吸收的所谓的机械应力屏蔽。因此，如果假体作为整体不具有与骨相似的模量，表面弹性模量不太重要。如果使用细粉，金属粉的单轴向压缩期间的载荷传递产生涉及高真空烧结期间起始压制形状变形的密度梯度。其为显著的缺陷，因为其涉及由于表面空隙闭合和妨碍骨结合而不可能在烧结步骤之后进行的机加工至最终形状的过程，。烧结中变形的存在且特别地在部件侧表面上层压粉末的“皮”的存在(由于从模具取出时发生的摩擦)已导致决定进行生坯加工，以打开孔隙且寻求为了获得烧结后最终形状和尺寸的最适合的尺度。一定的材料强度是生坯加工必须的，为了此目的一些参考文献和专利(例如US7674426B2)描述了冷等静压成型的使用。所有这些使系统更昂贵，此外，由于这些方法用细的钛或钛合金粉进行，最终所述孔之间的互连不超过10微米，因此多孔系统中的血管形成和有效的骨生长仍存在问题。
当材料植入体内时，发生对异物的免疫反应，导致植入物被包围并密封在纤维组织中，且与周围组织隔离。在某些应用中不期望该隔离，因为该隔离将不允许骨附着至植入物，且植入物将无法发挥其所设计的功能。为了防止上述问题，需要将植入物表面转化为生物活性表面，即能够附着至相邻的骨组织，或者用与骨更相似的材料(例如羟基磷灰石)涂布表面。该羟基磷灰石通常具有非晶特征或低结晶度，这意味着在血液介质中非常快速的溶解，产生假体不稳定的问题，以更换假体的手术以及很少或零骨结合性告终。
发明内容
为了解决上述问题，本发明的方法提出使用具有特定性质的钛粉及其与特定尺寸的盐、以特定比例的混合物。更具体地，本发明提出用于获得多孔钛部件的方法，其特征在于初始钛粉是纯的，具有200微米的平均粒径，93秒的流动速率，1.0g/cm3的表观密度，所述粉末以34重量％钛的比例与具有300微米至600微米的粒径且至少50重量％的NaCl混合。
这些特征导致孔之间的互连大于150微米，以及钛基材料的生物相容性，其使产品非常适于改善材料的骨结合性同时保持适当的疲劳强度
附图说明
为了根据本发明的优选实际实施方案帮助更好的理解本发明特征的目的，一组附图附于下列说明书，其中描述了下列附图的说明性特征。
图1a为用于本发明的具有200微米平均粒径的不规则钛粉的电子显微图像。
图1b为根据本发明制造的部件的微观结构图像，其中可见粒径和孔之间的互连大于150微米。
图2a为示出根据本发明的方法制造的部件的压缩破裂行为的图。
图2b为示出根据本发明的方法制造的椎间融合器(intersomatic cage)在使用条件下的疲劳行为的图。
图3描述了对于根据所要求保护的方法制造的结构，孔隙的尺寸相对于可被材料占据(侵入)的平均体积的对数。
图4为示出根据本发明生产的部件的高结晶度的图。
图5为成骨细胞在多孔材料表面的形态的图。
具体实施方式
本发明的一般方面起始于具有45微米至300微米的粒径分布的纯钛粉，其中超过90％的颗粒为75微米至250微米且平均粒径为200微米。所述粉末的流动速率为93秒，其表观密度为1.0g/cm3且其振实密度为1.25g/cm3。
根据ISO 4490标准计算材料的流动速率，根据ISO3923/1计算表观密度，且根据ISO 3953计算振实密度。为实心(solid，致密)材料密度的22％的表观密度(1.0g/cm3相对于4.51g/cm3的实心钛密度)表明存在高度不规则的粉末表面，连同200微米的平均粒径以及300微米至600微米的盐粒径，使得使用压制和烧结工艺实现了大于150微米的孔间互连尺寸是可行的。
将34重量％比例的钛与300微米至600微米且50重量％至80重量％的NaCl混合，添加至少15％至100％的比例的粘合剂。接着，为了移除粘合剂和盐，使材料经受热处理，随后在二次蒸馏水中连续冲洗，且在200MPa至400MPa、优选300Mpa压制材料之后，在1200℃至1400℃的温度(优选1300℃)和小于4×10-4毫巴的压力下使其烧结。利用这些参数，除了实现了适合的强度和均匀性之外，还实现了适当的孔隙率和孔之间的长度。
如图1a中所见，钛粉具有不规则形貌和大于150微米的粒径。
如图1b中可见，开发的材料的结构以大于150微米的互连尺寸完全互连。
图3示出水银孔隙度测定法的绘出的结果。在类似于这种情况的多孔互通结构中，最经常发生的最大强度值为孔间的互通通道的尺寸。因此最强的第二峰表示互连的孔隙的尺寸，其为大于150微米。第一峰代表小于10微米的所有内部孔隙，其在材料内部且在骨结合过程期间具有特定生物学功能，作为用于所述细胞生长的“食物”存储。
为了将钛表面转化成生物活性表面，使植入物表面的惰性二氧化钛(TiO2)层(其在钛及其合金表面自发生成)与5M氢氧化钠(NaOH)碱性溶液反应。用NaOH处理期间TiO2部分溶解以形成碱性溶液，作为溶液的氢氧根(OH-)的腐蚀作用的结果。因此，钛酸钠(Na2TiO3)凝胶层形成于表面上。然后借助H2O在60℃的温度下使碱性反应中和24小时。接着在600℃下进行热处理1小时以脱水、致密化且增加该钛酸钠凝胶层的基底粘附。从而形成稳定且部分结晶的Na2TiO3层，其促进了生物活性且改善了表面性质。
实施例椎间融合器：
使用粒径分布在45微米至300微米之间且平均粒径为200微米的纯钛2级粉。引入65体积％的尺寸为300微米至600微米的NaCl。向最终混合物添加15％乙二醇。其在双锥混合机中混合10分钟。将湿混合物引入具有最终几何结构的模具。由于烧结期间材料的均匀收缩，模具尺寸加大8％。在液压机中在300MPa下进行单轴压制，过量的粘合剂用来促进从模具脱模时的压力均匀分布。由于该作用，压制压力的传递非常均匀，因此压制材料的生坯密度也是均匀的且在最终经烧结部件中不会由于收缩率差异而引起变形。将具有钛和盐的经压制的部件在200℃下在6小时内通过炉以移除乙二醇残留物(乙二醇蒸发温度为约190℃)。在200℃下，不存在氧气被结合入钛结构中的风险，因此所述元素的可能污染被最小化。随后进行浴的循环工艺以移除间隔剂，直到离子导电率稳定在非常小的值或与用作溶剂的蒸馏水相似的值。所述清洗通过施加真空以加速盐溶解过程而进行。一旦盐已从部件移除，其被适当处理并放置在120℃的空气烘箱中4小时以使其完全干燥。
随后在高真空炉(<4×10-4毫巴)中在1200℃至1400℃、优选1300℃下烧结4小时。一旦烧结之后，机加工样品，将边缘修圆并降低颗粒脱落的可能性。最后，全部在超声下，进行蒸馏水、乙醇、丙酮中的循环洗涤工艺以适当清洁部件。
在经处理的和未经处理的样品上进行压缩试验，其结果在弹性极限、断裂载荷或断裂伸长率方面没有观察到显著差异。然而，当进行生物活性热处理时观察到朝向材料的弹性模量增加的特定趋势。机械抗压强度和弹性模量(10GPa)值及其良好的疲劳行为可保证此类多孔材料用于脊柱的椎间融合器应用的良好机械行为，且展示出用于硬组织替代的许多其他应用的可能性。图2a和图2b示出良好的单调弯曲和疲劳下的压缩行为，模拟脊柱的工作。在这些力学试验中，使用寿命期间无限寿命值超过350kg且无论如何不存在颗粒脱落。
为了评价植入材料在其表面形成磷灰石层的能力，遵照国际ISO23317标准(外科用植入物–磷灰石体外评价–植入材料的形成能力)的指导，用根据本发明方法制造的样品进行体外试验。该测试由以下组成：使材料浸入溶液中，该溶液具有与血浆几乎相等的离子浓度、pH和温度，其被称为模拟体液或SBF。
借助SBF的生物活性测试根据由于SBF和经化学处理和热处理表面之间发生的离子交换在表面上形成的磷灰石而评估。
当经热-化学处理的钛浸没于SBF中时，Na2TiO3的Na+离子与水性介质的H3O+交换且Ti-OH基团形成于金属表面。形成于表面上的Ti-OH基团与SBF的钙Ca2+离子结合以形成非晶态钛酸钙(CaTiO3)。Ti表面的Ti-OH基团带电，且导致Ca2+离子沉淀在表面上以与其结合。
部分钙离子与SBF的HPO4 2-磷酸根反应在植入物表面形成磷酸钙(CaP)。钠Na+离子连同SBF的H3O+离子的释放导致溶液pH增大。这进而产生更大的CaP离子活度，导致钛表面快速沉积磷灰石。
热-化学处理之后，样品提供例如图4中观察到的微观结构。由于所述处理为液体处理，所以处理渗透入整个植入物表面，因此可以看出钛酸钠覆盖整个表面乃至孔隙。因为并非涂覆工艺而是基于钛的结晶工艺，所以可以看到高结晶度且确保与植入物的附着。这确保抑制可能的细菌渗透(filtration)，所述细菌渗透发生在具有生物活性涂层的植入物中，因为层和基底之间存在细菌和微生物用来形成菌落的几微米。
用不同量的碱性溶液且随后借助热处理而处理的样品浸没于SBF中10天以确定表面生物活性，如ISO 23317标准中所示。可在浸没后确认所形成的磷灰石的晶体结构。磷灰石为结晶的非常重要。在通过血浆涂布有羟基磷灰石的植入物中，磷灰石大部分呈现为非晶态的。这造成磷灰石层被生理介质非常快速的溶解，而植入物和骨被保持分开一定距离，使得不发生骨结合。在这种情况下，磷灰石完全结晶且其溶解比非晶态磷灰石慢得多，其对骨结合过程是最佳的。
基于对SAOS-2成骨细胞孵育24小时且用LDH试剂培育10分钟之后获得的吸收度值，可以断定：
·未观察到由于SAOS-2细胞间接暴露于从分析样品获得的5浓度提取物的相关细胞毒性效应。
·在全部样品中，相对于阴性对照的吸收度值高于75％，因此该值在细胞毒性可认为不存在的允许值内。
在第1天和第14天之间观察到增殖的增加，因为细胞尚未开始分化并增殖。随后观察到增殖的一定降低，其(几乎绝对肯定)归因于14天的孵育之后的细胞分化的增加。所有这些行为在这种细胞中是正常的。ALP活性也在7天之后增加，表明细胞分化。ALP是分化开始的指示物，且认为在孵育7天后磷酸酶活性的增加之后，培养14天后磷酸酶活性下降是正常的。该现象在科学文献中被高度分类为典型早期细胞分化过程。随着培养时间增加，细胞数目和其渗透入材料的程度也增加。孵育14天的样品的图像已示出完全渗透入样品的程度，其相当于构件厚度的一半。
图5示出具有非常高的集中点(focal point)程度的来自AMES的在多孔材料表面上的成骨细胞的形貌，其确保良好的细胞附着和健康，如发现的骨钙素水平所示。与高骨钙素和基因表达水平形成对比的所述附着、增殖和分化确保加速了骨结合。

Claims (7)

1.一种用于获得多孔钛部件的方法，其特征在于初始钛粉为纯的，具有200微米的平均粒径，93秒的流动速率，1.0g/cm3的表观密度，且所述粉末以34重量％钛的比例与粒径为300微米至600微米的至少50重量％的NaCl混合。
2.根据权利要求1所述的方法，其特征在于其还包括下列步骤：
i)添加至少15％比例的粘合剂；
ii)以200MPa至400MPa压制所得材料；
iii)通过热处理随后在二次蒸馏水中持续冲洗来移除所述粘合剂和盐；
iv)在1200℃至1400℃的温度下和低于4×10-4毫巴的压力下烧结；
v)机械加工所述部件的表面。
3.根据权利要求2所述的方法，其特征在于所述部件在步骤v)之后被引入5M氢氧化钠(NaOH)碱性溶液中。
4.根据权利要求2至3中任一项所述的方法，其特征在于所述粘合剂为乙二醇。
5.根据权利要求2至4中任一项所述的方法，其特征在于步骤i)在双锥混合机中进行，步骤iii)通过将湿混合物引入模具中并随后单轴压制而进行。
6.根据权利要求5所述的方法，其特征在于所述单轴压制在液压机中进行。
7.根据前述权利要求中任一项制造的多孔金属材料。
CN201580016476.7A 2014-03-24 2015-03-24 用于制造用于生物医学应用的多孔金属材料的方法和通过所述方法获得的材料 Active CN106163580B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
ES201430408A ES2476065B1 (es) 2014-03-24 2014-03-24 Procedimiento para la fabricación de un material metálico poroso para aplicaciones biomédicas y material obtenido por dicho procedimiento
ESP201430408 2014-03-24
PCT/EP2015/056253 WO2015144702A1 (en) 2014-03-24 2015-03-24 Method for manufacturing a porous metal material for biomedical applications and material obtained by said method

Publications (2)

Publication Number Publication Date
CN106163580A true CN106163580A (zh) 2016-11-23
CN106163580B CN106163580B (zh) 2020-06-26

Family

ID=51063905

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201580016476.7A Active CN106163580B (zh) 2014-03-24 2015-03-24 用于制造用于生物医学应用的多孔金属材料的方法和通过所述方法获得的材料

Country Status (8)

Country Link
US (1) US20170100775A1 (zh)
EP (1) EP3122497B1 (zh)
CN (1) CN106163580B (zh)
DK (1) DK3122497T3 (zh)
ES (2) ES2476065B1 (zh)
PL (1) PL3122497T3 (zh)
PT (1) PT3122497T (zh)
WO (1) WO2015144702A1 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111450783A (zh) * 2020-04-08 2020-07-28 广州赛隆增材制造有限责任公司 超临界水氧化反应器用改性蒸发壁的制备方法

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103534538A (zh) 2011-03-08 2014-01-22 阿文戈亚太阳能公司 槽式太阳能集热器模块
DE102016226048A1 (de) * 2016-12-22 2018-06-28 Meotec GmbH & Co. KG Strukturiertes Leichtmetallbauteil
CN111230128B (zh) * 2020-03-11 2022-12-20 昆明理工大学 一种基于TiH2添加CaO制备多孔钛及钛合金的方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1490058A (zh) * 2002-10-18 2004-04-21 中国科学院金属研究所 一种生物活性钛及钛合金硬组织植入材料的制备方法
CN1695744A (zh) * 2005-06-14 2005-11-16 河北工业大学 用作人工骨骼的钛或钛合金生物医学材料及其制备方法
CN101537208A (zh) * 2008-03-21 2009-09-23 中国科学院金属研究所 一种钛或钛合金表面生物活性涂层及其制备方法
WO2013086504A1 (en) * 2011-12-09 2013-06-13 The Curators Of The University Of Missouri Method for fabricating biocompatible porous titanium

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0119652D0 (en) * 2001-08-11 2001-10-03 Stanmore Implants Worldwide Surgical implant
US8500843B2 (en) * 2004-07-02 2013-08-06 Praxis Powder Technology, Inc. Controlled porosity article
CN100493624C (zh) * 2006-04-07 2009-06-03 中国科学院金属研究所 一种生物医用多孔钛植入体及其制备方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1490058A (zh) * 2002-10-18 2004-04-21 中国科学院金属研究所 一种生物活性钛及钛合金硬组织植入材料的制备方法
CN1695744A (zh) * 2005-06-14 2005-11-16 河北工业大学 用作人工骨骼的钛或钛合金生物医学材料及其制备方法
CN101537208A (zh) * 2008-03-21 2009-09-23 中国科学院金属研究所 一种钛或钛合金表面生物活性涂层及其制备方法
WO2013086504A1 (en) * 2011-12-09 2013-06-13 The Curators Of The University Of Missouri Method for fabricating biocompatible porous titanium

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111450783A (zh) * 2020-04-08 2020-07-28 广州赛隆增材制造有限责任公司 超临界水氧化反应器用改性蒸发壁的制备方法
CN111450783B (zh) * 2020-04-08 2022-02-01 广州赛隆增材制造有限责任公司 超临界水氧化反应器用改性蒸发壁的制备方法

Also Published As

Publication number Publication date
ES2476065A1 (es) 2014-07-11
EP3122497A1 (en) 2017-02-01
PL3122497T3 (pl) 2021-04-06
ES2819280T3 (es) 2021-04-15
ES2476065B1 (es) 2015-03-09
CN106163580B (zh) 2020-06-26
EP3122497B1 (en) 2020-06-17
WO2015144702A1 (en) 2015-10-01
US20170100775A1 (en) 2017-04-13
PT3122497T (pt) 2020-09-16
DK3122497T3 (da) 2020-09-21

Similar Documents

Publication Publication Date Title
Uppal et al. Magnesium based implants for functional bone tissue regeneration–A review
KR101670435B1 (ko) 생체 분해성 스텐트 및 이의 제조 방법
Fattah-Alhosseini et al. A review of effective strides in amelioration of the biocompatibility of PEO coatings on Mg alloys
US11376349B2 (en) Biodegradable iron-containing compositions, methods of preparing and applications therefor
EP2457601B1 (de) Markerkomposit und medizinisches Implantat mit einem Röntgenmarker
DE102007023284A1 (de) Implantat mit einer oberflächennahen magnesiumhaltigen Diffusionsschicht und dazugehöriges Herstellungsverfahren
JP2007512083A (ja) 骨組織再生のための生体吸収性プラグインプラントおよび方法
CN104195368A (zh) 一种Zn-Sr系锌合金及其制备方法与应用
CN106163580A (zh) 用于制造用于生物医学应用的多孔金属材料的方法和通过所述方法获得的材料
Beltrán et al. Biofunctional and tribomechanical behavior of porous titanium substrates coated with a bioactive glass bilayer (45S5–1393)
Nilawar et al. Surface engineering of biodegradable implants: Emerging trends in bioactive ceramic coatings and mechanical treatments
US8257445B2 (en) Bone-compatible implant and method of producing the same
PL226891B1 (pl) Sposób wytwarzania implantu kostnego iimplant kostny
Yazdimamaghani et al. In vitro analysis of Mg scaffolds coated with polymer/hydrogel/ceramic composite layers
CN115414526B (zh) 一种仿生学结构的生物降解锌合金承重骨支架及加工方法
CN114748686B (zh) 一种个性化锌合金骨植入物及其制备方法与应用
KR100441765B1 (ko) 초미세 생체활성 다공성 표면을 갖는 생체 재료용티타늄계 합금 및 그 제조방법
KR101806373B1 (ko) 비대칭적 pei/plga 이중 코팅을 통해 부식저항성 및 혈관재협착 억제효과를 갖는 마그네슘 스텐트 및 이의 제조방법
Khanna et al. Biomaterials for implants
WO2015064130A1 (ja) 生体用インプラント
WO2018187756A1 (en) Bioresorbable magnesium-based sponge and foam materials, methods and devices
Bütev Öcal Designing of Ti-Mg composites for various applications
von Wilmowsky et al. Osseointegration of chemically modified titanium surfaces: an in vivo study
DE102008026558A1 (de) Elektrochemisches Tauchverfahren in einem wässrigen Elektrolyt zur Erzeugung einer biologisch degradationsstabilen Oberflächenschicht auf Grundkörpern aus Titan oder Titanbasislegierungen
Bernard Surface modification and fatigue behavior of nitinol for load bearing implants

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 1230108

Country of ref document: HK

GR01 Patent grant
GR01 Patent grant