WO2006000143A1 - Metal microcapsule for transplanting cell and tissue - Google Patents
Metal microcapsule for transplanting cell and tissue Download PDFInfo
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- WO2006000143A1 WO2006000143A1 PCT/CN2005/000804 CN2005000804W WO2006000143A1 WO 2006000143 A1 WO2006000143 A1 WO 2006000143A1 CN 2005000804 W CN2005000804 W CN 2005000804W WO 2006000143 A1 WO2006000143 A1 WO 2006000143A1
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- microcapsule
- metal
- titanium
- microcapsules
- base material
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- 239000003094 microcapsule Substances 0.000 title claims abstract description 64
- 229910052751 metal Inorganic materials 0.000 title claims abstract description 47
- 239000002184 metal Substances 0.000 title claims abstract description 40
- 239000000463 material Substances 0.000 claims abstract description 32
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000010936 titanium Substances 0.000 claims abstract description 26
- 229910052719 titanium Inorganic materials 0.000 claims abstract description 26
- 238000002054 transplantation Methods 0.000 claims abstract description 13
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000000956 alloy Substances 0.000 claims abstract description 9
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052742 iron Inorganic materials 0.000 claims abstract description 5
- 229910001069 Ti alloy Inorganic materials 0.000 claims description 9
- 239000007769 metal material Substances 0.000 claims description 7
- 238000007747 plating Methods 0.000 claims description 7
- 238000000576 coating method Methods 0.000 claims description 6
- 239000011248 coating agent Substances 0.000 claims description 5
- 239000010931 gold Substances 0.000 claims description 4
- 229910052737 gold Inorganic materials 0.000 claims description 4
- 230000007774 longterm Effects 0.000 abstract description 4
- 239000012528 membrane Substances 0.000 abstract description 3
- 229910045601 alloy Inorganic materials 0.000 abstract description 2
- 238000001727 in vivo Methods 0.000 abstract description 2
- 230000004083 survival effect Effects 0.000 abstract description 2
- 239000004005 microsphere Substances 0.000 abstract 3
- 239000011148 porous material Substances 0.000 abstract 2
- 230000003247 decreasing effect Effects 0.000 abstract 1
- 230000004962 physiological condition Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 30
- 238000003466 welding Methods 0.000 description 10
- 238000004381 surface treatment Methods 0.000 description 7
- 238000004140 cleaning Methods 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 230000006870 function Effects 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 4
- 239000002861 polymer material Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 230000007797 corrosion Effects 0.000 description 2
- 238000005260 corrosion Methods 0.000 description 2
- 238000002788 crimping Methods 0.000 description 2
- 238000009713 electroplating Methods 0.000 description 2
- 210000004153 islets of langerhan Anatomy 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000000823 artificial membrane Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000004053 dental implant Substances 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000005323 electroforming Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 238000001879 gelation Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000002650 immunosuppressive therapy Methods 0.000 description 1
- 238000005495 investment casting Methods 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 238000002324 minimally invasive surgery Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
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- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
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- 241001308709 unidentified virus Species 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/501—Inorganic compounds
Definitions
- the molecular mass, strength, chemical composition of the polymer material, and the thickness or number of layers of the encapsulating film change the permeability of the film.
- the micro-package is prepared.
- the concentration of the polymer solution used in the capsule, the time of the gelation reaction, the pH of the system, and the type and amount of the additive all have a significant effect on the permeability and biocompatibility of the membrane, allowing the cells to be embedded. Loss of apoptosis or function.
- microencapsulation of such materials often finds problems of excessive volume during the transplantation process.
- the present invention has the following technical effects: (1) using the metal microcapsules to embed biological cells, which can reduce the volume of the transplanted microcapsules, and enable the microcapsules to be transplanted into the human body. It does not cause water swelling in a physiological environment, so that the implanted cells can function normally and have long-term stability in the body; (2)
- the metal microcapsules are harmless to the human body and have good biocompatibility. Made of metal or alloy material, such as titanium metal, due to its light weight, good biocompatibility, non-toxicity, good corrosion resistance, good stability in the body, small thermal expansion coefficient, high melting point, etc., thus avoiding the use of polymer materials. Disadvantages: low mechanical strength, unclear degradation, short service life, exposure of xenogeneic cells to the human body may lead to problems such as unidentified viruses entering the human body and gene transfer. detailed description
- the base material is used as the base material; the base material is used as the base material in the diameter of the base material of the base material;
- the surface is plated with titanium coating, and then cut to obtain a bowl-shaped hemisphere. After cleaning and surface treatment on the hemisphere, the living cells are placed into the titanium hemisphere and assembled into microcapsules. The two hemispheres are spot welded at the seam. Welding is performed. .
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Prostheses (AREA)
- Materials For Medical Uses (AREA)
Abstract
The present invention disclosed a kind of metallic microcapsule for transplanting living cells and tissues. The said metallic microcapsule is based on biocompatible metal or alloy, such as titanium, aurum, iron, etc. The base materials of the microcapsule are coated or covered with a layer of titanium or alloyed titanium. The metallic microcapsules are hollow microspheres whereas some active cells or tissues for transplantation are put inside. 'The outside radius of the microsphere is generally between 0.05mm and 5mm. The thickness of membrane wall of the microsphere is generally between 0.001mm and 0.5mm. There are essential round shaped pores in the membrane walls whereas the radius of the pore is between 0.00005mm and 0.01mm. The volume of the transplanting microcapsule is decreased and the metallic microcapsules will not swell under physiological conditions after transplanting to the human body when the metallic microcapsule are used to encapsulate biological cells. As a result, the metallic microcapsules can maintain a long-term stability in vivo and prolong survival of the functional tissues or cells.
Description
细胞和组织移植用金属微囊 . 技术领域 Metal microcapsules for cell and tissue transplantation.
本发明涉及一种细胞微囊，特别是涉及采用金属或合金材料制成对生物细胞或组织进行 包埋移植的微囊。 The present invention relates to a cell microcapsule, and more particularly to a microcapsule made of a metal or alloy material for embedding a biological cell or tissue.
-背景技术 -Background technique
大多'数做完细胞或器官移植手术的患者在经历了痛苦的移植手术后，仍需花费一生的时 间进行免疫抑制治疗， 以对抗免疫排斥反应。 目前，一个解决方案是将外源性的细胞或器官 包埋在半透明性的人工膜中， 进行隔离，然后再移植到体内， 从而避兔植入的细胞或器官与 具有兔疫效应的细胞和体液进行直接接触， 从而起到免疫隔离的作用。 该技术起源于 20世 纪 60年代， 通常采用具有凝胶态的天然高分子材料或合成高分子材料作为微包囊的材料， 如藻酸盐， 琼脂， 壳聚糖， 聚丙烯酸脂， 聚乙 醇， 聚丙烯腈一氯乙烯共聚物等。 从材料方 面考虑， 高分子材料的分子质量， 强度，化学组成以及包囊膜的厚度或层数等的变化会使膜 的通透性发生变化， 从微包囊的制备工艺考虑，制作微包囊所用高聚物溶液的浓度，凝胶化 反应的时 |¾， 体系 PH值以及添加剂的种类和用量等都会对膜的通透性和生物相容性产生显 著影响， 使细胞在包埋过程中凋亡或功能丧失。而且， 这类材料的微包囊在移植过程中， 发 现往往存在体积过大的问题。例如以胰岛细胞移植为例， 为维持人体正常的血糖水平， 一般 应该维持 15， 000〜20, 000 islets/kg的人体重量浓度水平， 当采用通常制备的直径为 500 μ πι左右的微包囊时， 则为达到与一个胰岛所具有的相同数目胰岛细胞， 所需的微包囊总体 积约为一个标准胰岛体积^ 37倍。 同时， 在生理环境下， 釆用凝聚态材料制成的微包囊还 会发生吸水膨胀，导致微包囊体积变大和变形，从而会影响细胞功 的正常发挥和在体内的 长期稳定性。 发明内容 Most patients who have undergone cell or organ transplant surgery will spend a lifetime of immunosuppressive therapy to combat immune rejection after a painful transplant. At present, a solution is to embed exogenous cells or organs in a translucent artificial membrane, isolate them, and then transplant them into the body, thereby avoiding cells or organs implanted in rabbits and cells having a rabbit effect. Direct contact with body fluids to provide immune isolation. The technology originated in the 1960s, and usually uses a gelatinous natural polymer material or a synthetic polymer material as a material for microencapsulation, such as alginate, agar, chitosan, polyacrylate, polyethanol, Polyacrylonitrile-vinyl chloride copolymer and the like. From the material point of view, the molecular mass, strength, chemical composition of the polymer material, and the thickness or number of layers of the encapsulating film change the permeability of the film. From the preparation process of the microcapsule, the micro-package is prepared. The concentration of the polymer solution used in the capsule, the time of the gelation reaction, the pH of the system, and the type and amount of the additive all have a significant effect on the permeability and biocompatibility of the membrane, allowing the cells to be embedded. Loss of apoptosis or function. Moreover, microencapsulation of such materials often finds problems of excessive volume during the transplantation process. For example, in islet cell transplantation, in order to maintain the normal blood sugar level of the human body, the body weight concentration level of 15,000 to 20,000 islets/kg should generally be maintained, and a microcapsule having a diameter of about 500 μππ is usually prepared. At the time, to achieve the same number of islet cells as one islet, the total microcapsule volume required is about 37 times the standard islet volume. At the same time, under the physiological environment, the microcapsules made of condensed materials will also swell and cause the microcapsules to become larger and deformed, which will affect the normal function of cell function and long-term stability in vivo. Summary of the invention
本发明所要解决的技术问题是克服上述现有技术中的不足，提挺采用金属或合金材料制 成的对生物细胞或组织进行包埋移植的微囊，利用该金属微囊对生物细胞进行细胞包埋， 能 The technical problem to be solved by the present invention is to overcome the deficiencies in the prior art mentioned above, and to use a microcapsule for embedding and transplanting biological cells or tissues made of metal or alloy material, and using the metal microcapsules to perform cells on biological cells. Embedding
1 1
替换页
够减小移植的微包囊体积， 使微包囊移植入人体后， 不会在生理环境下发生吸水膨胀现象， 使植入的细胞能正常发挥其功能和在体内的长期稳定性。 Replacement page It is enough to reduce the volume of the transplanted microcapsules, so that after the microcapsules are transplanted into the human body, the water swelling phenomenon does not occur under the physiological environment, so that the implanted cells can normally exert their functions and long-term stability in the body.
为解决上述技术问题，本发明的细胞和组织移植用金属微囊由具有良好生物兼容性的金 属或合金材料制成， 金属微囊基本呈空心球状，其内空腔用于放置经分离、处理后的若干细 胞或生物组织； 所述金属微囊的外半径在 0..05〜5mm之间， 金属微囊的囊壁厚在 0. 001〜 0. 5mm之间， 金属微囊的囊壁上设置有若干基本呈圆形的通孔， 通孔的直径在 0. 00005〜 0. 01mm之间。 In order to solve the above technical problems, the metal microcapsules for cell and tissue transplantation of the present invention are made of a metal or alloy material having good biocompatibility, and the metal microcapsules are substantially hollow spheres, and the inner cavity is used for separation and treatment. And the outer wall of the metal microcapsules is between 0.. Between 0. 00005〜 0. 01毫米之间。 The diameter of the through hole is 0. 00005~ 0. 01mm.
所述金属微囊可以由钛制成。 所述金属微囊也可以由钛合金制成。 The metal microcapsules may be made of titanium. The metal microcapsules may also be made of a titanium alloy.
所述金属微囊可以是由金作为基底材料制成，该基底材料的表面设置有钛镀层；所述金 属微囊可以是由金作为基底材料制成， 该基底材料的表面设置有钛合金镀层。 The metal microcapsule may be made of gold as a base material, the surface of the base material is provided with a titanium plating layer; the metal microcapsule may be made of gold as a base material, and the surface of the base material is provided with a titanium alloy plating layer .
所述金属微囊也可以是由铁作为基底材料制成，该基底材料的表面设置有钛镀层；所述 金属微囊由铁作为基底材料制成， 该基底材料的表面设置有钛合金镀层。 The metal microcapsules may also be made of iron as a base material, the surface of which is provided with a titanium plating layer; the metal microcapsules are made of iron as a base material, and the surface of the base material is provided with a titanium alloy plating layer.
所述的微囊由两个碗状半球组成， 两个碗状半球之间通过紧配合、压接、粘接或激光焊 接方式连接为一个整体。 The microcapsules are composed of two bowl-shaped hemispheres, and the two bowl-shaped hemispheres are connected as a whole by tight fitting, crimping, bonding or laser welding.
与现有技术相比， 本发明具有以下技术效果： （一）利用该金属微囊对生物细胞进行细 胞包埋，'能够减小移植的微包囊体积， 使微包囊移植入人体后， 不会在生理环境下发生吸水 膨胀现象， 使植入的细胞能正常发挥其功能和在体内的长期稳定性； （二）金属微囊采用对 人体无害且具有较好的生物相容性的金属或合金材料制成， 如钛金属， 由于重量轻、生物相 容性好、 无毒性、耐腐蚀性好、 体内安定性良好、热膨胀系数小、熔点高等优点， 从而可避 免了采用高分子材料所具有的弊端： 机械强度低、 降解去向不明、使用寿命短、使异种细胞 暴露在人体内可能导致不明病毒进入人体和基因转移等问题。 具体实施方式 Compared with the prior art, the present invention has the following technical effects: (1) using the metal microcapsules to embed biological cells, which can reduce the volume of the transplanted microcapsules, and enable the microcapsules to be transplanted into the human body. It does not cause water swelling in a physiological environment, so that the implanted cells can function normally and have long-term stability in the body; (2) The metal microcapsules are harmless to the human body and have good biocompatibility. Made of metal or alloy material, such as titanium metal, due to its light weight, good biocompatibility, non-toxicity, good corrosion resistance, good stability in the body, small thermal expansion coefficient, high melting point, etc., thus avoiding the use of polymer materials. Disadvantages: low mechanical strength, unclear degradation, short service life, exposure of xenogeneic cells to the human body may lead to problems such as unidentified viruses entering the human body and gene transfer. detailed description
许多金属和合金由于对人体无害， 较好的生物相容性等优点而被广泛应用于临床治疗 中， 例如钛金属由于重量轻、 生物相容性好、无毒性、耐腐蚀性好、 体内安定性良好、 热膨 胀系数小、熔点高等优点而得到广泛的应用， 尤其在口腔医学中的牙体种植中。通过精密铸 造将钛金属制成半球或半胶囊状的薄壳，然后通过镀膜工艺，在金属表面镀上一层防止氧化 反应的薄膜。采用激光打孔技术在镀膜后的薄壳上打上一排排小进制通孔，这些小通孔允许 维持细胞存活的营养物质和氧的供给以及细胞代谢产生的废物排除，同时保证细胞分泌产生
的特定因子可以通过扩散作用进入全身的细胞外间隙，并且具有免疫效应的细胞不能通过小 通孔与移植细胞进行直接接触， 从而起到免疫隔离作用。将需移植的细胞放入薄壳中， 将两 个半球或半胶囊状的薄壳通过点焊的方式在接缝处进行焊接。最后将焊接好的微胶囊通过微 创手术植入人体内。 Many metals and alloys are widely used in clinical treatment because of their harm to the human body and good biocompatibility. For example, titanium metal is light in weight, biocompatible, non-toxic, and has good corrosion resistance. It has a wide range of applications due to its good stability, small coefficient of thermal expansion and high melting point, especially in dental implants in stomatology. The titanium metal is formed into a hemispherical or semi-capsule-shaped thin shell by precision casting, and then a metal film is coated with a film for preventing oxidation reaction by a coating process. Laser punching technology is used to apply a row of small-sized through-holes on the coated thin shell. These small through-holes allow the supply of nutrients and oxygen to maintain cell survival and the elimination of waste generated by cell metabolism, while ensuring cell secretion. The specific factor can enter the extracellular space of the whole body through diffusion, and the cells with immune effect can not directly contact the transplanted cells through the small through hole, thereby playing an immune isolation. The cells to be transplanted are placed in a thin shell, and two hemispheres or semi-capsule-shaped shells are welded at the seam by spot welding. Finally, the welded microcapsules are implanted into the human body through minimally invasive surgery.
本发明的对生物细胞或组织进行包埋移植的金属微囊基本呈空心球状，由两个碗状半 '球 组成。 釆用具有良好生物兼容性的金属或合金材料制成。 将该金属或合金制成壁厚 0. 001〜 0. 5mm, 半径在 0. 05〜5mm 的碗状半球， 视应用场合的不同在半球的球壁上打 0. 00005〜 0. 01mm 的小通孔， 将分离、 处理后的若干细胞或生物组织放入半球中， 然后通过紧配合、 压接、粘接或激光焊接等方式将两个半球合为一个整体， 成为金属或合金材料制成微囊， 然 后移植到人或生物体内。 用于疾病的治疗或替代某种器官的功能。 The metal microcapsules for embedding and transplanting biological cells or tissues of the present invention have a substantially hollow spherical shape and are composed of two bowl-shaped semi-balls.制成 Made of metal or alloy materials with good biocompatibility. 00005〜 0. 01毫米的小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小小Through holes, the separated or treated cells or biological tissues are placed in a hemisphere, and then the two hemispheres are combined into a whole by tight fitting, crimping, bonding or laser welding, and are made of metal or alloy material. The microcapsules are then transplanted into a human or organism. Used to treat or replace the function of an organ.
实施例之一： One of the examples:
在石蜡或塑料上加工出半径为 0. 05mm的凹面， 然后采用电镀（电铸） 的方法将纯钛镀 在石蜡或塑料模具上，壁厚为 0. 001腿，经过加热脱模、用激光打直径为 0. 00005mm的通孔， 而后切割得到碗状的钛半球， 在半球上， 经过清洗、表面处理， 将活细胞放入钛半球后组装 成微囊， 将两个半球通过点焊的方式在接缝处进行焊接。 The concave surface of a radius of 0. 05mm is processed on a paraffin or a plastic, and the pure titanium is plated on a paraffin or a plastic mold by electroplating (electroforming), the wall thickness is 0.001 leg, and the mold is heated and released by a laser. The through hole with a diameter of 0. 00005mm is cut, and then the bowl-shaped titanium hemisphere is obtained. After cleaning and surface treatment on the hemisphere, the living cells are put into the titanium hemisphere and assembled into microcapsules, and the two hemispheres are spot welded. The way to weld at the seam.
实施例之二: Embodiment 2:
在半径为 1. 2mm凹面规律排列的金箔上，通过电镀或离子喷镀的方式在金箔表面镀上一 层钛金属， '壁厚为 0. 11腿， 再用激光打直径为 0. 0002醒的通孔、 而后切割得到碗状的钛半 球， 在半球上， 经过清洗、表面处理， 将活细胞放入钛半球后组装成微囊， 将两个半球通过 点焊的方式在接缝处进行焊接。 0002醒。 The surface of the gold foil is plated with a layer of titanium metal, a wall thickness of 0. 11 legs, and then a laser with a diameter of 0. 0002 awake The through hole is then cut to obtain a bowl-shaped titanium hemisphere. After cleaning and surface treatment on the hemisphere, the living cells are placed into the titanium hemisphere and assembled into microcapsules. The two hemispheres are spot welded at the seam. welding.
实施例之三： Third embodiment:
用模具将钛合金成型为半径为 2. 4mm凹面的规律排列钛箔， 壁厚为 0. 22mm， 再用激光 打直径为 0. 003mm的通孔， 而后切割得到碗状的钛半球， 在半球上， 经过清洗、 表面处理， 将活细胞放入钛半球后组装成微囊， 将两个半球通过点焊的方式在接缝处进行焊接。 The titanium alloy is formed into a regular shape of a titanium foil having a radius of 2. 4 mm, and the wall thickness is 0.22 mm, and then a laser is used to punch a through hole having a diameter of 0.003 mm, and then a bowl of titanium hemisphere is obtained, in the hemisphere. After cleaning, surface treatment, the living cells are placed into the titanium hemisphere and assembled into microcapsules, and the two hemispheres are welded at the joint by spot welding.
实施例之四： Embodiment 4:
在模具上将金成型为半径为 2. 6醒凹面并规律排列的金箔， 壁厚为 0. 29ram， 用激光打 直径为 0. 005mm的通孔， 以此作为基底材料； 在该基底材料的表面电镀上钛镀层， 而后切割 得到碗状的半球， 在半球上， 经过清洗、表面处理， 将活细胞放入钛半球后组装成微囊， 将 两个半球通过点焊的方式在接缝处进行焊接。
实施例之五： The base material of the base material is formed by using a laser to make a through hole having a diameter of 0. 005 mm, using a laser to form a gold foil having a radius of 2.6. The surface is plated with titanium coating, and then cut to obtain a bowl-shaped hemisphere. After cleaning and surface treatment on the hemisphere, the living cells are placed into the titanium hemisphere and assembled into microcapsules. The two hemispheres are spot welded at the seam. Welding is performed. Example 5:
在模具上将金成型为半径为 3. 8mm凹面并规律排列的金箔， 壁厚为 0. 41mm， 用激光打 直径为 0. 007mm的通孔， 以此作为基底材料； 在该基底材料的表面电镀上钛合金镀层， 而后 切割得到碗状的半球，在半球上，经过清洗、表面处理，将活细胞放入钛半球后组装成微囊， 将两个半球通过点焊的方式在接缝处进行焊接。 The surface of the substrate material is formed by using a laser to make a through hole having a diameter of 0. 007 mm as a base material; Electroplating a titanium alloy coating, and then cutting to obtain a bowl-shaped hemisphere. After cleaning and surface treatment on the hemisphere, the living cells are placed into the titanium hemisphere and assembled into microcapsules. The two hemispheres are spot welded at the seam. Welding is performed.
实施例之六： Sixth embodiment:
在模具上将铁成型为半径为 4. 6mm凹面并规律排列的铢箔， 壁厚为 0. 45mm， 用激光打 直径为 0. 008mm的通孔， 以此作为基底材料； 在该基底材料的表面电镀上钛镀层， 而后切割 得到碗状的半球， 在半球上， 经过清洗、表面处理， 将活细胞放入钛半球后组装成微囊， 将 两个半球通过点焊的方式在接缝处进行焊接。 . The base material is used as the base material; the base material is used as the base material in the diameter of the base material of the base material; The surface is plated with titanium coating, and then cut to obtain a bowl-shaped hemisphere. After cleaning and surface treatment on the hemisphere, the living cells are placed into the titanium hemisphere and assembled into microcapsules. The two hemispheres are spot welded at the seam. Welding is performed. .
实施例之七： Seventh embodiment:
在模具上将铁成型为半径为 4. 9mm凹面并规律排列的铁箔 壁厚为 0. 48mm， 用激光打 直径为 0. 009皿的通孔， 以此作为基底材料； 在该基底材料的表面电镀上钛合金镀层， 而后 切割得到碗状的半球；在半球上，经过清洗、表面处理，将活细胞放入钛半球后组装成微囊， 将两个半球通过点焊的方式在接缝处进行焊接。
The base material of the substrate material is formed by using a laser to make a through hole having a diameter of 0.49 mm and a regular arrangement of the iron foil having a radius of 4. 9 mm and a regular thickness of 0. 48 mm. The surface is plated with a titanium alloy coating, and then cut to obtain a bowl-shaped hemisphere; on the hemisphere, after washing and surface treatment, the living cells are placed into the titanium hemisphere and assembled into microcapsules, and the two hemispheres are welded by spot welding. Welding is carried out.
Claims
1. 一种细胞和组织移植用金属微囊， 其特征在于， 所述金属微囊由具有良好生物兼容 性的金属或合金材料制成， 金属微囊基本呈现空心球状， 其内空腔用于放置经分离、处理后 的若干细胞或生物组织； 所述金属微囊的外半径在 0. 05〜5薩之间， 金属微囊的囊壁厚在 0. 001〜0. 5ram之间， 金属微囊的囊壁上设置有若干基本呈圆形的通孔， 通孔的直径在 0. 00005~0. 01隱之间。 A metal microcapsule for cell and tissue transplantation, characterized in that the metal microcapsule is made of a metal or alloy material having good biocompatibility, and the metal microcapsule substantially has a hollow spherical shape, and the inner cavity is used for the cavity. Between Between 0. 001~0. 5 ram, metal, between the outer and the outer surface of the metal microcapsules. 0005之间之间之间。 The microcapsules are provided with a plurality of substantially circular through holes, the diameter of the through holes is between 0. 00005~0. 01 hidden.
2. 根据权利要求 1所述的细胞和组织移植用金属微囊， 其特征在于， 所述金属微囊由 钛制成。 The metal microcapsule for cell and tissue transplantation according to claim 1, wherein the metal microcapsule is made of titanium.
3. 根据权利要求 1所述的细胞和组织移植用金属微囊， 其特征在于， 所述金属微囊由 钛合金制成。 The metal microcapsule for cell and tissue transplantation according to claim 1, wherein the metal microcapsule is made of a titanium alloy.
4. 根据权利要求 1所述的细胞和组织移植用金属微囊， 其特征在于 5 所述金属微囊由 金作为基底材料制成， 该基底材料的表面设置有钛镀层。 、4. The cell of claim 1 and claim tissue transplantation metal microcapsule, wherein the microcapsule 5, wherein the metal is made of gold as a base material, the surface of the base material is provided with a titanium coating. ,
5. 根据权利要求 1所述的细胞和组织移植用金属微囊， 其特征在于， 所述金属微囊由 金作为基底材料制成， 该基底材料的表面设置有钛合金镀层。 The metal microcapsule for cell and tissue transplantation according to claim 1, wherein the metal microcapsule is made of gold as a base material, and a surface of the base material is provided with a titanium alloy plating layer.
6. 根据权利要求 1所述的细胞和组织移植用金属微囊， 其特征在于， 所述金属微囊由 铁作为基底材料制成， 该基底材料的表面设置有钛镀层。 The metal microcapsule for cell and tissue transplantation according to claim 1, wherein the metal microcapsule is made of iron as a base material, and a surface of the base material is provided with a titanium plating layer.
7. 根 权利要求 1所述的细胞和组织移植用金属微囊， 其特征在于， 所述金属微囊由 铁作为基底材料制成， 该基底材料的表面.设置有钛合金镀层。 7. The metal microcapsule for cell and tissue transplantation according to claim 1, wherein the metal microcapsule is made of iron as a base material, and a surface of the base material is provided with a titanium alloy plating layer.
8. 根据权利要求 1所述的细胞和组织移植用金属微囊， 其特征在于， 所述的微囊由两 个碗状半球组成， 两个碗状半球之间通过紧配合、压接、粘接或激光焊接方式连接为一个整 体。
The metal microcapsule for cell and tissue transplantation according to claim 1, wherein the microcapsule is composed of two bowl-shaped hemispheres, and the two bowl-shaped hemispheres are tightly fitted, crimped, and adhered. Connected or laser welded to form a unit.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200410019819.9 | 2004-06-29 | ||
| CNB2004100198199A CN100457900C (en) | 2004-06-29 | 2004-06-29 | Metal microcapsule for transplanting cell and tissue |
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| Publication Number | Publication Date |
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| WO2006000143A1 true WO2006000143A1 (en) | 2006-01-05 |
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| PCT/CN2005/000804 WO2006000143A1 (en) | 2004-06-29 | 2005-06-08 | Metal microcapsule for transplanting cell and tissue |
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| WO (1) | WO2006000143A1 (en) |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002070028A1 (en) * | 2001-03-05 | 2002-09-12 | Bio-Smart, Ltd. | Composition of porous element for biomaterial |
| WO2003013396A1 (en) * | 2001-08-11 | 2003-02-20 | Stanmore Implants Worldwide Ltd. | Surgical implant |
| US20040167633A1 (en) * | 2003-02-24 | 2004-08-26 | Depuy Products, Inc. | Metallic implants having roughened surfaces and methods for producing the same |
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2004
- 2004-06-29 CN CNB2004100198199A patent/CN100457900C/en not_active Expired - Fee Related
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002070028A1 (en) * | 2001-03-05 | 2002-09-12 | Bio-Smart, Ltd. | Composition of porous element for biomaterial |
| WO2003013396A1 (en) * | 2001-08-11 | 2003-02-20 | Stanmore Implants Worldwide Ltd. | Surgical implant |
| US20040167633A1 (en) * | 2003-02-24 | 2004-08-26 | Depuy Products, Inc. | Metallic implants having roughened surfaces and methods for producing the same |
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| CN1594561A (en) | 2005-03-16 |
| CN100457900C (en) | 2009-02-04 |
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