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WO2001082987A1 - Procede de fabrication d'un support multipore de reparation de tissus et d'organes - Google Patents

Procede de fabrication d'un support multipore de reparation de tissus et d'organes Download PDF

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Publication number
WO2001082987A1
WO2001082987A1 PCT/IB2001/000632 IB0100632W WO0182987A1 WO 2001082987 A1 WO2001082987 A1 WO 2001082987A1 IB 0100632 W IB0100632 W IB 0100632W WO 0182987 A1 WO0182987 A1 WO 0182987A1
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WO
WIPO (PCT)
Prior art keywords
preparation
pore
product
acid
solution
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.)
Ceased
Application number
PCT/IB2001/000632
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English (en)
Chinese (zh)
Other versions
WO2001082987A8 (fr
Inventor
Ping Hu
Lingfei Jiang
Feng Gao
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.)
Tsinghua University
CLONETIC TECHNOLOGIES Ltd
Original Assignee
Tsinghua University
CLONETIC TECHNOLOGIES Ltd
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 Tsinghua University, CLONETIC TECHNOLOGIES Ltd filed Critical Tsinghua University
Priority to AU2001246763A priority Critical patent/AU2001246763A1/en
Publication of WO2001082987A1 publication Critical patent/WO2001082987A1/fr
Publication of WO2001082987A8 publication Critical patent/WO2001082987A8/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • 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

Definitions

  • the invention relates to the field of biomedical engineering. Specifically, it relates to a method for preparing a porous scaffold for organ and tissue repair. Background technique
  • Tissue and organ loss or dysfunction is one of the major hazards to human health, and it is also the leading cause of human disease and death. According to a data from the United States, millions of Americans suffer from various tissue and organ loss and dysfunction each year, and require 8 million operations to repair each year, with annual hospitalization days between 40-90 million. , Costing more than $ 400 billion annually. China is a country with a large population. The number of cases of tissue, organ loss or dysfunction caused by trauma and disease is the highest in the world. Every year, there are millions of patients who need skin transplantation because of burns.
  • tissue engineering It is a science that applies the principles of cell biology and engineering to the research and development of biological alternatives that repair and improve the scab and function of damaged tissues.
  • the basic principle and method is to adsorb normal tissue cells expanded and cultured in vitro on a porous biomaterial with good biocompatibility and absorbed by the body to form a complex, and implant the cell-biomaterial complex into the body tissues and organ In the damaged part, the cells form new corresponding tissues and organs with morphology and functions during the process of biological materials being gradually degraded and absorbed by the body, so as to achieve the purpose of repairing wounds and reconstructing functions.
  • the scaffold material plays a very important role in tissue engineering research, and it is the key to the industrialization of tissue engineering. And the processing method of the stent material plays an extremely important role in it.
  • Tissue engineering scaffolds need high porosity and pores communicate with each other, because only after the cells are implanted can they enter the inside of the stent, and the tissues formed in the future can be uniform. High porosity allows for water, inorganic salts and
  • tissue engineering scaffolds should be higher than 90%.
  • Non-woven fiber method which has the advantage of high porosity, but it is difficult to maintain the predetermined shape after implantation in the body
  • Solution casting, porogen Filtration method the content of pore-forming agent used in this method is low, because the solution is cast into the device, which causes the pore-forming agent to sink, the pores are unevenly distributed, and the upper and lower surface morphologies are different;
  • the porous membrane is then bonded to each other by a solvent to form a three-dimensional scaffold.
  • the method is complicated, and during the bonding process, the holes of the bonding part are closed, thereby forming an interface and making the internal shape of the material uneven.
  • Melt processing method This method is to blend the pore former and polymer into the mold above the melting point of the polymer, and cool it to obtain a porous stent of a predetermined shape.
  • the disadvantage of this method is that the melt It has a large difference from the density of the pore-forming agent, so it is difficult to mix uniformly, and some polymers, especially biodegradable polymers, are melt-processed.
  • Thermally degradable; 5 phase separation method the method using the mixture solution was cooled to below the melting point of the solvent, thereby producing a phase separation, and then by vacuum drying to obtain a porous scaffold.
  • High-pressure carbon dioxide method which uses exposing the polymer to high-pressure carbon dioxide, and then dissolves the polymer dissolved in the polymer under reduced pressure. Carbon dioxide is released to form a porous scaffold.
  • the disadvantage of this method is that the pores formed are closed.
  • An object of the present invention is to provide a method with good operability and effective preparation of a porous scaffold for tissue and organ repair.
  • the method has good controllability and can meet the requirements of various tissue engineering projects. Same need.
  • the basic principle of this method is to add a porogen during the forming process of the stent. After the product is formed, the pore-forming agent is extracted, and the space occupied by the original pore-forming agent forms the pores of the future scaffold.
  • the pore-forming agent is sodium chloride, potassium chloride, potassium acetate, sodium bicarbonate, sodium carbonate, citric acid, and citric acid. Potassium and so on.
  • FHB poly 3-hydroxybutyrate
  • PHB copolymer of 3-hydroxybutyric acid and 3-hydroxyhexanoic acid
  • PLB-HH polylactic acid
  • FLA polylactic acid
  • PLGA copolymer of lactic acid and glycolic acid
  • a copolymer of 3-hydroxybutyric acid and 3-hydroxyvaleric acid and one or more of biodegradable polymers such as polyglycolic acid are soluble in chloroform, 1,4-dioxane, 1, One of 2-dichloroethane, 1,4-dioxane-water mixture, pyridine and other solvents, the concentration is 5% ⁇ 303 ⁇ 4
  • the concentration of the biodegradable polymer varies with the type of pore-forming agent selected and the requirement of the pore size of the repaired tissue, It is preferably 6 to: 15%.
  • the mass ratio of the polymer to the pore-forming agent is selected so that the pore-forming agent in the obtained homogeneous mixture does not precipitate and flow normally.
  • the requirements of the cell vary, preferably 1: 15 ⁇ 1: 35; in the preparation method of the present invention, the molding conditions of the mixture in a mold are at 0.;! The mold is closed under a pressure of ⁇ 2 MPa, and then naturally dry at room temperature.
  • the drying of the product in step 5 is performed in a vacuum drying box, the temperature is normal temperature, the pressure is 0.005 MPa ⁇ 0 MPa, and the time is between 24-48 hours.
  • step 6 is a weakly acidic aqueous solution of hydrochloric acid, H + weak acid solution of a concentration between 2M ⁇ 10- 4 M.
  • the volume ratio of the product to deionized water or weakly acidic aqueous solution in step 6 is between 1: 50 ⁇ 1: 200, and the deionized water or acidity is replaced every 5 ⁇ 8 hours.
  • Aqueous solution is between 1: 50 ⁇ 1: 200, and the deionized water or acidity is replaced every 5 ⁇ 8 hours.
  • the re-drying of the product in step 7 is performed in a vacuum drying box, the temperature is normal temperature, and the pressure is 0.01 to 0 MPa. Time is between 24-48 hours.
  • a porous stent with pores communicating with each other can be obtained.
  • the advantage is that the expected pore diameter can be obtained by adjusting the particle diameter of the pore-forming agent; the concentration of the solution can be adjusted to change the pore-forming agent.
  • the pore-forming agent content required for this condition will not be precipitated to obtain stent with pores communicating with each other and having different porosity requirements; meanwhile, the stent obtained by the preparation method of the present invention has a higher porosity of more than 90% At the same rate, the product still meets the requirements for strength of the product, and has uniform hole formation, adjustable material degradation rate, and good product feel.
  • Figure 1 shows the scanning electrons of the surface of a porous poly-3-hydroxybutyrate scaffold obtained by this method.
  • FIG. 2 is a scanning electron microscope image of a cross section of a poly 3-hydroxybutyrate porous scaffold material obtained by this method
  • 3 is a scanning electron microscope image of a cross section of a porous scaffold of a copolymer of 3-hydroxybutyric acid and 3-hydroxyhexanoic acid obtained by this method;
  • Figure 4 shows the appearance of poly 3-hydroxybutyrate porous scaffolds with different porosities obtained by this method
  • Fig. 5 is a diagram showing the effect of generating bone tissue in nude mice after the poly-3-hydroxybutyrate porous scaffold material of the present invention is implanted on bone marrow stromal cells. The best way to implement the invention
  • FIG. 4 shows the appearance of the poly 3-hydroxybutyrate porous scaffold obtained in this example.
  • the polyhydroxybutyrate (FHB) scaffold material prepared in Example 1 was used to construct tissue engineering bones in nude mice. The entire experiment was performed in cooperation with the Tissue Engineering Laboratory of Jaw Surgery, Fourth Military Medical University School of Medicine.
  • the method for preparing a porous scaffold for tissue and organ repair according to the present invention has simple process and easy operation. According to the requirements of the porous scaffold material for actual tissue and organ repair, a porous scaffold with a certain degradation rate and adjustable pore diameter can be obtained. Moreover, the porous scaffold prepared by the method of the invention has good histocompatibility. It can be implanted under the skin of a living body, without obvious inflammation and rejection, without tissue necrosis and fibrous encapsulation, and can be used to construct tissues in immune animals. The engineering bone has a good industrial application prospect.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L'invention concerne un procédé de fabrication d'un support multipore de réparation de tissus et d'organes comprenant les opérations suivantes : tout d'abord sélection puis extraction d'un générateur de pores, dissolution du polymère dégradable dans un dissolvant pour obtenir une solution, addition du générateur de pores dans la solution polymère, homogénéisation du mélange, introduction du mélange dans un moule, fermeture du moule, séchage du contenu, démoulage, introduction du contenu dans une boîte de séchage sous vide, immersion du produit séché dans de l'eau désionisée ou dans une solution aqueuse faiblement acide. Finalement, le produit est séché sous vide et tient lieu de support multipore. Grâce au réglage de la granulométrie du générateur de pores et de la concentration de la solution, on obtient un support présentant des pores et des interstices qui sont mutuellement reliés ainsi qu'un pourcentage de pores pouvant varier.
PCT/IB2001/000632 2000-04-14 2001-04-17 Procede de fabrication d'un support multipore de reparation de tissus et d'organes Ceased WO2001082987A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001246763A AU2001246763A1 (en) 2000-04-14 2001-04-17 A preparation method for a porous framework used in the prostheses of tissue andorgans

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN 00105638 CN1117587C (zh) 2000-04-14 2000-04-14 一种组织和器官修复用多孔支架的制备方法
CN00105638.7 2000-04-14

Publications (2)

Publication Number Publication Date
WO2001082987A1 true WO2001082987A1 (fr) 2001-11-08
WO2001082987A8 WO2001082987A8 (fr) 2002-03-14

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PCT/IB2001/000632 Ceased WO2001082987A1 (fr) 2000-04-14 2001-04-17 Procede de fabrication d'un support multipore de reparation de tissus et d'organes

Country Status (3)

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CN (1) CN1117587C (fr)
AU (1) AU2001246763A1 (fr)
WO (1) WO2001082987A1 (fr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100457198C (zh) * 2003-06-25 2009-02-04 朱晓明 输尿管支架用可降解材料的制法
US20080103584A1 (en) * 2006-10-25 2008-05-01 Biosensors International Group Temporal Intraluminal Stent, Methods of Making and Using
CN101496908B (zh) * 2009-02-20 2012-10-31 杭州电子科技大学 一种具有多级微纳结构的珍珠粉人工骨支架材料及其生产工艺
CN101781815B (zh) * 2010-02-03 2013-05-08 东华大学 组织工程支架用降解速率可控的多孔纤维的制备方法
CN101837148B (zh) * 2010-03-31 2013-01-16 四川科伦新光医药有限公司 一种多孔性可生物降解支架及其制备方法
CN101979103A (zh) * 2010-10-26 2011-02-23 中南大学 多孔组织工程支架的制备方法
CN102357262A (zh) * 2011-10-09 2012-02-22 清华大学 左旋聚乳酸/珍珠粉的多孔复合支架及其制备方法
CN103433493B (zh) * 2013-08-30 2015-09-16 西北工业大学 一种组织工程细胞培养支架的制备方法
CN109364366A (zh) * 2018-09-21 2019-02-22 华中科技大学 模板法制备多孔聚合物微针的方法及其应用
CN115645609A (zh) * 2021-12-30 2023-01-31 盐城工业职业技术学院 一种三维多孔生物可降解聚合物人工食管支架及其制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5502092A (en) * 1994-02-18 1996-03-26 Minnesota Mining And Manufacturing Company Biocompatible porous matrix of bioabsorbable material
US5686091A (en) * 1994-03-28 1997-11-11 The Johns Hopkins University School Of Medicine Biodegradable foams for cell transplantation
CN1183051A (zh) * 1995-05-01 1998-05-27 株式会社三养社 可植入的可生物再吸收的膜及其制备方法
WO1999032166A2 (fr) * 1997-12-23 1999-07-01 The Board Of Regents Of The University Of Texas System Implants osseux a permeabilite variable et procedes de fabrication et d'utilisation correspondants

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5502092A (en) * 1994-02-18 1996-03-26 Minnesota Mining And Manufacturing Company Biocompatible porous matrix of bioabsorbable material
US5686091A (en) * 1994-03-28 1997-11-11 The Johns Hopkins University School Of Medicine Biodegradable foams for cell transplantation
CN1183051A (zh) * 1995-05-01 1998-05-27 株式会社三养社 可植入的可生物再吸收的膜及其制备方法
WO1999032166A2 (fr) * 1997-12-23 1999-07-01 The Board Of Regents Of The University Of Texas System Implants osseux a permeabilite variable et procedes de fabrication et d'utilisation correspondants

Also Published As

Publication number Publication date
WO2001082987A8 (fr) 2002-03-14
AU2001246763A1 (en) 2001-11-12
CN1117587C (zh) 2003-08-13
CN1269247A (zh) 2000-10-11

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