CN1117587C - Method for mfg. porous holder for repairing tissue and organ - Google Patents

Method for mfg. porous holder for repairing tissue and organ Download PDF

Info

Publication number
CN1117587C
CN1117587C CN 00105638 CN00105638A CN1117587C CN 1117587 C CN1117587 C CN 1117587C CN 00105638 CN00105638 CN 00105638 CN 00105638 A CN00105638 A CN 00105638A CN 1117587 C CN1117587 C CN 1117587C
Authority
CN
China
Prior art keywords
hours
acid
aqueous solution
acidic aqueous
deionized water
Prior art date
Application number
CN 00105638
Other languages
Chinese (zh)
Other versions
CN1269247A (en
Inventor
胡平
蒋凌飞
高峰
Original Assignee
清华大学
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 清华大学 filed Critical 清华大学
Priority to CN 00105638 priority Critical patent/CN1117587C/en
Publication of CN1269247A publication Critical patent/CN1269247A/en
Application granted granted Critical
Publication of CN1117587C publication Critical patent/CN1117587C/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58Materials at least partially resorbable by the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56Porous materials, e.g. foams or sponges

Abstract

本发明涉及一种组织和器官修复用多孔支架的制备方法,首先选取成孔剂,将可降解聚合物溶于溶剂中,然后将成孔剂加入到溶液中,把混合物加入到模具中,合模,干燥,待制品干燥后,脱模,再放入真空干燥箱中干燥,把干燥过的制品浸入去离子水或酸性水溶液中浸泡,最后再次对制品进行真空干燥,即得到本发明的多孔支架。 The present invention relates to tissue and organ repair method for preparing a porous scaffold, first select the pore-forming agent, the biodegradable polymer is dissolved in a solvent and then added to the wells become agent to the solution, the mixture was added to a mold, closing the mold , dried, after drying the article, releasing, and then placed in a vacuum drying oven, the dried product was immersed in deionized water or immersed in an acidic aqueous solution, the final product was vacuum-dried again, i.e., to obtain a porous scaffold of the present invention. . 本发明通过调整成孔剂的粒径和溶液的浓度,得到孔与孔之间相互连通、孔隙率要求不同的支架。 The present invention, by adjusting the particle diameter and a concentration of the pore forming agent solution, and the obtained communicate with each other between the bore hole, the porosity requirements of different stents.

Description

一种组织和器官修复用多孔支架的制备方法 A tissue and organs with porous scaffolds prepared repair

本发明属生物医学工程领域。 The present invention belongs to the field of biomedical engineering. 具体涉及一种器官和组织修复用多孔支架的制备方法。 Organs and in particular to a method for preparing a porous tissue repair scaffold.

组织、器官的丧失或功能障碍是人类健康所面临的主要危害之一,也是人类疾病和死亡的最主要原因。 Tissue, organ dysfunction or loss is a major hazard to human health facing the main causes of human disease and death. 据美国的一份资料显示,每年有数以百万计的美国人患有各种组织、器官的丧失和功能障碍。 According to the US of an information display, every year millions of Americans suffering from various tissues, organ loss and dysfunction. 每年需要进行800万次手术进行修复,年住院日在4000-9000万之间,年耗资超过4000亿美元。 8 million per year needed surgery to repair, in length of stay between 4000-9000 million, annual cost of more than $ 400 billion. 我国是一个人口大国,因创伤和疾病造成的组织、器官丧失或功能障碍病例据世界各国之首,每年仅因烧伤需要进行皮肤移植的患者就达百万之多。 Our country is a populous country, the organization due to trauma and disease caused by the loss or organ dysfunction cases, according to the first countries in the world, each year only because burn patients requiring skin grafts amounted to many millions.

随着生命科学、材料科学以及相关物理、化学学科的发展,人们提出了一个新的概念—组织工程。 With the development of life science, materials science and related physics, chemistry, people put forward a new concept - tissue engineering. 它是应用细胞生物学和工程学的原理,研究开发修复、改善损伤组织结构和功能的生物替代物的一门科学。 It is the application of the principles of cell biology and engineering, a scientific research and development of repair, improve the organizational structure and function of biological damage substitute. 其基本原理和方法是将体外培养扩增的正常组织细胞吸附于一种生物相容性良好并被机体吸收的多孔生物材料上形成复合物,将细胞—生物材料复合物植入机体组织、器官病损部位,细胞在生物材料逐渐被机体降解吸收的过程中形成新的具有形态和功能的相应组织、器官,达到修复创伤和重建功能的目的。 The basic principles and methods are normal cells cultured in vitro amplification is adsorbed to a biocompatible and well formed on the porous composite biomaterial absorbed by the body, the cells - implanted biomaterial composite body tissues, organs lesion site, the cells formed during the biological material is gradually absorbed by the body tissue degradation with a corresponding new form and function of the organ, the purpose of trauma repair and reconstruction of function.

支架材料在组织工程研究中起着非常重要的作用,它是组织工程实现产业化的关键。 Scaffold plays an important role in tissue engineering research, it is crucial to realize the industrialization of tissue engineering. 而支架材料的加工方法在其中又占有极其重要的地位。 The processing method in which the scaffold material also occupies an extremely important position. 组织工程用支架需要较高的孔隙率并且孔与孔之间相互连通,因为只有这样细胞植入后才能进入支架的内部,将来形成的组织才能均匀。 Need scaffold for tissue engineering and higher porosity and communicate with each other between the bore hole, because the only way to enter the interior of the cells after implantation of the stent, the tissue can be formed uniformly in the future. 高的孔隙率使得细胞生长所需的水份、无机盐以及其它营养物质容易渗透到材料内部,这样内部的细胞才能很好的生长、繁殖、形成的组织质量和性能才好。 High porosity such that cell growth of water, inorganic salts and other nutrients required to readily penetrate into the material, so that the internal cells to good growth, reproduction, tissue formation and quality properties go. 一般认为组织工程用支架的孔隙率应高于90%。 It is generally believed that tissue engineering scaffold porosity should be higher than 90%.

国外已对组织工程所用支架的制备方法已有广泛的研究。 Extensive research has been abroad for preparation of tissue engineering scaffold used. 到目前为止,可基本把制备方法分为1、非编织的纤维法,该法的优点是孔隙率较高,但植入体内后,难以保持预定的形状。 So far, the production method can be divided into a basic, non-woven fiber method, advantages of this method is that higher porosity, but after implantation in vivo, it is difficult to maintain a predetermined shape. 2、溶液浇铸,成孔剂滤出法。 2, solution casting, pore-forming agent was filtered off method. 该法所用的成孔剂含量低,由于采用溶液浇铸于器皿中,从而导致成孔剂下沉,孔隙分布不均匀以及上下表面形态出现差异。 Low pore forming agent used in the method of the content, the use in the casting solution in the vessel, thereby causing subsidence porogen, non-uniform pore distribution and morphology of the upper and lower surfaces of variance. 3、三维层化法。 3, three-dimensional layer method. 通过制备多孔膜,然后再通过溶剂把各层粘接起来,从而形成三维的支架。 By preparing a porous membrane, and then the layers were bonded together by the solvent, thereby forming a three-dimensional scaffold. 该法工艺复杂,而且在粘接过程中,粘接部分孔被封闭,从而形成界面,使材料内部形态不均匀。 The process is complex process, but also during the bonding process, the adhesive portion of the hole is closed, thereby forming the interface, the internal morphology of the material uniform. 4、熔融加工法。 4, melt processing methods. 该法在聚合物的熔点以上,把成孔剂与聚合物共混挤入模具。 The process above the melting point of the polymer, the porogen polymer blend extruded into the mold. 冷却得到预定形状的多孔支架。 Cooling to obtain a porous scaffold of predetermined shape. 该法的缺点是在挤出机里,由于熔体与成孔剂的密度相差较大,因而混合难以均匀。 A disadvantage of this method is that in an extruder, and the melt because of the density difference between the larger pore former, and thus difficult to uniformly mix. 而且部分聚合物,尤其是生物可降解的聚合物在熔融加工时,容易热降解。 And some polymers, in particular biodegradable polymer during melt processing is easily thermally degraded. 5、相分离法。 5, phase separation method. 该法采用溶液混合物冷却到溶剂的熔点以下,从而产生相分离。 The method uses a solvent solution mixture is cooled to below the melting point, thereby cause phase separation. 再通过真空干燥,从而得到多孔支架。 And then by vacuum drying to obtain a porous scaffold. 该法的缺点是所得的孔径一般在100微米以下,而且控制较为困难。 A disadvantage of this method is that the resultant pore size generally below 100 microns, and more difficult to control. 6、高压二氧化碳法。 6, high pressure carbon dioxide method. 该法采用把已成型的聚合物暴露于高压二氧化碳。 The method uses the already formed polymer is exposed to high pressure carbon dioxide. 再通过减压把溶于聚合物中的二氧化碳释放出来,从而形成多孔支架。 Under reduced pressure and then carbon dioxide dissolved in the polymer is released, thereby forming a porous scaffold. 该法的缺点是所形成的孔是封闭的。 A disadvantage of this method is that the formed hole is closed.

国内尚未见有组织工程用多孔支架制备新方法的报道。 Not yet reported a new method for the preparation of the project organized by the porous scaffold. 已有的方法也为直接从国外照搬过来。 Existing methods also came as a copy directly from abroad.

本发明的目的在于提供一种操作性好、有效的制备组织及器官修复用多孔支架的方法。 Object of the present invention is to provide one kind of good operability, and a method for efficiently producing organ repair tissue with porous scaffolds. 该法的可控性好,能满足各种组织工程的不同需要。 The law of good controllability, to meet the different needs of a variety of tissue engineering. 本法的基本原理是通过在支架的成型过程中,加入成孔剂。 The basic principle of this law by the molding process of the stent, the addition of a pore-forming agent. 制品成型后,把成孔剂萃取出来,则原来成孔剂的占位空间就形成了将来支架的孔隙。 After the molded article, the pore-forming agent is extracted, the original footprint of the porogen to form a scaffold porosity future.

本发明提出的组织和器官修复用多孔支架的制备方法,包括如下各步骤:1、通过标准筛筛得粒径在50微米~500微米范围内的成孔剂,该成孔剂为氯化钠、氯化钾、醋酸钾、碳酸氢钠、碳酸钠、柠檬酸,柠檬酸钾等。 The present invention is proposed tissue and organ repair method for preparing a porous scaffold, comprising the steps of: 1, through a standard sieve having a particle diameter in a pore-forming agent within the range of 50 microns to 500 microns, the porogen is sodium chloride , potassium chloride, potassium acetate, sodium bicarbonate, sodium citrate, and potassium citrate.

2、将聚3-羟基丁酸酯、3-羟基丁酸和3-羟基己酸的共聚物、聚乳酸、乳酸和羟基乙酸的共聚物、3-羟基丁酸和3-羟基戊酸的共聚物、聚羟基乙酸等其它生物可降解聚合物中的一种或几种溶于氯仿、1,4-二氧环六烷、1,2二氯乙烷、吡啶等溶剂中的一种中,浓度在5%~30%(聚合物质量与溶剂体积之比)之间。 2, the poly-3-hydroxybutyrate, copolymers of 3-hydroxybutyric acid and 3-hydroxy hexanoic acid, polylactic acid, copolymers of lactic acid and glycolic acid, 3-hydroxybutyric acid and 3-hydroxyvaleric acid copolymer was polyglycolic acid and other biodegradable polymer is dissolved in chloroform or several a 1,4-ring-hexadecane, 1,2-dichloroethane, in a solvent such as pyridine, at a concentration of between 5% to 30% (mass ratio of polymer to solvent volume).

3、按1∶10~1∶40的比例(聚合物与成孔剂的质量比)(具体数与溶液浓度项匹配)把步骤1中的成孔剂加入到步骤2所述的溶液中,搅拌均匀。 3, 1:10 to 1:40 (mass ratio of polymer to pore former) (specifically, the number of entries that match with a solution concentration) in the step 1 was added to a solution of pore forming agent said second step, stir. 该比例成孔剂的含量使得所得到的均匀混合物中的成孔剂不发生沉淀和常规流动。 The content ratio of the porogen so that the porogen homogeneous mixture thus obtained is precipitated and a conventional flow does not occur.

4、把该混合物加入到模具中,在0~5MPa的压力下合模。 4, the mixture was added to a mold, closing the mold under a pressure of 0 ~ 5MPa. 空气中自然干燥,温度为常温。 Natural air drying, normal temperature.

5、待制品干燥后,脱模。 5, after the article to be dried, releasing. 再放入真空干燥箱中干燥,温度为常温,压力为0.005MPa~0MPa。 And then put into a vacuum drying oven at a temperature of room temperature and a pressure of 0.005MPa ~ 0MPa. 时间在24~48小时之间,使全部溶剂挥发干净。 Time between 24 to 48 hours, so that all the solvent to evaporate.

6、把干燥过的制品浸入去离子水或酸性水溶液中(H+浓度在2M~10-4M之间)(制品与去离子水或酸性水溶液的体积比在1∶50~1∶200之间),每8小时更换一次去离子水或酸性水溶液。 6, the dried product was immersed in deionized water or an acidic aqueous solution (H + concentration between 2M ~ 10-4M) (volume of product with deionized water or acidic aqueous solution to the ratio between 1:50 to 1:200) every 8 hours to replace a deionized water or an acidic aqueous solution. 总浸泡时间在72~80小时之间。 The total soaking time is between 72 to 80 hours.

7、再次对制品进行真空干燥,温度为常温,压力为0.01~0MPa。 7, vacuum drying the article again, normal temperature, the pressure is 0.01 ~ 0MPa. 时间在24~48小时之间。 Time between 24 to 48 hours. 若在上述步骤6中选用了酸性水溶液,则需再在去离子水浸泡72~80小时之间,每8小时更换一次水。 If the selection of the acidic aqueous solution in the step 6, and then need to soak in deionized water between 72 to 80 hours, once every eight hours to replace water. 然后再行使本步骤,则得到本发明的孔与孔之间相互连通的多孔支架。 This step then exercise, porous scaffold is obtained and the mutual communication between the bore hole of the present invention.

本发明的优点在于通过调整成孔剂的粒径,可得到预期的孔径。 Advantage of the present invention is that by adjusting the particle size of the porogen, the desired pore size can be obtained. 通过调整溶液的浓度,从而改变满足成孔剂不会沉淀这一条件所需的成孔剂含量,从而得到孔与孔之间相互连通、孔隙率要求不同的的支架。 By adjusting the concentration of the solution to change to meet the porogen porogen content does not precipitate the condition required to obtain and communicate with each other between the bore hole, the porosity require different stent.

附图说明 BRIEF DESCRIPTION

:

图1采用本发明的方法得到的聚3-羟基丁酸酯多孔支架表面的扫描电镜图图2采用本发明的方法得到的聚3-羟基丁酸酯多孔支架材料截面的扫描电镜图图3采用本发明的方法得到的3-羟基丁酸与3-羟基己酸共聚物的多孔支架截面的扫描电镜图图4采用本发明的方法得到的不同孔隙率得聚3-羟基丁酸酯多孔支架外观下面介绍本发明的实施例。 SEM view of the surface of the stent poly 3-hydroxybutyrate porous method of the present invention. FIG. 2 is obtained using a method of the present invention obtained by a scanning electron microscope view ester porous material is poly 3-hydroxybutyrate-sectional stent using 3 4 different porosity according to the present invention is a scanning electron microscope cross-sectional view of the porous scaffold of the method of the present invention obtained 3-hydroxybutyric acid and 3-hydroxy-hexanoic acid copolymer obtained by the method of the poly-3-hydroxybutyrate porous scaffold appearance embodiments of the present invention are described below.

实施例一:1、通过标准筛筛得粒径在200~400微米范围内的氯化钠粒子。 Example a: 1, through a standard sieve having a particle diameter of particles of sodium chloride in the range of 200 to 400 microns.

2、称取2.0克的聚3-羟基丁酸酯(PHB),倒入20ml氯仿。 2, weighed 2.0 g of poly-3-hydroxybutyrate (the PHB), poured into 20ml of chloroform. 在65℃下水浴加热30分钟。 It was heated in a water bath at 65 ℃ 30 minutes. 聚合物完全溶解。 The polymer was completely dissolved.

3、加入60克孔径范围在200微米∽400微米的氯化钠成孔剂于上述溶液,充分搅拌,使其混合均匀。 3, 60 g in the pore diameter range above solution was stirred well at 200 [mu] m sodium chloride porogen ∽400 microns, for homogenization.

4、把上述均匀混合物倒入模具中,0.2MPa压力下合模。 4, the above mixture was uniformly poured into a mold, closing the mold under pressure of 0.2MPa. 在室温中,干燥48小时。 At room temperature, dried for 48 hours.

5、脱模,把已成型的制品放入真空烘箱中干燥,压力为0.01MPa,时间为48小时。 5, the release, the molded article has been placed in a vacuum oven, the pressure is 0.01MPa, for 48 hours.

6、把制品浸泡入200ml去离子水中。 6, the article immersed into 200ml of deionized water. 每8小时更换去离子水。 Every eight hours to replace deionized water. 72小时后取出制品。 After 72 hours, remove the article.

7、再次把制品放入真空烘箱中干燥,真空烘箱内的压力为0.01MPa,时间为48小时。 7, again the article placed in a vacuum oven, the pressure in the vacuum oven to 0.01MPa, for 48 hours. 取出制品,如此则多孔支架已制成。 Remove the article, so it is made of a porous scaffold. 经测定孔隙率为92%,孔形态如附图一,图二。 It was determined that a porosity of 92%, a pore morphology as the drawings, Figure II.

实施例二1、通过标准筛筛得粒径在50~200微米范围内的醋酸钾粒子。 1 according to the second embodiment, through a standard sieve having a particle diameter in the range of 50 to 200 microns potassium acetate particles.

2、称取2.0克的3-羟基丁酸与3-羟基己酸的共聚物(PHB-HH),倒入20ml的氯仿,在65℃下水浴加热30分钟。 2, weighed 2.0 g of a copolymer of 3-hydroxybutyric acid and 3-hydroxy hexanoic acid (PHB-HH), poured into 20ml of chloroform was heated at 65 deg.] C water bath for 30 minutes. 聚合物完全溶解。 The polymer was completely dissolved.

3、加入60克孔径范围在50∽200微米的醋酸钾成孔剂于上述溶液。 3, 60 g in the pore diameter range above solution 50∽200 microns potassium acetate porogen. 充分搅拌,使其混合均匀。 Sufficiently stirred to mix uniformly.

其余的步骤与实施例一的对应步骤相同。 A step corresponding to the same procedure as in Example rest.

取出制品,如此则多孔支架已制成。 Remove the article, so it is made of a porous scaffold. 经测定孔隙率为93%,制品外观如图3。 It was determined that a porosity of 93%, the appearance of the article shown in Figure 3.

实施例三:1、通过标准筛筛得粒径在300~500微米范围内的碳酸氢钠粒子。 Example Three: 1, through a standard sieve having a particle diameter in the sodium bicarbonate particles 300 to 500 microns.

2、称取2.0克的聚乳酸,倒入40ml氯仿。 2, weighed 2.0 g of polylactic acid was poured into 40ml of chloroform. 在65℃下水浴加热30分钟,聚合物完全溶解。 Water bath for 30 minutes at 65 ℃, the polymer was completely dissolved.

3、加入80克孔径范围在300微米∽500微米的碳酸氢钠成孔剂于上述溶液。 3, 80 g of sodium bicarbonate solution to the pore diameter range porogen ∽500 microns 300 microns. 充分搅拌,使其混合均匀。 Sufficiently stirred to mix uniformly.

4、把上述均匀混合物倒入模具中,0.1MPa压力下合模。 4, the above mixture was uniformly poured into a mold, closing the mold under pressure of 0.1MPa. 在室温中,保压干燥48小时。 At room temperature, dried for 48 hours dwell.

5、脱模,把已成型的制品放入真空烘箱中干燥,压力为0.01MPa,时间为48小时。 5, the release, the molded article has been placed in a vacuum oven, the pressure is 0.01MPa, for 48 hours.

6、把制品浸泡入200ml浓度为0.5M的盐酸中,每8小时更换0.5M的盐酸。 6, the article is immersed into 200ml of 0.5M hydrochloric acid concentration, replacing every 8 hours in 0.5M hydrochloric acid. 72小时后取出制品。 After 72 hours, remove the article.

7、把制品浸泡入200ml去离子水中。 7, the article immersed into 200ml of deionized water. 每8小时更换去离子水,72小时后取出制品。 Replace every 8 hours of deionized water, the product was released after 72 hours.

8、把制品放入真空烘箱中干燥,温度为常温,真空烘箱内的压力为0.01MPa,时间为48小时。 8, the product was dried in a vacuum oven, the temperature is room temperature, the pressure in the vacuum oven to 0.01MPa, for 48 hours.

取出制品,如此则多孔支架已制成。 Remove the article, so it is made of a porous scaffold.

实施例四:1、通过标准筛筛得粒径在50~200微米范围内的柠檬酸粒子。 Example Four: 1, through a standard sieve having a particle diameter in the range of 50 to 200 particles citrate microns.

2、称取2.0克的乳酸与羟基乙酸的共聚物,倒入10ml氯仿。 2, said copolymer taking 2.0 grams of lactic acid and glycolic acid, poured into 10ml of chloroform. 在65℃下水浴加热30分钟。 It was heated in a water bath at 65 ℃ 30 minutes. 聚合物完全溶解。 The polymer was completely dissolved.

3、加入40克孔径范围在50∽200微米的柠檬酸成孔剂于上述溶液。 3, 40 g of citric acid in the pore size range porogen 50∽200 m in the above solution. 充分搅拌,使其混合均匀。 Sufficiently stirred to mix uniformly.

其余的步骤与实施例一的对应步骤相同。 A step corresponding to the same procedure as in Example rest.

如此则多孔材料已制成。 Thus the porous material is formed.

实施例五:1、通过标准筛筛得粒径在200~400微米范围内的碳酸钠粒子。 Example Five: 1, through a standard sieve having a particle diameter of particles of sodium carbonate in 200 to 400 microns.

2、称取2.0克的3-羟基丁酸和3-羟基戊酸的共聚物,倒入6.7ml氯仿。 2, weighed 2.0 g of 3-hydroxybutyric acid and 3-hydroxy valeric acid, 6.7ml chloroform was poured. 在65℃下水浴加热30分钟。 It was heated in a water bath at 65 ℃ 30 minutes. 聚合物完全溶解。 The polymer was completely dissolved.

3、加入20克孔径范围在200∽400微米的碳酸钠成孔剂于上述溶液。 3, 20 g of sodium carbonate in the pore size range porogen 200∽400 m in the above solution. 充分搅拌,使其混合均匀。 Sufficiently stirred to mix uniformly.

其余的步骤与实施例一的对应步骤相同。 A step corresponding to the same procedure as in Example rest.

取出制品,如此则多孔支架已制成。 Remove the article, so it is made of a porous scaffold.

实施例六:1、通过标准筛筛得粒径在50~500微米范围内的氯化钠粒子。 Example Six: 1, through a standard sieve having a particle diameter of particles of sodium chloride in the range of 50 to 500 microns.

2、称取2.0克的3-羟基丁酸和3-羟基己酸的共聚物,倒入25ml的1,4-二氧环六烷。 2, weighed 2.0 g of a copolymer of 3-hydroxybutyric acid and 3-hydroxy hexanoic acid, poured into 25ml of 1,4-dioxane cyclic hexapeptide. 在65℃下水浴加热30分钟。 It was heated in a water bath at 65 ℃ 30 minutes. 聚合物完全溶解。 The polymer was completely dissolved.

3、加入70克孔径范围在200∽500微米的氯化钠成孔剂于上述溶液。 3, 70 g of sodium chloride in the pore size range porogen 200∽500 m in the above solution. 充分搅拌,使其混合均匀。 Sufficiently stirred to mix uniformly.

其余的步骤与实施例一的对应步骤相同。 A step corresponding to the same procedure as in Example rest.

取出制品,如此则多孔支架已制成。 Remove the article, so it is made of a porous scaffold.

Claims (1)

1.一种组织和器官修复用多孔支架的制备方法,其特征在于,该方法包括如下各步骤:(1)通过标准筛筛得粒径在50微米~500微米范围内的成孔剂,该成孔剂为氯化钠、醋酸钾、碳酸氢钠、碳酸钠、柠檬酸中的任何一种;(2)将生物可降解聚合物溶于溶剂中,使溶液的浓度为5%~30%,其中聚合物为聚3-羟基丁酸酯、3-羟基丁酸和3-羟基己酸的共聚物、聚乳酸、乳酸和羟基乙酸的共聚物、3-羟基丁酸和3-羟基戊酸的共聚物中的任何一种或两种以上,溶剂为氯仿或1,4-二氧环六烷;(3)按聚合物与成孔剂的质量比1∶20~40的比例,把步骤1中的成孔剂加入到步骤2所述的溶液中,搅拌均匀;(4)把该混合物加入到模具中,在0~5MPa的压力下合模,空气中自然干燥,温度为常温;(5)待制品干燥后,脱模,再放入真空干燥箱中干燥,温度为常温,压力为0.005MPa~0Mpa,时间 1. A tissue and organ repair method for preparing a porous scaffold, wherein the method comprises the steps of: (1) through a standard sieve having a particle diameter in a pore-forming agent within the range of 50 microns to 500 microns, the pore-forming agent is sodium chloride, potassium acetate, sodium bicarbonate, citric any; (2) a biodegradable polymer dissolved in a solvent, the concentration of the solution is 5% to 30% wherein the polymer is a copolymer of 3-hydroxybutyrate, copolymers of 3-hydroxybutyric acid and 3-hydroxy hexanoic acid, polylactic acid, lactic acid and glycolic acid, 3-hydroxybutyric acid and 3-hydroxyvaleric acid any one or two or more copolymers, the solvent is chloroform or 1,4-hexadecane cycloalkyl; (3) a mass of polymer and porogen ratio of 1:20 to 40, the step of 1 porogen is added to the solution of the second step, stir; (4) the mixture was added to a mold, closing the mold under a pressure of 0 ~ 5MPa, natural air drying, normal temperature; ( 5) after drying the article, releasing, and then placed in a vacuum drying oven at a temperature of room temperature and a pressure of 0.005MPa ~ 0Mpa, time 24~48小时之间,使全部溶剂挥发干净;(6)把干燥过的制品浸入去离子水或酸性水溶液中,酸性水溶液中的H+浓度在2M~10-4M之间,制品与去离子水或酸性水溶液的体积比在1∶50~1∶200之间,每8小时更换一次去离子水或酸性水溶液,总浸泡时间在72~80小时之间;(7)再次对制品进行真空干燥,温度为常温,压力为0.01~0Mpa,时间在24~48小时之间,若在上述步骤6中选用了酸性水溶液,则需再在去离子水浸泡72~80小时之间,每8小时更换一次水,然后再行使本步骤,则得到本发明的多孔支架。 Between 24 to 48 hours, so that all the solvent to evaporate; (6) The dried product was immersed in deionized water or an acidic aqueous solution, an acidic aqueous solution in the H + concentration between 2M ~ 10-4M, products with deionized water or an acidic aqueous solution volume ratio of between 1:50 to 1:200, every 8 hours to replace a deionized water or an acidic aqueous solution, the total immersion time is between 72 to 80 hours; (7) the article is dried again in vacuo normal temperature, the pressure is 0.01 ~ 0Mpa, time between 24 to 48 hours, when an acidic aqueous solution selected in step 6, and then in deionized water is required between 72 to 80 hours soaking, replaced once every 8 hours water, and then exercise the step, the obtained porous scaffold of the present invention.
CN 00105638 2000-04-14 2000-04-14 Method for mfg. porous holder for repairing tissue and organ CN1117587C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN 00105638 CN1117587C (en) 2000-04-14 2000-04-14 Method for mfg. porous holder for repairing tissue and organ

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN 00105638 CN1117587C (en) 2000-04-14 2000-04-14 Method for mfg. porous holder for repairing tissue and organ
AU4676301A AU4676301A (en) 2000-04-14 2001-04-17 A preparation method for a porous framework used in the prostheses of tissue andorgans
PCT/IB2001/000632 WO2001082987A1 (en) 2000-04-14 2001-04-17 A preparation method for a porous framework used in the prostheses of tissue and organs

Publications (2)

Publication Number Publication Date
CN1269247A CN1269247A (en) 2000-10-11
CN1117587C true CN1117587C (en) 2003-08-13

Family

ID=4577840

Family Applications (1)

Application Number Title Priority Date Filing Date
CN 00105638 CN1117587C (en) 2000-04-14 2000-04-14 Method for mfg. porous holder for repairing tissue and organ

Country Status (3)

Country Link
CN (1) CN1117587C (en)
AU (1) AU4676301A (en)
WO (1) WO2001082987A1 (en)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100457198C (en) 2003-06-25 2009-02-04 朱晓明 Method for making degradable material of ureter bracket
US20080103584A1 (en) * 2006-10-25 2008-05-01 Biosensors International Group Temporal Intraluminal Stent, Methods of Making and Using
CN101496908B (en) 2009-02-20 2012-10-31 杭州电子科技大学 Pearl powder artificial bone supporting material with multi-stage micro-nano structure and technique for producing the same
CN101781815B (en) 2010-02-03 2013-05-08 东华大学 Preparation method of porous fiber with controllable degradation rate for tissue engineering scaffold
CN101837148B (en) * 2010-03-31 2013-01-16 四川科伦新光医药有限公司 Porous biodegradable stent and preparation method thereof
CN101979103A (en) * 2010-10-26 2011-02-23 中南大学 Method for preparing porous tissue engineering scaffold
CN102357262A (en) * 2011-10-09 2012-02-22 清华大学 Porous composite scaffold of PLLA (polylactic acid)/pearl powder and its preparation method
CN103433493B (en) * 2013-08-30 2015-09-16 西北工业大学 Preparing a tissue engineering scaffold Cell Culture

Family Cites Families (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
CN1136922C (en) * 1995-05-01 2004-02-04 株式会社三养社 Implantable bioresorbable membrane and method for preparation thereof
US6187329B1 (en) * 1997-12-23 2001-02-13 Board Of Regents Of The University Of Texas System Variable permeability bone implants, methods for their preparation and use

Also Published As

Publication number Publication date
AU4676301A (en) 2001-11-12
WO2001082987A8 (en) 2002-03-14
WO2001082987A1 (en) 2001-11-08
CN1269247A (en) 2000-10-11

Similar Documents

Publication Publication Date Title
Ma et al. A preliminary in vitro study on the fabrication and tissue engineering applications of a novel chitosan bilayer material as a scaffold of human neofetal dermal fibroblasts
Papenburg et al. One-step fabrication of porous micropatterned scaffolds to control cell behavior
Sachlos et al. Novel collagen scaffolds with predefined internal morphology made by solid freeform fabrication
US6875442B2 (en) Process for growing tissue in a biocompatible macroporous polymer scaffold and products therefrom
Gao et al. Macroporous elastomeric scaffolds with extensive micropores for soft tissue engineering
US5512600A (en) Preparation of bonded fiber structures for cell implantation
Kim et al. Development of biocompatible synthetic extracellular matrices for tissue engineering
US5589176A (en) Methods of making doubly porous device
US6793675B2 (en) Polysaccharide sponges for cell culture and transplantation
Choi et al. Chitosan‐based inverse opals: Three‐dimensional scaffolds with uniform pore structures for cell culture
Gomes et al. Alternative tissue engineering scaffolds based on starch: processing methodologies, morphology, degradation and mechanical properties
Lu et al. The importance of new processing techniques in tissue engineering
Faraj et al. Construction of collagen scaffolds that mimic the three-dimensional architecture of specific tissues
Do Kim et al. Effect of PEG–PLLA diblock copolymer on macroporous PLLA scaffolds by thermally induced phase separation
US20030012805A1 (en) Implant for cartilage tissue regeneration
Mikos et al. Preparation of poly (glycolic acid) bonded fiber structures for cell attachment and transplantation
JP4499143B2 (en) Tubular porous scaffold and a method of manufacturing artificial vascular bilayer membrane structure
Mikos et al. Formation of highly porous biodegradable scaffolds for tissue engineering
JP4017977B2 (en) Stand for the hair treated with tissue engineering
US20040258729A1 (en) Tissue engineering scaffolds
AU2004245235B2 (en) Matrix, cell implantation and method for their production and use
ES2291189T3 (en) Process for the preparation of polymeric, porous, biocompatible, biodegradable scaffolds for tissue engineering.
Ma et al. Synthetic nano‐scale fibrous extracellular matrix
EP1443982B1 (en) Porous polymeric prostheses and methods for making same
CN1169494C (en) Cell scaffold with composite structure for tissue engineering and its preparing process and application

Legal Events

Date Code Title Description
C10 Request of examination as to substance
C06 Publication
C14 Granted
C17 Cessation of patent right