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Publication numberCN104473706 A
Publication typeApplication
Application numberCN 201410750552
Publication dateApr 1, 2015
Filing dateDec 9, 2014
Priority dateDec 9, 2014
Also published asCN104473706B
Publication number201410750552.4, CN 104473706 A, CN 104473706A, CN 201410750552, CN-A-104473706, CN104473706 A, CN104473706A, CN201410750552, CN201410750552.4
Inventors杜小文
Applicant金华市人民医院
Export CitationBiBTeX, EndNote, RefMan
External Links: SIPO, Espacenet
Biodegradable composite type tubular urethral stent and preparation method
CN 104473706 A
Abstract
The invention provides a biodegradable composite type tubular urethral stent and a preparation method. By the biodegradable composite type tubular urethral stent and the preparation method, the shortcomings that the using quantity of the existing patch materials is limited and complications are easily caused on sampled portions are overcome. The biodegradable tissue engineering stent comprises an inner layer and an outer layer, wherein the inner layer is tubular; the outer layer is arranged on the outer surface of the inner layer; the inner layer and the outer layer are made of degradable high polymer materials and acellular stromata; the degradable high polymer materials are polylactic acid- polylactic-co-glycolic acid (PLGA) films; the acellular stromata are small intestinal submucosa (SIS) films; and the polylactic acid- polylactic-co-glycolic acid (PLGA) films and the small intestinal submucosa (SIS) films are connected to one another. By the biodegradable composite type tubular urethral stent, autologous sampling is not required during urethral canal compounding and reestablishment, and the complications which are possibly caused on the sampled portions are avoided.
Claims(10)  translated from Chinese
1.一种可降解的复合型管状尿道支架,其特征在于该可降解的复合型管状尿道支架是一种可降解的组织工程支架,包括内层和外层,内层为管状,外层设在内层的外表面上;所述的内层和外层均采用可降解的高分子材料和脱细胞基质制成。 A biodegradable composite tubular urethral stent, characterized in that the degradable composite tubular urethral stent is a degradable scaffold for tissue engineering, including inner and outer layers, the inner layer of the tubular outer layer is provided the outer surface of the inner layer; the inner and outer layers are made of biodegradable polymer materials and acellular matrix material.
2.根据权利要求1所述的一种可降解的复合型管状尿道支架,其特征在于所述的制成内层和外层的可降解高分子材料采用聚乳酸-羟基乙酸共聚物PLGA薄膜,所述的脱细胞基质采用小肠脱细胞基质SIS薄膜;聚乳酸-羟基乙酸共聚物PLGA薄膜与小肠脱细胞基质SIS薄膜之间相互连接在一起。 2. According to one one of the degradable composite tubular urethral stent as claimed in claim wherein said inner and outer layers made of biodegradable polymer materials polylactic acid - glycolic acid copolymer PLGA film, The acellular matrix using small intestine acellular SIS matrix film; polylactic acid - SIS between extracellular matrix thin-film-glycolic acid copolymer PLGA film and the small intestine connected to each other off.
3.根据权利要求1或2所述的一种可降解的复合型管状尿道支架,其特征在于所述的外层2通过螺旋方式缠绕在内层的外表面上。 3. A 1 or 2, wherein the degradable composite tubular urethral stent of claim 2 wherein said outer layer is wound on the outer surface of the inner layer by a spiral fashion.
4.根据权利要求2所述的一种可降解的复合型管状尿道支架,其特征在于所述的聚乳酸-羟基乙酸共聚物PLGA薄膜与小肠脱细胞基质SIS薄膜之间通过线缝合在一起;所述的聚乳酸-羟基乙酸共聚物PLGA薄膜与小肠脱细胞基质SIS薄膜均呈条形结构。 4. A 2, wherein the degradable composite tubular urethral stent as claimed in claim wherein said polylactic acid - glycolic acid PLGA between the film and the film SIS intestinal acellular matrix together by suture; The polylactic acid - glycolic acid PLGA film and intestinal acellular SIS matrix thin-film structure showed stripe.
5.根据权利要求4所述的一种可降解的复合型管状尿道支架,其特征在于所述的内层上的聚乳酸-羟基乙酸共聚物PLGA薄膜和小肠脱细胞基质SIS薄膜水平放置,纵向间隔排布缝合在一起呈片状,环绕导尿管外侧缝合成管状。 A 4 according to the degradable composite tubular urethral stent as claimed in claim wherein said inner layer of polylactic acid on - glycolic acid copolymer PLGA film and SIS intestinal acellular matrix film horizontal, longitudinal spaced arrangement stitched together flaky, sewn into a tube around the outside catheter.
6.根据权利要求4所述的一种可降解的复合型管状尿道支架,其特征在于所述的外层上的聚乳酸-羟基乙酸共聚物PLGA薄膜和小肠脱细胞基质SIS薄膜水平间隔排布并缝合在一起呈长条状。 6. A 4, wherein the degradable composite tubular urethral stent as claimed in claim wherein said outer layer of polylactic acid on - glycolic acid copolymer PLGA film and intestine removal SIS matrix film arranged spaced horizontal cells and elongated strips sewn together.
7.根据权利要求1至6中任一项所述的一种可降解的复合型管状尿道支架的制备方法,其特征在于该制备方法包括以下步骤: (1)将高分子材料聚乳酸PLA和聚羟基乙酸PGA按50:50〜85:15的摩尔比混合,采用静电纺丝技术制得聚乳酸-羟基乙酸共聚物PLGA纳米级电纺纤维膜,在制得的电纺纤维膜表面接枝I型胶原蛋白进行改性,得到改性后的聚乳酸-羟基乙酸共聚物PLGA薄膜; (2)将小肠粘膜下层细胞组织浸泡于由体积浓度为0.2%的聚乙二醇辛基苯基醚-100 (Triton X-100)和体积浓度为0.03 %的氨水混合制成的脱细胞液中,振荡脱细胞后在-40C〜_50C温度下进行低温冷冻并真空干燥处理,得到小肠脱细胞基质SIS薄膜; (3)根据尿道管径要求,将由步骤(I)得到的聚乳酸-羟基乙酸共聚物PLGA薄膜和步骤(2)得到的小肠脱细胞基质SIS薄膜制成规则的矩形,用线缝合得到内层和外层。 1 was prepared according to a method according to any one degradable composite tubular urethral stent as claimed in any one of claim 6, wherein the preparation process comprises the following steps: (1) The polylactic acid PLA polymer material and polyglycolic acid PGA at 50: 50~85: 15 molar ratio of mixing, using electrospinning technology to obtain polylactic acid - glycolic acid PLGA electrospun nano fiber membrane graft in electrospun fibers obtained membrane surface Type I collagen is modified to obtain a modified polylactic acid - glycolic acid PLGA film; (2) small intestinal submucosa tissue soaked in a concentration of 0.2% by the volume of polyethylene glycol octylphenyl ether -100 (Triton X-100) and the volume concentration of 0.03% aqueous ammonia blend of decellularization solution, after shaking off the cells were frozen at -40 C~_50 C temperature and dried in vacuo to give small intestine SIS acellular matrix film; (3) according to claim urethral diameter, from step (I) obtained polylactic acid - glycolic acid PLGA film and the step (2) obtained in the small intestine SIS acellular matrix film formed rectangular rule, suture obtained by inner and outer layers.
8.根据权利要求7所述的一种可降解的复合型管状尿道支架的制备方法,其特征在于所述的线采用尼龙线。 8. A process for preparing a degradable 7, wherein the tubular composite according to claim urethral stent, wherein said wire nylon line.
9.根据权利要求7或8所述的一种可降解的复合型管状尿道支架的制备方法,其特征在于所述的聚乳酸PLA和聚羟基乙酸PGA的摩尔比为75:25。 9. A process for preparing a molar ratio of 7 or 8, wherein the tubular composite degradable urethral stent according to claim, characterized in that said PLA polylactic acid and polyglycolic acid PGA of 75:25.
10.根据权利要求7或8所述的一种可降解的复合型管状尿道支架的制备方法,其特征在于采用气液相培养方法在内层上接种血管内皮生长因子(VEGF) 165基因转染的脂肪间充质干细胞,在外层上接种由脂肪间充质干细胞转化的平滑肌细胞。 10. A process for preparing a 7 or 8, wherein the degradable composite tubular urethral stent according to claim, characterized in that a gas-liquid culture method was inoculated in the inner layer of vascular endothelial growth factor (VEGF) 165 gene transfer The adipose-derived mesenchymal stem cells on the outer layer of smooth muscle cells were seeded by the adipose-derived mesenchymal stem cell transformation.
Description  translated from Chinese
一种可降解的复合型管状尿道支架及制备方法 Tubular complex urethral stent and method for preparing a degradable

技术领域 TECHNICAL FIELD

[0001] 本发明涉及医学技术领域,特别是一种可降解的复合型管状尿道支架及制备方法。 [0001] The present invention relates to the field of medical technology, particularly a biodegradable composite tubular urethral stent and method of preparation.

背景技术 Background technique

[0002] 外伤性或医源性尿道损伤,淋菌性或非特异性尿道炎及先天性尿道病变等各种因素引起的尿道狭窄,是泌尿外科医师面临的难题之一。 [0002] traumatic or iatrogenic urethral injury, urethral gonococcal or non-specific urethritis various factors and congenital urinary tract lesions caused by stenosis, is one of the problems faced by urologists. 常规治疗方法包括尿道扩张、尿道内切开、尿道端端吻合术等仅适用于距离较短的尿道狭窄患者,针对长段尿道狭窄的患者主要采用替代手术治疗,生殖器皮肤、膀胱黏膜、阴茎白膜、口腔黏膜以及舌黏膜都被用于作为尿道修复手术的补片材料;但取材通常会引起取材部位的并发症,且取材量受到限制。 Conventional treatment methods include urethral dilatation, internal urethrotomy, urethral anastomosis and so applies only to patients with urethral stricture shorter distance for urethral stenosis long segment mainly uses alternative to surgical treatment, genital skin, bladder, penis white film, oral mucosa and tongue mucosa are used as urethral surgery to repair patch material; however drawn drawn parts usually cause complications, and the amount of coverage is limited.

发明内容 SUMMARY OF THE INVENTION

[0003] 本发明的目的是针对现有长段尿道狭窄治疗方法中存在取材时造成创伤、材料取量受限、取材部位易引起并发症的不足之处,提供一种可降解的复合型管状尿道支架及制备方法。 [0003] The object of the present invention is caused by the presence of traumatic urethral stricture long drawn existing treatment methods for materials take a limited amount, drawn parts can lead to deficiencies of complications, there is provided a biodegradable composite tubular urethral stent and method of preparation.

[0004] 本发明是通过如下方式完成的:一种可降解的复合型管状尿道支架,该可降解的复合型管状尿道支架是一种可降解的组织工程支架,包括内层和外层,内层为管状,外层设在内层的外表面上;所述的内层和外层均采用可降解的高分子材料和脱细胞基质制成。 [0004] The present invention has been accomplished in the following way: one degradable composite tubular urethral stent, the degradable composite tubular urethral stent is a degradable scaffold for tissue engineering, including inner and outer layers, inner layer tubular outer layer disposed on the outer surface of the inner layer; the inner and outer layers are made of biodegradable polymer materials and acellular matrix material.

[0005] 在所述的一种可降解的复合型管状尿道支架中,所述的制成内层和外层的可降解高分子材料采用聚乳酸-羟基乙酸共聚物薄膜,所述的脱细胞基质采用小肠脱细胞基质313薄膜;聚乳酸-羟基乙酸共聚物? [0005] In one of the degradable composite tubular urethral stent, made of inner and outer layers of the biodegradable polymer materials using polylactic acid - glycolic acid copolymer film, the acellular acellular matrix using the intestinal stromal 313 films; poly lactic acid - glycolic acid? ⑷八薄膜与小肠脱细胞基质313薄膜之间相互连接在一起。 ⑷ off eight films and small intestine connected to each other between the extracellular matrix 313 films.

[0006] 在所述的一种可降解的复合型管状尿道支架中,所述的聚乳酸-羟基乙酸共聚物薄膜与小肠脱细胞基质313薄膜之间通过线缝合在一起;所述的聚乳酸-羟基乙酸共聚物? [0006] In one of the composite tubular biodegradable urethral stent, the polylactic acid - between cell-matrix thin-film-glycolic acid copolymer film 313 and the small intestine off together by suture; the polylactic acid - glycolic acid? 化八薄膜与小肠脱细胞基质313薄膜均呈条形结构;所述的线是采用9/0尼龙线。 Of the eight films and small intestine showed acellular matrix 313 film stripe structure; the line is to use 9/0 nylon line.

[0007] 在所述的一种可降解的复合型管状尿道支架中,所述的外层通过螺旋方式缠绕在内层的外表面上。 [0007] In a degradable said composite tubular urethral stent, the outer layer of the winding in a spiral manner by the outer surface of the inner layer.

[0008] 在所述的一种可降解的复合型管状尿道支架中,所述的内层上的聚乳酸-羟基乙酸共聚物薄膜和小肠脱细胞基质313薄膜水平放置,纵向间隔排布缝合在一起呈片状,环绕导尿管外侧缝合成管状。 [0008] In one degradable composite tubular urethral stent according to the polylactic acid on the inner layer - glycolic acid films and 313 films intestinal level acellular matrix copolymer is placed, the suture arranged in longitudinally spaced Together flaky around the outside of the catheter into a tubular suture.

[0009] 在所述的一种可降解的复合型管状尿道支架中,所述的外层上的聚乳酸-羟基乙酸共聚物薄膜和小肠脱细胞基质313薄膜水平间隔排布并缝合在一起呈长条状。 [0009] In one of the degradable composite tubular stent in the urethra, the polylactic acid on said outer - glycolic acid films and 313 films intestinal level acellular matrix copolymer spaced arrangement and are sewn together form long strips.

[0010] 在所述的一种可降解的复合型管状尿道支架中,所述的内层由二条矩形的聚乳酸-羟基乙酸共聚物? [0010] In one of the composite tubular biodegradable urethral stent, the inner rectangle from the two polylactic acid - glycolic acid? ⑷八薄膜与二条矩形的小肠脱细胞基质313薄膜纵向间隔排布组成;所述的外层由二条矩形状的聚乳酸-羟基乙酸共聚物薄膜与二条矩形状的小肠脱细胞基质313薄膜水平间隔排布并缝合在一起。 ⑷ eight films and two rectangular small intestine acellular matrix 313 film consisting of longitudinally spaced arrangement; outer layer by two rectangular polylactic acid - glycolic acid copolymer film with two rectangular small intestine acellular matrix horizontally spaced 313 film arrangement and stitched together.

[0011] 本发明的一种可降解的复合型管状尿道支架的制备方法包括以下步骤: [0011] A production method of the present invention, the compound of the tubular biodegradable urethral stent comprises the steps of:

[0012] (1)将高分子材料聚乳酸? [0012] (1) The polymer material polylactic acid? “和聚羟基乙酸?以按50: 50〜85: 15的摩尔比混合,采用静电纺丝技术制得聚乳酸-羟基乙酸共聚物纳米级电纺纤维膜,在制得的电纺纤维膜表面接枝I型胶原蛋白进行改性,得到改性后的聚乳酸-羟基乙酸共聚物?化八薄膜; "And polyglycolic acid with a 50: 50~85: 15 molar ratio of mixing, using electrospinning technology to obtain polylactic acid - glycolic acid copolymer electrospun nano fiber membrane, the membrane surface in electrospun fibers obtained? Graft type I collagen is modified to obtain the modified polylactic acid - glycolic acid copolymer film of eight?;

[0013] (2)将小肠黏膜下层细胞组织浸泡于脱细胞液中,脱细胞液由体积浓度为0.2%的聚乙二醇辛基苯基醚-100 ^-100)和体积浓度为0.03 %的氨水混合制成,振荡脱细胞后在-40X:〜-50X:温度下进行低温冷冻并真空干燥得到小肠脱细胞基质313薄膜; [0013] (2) The small intestinal submucosa acellular tissue soaked in liquid, acellular liquid by the volume concentration of 0.2% polyethylene glycol octylphenyl ether ^ -100 -100) and the volume concentration of 0.03% aqueous ammonia blend, after shaking in -40X acellular: ~-50X: be frozen at a temperature and dried in vacuo to give 313 intestinal acellular matrix film;

[0014] (3)根据尿道管径要求,将由步骤⑴得到的聚乳酸-羟基乙酸共聚物? [0014] (3) according to claim urethral diameter, obtained from step ⑴ polylactic acid - glycolic acid copolymer? ⑷八薄膜和步骤(2)得到的小肠脱细胞基质313薄膜制成规则的矩形,用线缝合得到内层和外层。 ⑷ eight films and step (2) to give a rectangular intestinal acellular matrix film 313 made of rules, to obtain an inner layer and an outer layer with suture.

[0015] 在所述的一种可降解的复合型管状尿道支架的制备方法中,所述的线采用尼龙线。 [0015] In the preparation process of a degradable composite tubular stent in the urethra, said line nylon line.

[0016] 在所述的一种可降解的复合型管状尿道支架的制备方法中,所述的聚乳酸? [0016] In the preparation process of a degradable composite tubular stent in the urethra, the polylactic acid? I^和聚羟基乙酸? I ^ and polyglycolic acid? 以的摩尔比为75:25。 With a molar ratio of 75:25.

[0017] 在所述的一种可降解的复合型管状尿道支架的制备方法中,所述的步骤(1)制得的聚乳酸-羟基乙酸共聚物八的纳米级电纺纤维膜厚度为0.35〜0.45臟1,孔隙率为85 %〜95 %,电纺丝直径为300〜45011111,孔径为60〜100 V爪。 [0017] In the preparation process of a degradable composite tubular stent in the urethra, the step (1) was obtained polylactic acid - fiber electrospun nanoscale film thickness glycolic acid copolymer eight 0.35 ~0.45 dirty 1, the porosity of 85% ~ 95%, electrospinning 300~45011111 diameter, pore diameter of 60~100 V claws.

[0018] 在所述的一种可降解的复合型管状尿道支架的制备方法中,所述的一种可降解的复合型管状尿道支架的制备方法采用气液相培养方法在内层上接种血管内皮生长因子(犯即)165基因转染的脂肪间充质干细胞,在外层上接种由脂肪间充质干细胞转化的平滑肌细胞。 [0018] In the preparation process of a degradable composite tubular stent in the urethra, the preparation of a biodegradable composite tubular urethral stent method using gas-liquid culture was inoculated in the inner vessel endothelial growth factor (ie guilty) between 165 gene transfected adipose mesenchymal stem cells in the outer layer of vaccination by the adipose-derived mesenchymal stem cells into smooth muscle cells.

[0019] 本发明一种可降解的复合型管状尿道支架的支架微观结构为三维多孔状,具有良好的生物相容性及力学性质,兼备弹性与柔韧性,能在体内保持稳定的管状形态;本发明采用的是高分子生物材料和脱细胞基质,有利于种子细胞黏附、增殖和分化,促进周围组织的生长;两种材料在体内可按各自的方式逐步分解为小分子物质而自然吸收,无需取出。 [0019] The present invention is a scaffold microstructure of the composite tubular biodegradable urethral stent is a three-dimensional porous, has good biocompatibility and mechanical properties, both elasticity and flexibility, can maintain a stable tubular form in the body; The present invention uses a polymer biomaterials and acellular matrix, is conducive to seed cell adhesion, proliferation and differentiation, promote the growth of the surrounding tissue; two materials in the body can be their way gradually decompose into small molecules and natural absorption, no need to remove it.

[0020] 采用本发明进行尿道修复与重建,无需进行自体取材,避免了取材部位可能引起的并发症;尿道粘膜上皮细胞、干细胞、平滑肌细胞等能在支架上粘附和增殖,可直接用于尿道修复与重建,适合临床应用。 [0020] The present invention urethral repair and reconstruction, without the need for autologous drawn, drawn parts to avoid the complications that may arise; urethral epithelial cells, stem cells, smooth muscle cells can adhere and proliferate on the stand, can be used directly urethral repair and reconstruction, suitable for clinical application.

附图说明 Brief Description

[0021] 图1为本发明一种可降解的复合型管状尿道支架内层的结构示意图。 [0021] FIG. 1 is a schematic structural diagram of an invention biodegradable composite tubular inner urethral stent.

[0022] 图2为本发明一种可降解的复合型管状尿道支架外层的结构示意图。 [0022] FIG. 2 is a schematic structural composite tubular outer urethral stent schematic of one biodegradable.

[0023] 图3为图1的展开示意图。 [0023] Figure 3 is a schematic view of Figure 1 expanded.

[0024] 图4为图2的展开示意图。 [0024] Figure 4 is a schematic view of Figure 2 expanded.

[0025] 图5为聚乳酸-羟基乙酸共聚物? [0025] FIG. 5 is a polylactic acid - glycolic acid? 1^八薄膜的电镜图。 1 ^ electron micrograph of eight films.

[0026] 图6为小肠脱细胞基质313薄膜的电镜图。 [0026] FIG. 6 is de-electron micrograph of intestinal cell matrix 313 films.

[0027] 在附图1〜6中,1表示内层;2表示外层;3表示聚乳酸-羟基乙酸共聚物? [0027] In the drawings 1~6, 1 denotes an inner layer; 2 represents the outer; 3, polylactic acid - glycolic acid? ⑷八薄膜;4表示小肠脱细胞基质313薄膜。 ⑷ eight films; 4 represents small intestine acellular matrix 313 films.

具体实施方式 DETAILED DESCRIPTION

[0028] 下面对照附图1〜6,通过实施例对本发明作进一步说明。 [0028] The following figures 1~6 controlled by embodiments of the present invention will be further described below.

[0029] 实施例1 [0029] Example 1

[0030] 一种可降解的复合型管状尿道支架的制备方法,该制备方法包括以下步骤: [0030] The method for preparing a degradable composite tubular urethral stent, which preparation process comprises the steps of:

[0031] (1)将高分子材料聚乳酸? [0031] (1) The polymer material polylactic acid? “和聚羟基乙酸?以按摩尔比50:50的比例混合,采用静电纺丝技术制得聚乳酸-羟基乙酸共聚物纳米级电纺纤维膜,在制得的电纺纤维膜表面接枝I型胶原蛋白进行改性,得到改性后的聚乳酸-羟基乙酸共聚物?化八薄膜; "And polyglycolic acid in a molar ratio of 50:50 mix, prepared using electrospinning polylactic acid -? Glycolic acid nanoscale electrospun fiber membrane, the membrane surface in electrospun fibers obtained graft I Collagen was modified to give the modified polylactic acid - glycolic acid copolymer of the eight film?;

[0032] (2)将小肠粘膜下层细胞组织浸泡于由体积浓度为0.2%的聚乙二醇辛基苯基醚-100(011 ^-100)和体积浓度为0.03 %的氨水混合制成的脱细胞液中,振荡脱细胞后在-40X:温度下进行低温冷冻并真空干燥处理,得到小肠脱细胞基质313薄膜; [0032] (2) The small intestinal submucosa tissue soaked in a concentration of 0.2% by the volume of polyethylene glycol octylphenyl ether -100 (011 ^ -100) and the volume concentration of 0.03% ammonia blend of decellularization solution, after shaking in acellular -40X: low temperature under the freezing temperature and dried in vacuo to give 313 intestinal acellular matrix film;

[0033] (3)根据尿道管径要求,将由步骤⑴得到的聚乳酸-羟基乙酸共聚物? [0033] (3) according to claim urethral diameter, obtained from step ⑴ polylactic acid - glycolic acid copolymer? ⑷八薄膜和步骤(2)得到的小肠脱细胞基质313薄膜制成规则的矩形,用9/0尼龙线缝合得到内层1和外层2。 ⑷ eight rectangular film and the step (2) to give the de-intestinal cell matrix 313 a thin film made of the rule, obtained by 9/0 nylon suture inner layer 1 and the outer layer 2.

[0034] 无菌取出新西兰大白兔的腹股沟脂肪,胶原酶法分离出兔脂肪间充质干细胞0013(:8),并进行贴壁培养法体外培养;对培养后的脂肪间充质干细胞0013()采用慢病毒转染的方法构建过表达血管内皮生长因子02(^)165,获得血管内皮生长因子(犯即)165基因转染的脂肪间充质干细胞;培养后的脂肪间充质干细胞(八013()在20118/1111的血小板衍生生长因子常规培养条件下诱导2周,分化成平滑肌细胞;采用气液相培养方法在由上述制备方法得到的内层1上接种血管内皮生长因子(犯即)165基因转染的脂肪间充质干细胞,在外层2上接种由脂肪间充质干细胞转化的平滑肌细胞;外层2设在内层1的外侧面上;所述的内层1为管状结构,由二条长度为宽度为的长方形状的聚乳酸-羟基乙酸共聚物薄膜与二条长度为30111111、宽度为3111111长方形状的小肠脱细胞基质313薄膜纵向间隔排布缝合在一起呈片状,环绕导尿管外侧缝合成管状;外层2由二条长度为30111111、宽度为3111111长方形状的聚乳酸-羟基乙酸共聚物?⑷八与二条长度为30皿、宽度为3皿长方形状的小肠脱细胞基质313水平间隔排布并缝合制成长条状,外层2螺旋缠绕在内层1的外表面上。 [0034] New Zealand white rabbits were removed aseptically groin fat, collagenase digestion was isolated rabbit adipose mesenchymal stem cells 0013 (: 8), and adherent culture in vitro method; inter-fat cultured mesenchymal stem cells 0013 ( ) using lentiviral transfection method for constructing over-expression of vascular endothelial growth factor 02 (^) 165, obtain vascular endothelial growth factor (guilty ie) among 165 gene transfected adipose mesenchymal stem cells; among cultured adipose mesenchymal stem cells (viii 013 () at 20118/1111 platelet-derived growth factor-induced two weeks under normal culture conditions, to differentiate into smooth muscle cells; the use of gas-liquid culture method in preparation obtained by the above inner inoculation of vascular endothelial growth factor 1 (ie guilty) between 165 gene transfected adipose-derived mesenchymal stem cells on the outer layer 2 by the smooth muscle cells were seeded derived mesenchymal stem cells into; the outer layer 2 provided on the outer surface of the inner layer 1; said inner layer 1 tubular structure, the length of the width of two rectangular-shaped polylactic acid - glycolic acid copolymer film with two lengths of 30,111,111, 3,111,111 rectangular width of the small intestine acellular matrix 313 film stitched together longitudinally spaced arrangement flaky outer surround sewn into a tubular catheter; an outer layer 2 is made of two lengths of 30,111,111, 3,111,111 rectangular width of polylactic acid - glycolic acid copolymer ⑷ eight and two length of 30 dishes, a width of 3 rectangular dish small intestine? acellular matrix 313 arranged horizontally spaced and suture system into strips, the outer layer 2 is spirally wound on the outer surface of the inner layer 1.

[0035] 图5为获得的聚乳酸-羟基乙酸共聚物? [0035] FIG. 5 is obtained polylactic acid - glycolic acid copolymer? 化八薄膜的电镜图;图6为获得的小肠脱细胞基质313薄膜的电镜图。 SEM of eight films; Figure 6 is small intestine electron micrographs obtained off the cell matrix 313 films.

[0036] 实施例2 [0036] Example 2

[0037] 一种可降解的复合型管状尿道支架的制备方法,该制备方法包括以下步骤: [0037] The method for preparing a degradable composite tubular urethral stent, which preparation process comprises the steps of:

[0038] (1)将高分子材料聚乳酸和聚羟基乙酸? [0038] (1) The polymer material polylactic acid and polyglycolic acid? 以按摩尔比75:25的比例混合,采用静电纺丝技术制得聚乳酸-羟基乙酸共聚物纳米级电纺纤维膜,厚度为0.4111111,孔隙率为90%,电纺丝直径为300-45011111,孔径为60-100 V0 ;在制得的电纺纤维膜表面接枝I型胶原蛋白进行改性,得到改性后的聚乳酸-羟基乙酸共聚物? With a molar ratio of 75:25 by mixing electrospinning technology to obtain polylactic acid - glycolic acid copolymer electrospun nano fiber membrane thickness of 0.4111111, a porosity of 90%, electrospinning diameter 300-45011111 , a pore size of 60-100 V0; electrospun fibers in the surface of the film obtained by graft type I collagen is modified to obtain the modified polylactic - glycolic acid copolymer? 1^八薄膜; 1 ^ eight films;

[0039] (2)将小肠粘膜下层细胞组织浸泡于由体积浓度为0.2%的聚乙二醇辛基苯基醚-100(011 ^-100)和体积浓度为0.03 %的氨水混合制成的脱细胞液中,振荡脱细胞后在-421:温度下进行低温冷冻处理并真空干燥处理,得到小肠脱细胞基质313薄膜; [0039] (2) The small intestinal submucosa tissue soaked in a concentration of 0.2% by the volume of polyethylene glycol octylphenyl ether -100 (011 ^ -100) and the volume concentration of 0.03% ammonia blend of decellularization solution, after shaking in acellular -421: at cryogenic temperature treatment and dried in vacuo to give 313 intestinal acellular matrix film;

[0040] (3)根据尿道管径要求,将由步骤⑴得到的聚乳酸-羟基乙酸共聚物? [0040] (3) according to claim urethral diameter, obtained from step ⑴ polylactic acid - glycolic acid copolymer? ⑷八薄膜和步骤(2)得到的小肠脱细胞基质313薄膜裁剪成规则的矩形,用9/0尼龙线缝合得到内层1和外层2。 ⑷ eight rectangular film and the step (2) obtained in the small intestine acellular matrix film was cut into a rule 313 by 9/0 nylon suture obtain an inner layer and an outer layer 2.

[0041] 无菌取出新西兰大白兔的腹股沟脂肪,胶原酶法分离出兔脂肪间充质干细胞0013(:8),并进行贴壁培养法体外培养;对培养后的脂肪间充质干细胞0013()采用慢病毒转染的方法构建过表达血管内皮生长因子02(^)165,获得血管内皮生长因子(犯即)165基因转染的脂肪间充质干细胞;培养后的脂肪间充质干细胞(八013()在20118/1111的血小板衍生生长因子$0(^-88)常规培养条件下诱导2周,分化成平滑肌细胞;采用气液相培养方法在由上述制备方法得到的内层1上接种血管内皮生长因子(犯即)165基因转染的脂肪间充质干细胞,在外层2上接种由脂肪间充质干细胞转化的平滑肌细胞;外层2设在内层1的外侧面上;所述的内层1为管状结构,由二条长度为宽度为的长方形状的聚乳酸-羟基乙酸共聚物?1^八薄膜与二条长度为30111111、宽度为3111111长方形状的小肠脱细胞基质313薄膜纵向间隔排布缝合在一起呈片状,环绕导尿管外侧缝合成管状;外层2由二条长度为30111111、宽度为3111111长方形状的聚乳酸-羟基乙酸共聚物?⑷八与二条长度为30皿、宽度为3皿长方形状的小肠脱细胞基质313水平间隔排布并缝合制成长条状,外层2螺旋缠绕在内层1的外表面上。 [0041] New Zealand white rabbits were removed aseptically groin fat, collagenase digestion was isolated rabbit adipose mesenchymal stem cells 0013 (: 8), and adherent culture in vitro method; inter-fat cultured mesenchymal stem cells 0013 ( ) using lentiviral transfection method for constructing over-expression of vascular endothelial growth factor 02 (^) 165, obtain vascular endothelial growth factor (guilty ie) among 165 gene transfected adipose mesenchymal stem cells; among cultured adipose mesenchymal stem cells (viii 013 () at 20118/1111 platelet-derived growth factor $ 0 (^ - under 88) conventional culture conditions induced by two weeks, to differentiate into smooth muscle cells; the use of gas-liquid culture method in preparation obtained by the above inner layer 1 inoculated vascular endothelial growth factor (ie guilty) between 165 gene transfected adipose-derived mesenchymal stem cells on the outer layer 2 was inoculated by the adipose-derived mesenchymal stem cells into smooth muscle cells; the outer layer 2 is provided on the outer surface of the inner layer 1; The inner layer of a tubular structure, the length of the width of two rectangular-shaped polylactic acid -? glycolic acid copolymer 1 ^ eight films and two lengths of 30,111,111, 3,111,111 rectangular width of the small intestine acellular matrix 313 film longitudinally spaced arrangement stitched together flaky around the outside of the catheter sewn into a tube; an outer layer 2 is made of two lengths of 30,111,111, 3,111,111 rectangular width of polylactic acid - glycolic acid copolymer ⑷ eight and two length of 30? dish, the width of the small intestine of a rectangular dish 3 acellular matrix 313 arranged horizontally spaced manufactured into strips and sewn, two outer helically wound on the outer surface of the inner layer 1.

[0042] 实施例3 [0042] Example 3

[0043] 一种可降解的复合型管状尿道支架的制备方法,该制备方法包括以下步骤: [0043] The method for preparing a degradable composite tubular urethral stent, which preparation process comprises the steps of:

[0044] (1)将高分子材料聚乳酸和聚羟基乙酸? [0044] (1) The polymer material polylactic acid and polyglycolic acid? 以按摩尔比85:15的比例混合,采用静电纺丝技术制得聚乳酸-羟基乙酸共聚物纳米级电纺纤维膜,在制得的电纺纤维膜表面接枝I型胶原蛋白进行改性,得到改性后的聚乳酸-羟基乙酸共聚物? With a molar ratio of 85:15 by mixing electrospinning technology to obtain polylactic acid - glycolic acid copolymer electrospun nano fiber membrane, the membrane surface in electrospun fibers obtained by graft modification of type I collagen to obtain the modified polylactic acid - glycolic acid? 化八薄膜; Of eight films;

[0045] (2)将小肠粘膜下层细胞组织浸泡于由体积浓度为0.2%的聚乙二醇辛基苯基醚-100(011 ^-100)和体积浓度为0.03 %的氨水混合制成的脱细胞液中,振荡脱细胞后在-501:温度下进行低温冷冻并真空干燥处理,得到小肠脱细胞基质313薄膜; [0045] (2) The small intestinal submucosa tissue soaked in a concentration of 0.2% by the volume of polyethylene glycol octylphenyl ether -100 (011 ^ -100) and the volume concentration of 0.03% ammonia blend of decellularization solution, after shaking in acellular -501: low temperature under the freezing temperature and dried in vacuo to give 313 intestinal acellular matrix film;

[0046] (3)根据尿道管径要求,将由步骤⑴得到的聚乳酸-羟基乙酸共聚物? [0046] (3) according to claim urethral diameter, obtained from step ⑴ polylactic acid - glycolic acid copolymer? ⑷八薄膜和步骤(2)得到的小肠脱细胞基质313薄膜裁剪成规则的矩形,用9/0尼龙线缝合得到内层1和外层2。 ⑷ eight rectangular film and the step (2) obtained in the small intestine acellular matrix film was cut into a rule 313 by 9/0 nylon suture obtain an inner layer and an outer layer 2.

[0047] 无菌取出新西兰大白兔的腹股沟脂肪,胶原酶法分离出兔脂肪间充质干细胞0013(:8),并进行贴壁培养法体外培养;对培养后的脂肪间充质干细胞0013()采用慢病毒转染的方法构建过表达血管内皮生长因子02(^)165,获得血管内皮生长因子(犯即)165基因转染的脂肪间充质干细胞;培养后的脂肪间充质干细胞(八013()在20118/1111的血小板衍生生长因子常规培养条件下诱导2周,分化成平滑肌细胞;采用气液相培养方法在由上述制备方法得到的内层1上接种血管内皮生长因子(犯即)165基因转染的脂肪间充质干细胞,在外层2上接种由脂肪间充质干细胞转化的平滑肌细胞;外层2设在内层1的外侧面上;所述的内层1为管状结构,由二条长度为宽度为的长方形状的聚乳酸-羟基乙酸共聚物薄膜与二条长度为30111111、宽度为3111111长方形状的小肠脱细胞基质313薄膜纵向间隔排布缝合在一起呈片状,环绕导尿管外侧缝合成管状;外层2由二条长度为30111111、宽度为3111111长方形状的聚乳酸-羟基乙酸共聚物?⑷八与二条长度为30皿、宽度为3皿长方形状的小肠脱细胞基质313水平间隔排布并缝合制成长条状,外层2螺旋缠绕在内层1的外表面上。 [0047] New Zealand white rabbits were removed aseptically groin fat, collagenase digestion was isolated rabbit adipose mesenchymal stem cells 0013 (: 8), and adherent culture in vitro method; inter-fat cultured mesenchymal stem cells 0013 ( ) using lentiviral transfection method for constructing over-expression of vascular endothelial growth factor 02 (^) 165, obtain vascular endothelial growth factor (guilty ie) among 165 gene transfected adipose mesenchymal stem cells; among cultured adipose mesenchymal stem cells (viii 013 () at 20118/1111 platelet-derived growth factor-induced two weeks under normal culture conditions, to differentiate into smooth muscle cells; the use of gas-liquid culture method in preparation obtained by the above inner inoculation of vascular endothelial growth factor 1 (ie guilty) between 165 gene transfected adipose-derived mesenchymal stem cells on the outer layer 2 by the smooth muscle cells were seeded derived mesenchymal stem cells into; the outer layer 2 provided on the outer surface of the inner layer 1; said inner layer 1 tubular structure, the length of the width of two rectangular-shaped polylactic acid - glycolic acid copolymer film with two lengths of 30,111,111, 3,111,111 rectangular width of the small intestine acellular matrix 313 film stitched together longitudinally spaced arrangement flaky outer surround sewn into a tubular catheter; an outer layer 2 is made of two lengths of 30,111,111, 3,111,111 rectangular width of polylactic acid - glycolic acid copolymer ⑷ eight and two length of 30 dishes, a width of 3 rectangular dish small intestine? acellular matrix 313 arranged horizontally spaced and suture system into strips, the outer layer 2 is spirally wound on the outer surface of the inner layer 1.

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