CN104473706A - Biodegradable composite type tubular urethral stent and preparation method - Google Patents

Biodegradable composite type tubular urethral stent and preparation method Download PDF

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CN104473706A
CN104473706A CN 201410750552 CN201410750552A CN104473706A CN 104473706 A CN104473706 A CN 104473706A CN 201410750552 CN201410750552 CN 201410750552 CN 201410750552 A CN201410750552 A CN 201410750552A CN 104473706 A CN104473706 A CN 104473706A
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film
urethral
glycolic acid
polylactic acid
composite tubular
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CN 201410750552
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CN104473706B (en )
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杜小文
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金华市人民医院
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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.

Description

一种可降解的复合型管状尿道支架及制备方法 Composite tubular urethral stent and its preparation method degradable

技术领域 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 medical technical field, particularly to a biodegradable composite tubular urethral stent and its preparation method.

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 injuries, urethral gonococcal or non-specific urethritis of 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 treatments include urethral dilation, internal urethrotomy, urethral anastomosis, etc. only for a short distance urethral stenosis, for a patient of long urethral stenosis mainly replace surgery, genital skin, bladder mucosa, white penis film, lingual oral mucosa and urethral mucosa were used as a surgical repair patch materials; however, complications often drawn drawn part, and the amount of coverage is limited.

发明内容 SUMMARY

[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 traumatic for the presence of long drawn prior urethral stricture method of treatment, the amount of material taken limited drawn parts deficiencies can lead to complications, there is provided a biodegradable composite tubular urethral stent and its preparation method.

[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 is accomplished by: A composite tubular degradable urethral stent, the degradable composite tubular stent is a urethral degradable scaffold for tissue engineering, comprising inner and outer layers, the inner tubular layer, the outer layer is provided on the outer surface of the inner layer; said inner and outer layers are made of polymer materials and biodegradable acellular matrix is ​​made.

[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, the inner and outer layers made of polymeric material using the biodegradable polylactic acid - glycolic acid copolymer film, the decellularized an acellular matrix substrate 313 using a thin film of the small intestine; polylactic acid - glycolic acid copolymer? 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 eight intestinal release film between the matrix and the film 313 are connected to each other.

[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 degradable composite tubular urethral stent, the polylactic acid - glycolic acid copolymer film between release and intestinal cell matrix 313 a thin film by a wire sewn together; the polylactic acid - glycolic acid copolymer? 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。 Eight small intestine of the acellular matrix film 313 showed film stripe structure; the line is to use nylon 9/0.

[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 one of the degradable composite tubular urethral stent, the outer layer is wound on the outer surface of the inner layer by a spiral manner.

[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 of the degradable composite tubular urethral stent, the polylactic acid on the inner layer - glycolic acid copolymer film and intestinal acellular matrix thin film 313 is placed horizontally, longitudinally spaced arranged sewn flaky together, sewn around the outside of a tubular catheter.

[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 urethral stent, the outer layer of the polylactic acid - glycolic acid copolymer film and intestinal acellular matrix thin film 313 are arranged horizontally spaced and sewn together in the 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 degradable composite tubular urethral stent, the inner layer of the two rectangular polylactic acid - glycolic acid copolymer? 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 small intestine eight rectangular film and the two acellular matrix thin film 313 composed of longitudinally spaced arranged; said two rectangular outer layer of polylactic acid - glycolic acid copolymer film with two rectangular intestinal acellular matrix thin film 313 horizontally spaced arrangement and sewn 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] The present invention is a method for preparing biodegradable composite tubular urethral stent comprises the steps of:

[0012] (1)将高分子材料聚乳酸? [0012] (1) A polylactic acid polymer material? “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 according to 50: 50~85: 15 molar mixing ratio, prepared by electrospinning a polylactic acid - glycolic acid copolymer nanoscale electrospun fiber membranes, the surface of the dielectric film made of spun fibers? graft modified type I collagen, the resulting 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) small intestine submucosa tissue immersed in a decellularization solution, 0.2% decellularization solution of polyethylene glycol octylphenyl ether -100 -100 ^) and a volume concentration of 0.03% volume concentration prepared by mixing aqueous ammonia, was shaken in acellular -40X: ~-50X: carried out at a temperature of frozen intestinal and dried in vacuo to give 313 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 film and step (2) to give a rectangular intestinal acellular matrix film made rules 313, with the inner and outer layers to give 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 production method of a biodegradable composite tubular urethral stent, the nylon wire 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 production method of a biodegradable composite tubular urethral stent, the polylactic acid? I^和聚羟基乙酸? I ^ and polyglycolic acid? 以的摩尔比为75:25。 In 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 production method of a biodegradable composite tubular urethral stent, said step (1) was obtained polylactic acid - nanoscale dielectric film thickness spun fibers eight glycolic acid copolymer 0.35 1 ~0.45 dirty, a porosity of 85% ~ 95%, electrospinning 300~45011111 diameter, a pore size of 60~100 V pawl.

[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 production method of a biodegradable composite tubular urethral stent, a method for preparing a degradable composite tubular urethral stent using gas-liquid culture inoculation vessel on the inner layer endothelial growth factor (i.e. committed) between 165 gene transfected adipose stem cells, seeded by a transformation derived mesenchymal stem cells on the outer layer of 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 provides a stent microstructure degradable composite tubular urethral stent is a three-dimensional porous, has good mechanical properties and biocompatibility, both elasticity and flexibility, can maintain a stable form in the tubular body; the present invention uses a polymer biomaterials and acellular matrix, conducive seed cell adhesion, proliferation and differentiation and promote the growth of surrounding tissue; in vivo, the two materials may be gradually broken down into their way naturally absorb small molecules, no need to remove.

[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, autologous without coverage, avoids complications that may arise drawn parts; urethral epithelial cells, stem cells, smooth muscle cell proliferation and the like can adhere to the holder, it 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 structure of a degradable composite tubular inner urethral stent of the present invention.

[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 structure of composite tubular outer urethral stent of the present invention one degradable.

[0023] 图3为图1的展开示意图。 [0023] FIG. 3 is a developed perspective view showing FIG. 1.

[0024] 图4为图2的展开示意图。 [0024] FIG. 4 is an expanded schematic diagram of FIG.

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

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

[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 1~6 in the drawings, 1 denotes an inner layer; 2 represents the outer; 3 represents polylactic - glycolic acid copolymer? ⑷八薄膜;4表示小肠脱细胞基质313薄膜。 ⑷ eight films; 4 acellular matrix 313 represents small intestine film.

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] reference to the drawings 1~6 below, by way of example of the present invention will be further described.

[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 producing a composite tubular degradable urethral stent, which method comprises the steps of preparing:

[0031] (1)将高分子材料聚乳酸? [0031] (1) A polylactic acid polymer material? “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; "Polyglycolic acid and mixed in a molar ratio of 50:50, made by electrospinning a polylactic acid -? Glycolic acid nanoscale electrospun fiber membranes, the surface of the dielectric film spun fibers Grafted I modified collagen, the resulting modified polylactic acid - glycolic acid copolymer film of eight?;

[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(¾011 ^-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) small intestinal submucosa tissue soaked in a concentration of 0.2% by volume of polyethylene glycol octylphenyl ether -100 (¾011 ^ -100) and a volume concentration of 0.03% ammonia water made by mixing decellularization solution, after shaking off cells -40X: freezing temperature of low 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。 Rectangles (2) obtained in the step of film and small intestine eight ⑷ acellular matrix film made rules 313, obtained by 9/0 nylon suture inner 1 and outer 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(¾)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(¾)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 [0034] New Zealand white rabbits were removed aseptically groin fat, the rabbit isolated by collagenase digestion and adipose-derived mesenchymal stem cells 0013 (: 8), and cultured in vitro adherent culture; after culturing of adipose mesenchymal stem cells 0013 ( ¾) method lentivirus construct overexpression of vascular endothelial growth factor 02 (^) 165 to obtain between 165 gene transfected adipose-derived mesenchymal stem cells, vascular endothelial growth factor (guilty i.e.); adipose after culturing mesenchymal stem cells (viii 013 (¾) of the platelet-derived 20118/1111 induced two weeks under conventional culture conditions, growth factors, differentiation into smooth muscle cells; culture method using gas-liquid phase in the inner layer obtained by the above production method seeded vascular endothelial growth factor 1 (i.e. committed) between 165 gene transfected adipose mesenchymal stem cells, smooth muscle cells on the outer layer 2 of the seeded transformed derived mesenchymal stem cells; an outer layer 2 provided on the outer surface of the inner layer 1; the inner layer 1 a tubular structure, a length of the width of the two rectangular polylactic acid - glycolic acid copolymer film with a length of two 30111111, 3111111 rectangular width intestinal acellular matrix thin film 313 longitudinally spaced rows 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。 Flaky cloth sewn together, sewn around the outside of a tubular catheter; an outer layer 2 is made of two lengths of 30111111, 3111111 rectangular width polylactic - glycolic acid copolymer ⑷ eight dish 30 with a length of two, the width? 3 is a rectangular dish off the intestinal cell matrix 313 are arranged horizontally spaced manufactured into strips and sewn, 2 outer helically 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 off the electron micrograph of the film substrate 313 cells are obtained from the small intestine.

[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 producing a composite tubular degradable urethral stent, which method comprises the steps of preparing:

[0038] (1)将高分子材料聚乳酸和聚羟基乙酸? [0038] (1) The polymer material of 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? In a molar ratio of 75:25 were mixed by electrospinning obtained polylactic - glycolic acid copolymer fiber electrospun nanoscale film thickness of 0.4111111, a porosity of 90%, a diameter of electrospinning 300-45011111 , a pore size of 60-100 V0; graft type I collagen on the surface of dielectric film made of spun fibers modified, the modified polylactic acid - glycolic acid copolymer? 1^八薄膜; 1 ^ eight film;

[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(¾011 ^-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) small intestinal submucosa tissue soaked in a concentration of 0.2% by volume of polyethylene glycol octylphenyl ether -100 (¾011 ^ -100) and a volume concentration of 0.03% ammonia water made by mixing decellularization solution, after shaking off -421 cells: treatment carried out at a temperature of cryogenic and vacuum dried 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。 Rectangles (2) obtained in the step of film and small intestine eight ⑷ acellular matrix thin film 313 in a regular cut, to obtain an inner layer and an outer layer 2 by 9/0 nylon suture.

[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(¾)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(¾)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 [0041] New Zealand white rabbits were removed aseptically groin fat, the rabbit isolated by collagenase digestion and adipose-derived mesenchymal stem cells 0013 (: 8), and cultured in vitro adherent culture; after culturing of adipose mesenchymal stem cells 0013 ( ¾) method lentivirus construct overexpression of vascular endothelial growth factor 02 (^) 165 to obtain between 165 gene transfected adipose-derived mesenchymal stem cells, vascular endothelial growth factor (guilty i.e.); adipose after culturing mesenchymal stem cells (viii 013 (¾) of the platelet-derived growth factor 20118/1111 $ 0 (^ - induced at 88) were cultured for 2 weeks, differentiate into smooth muscle cells; culture method using gas-liquid phase in the inner layer obtained by the above production method 1 inoculated with vascular endothelial growth factor (i.e. committed) between 165 gene transfected adipose mesenchymal stem cells, inoculated on the outer layer 2 by the mesenchymal stem cells into smooth muscle cells of the adipose; an outer layer 2 provided on the outer surface of the inner layer 1; said inner tubular structure 1, a length of the width of the two rectangular polylactic acid -? 1 ^ glycolic acid copolymer film and the two eight 30111111 length, width intestinal 3,111,111 rectangular thin acellular matrix 313 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。 Arranged longitudinally spaced flaky sewn together, sewn around the outside of a tubular catheter; an outer layer 2 is made of two lengths of 30111111, 3111111 rectangular width polylactic - glycolic acid copolymer and two eight ⑷ length of 30? dish, a width of a rectangular dish 3 intestinal acellular matrix 313 are arranged horizontally spaced manufactured into strips and sewn, 2 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 producing a composite tubular degradable urethral stent, which method comprises the steps of preparing:

[0044] (1)将高分子材料聚乳酸和聚羟基乙酸? [0044] (1) The polymer material of 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? In a molar ratio of 85:15 were mixed by electrospinning obtained polylactic - glycolic acid copolymer nanoscale electrospun fiber membranes, the modified surface of the dielectric film obtained spun fibers graft type I collagen , polylactic acid obtained after modification - glycolic acid copolymer? 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(¾011 ^-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) small intestinal submucosa tissue soaked in a concentration of 0.2% by volume of polyethylene glycol octylphenyl ether -100 (¾011 ^ -100) and a volume concentration of 0.03% ammonia water made by mixing decellularization solution, after shaking off -501 cells: freezing at a temperature and low temperature vacuum drying, to obtain intestinal acellular matrix thin film 313;

[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。 Rectangles (2) obtained in the step of film and small intestine eight ⑷ acellular matrix thin film 313 in a regular cut, to obtain an inner layer and an outer layer 2 by 9/0 nylon suture.

[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(¾)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(¾)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 [0047] New Zealand white rabbits were removed aseptically groin fat, the rabbit isolated by collagenase digestion and adipose-derived mesenchymal stem cells 0013 (: 8), and cultured in vitro adherent culture; after culturing of adipose mesenchymal stem cells 0013 ( ¾) method lentivirus construct overexpression of vascular endothelial growth factor 02 (^) 165 to obtain between 165 gene transfected adipose-derived mesenchymal stem cells, vascular endothelial growth factor (guilty i.e.); adipose after culturing mesenchymal stem cells (viii 013 (¾) of the platelet-derived 20118/1111 induced two weeks under conventional culture conditions, growth factors, differentiation into smooth muscle cells; culture method using gas-liquid phase in the inner layer obtained by the above production method seeded vascular endothelial growth factor 1 (i.e. committed) between 165 gene transfected adipose mesenchymal stem cells, smooth muscle cells on the outer layer 2 of the seeded transformed derived mesenchymal stem cells; an outer layer 2 provided on the outer surface of the inner layer 1; the inner layer 1 a tubular structure, a length of the width of the two rectangular polylactic acid - glycolic acid copolymer film with a length of two 30111111, 3111111 rectangular width intestinal acellular matrix thin film 313 longitudinally spaced rows 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。 Flaky cloth sewn together, sewn around the outside of a tubular catheter; an outer layer 2 is made of two lengths of 30111111, 3111111 rectangular width polylactic - glycolic acid copolymer ⑷ eight dish 30 with a length of two, the width? 3 is a rectangular dish off the intestinal cell matrix 313 are arranged horizontally spaced manufactured into strips and sewn, 2 outer helically wound on the outer surface of the inner layer 1.

Claims (10)

  1. 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 stent is a urethral degradable scaffold for tissue engineering, comprising inner and outer layers, inner tube, an outer layer disposed the outer surface of the inner layer; said inner and outer layers are made of polymer materials and biodegradable acellular matrix is ​​made.
  2. 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。 1 2. The one of the degradable composite tubular urethral stent as claimed in claim, wherein said inner and outer layers made of polymeric material using the biodegradable polylactic acid - glycolic acid PLGA film, the use of acellular matrix SIS intestinal acellular matrix film; polylactic acid - glycolic acid copolymer film and a PLGA matrix between SIS intestinal release film connected to each other.
  3. 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. According to one claim 1 or 2 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 manner.
  4. 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。 2, according to one of the degradable composite tubular urethral stent as claimed in claim, wherein said polylactic acid - glycolic acid copolymer PLGA between the film and the acellular matrix SIS intestinal suture through the film together; a polylactic acid - glycolic acid copolymer film PLGA small intestine showed acellular matrix SIS film stripe structure.
  5. 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。 5. According to a 4 degradable composite tubular claim urethral stent, wherein the polylactic acid on the inner layer - glycolic acid copolymer PLGA films and film intestinal acellular matrix SIS horizontally disposed, longitudinal spacer arranged flaky sewn together, sewn around the outside of a tubular catheter.
  6. 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. According to one of the 4 degradable composite tubular urethral stent as claimed in claim, wherein the polylactic acid on the outer - glycolic acid copolymer and PLGA film release matrix SIS intestinal cell compartments arranged horizontally film strip-shaped and stitched together.
  7. 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-40°C〜_50°C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 7. The method for preparing a biodegradable composite tubular urethral stent according to any of claims 1-6, wherein the preparation process comprises the steps of: (1) The polylactic acid PLA polymer material and polyglycolic acid PGA by 50: 50~85: 15 molar mixing ratio, prepared by electrospinning a polylactic acid - glycolic acid PLGA nanoscale electrospun fiber membranes, grafted on the surface of dielectric film made of spun fibers type I collagen was modified to give the modified polylactic - glycolic acid PLGA film; (2) small intestinal submucosa tissue soaked in a concentration of 0.2% by volume of polyethylene glycol octylphenyl ether -100 (Triton X-100) and a volume concentration of 0.03% decellularization solution made by mixing aqueous ammonia, 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, obtained from step (I) of polylactic acid - glycolic acid PLGA film and the step (2) to give the SIS intestinal acellular matrix thin film made of a rectangular rule, with inner and outer layers to give suture.
  8. 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 method for preparing a 7 degradable composite tubular urethral stent according to claim, wherein said nylon cord lines.
  9. 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 method for preparing a molar ratio of 7 or 8 degradable composite tubular urethral stent according to claim, wherein said PLA polylactic acid and polyglycolic acid PGA 75:25.
  10. 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 method for preparing a 7 or 8 degradable composite tubular urethral stent according to claim, characterized in that a gas-liquid culture inoculation of vascular endothelial growth factor (VEGF) on the inner layer 165 gene transfection the adipose-derived stem cells, smooth muscle cells seeded on the outer layer of adipose-derived stem cells transformed.
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