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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Publication number
CN104473706A
CN104473706A CN201410750552.4A CN201410750552A CN104473706A CN 104473706 A CN104473706 A CN 104473706A CN 201410750552 A CN201410750552 A CN 201410750552A CN 104473706 A CN104473706 A CN 104473706A
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thin film
lactide
poly
internal layer
composite tubular
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CN104473706B (en
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杜小文
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Jinhua City People S Hospital
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Jinhua City People S Hospital
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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

A kind of degradable composite tubular urethra rack and preparation method
Technical field
The present invention relates to medicine technology field, particularly a kind of degradable composite tubular urethra rack and preparation method.
Background technology
Traumatic or iatrogenic urethral injury, the urethral stricture that the gonococcal or various factors such as nonspecific urethritis and congenital urethra pathological changes causes is one of difficult problem of facing of urological surgeon.Conventional treatments comprises urethral dilatation, internal urethrotomy, end-to-end anastomosis of urethra etc. and is only applicable to the shorter urethral stricture patient of distance, patient for long section urethral stricture mainly adopts alternative operative treatment, and genital skin, bladder mucosa, albuginea penis, oral mucosa and lingual mucous membrane are all used as the patching material of urethra prosthesis; But draw materials and usually can cause the complication at position of drawing materials, and the amount of drawing materials is restricted.
Summary of the invention
The object of the invention is to cause for when existing and draw materials in existing long section urethral stricture Therapeutic Method the weak point that wound, material taken amount are limited, position of drawing materials easily leads to complications, a kind of degradable composite tubular urethra rack and preparation method are provided.
The present invention completes in the following way: a kind of degradable composite tubular urethra rack, this degradable composite tubular urethra rack is a kind of degradable tissue engineering bracket, comprise internal layer and skin, internal layer is tubulose, and skin is located on the outer surface of internal layer; Described internal layer and skin all adopt degradable macromolecular material and acellular matrix to make.
In the degradable composite tubular urethra rack of described one, described makes internal layer and outer field degradable high polymer material employing Poly(D,L-lactide-co-glycolide PLGA thin film, and described acellular matrix adopts small intestinal acellular matrix SIS thin film; Interconnect between Poly(D,L-lactide-co-glycolide PLGA thin film and small intestinal acellular matrix SIS thin film.
In the degradable composite tubular urethra rack of described one, pass through between described Poly(D,L-lactide-co-glycolide PLGA thin film with small intestinal acellular matrix SIS thin film together with suturing with thread management; Described Poly(D,L-lactide-co-glycolide PLGA thin film and small intestinal acellular matrix SIS thin film are all in strip structure; Described line is employing 9/0 nylon wire.
In the degradable composite tubular urethra rack of described one, described skin is wrapped on the outer surface of internal layer by spiral way.
In the degradable composite tubular urethra rack of described one, Poly(D,L-lactide-co-glycolide PLGA thin film on described internal layer and the placing flat of small intestinal acellular matrix SIS film water, longitudinal separation arrangement is stitched together in the form of sheets, around catheter external latasuture synthesis tubulose.
In the degradable composite tubular urethra rack of described one, the Poly(D,L-lactide-co-glycolide PLGA thin film on described skin and small intestinal acellular matrix SIS thin film level are intervally arranged and are stitched together in strip.
In the degradable composite tubular urethra rack of described one, described internal layer is arranged by the Poly(D,L-lactide-co-glycolide PLGA thin film of two rectangles and the small intestinal acellular matrix SIS thin film longitudinal separation of two rectangles and is formed; Described skin is intervally arranged by two rectangular-shaped Poly(D,L-lactide-co-glycolide PLGA thin film and two rectangular-shaped small intestinal acellular matrix SIS thin film levels and is stitched together.
The preparation method of a kind of degradable composite tubular urethra rack of the present invention comprises the following steps:
(1) macromolecular material polylactic acid PLA and polyglycolic acid PGA are pressed the mixed in molar ratio of 50:50 ~ 85:15, electrostatic spinning technique is adopted to obtain Poly(D,L-lactide-co-glycolide PLGA nanoscale electrospun fiber membrane, carry out modification in obtained electrospinning fibre film surface grafting I-type collagen, obtain modified Poly(D,L-lactide-co-glycolide PLGA thin film;
(2) small intestinal submucosa cell tissue is soaked in de-Cell sap, de-Cell sap by volumetric concentration be 0.2% Triton X-100-100 (Triton X-100) and volumetric concentration be 0.03% ammonia be mixed, vibration at-40 DEG C ~-50 DEG C temperature, carries out freezing after taking off cell and vacuum drying obtains small intestinal acellular matrix SIS thin film;
(3) according to the requirement of urethra caliber, the small intestinal acellular matrix SIS thin film Poly(D,L-lactide-co-glycolide PLGA thin film obtained by step (1) and step (2) obtained makes the rectangle of rule, obtains internal layer and skin with suturing with thread management.
In the preparation method of described a kind of degradable composite tubular urethra rack, described line adopts nylon wire.
In the preparation method of described a kind of degradable composite tubular urethra rack, the mol ratio of described polylactic acid PLA and polyglycolic acid PGA is 75:25.
In the preparation method of described a kind of degradable composite tubular urethra rack, the nanoscale electrospinning fibre film thickness of the Poly(D,L-lactide-co-glycolide PLGA that described step (1) is obtained is 0.35 ~ 0.45mm, porosity is 85% ~ 95%, Electrospun diameter is 300 ~ 450nm, and aperture is 60 ~ 100 μm.
In the preparation method of described a kind of degradable composite tubular urethra rack, the preparation method of described a kind of degradable composite tubular urethra rack adopts liquid phase cultural method on internal layer, inoculate the fat mesenchymal stem cell of VEGF (VEGF) 165 gene transfection, and skin is inoculated the smooth muscle cell transformed by fat mesenchymal stem cell.
The support microstructure of a kind of degradable composite tubular urethra rack of the present invention is three-dimensional porous shape, has good biocompatibility and mechanical property, has both elasticity and pliability, can keep stable tube-like condition in vivo; What the present invention adopted is polymeric biomaterial and acellular matrix, is conducive to seed cell and sticks, breeds and break up, and promotes the growth of surrounding tissue; Bi-material can progressively be decomposed into small-molecule substance by respective mode and naturally absorb in vivo, without the need to taking out.
Adopting the present invention to carry out urethra Reparation and Reconstruction, without the need to carrying out autologous drawing materials, avoiding the complication that position of drawing materials may cause; Mucous membrane of urethra epithelial cell, stem cell, smooth muscle cell etc. can adhere to and breed on support, can be directly used in urethra Reparation and Reconstruction, are applicable to clinical practice.
Accompanying drawing explanation
Figure l is the structural representation of a kind of degradable composite tubular urethra rack internal layer of the present invention.
Fig. 2 is the outer field structural representation of a kind of degradable composite tubular urethra rack of the present invention.
Fig. 3 is the expansion schematic diagram of Fig. 1.
Fig. 4 is the expansion schematic diagram of Fig. 2.
Fig. 5 is the Electronic Speculum figure of Poly(D,L-lactide-co-glycolide PLGA thin film.
Fig. 6 is the Electronic Speculum figure of small intestinal acellular matrix SIS thin film.
In accompanying drawing 1 ~ 6,1 represents internal layer; 2 represent outer; 3 represent Poly(D,L-lactide-co-glycolide PLGA thin film; 4 represent small intestinal acellular matrix SIS thin film.
Detailed description of the invention
Contrast accompanying drawing 1 ~ 6 below, by embodiment, the invention will be further described.
Embodiment 1
A preparation method for degradable composite tubular urethra rack, this preparation method comprises the following steps:
(1) by the ratio mixing of macromolecular material polylactic acid PLA and polyglycolic acid PGA 50:50 in molar ratio, electrostatic spinning technique is adopted to obtain Poly(D,L-lactide-co-glycolide PLGA nanoscale electrospun fiber membrane, carry out modification in obtained electrospinning fibre film surface grafting I-type collagen, obtain modified Poly(D,L-lactide-co-glycolide PLGA thin film;
(2) submucous layer of small intestine cell tissue is soaked in by volumetric concentration be 0.2% Triton X-100-100 (Triton X-100) and volumetric concentration be in the de-Cell sap that is mixed of ammonia of 0.03%, at-40 DEG C of temperature, carry out freezing and vacuum drying treatment after the de-cell of vibration, obtain small intestinal acellular matrix SIS thin film;
(3) according to the requirement of urethra caliber, the small intestinal acellular matrix SIS thin film Poly(D,L-lactide-co-glycolide PLGA thin film obtained by step (1) and step (2) obtained makes the rectangle of rule, obtains internal layer 1 and outer 2 with 9/0 nylon line suture.
The groin fat of aseptic taking-up new zealand white rabbit, collagenase method isolates rabbit fat mesenchymal stem cell (ADMSCs), and carries out stationary culture In vitro culture; Adopt the method for slow-virus transfection to build process LAN VEGF (VEGF) 165 to the fat mesenchymal stem cell (ADMSCs) after cultivating, obtain the fat mesenchymal stem cell of VEGF (VEGF) 165 gene transfection; Fat mesenchymal stem cell (ADMSCs) after cultivation is induced 2 weeks under platelet derived growth factor (PDGF-BB) conventional culture conditions of 20ng/ml, is divided into smooth muscle cell; Adopt liquid phase cultural method on the internal layer 1 obtained by above-mentioned preparation method, inoculate the fat mesenchymal stem cell of VEGF (VEGF) 165 gene transfection, on outer 2, inoculate the smooth muscle cell transformed by fat mesenchymal stem cell; Outer 2 are located on the lateral surface of internal layer 1; Described internal layer 1 is tubular structure, by two length be 30mm, width is that the OBL Poly(D,L-lactide-co-glycolide PLGA thin film of 3mm and two length are 30mm, width is that 3mm OBL small intestinal acellular matrix SIS thin film longitudinal separation is arranged and is stitched together in the form of sheets, around catheter external latasuture synthesis tubulose; Outer 2 by two length be 30mm, width is that 3mm OBL Poly(D,L-lactide-co-glycolide PLGA and two length is 30mm, width is arrange and sew up and make strip in 3mm OBL small intestinal acellular matrix SIS horizontal interval, skin 2 is spirally wound on the outer surface of internal layer 1.
Fig. 5 is the Electronic Speculum figure of the Poly(D,L-lactide-co-glycolide PLGA thin film obtained; Fig. 6 is the Electronic Speculum figure of the small intestinal acellular matrix SIS thin film obtained.
Embodiment 2
A preparation method for degradable composite tubular urethra rack, this preparation method comprises the following steps:
(1) by the ratio mixing of macromolecular material polylactic acid PLA and polyglycolic acid PGA 75:25 in molar ratio, electrostatic spinning technique is adopted to obtain Poly(D,L-lactide-co-glycolide PLGA nanoscale electrospun fiber membrane, thickness is 0.4mm, porosity is 90%, Electrospun diameter is 300-450nm, and aperture is 60-100 μm; Carry out modification in obtained electrospinning fibre film surface grafting I-type collagen, obtain modified Poly(D,L-lactide-co-glycolide PLGA thin film;
(2) submucous layer of small intestine cell tissue is soaked in by volumetric concentration be 0.2% Triton X-100-100 (Triton X-100) and volumetric concentration be in the de-Cell sap that is mixed of ammonia of 0.03%, at-42 DEG C of temperature, carry out freezing process and vacuum drying treatment after the de-cell of vibration, obtain small intestinal acellular matrix SIS thin film;
(3) according to the requirement of urethra caliber, the small intestinal acellular matrix SIS thin film Poly(D,L-lactide-co-glycolide PLGA thin film obtained by step (1) and step (2) obtained is cut into the rectangle of rule, obtains internal layer 1 and outer 2 with 9/0 nylon line suture.
The groin fat of aseptic taking-up new zealand white rabbit, collagenase method isolates rabbit fat mesenchymal stem cell (ADMSCs), and carries out stationary culture In vitro culture; Adopt the method for slow-virus transfection to build process LAN VEGF (VEGF) 165 to the fat mesenchymal stem cell (ADMSCs) after cultivating, obtain the fat mesenchymal stem cell of VEGF (VEGF) 165 gene transfection; Fat mesenchymal stem cell (ADMSCs) after cultivation is induced 2 weeks under platelet derived growth factor (PDGF-BB) conventional culture conditions of 20ng/ml, is divided into smooth muscle cell; Adopt liquid phase cultural method on the internal layer 1 obtained by above-mentioned preparation method, inoculate the fat mesenchymal stem cell of VEGF (VEGF) 165 gene transfection, on outer 2, inoculate the smooth muscle cell transformed by fat mesenchymal stem cell; Outer 2 are located on the lateral surface of internal layer 1; Described internal layer 1 is tubular structure, by two length be 30mm, width is that the OBL Poly(D,L-lactide-co-glycolide PLGA thin film of 3mm and two length are 30mm, width is that 3mm OBL small intestinal acellular matrix SIS thin film longitudinal separation is arranged and is stitched together in the form of sheets, around catheter external latasuture synthesis tubulose; Outer 2 by two length be 30mm, width is that 3mm OBL Poly(D,L-lactide-co-glycolide PLGA and two length is 30mm, width is arrange and sew up and make strip in 3mm OBL small intestinal acellular matrix SIS horizontal interval, skin 2 is spirally wound on the outer surface of internal layer 1.
Embodiment 3
A preparation method for degradable composite tubular urethra rack, this preparation method comprises the following steps:
(1) by the ratio mixing of macromolecular material polylactic acid PLA and polyglycolic acid PGA 85:15 in molar ratio, electrostatic spinning technique is adopted to obtain Poly(D,L-lactide-co-glycolide PLGA nanoscale electrospun fiber membrane, carry out modification in obtained electrospinning fibre film surface grafting I-type collagen, obtain modified Poly(D,L-lactide-co-glycolide PLGA thin film;
(2) submucous layer of small intestine cell tissue is soaked in by volumetric concentration be 0.2% Triton X-100-100 (Triton X-100) and volumetric concentration be in the de-Cell sap that is mixed of ammonia of 0.03%, at-50 DEG C of temperature, carry out freezing and vacuum drying treatment after the de-cell of vibration, obtain small intestinal acellular matrix SIS thin film;
(3) according to the requirement of urethra caliber, the small intestinal acellular matrix SIS thin film Poly(D,L-lactide-co-glycolide PLGA thin film obtained by step (1) and step (2) obtained is cut into the rectangle of rule, obtains internal layer 1 and outer 2 with 9/0 nylon line suture.
The groin fat of aseptic taking-up new zealand white rabbit, collagenase method isolates rabbit fat mesenchymal stem cell (ADMSCs), and carries out stationary culture In vitro culture; Adopt the method for slow-virus transfection to build process LAN VEGF (VEGF) 165 to the fat mesenchymal stem cell (ADMSCs) after cultivating, obtain the fat mesenchymal stem cell of VEGF (VEGF) 165 gene transfection; Fat mesenchymal stem cell (ADMSCs) after cultivation is induced 2 weeks under platelet derived growth factor (PDGF-BB) conventional culture conditions of 20ng/ml, is divided into smooth muscle cell; Adopt liquid phase cultural method on the internal layer 1 obtained by above-mentioned preparation method, inoculate the fat mesenchymal stem cell of VEGF (VEGF) 165 gene transfection, on outer 2, inoculate the smooth muscle cell transformed by fat mesenchymal stem cell; Outer 2 are located on the lateral surface of internal layer 1; Described internal layer 1 is tubular structure, by two length be 30mm, width is that the OBL Poly(D,L-lactide-co-glycolide PLGA thin film of 3mm and two length are 30mm, width is that 3mm OBL small intestinal acellular matrix SIS thin film longitudinal separation is arranged and is stitched together in the form of sheets, around catheter external latasuture synthesis tubulose; Outer 2 by two length be 30mm, width is that 3mm OBL Poly(D,L-lactide-co-glycolide PLGA and two length is 30mm, width is arrange and sew up and make strip in 3mm OBL small intestinal acellular matrix SIS horizontal interval, skin 2 is spirally wound on the outer surface of internal layer 1.

Claims (10)

1. a degradable composite tubular urethra rack, it is characterized in that this degradable composite tubular urethra rack is a kind of degradable tissue engineering bracket, comprise internal layer and skin, internal layer is tubulose, and skin is located on the outer surface of internal layer; Described internal layer and skin all adopt degradable macromolecular material and acellular matrix to make.
2. the degradable composite tubular urethra rack of one according to claim 1, it is characterized in that described making internal layer and outer field degradable high polymer material adopts Poly(D,L-lactide-co-glycolide PLGA thin film, described acellular matrix adopts small intestinal acellular matrix SIS thin film; Interconnect between Poly(D,L-lactide-co-glycolide PLGA thin film and small intestinal acellular matrix SIS thin film.
3. the degradable composite tubular urethra rack of one according to claim 1 and 2, is characterized in that described skin 2 is wrapped on the outer surface of internal layer by spiral way.
4. the degradable composite tubular urethra rack of one according to claim 2, is characterized in that between described Poly(D,L-lactide-co-glycolide PLGA thin film with small intestinal acellular matrix SIS thin film by together with suturing with thread management; Described Poly(D,L-lactide-co-glycolide PLGA thin film and small intestinal acellular matrix SIS thin film are all in strip structure.
5. the degradable composite tubular urethra rack of one according to claim 4, it is characterized in that the Poly(D,L-lactide-co-glycolide PLGA thin film on described internal layer and the placing flat of small intestinal acellular matrix SIS film water, longitudinal separation arrangement is stitched together in the form of sheets, around catheter external latasuture synthesis tubulose.
6. the degradable composite tubular urethra rack of one according to claim 4, is characterized in that Poly(D,L-lactide-co-glycolide PLGA thin film on described skin and small intestinal acellular matrix SIS thin film level are intervally arranged and are stitched together in strip.
7. the preparation method of a kind of degradable composite tubular urethra rack according to any one of claim 1 to 6, is characterized in that this preparation method comprises the following steps:
(1) macromolecular material polylactic acid PLA and polyglycolic acid PGA are pressed the mixed in molar ratio of 50:50 ~ 85:15, electrostatic spinning technique is adopted to obtain Poly(D,L-lactide-co-glycolide PLGA nanoscale electrospun fiber membrane, carry out modification in obtained electrospinning fibre film surface grafting I-type collagen, obtain modified Poly(D,L-lactide-co-glycolide PLGA thin film;
(2) submucous layer of small intestine cell tissue is soaked in by volumetric concentration be 0.2% Triton X-100-100 (Triton X-100) and volumetric concentration be in the de-Cell sap that is mixed of ammonia of 0.03%, at-40 DEG C ~-50 DEG C temperature, carry out freezing and vacuum drying treatment after the de-cell of vibration, obtain small intestinal acellular matrix SIS thin film;
(3) according to the requirement of urethra caliber, the small intestinal acellular matrix SIS thin film Poly(D,L-lactide-co-glycolide PLGA thin film obtained by step (1) and step (2) obtained makes the rectangle of rule, obtains internal layer and skin with suturing with thread management.
8. the preparation method of a kind of degradable composite tubular urethra rack according to claim 7, is characterized in that described line adopts nylon wire.
9. the preparation method of a kind of degradable composite tubular urethra rack according to claim 7 or 8, is characterized in that the mol ratio of described polylactic acid PLA and polyglycolic acid PGA is 75:25.
10. the preparation method of a kind of degradable composite tubular urethra rack according to claim 7 or 8, it is characterized in that adopting liquid phase cultural method on internal layer, inoculate the fat mesenchymal stem cell of VEGF (VEGF) 165 gene transfection, skin is inoculated the smooth muscle cell transformed by fat mesenchymal stem cell.
CN201410750552.4A 2014-12-09 2014-12-09 Biodegradable composite type tubular urethral stent and preparation method Expired - Fee Related CN104473706B (en)

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CN108853579A (en) * 2018-07-27 2018-11-23 吉林大学 A kind of preparation method of artificial tubular biomaterial
CN110680961A (en) * 2019-11-12 2020-01-14 东南大学 Preparation method of multilayer spiral urethral tissue engineering scaffold
CN113244021A (en) * 2021-05-12 2021-08-13 太原理工大学 Support for preventing external auditory canal stenosis through 3D printing acellular matrix and preparation method

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CN107596447A (en) * 2017-10-11 2018-01-19 广州新诚生物科技有限公司 A kind of biological medicinal membrane with tissue repair function and preparation method thereof
CN108853579A (en) * 2018-07-27 2018-11-23 吉林大学 A kind of preparation method of artificial tubular biomaterial
CN110680961A (en) * 2019-11-12 2020-01-14 东南大学 Preparation method of multilayer spiral urethral tissue engineering scaffold
CN113244021A (en) * 2021-05-12 2021-08-13 太原理工大学 Support for preventing external auditory canal stenosis through 3D printing acellular matrix and preparation method

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