CN105999419B - A kind of biomimetic type can absorb dural patch and the preparation method and application thereof - Google Patents
A kind of biomimetic type can absorb dural patch and the preparation method and application thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/0063—Implantable repair or support meshes, e.g. hernia meshes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2210/0076—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof multilayered, e.g. laminated structures
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
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Abstract
The invention discloses a kind of biomimetic type adsorbable artificial dural patches and the preparation method and application thereof.The biomimetic type artificial dura mater sticking patch has double-layer structure, is lubricant layer with brain tissue contact side, internal to contain the natural polymer with lubricating action；Promote endocranium regeneration zone away from side with brain tissue, internal nanofiber is in height-oriented arrangement.The microstructure of biomimetic type adsorbable artificial dural patch provided by the invention bionical natural endocranium completely, both bootable cell directional was creeped, and brain tissue can also be protected injured from abrasion, prevent tissue adhesion.Biocompatibility, flexibility and adhesion are good simultaneously, and industrialization production easy to accomplish has a good application prospect.
Description
Technical field
The invention belongs to biomedical material technologies, and in particular to a kind of biomimetic type can absorb dural patch and its
Preparation method and application.
Background technique
Endocranium is one layer of connective tissue being located on the inside of skull and on the outside of brain, is the natural barrier for protecting brain tissue.
The reasons such as open craniocerebral bone injury, meningioma and other brainpan illness will cause dura defect, and then lead to leakage of cerebrospinal
Generation.If not treated will lead to intracranial infection, cause archnoiditis or meningitis, or even develops into brain abscess and encephalic
A series of complication for threatening patient vitals of bleeding etc..Mostly it is for the main means of cerebral dura mater repairing defect clinically at present
The biological sticking patch or polyurethane, varicosity obtained using the materials tissues such as autospasy cellular allograft or animal sources corium, pericardium is poly-
The non-degradables macromolecular fibre sticking patch such as tetrafluoroethene.
Natural endocranium is made of the periosteal layer in outside and the meninx layer double-layer structure of inside, and wherein periosteal layer is rich in blood
Pipe, nerve and a large amount of collagenous fibres, main function are that mechanics protection is provided for cerebral tissue；Meninx layer is mainly thin by smooth mesothelium
Born of the same parents' composition, can secrete endogenous hyaluronic acid sodium, provide lubrication, make the not frayed injury of brain tissue.But current list marketing
Meninx sticking patch product is single layer structure, cannot well simultaneously meet promote defect meninx regeneration and prevent brain tissue abrasion by
The effect of wound.
In addition, natural endocranium is a kind of anisotropic material, its micro-structure or mechanical characteristic are embodied in each
It is not quite similar on direction, basic component units --- collagen microfibrils is special in the orientations that specific region shows height
Property.Studies have shown that the collagen microfibrils being distributed in endocranium shows left and right high degree of symmetry structure along median sagittal plane, in left and right
Two sides temporo area is until the collagenous fibres being distributed in sinus sagittalis superior region are height-oriented arrangement, while also having portion in volume side and back side
There are the collagenous fibres of height-oriented arrangement (Malinin et.al., Quantification of the inside subregion
collagen fiber architecture of human cranial dura mater,J.Anat.,1998,192:99-
106).But it has been at present isotropic material in the various dural patches of clinical application, it is bionical well not in structure
Natural endocranium micro-structure, therefore it cannot fully meet reparation as dural patch and require.
Chinese invention patent ZL 200910037736.5, denomination of invention are as follows: a kind of " nanometer people for having multiple functional layers
Work endocranium and preparation method thereof ", 101507661 B of Authorization Notice No. CN are disclosed a kind of at least two functional layers
Artificial dura mater is prevented adhesion by the cerebripetal hydrophobicity in face and electrospinning layer and carries on the back cerebripetal hydrophilic nano cytoskeleton layer group
At.Wherein hydrophobicity antiblocking layers are made of hydrophobic polymer through the tunica fibrosa that electrospinning obtains, hydrophilic cell shelf layer by
The tunica fibrosa obtained after hydrophobic polymer composite hydrophilic macromolecule through electrospinning is constituted.In embodiment, prevent adhesion layer choosing
Hydrophobic l-polylactic acid and 6-caprolactone are selected, the two ratio is 50:50；Cytoskeleton layer choosing selects polyethylene glycol and chondroitin sulfate
Element, the two mass ratio are 70:30, and the final nano artificial endocranium is combined by above-mentioned two layers.But this artificial dura mater is deposited
In following disadvantage: (1) using hydrophobicity electrospinning layer towards brain side, be free of Natural hydrophilic macromolecule；And natural endocranium
In in the meninx layer towards brain side containing endogenous greasing substances such as Sodium Hyaluronates, therefore the artificial dura mater fails pair
Meninx layer composition carries out bionical；It (2) is the cytoskeleton layer of isotropic backwards to brain side, interior hydrophilic macromolecule is
It is disorderly arranged；And the collagen microfibrils in natural endocranium periosteal layer temporo area and volume side, posterior components region is height-oriented row
Column, thus the artificial dura mater fail to periosteal layer structure carry out it is bionical.
Therefore, at present clinically there are no one kind can completely bionical natural endocranium structure, simultaneously preparation process it is simple,
The wide artificial hard brain (ridge) membrane patching material of industrialization prospect.
Summary of the invention
The purpose of the present invention is provide for clinic a kind of with anisotropic microstructure knot from bionical natural endocranium structure
Structure and natural double-layer structure, flexibility and adhesion is good, resistance to suture, histocompatbility and mechanical strength is good, degradation rate
It is moderate and in vivo Wholly-degradable absorb, can remarkably promote endocranium regeneration and prevention tissue adhesion, be easy to cut out, saves together
When clinical use absorbable dural patch easy to operate.
It is a further object of the present invention to provide preparation methods and application that this can absorb dural patch.
Biomimetic type artificial dura mater sticking patch provided by the present invention, the artificial dura mater sticking patch have double-layer structure, by
Lubricant layer and rush endocranium regeneration zone composition；
It wherein, is lubricant layer with brain tissue contact side；
Promote endocranium regeneration zone away from side with brain tissue；
The lubricant layer and rush endocranium regeneration zone are made of nanofiber, and the nanofiber inside the lubricant layer
With lubricating action, the nanofiber promoted inside endocranium regeneration zone is oriented in arrangement；
The nanofiber for constituting the lubricant layer is to be made using materials A and material B as raw material；
Constituting the oriented nanofibers for promoting meninx regeneration zone is to be made using materials A and material C as raw material；
The materials A is degradable synthesising biological high molecular material；
The material B is native biopolymer；
The material C is that hydrophily synthesizes macromolecule.
In above-mentioned artificial dura mater sticking patch, the materials A is selected from polylactic acid, polycaprolactone, polyglycolic acid, gathers to dioxy
Cyclohexanone, polytrimethylene carbonate, polyethylene glycol, poly butyric ester, poly- hydroxyl valerate, poly butylene succinate and
The copolymer of one or more of polyurethane；
Wherein, the polylactic acid concretely l-lactic acid；
More specifically, the materials A can be selected from polylactic-co-glycolic acid, l-lactic acid, polylactic acid-caprolactone
Copolymer, polytrimethylene carbonate；Wherein, the weight average molecular weight of the polylactic-co-glycolic acid can be 120,000；It is described
The weight average molecular weight of l-lactic acid can be 50,000 to 500,000, preferably 300,000；Polylactic acid-the caprolactone copolymer is divided equally again
Son amount can be 50,000 to 500,000, preferably 300,000；The weight average molecular weight of the polytrimethylene carbonate can be 50,000 to 500,000, preferably
150000；
The material B is selected from Sodium Hyaluronate, carboxymethyl chitosan, sodium carboxymethylcellulose, chondroitin sulfate, modified fibre
Tie up at least one of element, modification of chitosan, alginic acid, collagen and fibrin；
Wherein, the relative molecular weight of the carboxymethyl chitosan concretely 50,000 to 500,000, preferably 200,000；
The material C is selected from polyethylene glycol, polypropylene glycol, polyvinylpyrrolidone, polyacrylamide, polyvinyl alcohol, gathers
At least one of ethylene oxide and carbomer；
Wherein, the weight average molecular weight of the polyvinylpyrrolidone can be 50,000 to 500,000, preferably 300,000；The poly- second two
The weight average molecular weight of alcohol can be 5000 to 50000, preferably 10,000；The weight average molecular weight of the carbomer can be 20,000 to 100,000, excellent
Select 50,000；The weight average molecular weight of the polyacrylamide can be 20,000 to 100,000, preferably 50,000；
Preferably, materials A of the present invention selects polylactic-co-glycolic acid, material B selects Sodium Hyaluronate, material
Expect that C selects polyvinylpyrrolidone.
The materials A and the weight ratio of material B are 99:1-70:30, concretely 95:5 or 96:4 or 97:3；It is preferred that 95:
5；
The weight ratio of the materials A and material C is 99:1-80:20, concretely 90:10 or 95:5；It is preferred that 90:10；
The nanofiber for constituting the lubricant layer concretely passes through electrospinning process using materials A and material B as raw material
It is made；
Constituting the oriented nanofibers for promoting meninx regeneration zone, to be concretely that raw material passes through using materials A and material C quiet
Electrical spinning method is made；
The lubricant layer with a thickness of 0.05-1.5 millimeters, concretely 0.15 millimeter, 0.2 millimeter or 0.25 millimeter；It receives
The diameter of rice fiber is 100-1000 nanometers, and aperture is 300-3000 nanometers between fiber.
It is described promote meninx regeneration zone with a thickness of 0.05-0.5 millimeters, concretely 0.05 millimeter；Promote endocranium regeneration zone
Internal nanofiber is in height-oriented arrangement, and diameter is 100-1000 nanometers, and aperture is 300-3000 nanometers between fiber.
Containing the natural polymer with lubricating action inside lubricant layer of the present invention, with natural endocranium mesothelial cell
The endogenous hyaluronic acid sodium effect of secretion is similar, can protect brain tissue from abrasion.Meanwhile composite fibre in the lubricant layer
Aperture be much smaller than fibroblastic average-size, effectively fibroblast is prevented to move into inside lubricant layer, thus very well
Ground prevents the generation with brain tissue adhesion.
The hydrophilic macromolecule composite nano fiber of the present invention promoted inside meninx regeneration zone is height-oriented arrangement.One
Aspect, the hydrophilic surface for promoting regeneration zone are conducive to the adherency and proliferation of cell；On the other hand, with glue in natural endocranium temporo area
The composite nano fiber of the arrangement mode of former microfibre is conducive to that cell is guided to creep along nanofiber orientation, this is to most
Dural regeneration effect remarkably promotes effect eventually.Compared with the disorderly arranged nano fibrous membrane of isotropic, anisotropy is taken
There is significant advantage in terms of the dural reparation speed of defect and regeneration endocranium to fiber arranged film.
The present invention also provides a kind of methods for preparing the artificial dura mater sticking patch, and this method comprises the following steps:
1) lubricant layer electrostatic spinning solution is prepared respectively and promotees meninx regeneration zone electrostatic spinning solution, is denoted as spinning solution respectively
A and spinning solution b；
Wherein, the spinning solution a is to be made of the materials A, material B and spin solvent；
The spinning solution b is to be made of the materials A, material C and spin solvent；
2) after spinning solution a obtained by step 1) being carried out electrospinning, the lubricant layer is obtained；
3) spinning solution b obtained by step 1) is subjected to electrospinning on the lubricant layer obtained by step 2), obtains the rush endocranium again
Generating layer, then be dried in vacuo, obtain the artificial dura mater sticking patch.
In the step 1) of the above method, the weight ratio of the materials A and material B are 99:1-70:30, concretely 95:5
Or 96:4 or 97:3；It is preferred that 95:5；
The weight ratio of the materials A and material C is 99:1-80:20, concretely 90:10 or 95:5；It is preferred that 90:10；
In the spinning solution a and spinning solution b, high molecular total weight percentage composition is 1-20%, and preferably 10%；
It is acetone, dimethylformamide, dimethyl acetamide, tetrahydrofuran, methylene chloride, three chloromethanes that the solvent, which is selected from,
At least one of alkane, deionized water, 1,4- dioxane, hexafluoroisopropanol, ethyl alcohol, dimethyl sulfoxide and trifluoroacetic acid；
The solvent concretely hexafluoroisopropanol, methylene chloride, chloroform, deionized water, by dimethylformamide
With the mixed solution of tetrahydrofuran composition；Wherein, in the mixed solution being made of dimethylformamide and tetrahydrofuran, two
Methylformamide and the volume ratio of tetrahydrofuran are 4:1；The preferred hexafluoroisopropanol of solvent；
In the step 2) and step 3) eiectrospinning steps, the supply flow rate of spinning solution is 0.1-20 mls/hour, specifically
It can be 1 ml/hour, 1.5 mls/hour, 2 mls/hour, 2.5 mls/hour or 3 mls/hour；
It is 3 centimetres -30 centimetres that end, which occurs, for high pressure with the distance between collection device, concretely 10 centimetres, 12.5 lis
Rice or 15 centimetres；
The voltage of high pressure generator is 0.1-40 kilovolts, concretely 12.5 kilovolts or 15 kilovolts；
Collecting substrate is roller, and diameter is 2-20 centimetres, and concretely 8 centimetres or 10 centimetres；
Wherein in step 2), the revolving speed of the roller is 100-1000 revs/min；In step 3), the revolving speed of the roller is
1000-5000 revs/min, concretely 3000 revs/min or 3000-5000 revs/min.
In the vacuum drying step, dry temperature is 25-50 DEG C, preferably 37 DEG C；Time is 24-72h, preferably 48h；
Vacuum degree is -0.1MPa-0.1MPa, preferably -0.1MPa；
Specifically, the step 2) eiectrospinning steps can specifically carry out in accordance with the following steps: first by spinning solution a obtained by step 1)
It is packed into Electrospun liquid supplying device；It is 0.1-20 mls/hour by the supply flow rate that flow pump regulates and controls Electrospun liquid；It adjusts high
Pressure cause trouble the distance between same collection device be 3 centimetres -30 centimetres；Height is provided to electro-spinning process by high pressure generator
Pressure, can regulate and control between 0.1-40 kilovolts；It is 100-1000 revs/min by revolving speed, the roller and ground terminal that diameter is 2-20 centimetres
It is connected, the collection substrate as electro-spinning process；Obtaining after collecting on a rotating drum has thickness at 0.05-1.5 millimeters
Lubricant layer tunica fibrosa.
Step 3) the eiectrospinning steps can specifically carry out in accordance with the following steps: spinning solution b obtained by step 1) being first packed into electricity
Spinning liquid supplying device, supply flow rate are 0.1-20 mls/hour；It is 3 lis that end, which occurs, for high pressure with the distance between collection device
- 30 centimetres of rice；High pressure regulates and controls between 0.1-40 kilovolts；By the rolling that revolving speed is 1000-5000 revs/min, diameter is 2-20 centimetres
Collection substrate of the cylinder as electro-spinning process；It is collected on the rotating cylinder that surface is deposited with lubricant layer and obtains thickness in 0.05-
0.5 millimeter of rush regeneration zone tunica fibrosa.
Above-mentioned steps 2) and 3) in, preferably, supply flow rate is set as 3 mls/hour, the same collection device in end occurs for high pressure
The distance between be set as 10 centimetres, high pressure is set as 15 kilovolts, and the revolving speed in step 2) is set as 100 revs/min, in step 3)
Revolving speed be set as 3000 revs/min, diameter of cylinder is 8 centimetres, and lubricant layer promotees regeneration zone with a thickness of 0.2 millimeter with a thickness of 0.05
Millimeter.
In addition, product of the artificial dura mater sticking patch of aforementioned present invention offer in the repairing for preparing endocranium or pachymeninx
In application, also belong to protection scope of the present invention.
Biomimetic type double-layer nanometer tunica fibrosa provided by the invention is used as dural repairment material, has the advantages that
1, microstructure bionical natural endocranium completely, has and promotees endocranium regeneration zone and lubricant layer double-layer structure, wherein
Promoting nanofiber inside meninx regeneration zone is in height-oriented arrangement, and lubricant layer contains the natural polymer with lubricating action.
2, promote the bootable fibroblast orientation of the orientation fiber inside meninx regeneration zone to creep, while hydrophilic surface has
Conducive to the attaching and proliferation of cell, it is more advantageous to the regeneration of defect endocranium；Lubricant layer can both protect brain tissue injured from abrasion,
Prevented also from tissue adhesion.
3, biocompatibility is good, does not cause inflammatory reaction after implanting.
4, it slowly degrades as time went on after implanting, it finally can degradable and absorption.
5, flexibility and adhesion are good, can realize that exempting from suture fixes in clinical use.
6, product form and preparation process are simple, and product quality is easily controllable, are able to achieve the industrialization of high-efficiency and low-cost
Production.
Therefore, biomimetic type artificial dura mater sticking patch provided by the invention is the novel doctor of a kind of structure novel, superior performance
With biomaterial, good application prospect is shown repairing dura defect field.
Detailed description of the invention
Fig. 1 is the dural structural schematic diagram of biomimetic type bilayer degradable artificial.
Fig. 2 is the dural microscopic appearance of biomimetic type bilayer degradable artificial, wherein a) is disorderly arranged in lubricant layer
The microscopic appearance of fiber；B) microscopic appearance to promote orientations fiber in meninx regeneration zone.Scale is 2 microns.
Specific embodiment
The present invention is further elaborated combined with specific embodiments below, but the present invention is not limited to following embodiments.Institute
State method is conventional method unless otherwise instructed.The raw material can obtain unless otherwise instructed from public commercial source.
Embodiment 1:
The polylactic-co-glycolic acid that weight average molecular weight is 120,000 is dissolved in hexafluoroisopropanol, concentration 0.1
Grams per milliliter；The Sodium Hyaluronate that relative molecular weight is 1,200,000 is dissolved in deionized water, concentration is 0.06 grams per milliliter；Respectively
The solution of stable homogeneous is formed after being stirred at room temperature.Two kinds of solution are uniformly mixed under high velocity agitation later, volume ratio is
95:5, as spinning solution a.
The mixed solution is placed in syringe, high voltage power supply is connected at syringe needle.Solution supply flow rate is controlled 3
Ml/hour, applying voltage is 15 kilovolts, and high-voltage end is 15 centimetres with the distance of ground terminal, the rotation for the use of diameter being 8 centimetres
For roller as collection device, revolving speed is 100 revs/min.Spinning collects thickness after 5 hours disorderly arranged at 0.2 millimeter or so
Lubricant layer tunica fibrosa (Fig. 2 a).
By weight average molecular weight be 120,000 polylactic-co-glycolic acid and weight average molecular weight be 300,000 polyvinyl pyrrole
Alkanone is dissolved in hexafluoroisopropanol, and the mass ratio of the two is 90:10, and solution total concentration is 0.1 grams per milliliter, is stirred at room temperature
The solution of stable homogeneous, as spinning solution b are formed afterwards.
Solution supply flow rate is controlled at 1 ml/hour, and applying voltage is 15 kilovolts, and high-voltage end is with the distance of ground terminal
15 centimetres, use the rotating cylinder for being deposited with lubricant layer tunica fibrosa as collection device, revolving speed is 3000 revs/min.Spinning 1 hour
The rush regeneration zone tunica fibrosa (Fig. 2 b) that thickness is arranged in 0.05 millimeter of left-right orientation is collected afterwards.
Obtained biomimetic type double-layer nanometer tunica fibrosa will finally be collected in 37 DEG C of vacuum drying ovens (vacuum degree is -0.1MPa)
It is 48 hours dry, it sterilizes after taking-up and is cut into the artificial dura mater sticking patch with specific shape and size as needed, obtain
Biomimetic type adsorbable artificial dural patch provided by the invention.
Embodiment 2:
The l-lactic acid that weight average molecular weight is 300,000 is dissolved in methylene chloride, concentration is 0.08 grams per milliliter；By phase
The carboxymethyl chitosan for being 200,000 to molecular weight is dissolved in deionized water, and concentration is 0.02 grams per milliliter.By two kinds of solution in high speed
The lower uniformly mixing of stirring, volume ratio 95:5, as spinning solution a.
Solution supply flow rate is controlled at 1 ml/hour, and applying voltage is 12.5 kilovolts, distance of the high-voltage end with ground terminal
It is 10 centimetres, uses the rotating cylinder that diameter is 8 centimetres as collection device, revolving speed is 100 revs/min.It can be received after spinning 6 hours
Collect thickness in 0.15 millimeter or so disorderly arranged lubricant layer tunica fibrosa.
By weight average molecular weight be 300,000 l-lactic acid and weight average molecular weight be 10,000 polyethylene glycol be dissolved in dichloromethane
In alkane, the mass ratio of the two is 90:10, and solution total concentration is 0.08 grams per milliliter, as spinning solution b.
Solution supply flow rate is controlled at 2.5 mls/hour, and applying voltage is 12.5 kilovolts, high-voltage end with ground terminal away from
From being 10 centimetres, use the rotating cylinder for being deposited with lubricant layer tunica fibrosa as collection device, revolving speed is 3000 revs/min.Spinning 1
The rush regeneration zone tunica fibrosa that thickness is arranged in 0.05 millimeter of left-right orientation is collected after hour.
Obtained double-layer nanometer tunica fibrosa will finally be collected dry 48 in 37 DEG C of vacuum drying ovens (vacuum degree is -0.1MPa)
Hour, it sterilizes and saves after taking-up, obtain biomimetic type adsorbable artificial dural patch provided by the invention.
Embodiment 3:
Polylactic acid-caprolactone copolymer that weight average molecular weight is 300,000 is dissolved in dimethylformamide and tetrahydrofuran
In mixed solution (volume ratio 4:1), concentration is 0.12 grams per milliliter；Sodium carboxymethylcellulose is dissolved in deionized water, concentration
For 0.01 grams per milliliter.Two kinds of solution are uniformly mixed under high velocity agitation afterwards, volume ratio 97:3, as spinning solution a.
Solution supply flow rate is controlled at 1.5 mls/hour, and applying voltage is 15 kilovolts, distance of the high-voltage end with ground terminal
It is 12.5 centimetres, uses the rotating cylinder that diameter is 8 centimetres as collection device, revolving speed is 100 revs/min.It can after spinning 7 hours
Thickness is collected in 0.25 millimeter or so disorderly arranged lubricant layer tunica fibrosa.
By weight average molecular weight be 300,000 polylactic acid-caprolactone copolymer and weight average molecular weight be 50,000 carbomer dissolution
In the mixed solution (volume ratio 4:1) of dimethylformamide and tetrahydrofuran, the mass ratio of the two is 95:5, and solution is always dense
Degree is 0.08 grams per milliliter, and the solution of stable homogeneous, as spinning solution b are formed after stirring at room temperature.
Solution supply flow rate is controlled at 1.5 mls/hour, and applying voltage is 12.5 kilovolts, high-voltage end with ground terminal away from
From being 10 centimetres, use the rotating cylinder for being deposited with lubricant layer tunica fibrosa as collection device, revolving speed is 3000 revs/min.Spinning 1
The rush regeneration zone tunica fibrosa that thickness is arranged in 0.05 millimeter of left-right orientation is collected after hour.
Obtained double-layer nanometer tunica fibrosa will finally be collected dry 48 in 37 DEG C of vacuum drying ovens (vacuum degree is -0.1MPa)
Hour, it sterilizes and saves after taking-up, obtain biomimetic type adsorbable artificial dural patch provided by the invention.
Embodiment 4:
The polytrimethylene carbonate that weight average molecular weight is 150,000 is dissolved in chloroform, concentration is 0.15 gram/milli
It rises；Chondroitin sulfate is dissolved in deionized water, concentration is 0.015 grams per milliliter.It is afterwards that two kinds of solution are uniform under high velocity agitation
Mixing, volume ratio 96:4, as spinning solution a.
Solution supply flow rate is controlled at 2 mls/hour, and applying voltage is 12.5 kilovolts, distance of the high-voltage end with ground terminal
It is 10 centimetres, uses the rotating cylinder that diameter is 10 centimetres as collection device, revolving speed is 100 revs/min.It can after spinning 5 hours
Thickness is collected in 0.2 millimeter or so disorderly arranged lubricant layer tunica fibrosa.
By weight average molecular weight be 150,000 polytrimethylene carbonate and weight average molecular weight be 50,000 polyacrylamide dissolution
In chloroform, the mass ratio of the two is 95:5, and solution total concentration is 0.1 grams per milliliter, is formed after stirring at room temperature uniform steady
Fixed solution, as spinning solution b.
Solution supply flow rate is controlled at 1 ml/hour, and applying voltage is 12.5 kilovolts, distance of the high-voltage end with ground terminal
It is 10 centimetres, uses the rotating cylinder for being deposited with lubricant layer tunica fibrosa as collection device, revolving speed is 3000 revs/min.Spinning 1 is small
When after collect the rush regeneration zone tunica fibrosa that thickness is arranged in 0.05 millimeter of left-right orientation.
Obtained double-layer nanometer tunica fibrosa will finally be collected dry 48 in 37 DEG C of vacuum drying ovens (vacuum degree is -0.1MPa)
Hour, it sterilizes and saves after taking-up, obtain biomimetic type adsorbable artificial dural patch provided by the invention.
Obtained by above-described embodiment 1-4, obtain in biomimetic type adsorbable artificial dural patch provided by the invention, lubricant layer
The diameter of middle nanofiber is 100-1000 nanometers, and aperture is 300-3000 nanometers between fiber；Promote receiving inside meninx regeneration zone
Rice fiber is in height-oriented arrangement, and diameter is 100-1000 nanometers, and aperture is 300-3000 nanometers between fiber.
Embodiment 5:
Using new zealand rabbit 20 of healthy adult, at 19 monthly ages, for weight between 2.3 and 3.1 kilograms, male and female are unlimited.
Auricular vein injects 3% yellow Jackets (30 mg/kg) anesthesia.Along head median incision longitudinal incision scalp, successively divide
From to cranial periosteum, miniature abrasive drilling prepares about 1.2 centimetres of diameter of symmetrical round bone window in bilateral calvarium portion, in surgical operation microscope
10 × 10mm of lower preparation2Size dura defect.
The biomimetic type artificial dura mater sticking patch that embodiment 1-4 any embodiment is prepared is cut into 13 × 13mm2Size,
It is attached to right side dura defect area, left side is without any processing to be used as blank control.After artificial dura mater sticking patch is implanted into,
Skin of head is sutured.Animal is put to death after implantation 6 months, dural patch and surrounding tissue is taken out, observes its appearance shape
Whether looks, dural reconstruciton situation have detected whether inflammatory reaction and have sticked together with surrounding tissue.Postoperative experimental animal single cage
Raising maintains environment temperature and periodically feeds feed.
Postoperative all experimental rabbits are kept fit, and do not have the abnormal behaviours such as apparent epilepsy.Wound healing is good, hand
Art position is without tumour and bulging, no leakage of cerebrospinal.In addition, obvious degradation occurs for artificial dura mater sticking patch, with surrounding tissue without viscous
Even, implant site has one layer of newborn class endocranium connective tissue to generate.
The basic principles, main features and advantages of the present invention have been shown and described above.The technology of the industry
Personnel are it should be appreciated that the present invention is not limited to the above embodiments, and the above embodiments and description only describe this
The principle of invention, various changes and improvements may be made to the invention without departing from the spirit and scope of the present invention, these changes
Change and improvement all fall within the protetion scope of the claimed invention.The claimed scope of the invention by appended claims and its
Equivalent defines.
Claims (8)
1. a kind of biomimetic type adsorbable artificial dural patch, it is characterised in that: the artificial dura mater sticking patch has the double-deck knot
Structure is made of lubricant layer and rush endocranium regeneration zone；
It wherein, is lubricant layer with brain tissue contact side；
Promote endocranium regeneration zone away from side with brain tissue；
The lubricant layer and rush endocranium regeneration zone are made of nanofiber, the Nanowire promoted inside endocranium regeneration zone
Dimension is oriented in arrangement；
The nanofiber for constituting the lubricant layer is to be made using materials A and material B as raw material；The weight of the materials A and material B
Than for 99:1-70:30；
Constituting the oriented nanofibers for promoting meninx regeneration zone is to be made using materials A and material C as raw material；The materials A with
The weight ratio of material C is 99:1-80:20；
The materials A is degradable synthesising biological high molecular material；
The material B is native biopolymer；
The material C is that hydrophily synthesizes macromolecule；
The materials A is selected from polylactic acid, polycaprolactone, polyglycolic acid, polydioxanone, polytrimethylene carbonate, gathers
The copolymerization of one or more of ethylene glycol, poly butyric ester, poly- hydroxyl valerate, poly butylene succinate and polyurethane
Object；
The material B is selected from Sodium Hyaluronate, chondroitin sulfate, modified cellulose, modification of chitosan, alginic acid, collagen
At least one of with fibrin；
The material C is selected from polyethylene glycol, polypropylene glycol, polyvinylpyrrolidone, polyacrylamide, polyvinyl alcohol, polyoxygenated
At least one of ethylene and carbomer.
2. artificial dura mater sticking patch according to claim 1, it is characterised in that: the lubricant layer with a thickness of 0.05-1.5
Millimeter；
It is described promote meninx regeneration zone with a thickness of 0.05-0.5 millimeters.
3. artificial dura mater sticking patch according to claim 1 or 2, it is characterised in that: the weight of the materials A and material B
Than for 95:5；
The weight ratio of the materials A and material C is 90:10.
4. a kind of method for preparing any artificial dura mater sticking patch in claim 1-3, includes the following steps:
1) respectively prepare lubricant layer electrostatic spinning solution and promote meninx regeneration zone electrostatic spinning solution, be denoted as respectively spinning solution a and
Spinning solution b；
Wherein, the spinning solution a is to be made of the materials A, material B and spin solvent；
The spinning solution b is to be made of the materials A, material C and spin solvent；
In the step 1), the weight ratio of materials A and material B are 99:1-70:30；
The weight ratio of the materials A and material C is 99:1-80:20；
2) after spinning solution a obtained by step 1) being carried out electrospinning, the lubricant layer is obtained；
3) spinning solution b obtained by step 1) is subjected to electrospinning on the lubricant layer obtained by step 2), obtains the rush endocranium regeneration zone,
It is dried in vacuo again, obtains the artificial dura mater sticking patch.
5. according to the method described in claim 4, it is characterized by: in step 1), in the spinning solution a and spinning solution b, high score
The total weight percentage composition of son is 1-20%；
The solvent be selected from for acetone, dimethylformamide, dimethyl acetamide, tetrahydrofuran, methylene chloride, chloroform,
At least one of deionized water, 1,4- dioxane, hexafluoroisopropanol, ethyl alcohol, dimethyl sulfoxide and trifluoroacetic acid.
6. method according to claim 4 or 5, it is characterised in that: in the step 2) and step 3) eiectrospinning steps, spinning
The supply flow rate of liquid is 0.1-20 mls/hour；
It is 3 centimetres -30 centimetres that end, which occurs, for high pressure with the distance between collection device；
The voltage of high pressure generator is 0.1-40 kilovolts；
Collecting substrate is roller, and diameter is 2-20 centimetres；
Wherein in the step 2), the revolving speed of the roller is 100-1000 revs/min；
In the step 3), the revolving speed of the roller is 1000-5000 revs/min.
7. method according to claim 4 or 5, it is characterised in that: in the vacuum drying step, dry temperature is
25-50 DEG C, time 24-72h, vacuum degree is -0.1MPa-0.1MPa.
8. any artificial dura mater sticking patch is preparing answering in endocranium or pachymeninx repair products in claim 1-3
With.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101507661A (en) * | 2009-03-10 | 2009-08-19 | 广州迈普再生医学科技有限公司 | Nano artificial dura mater with multi functional-layers and preparation method thereof |
| CN101692986A (en) * | 2009-03-10 | 2010-04-14 | 广州迈普再生医学科技有限公司 | Artificial dura mater with bioactivity and preparation method thereof |
| WO2010102533A1 (en) * | 2009-03-10 | 2010-09-16 | 广州迈普再生医学科技有限公司 | Artificial dura mater and manufacturing method thereof |
| CN102698318A (en) * | 2012-03-02 | 2012-10-03 | 首都医科大学附属北京朝阳医院 | Biological-material complex patch |
| CN104414773A (en) * | 2013-08-23 | 2015-03-18 | 深圳迈普再生医学科技有限公司 | Anti-adhesion tissue repair membrane and preparation method thereof |
-
2016
- 2016-05-05 CN CN201610293457.5A patent/CN105999419B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101507661A (en) * | 2009-03-10 | 2009-08-19 | 广州迈普再生医学科技有限公司 | Nano artificial dura mater with multi functional-layers and preparation method thereof |
| CN101692986A (en) * | 2009-03-10 | 2010-04-14 | 广州迈普再生医学科技有限公司 | Artificial dura mater with bioactivity and preparation method thereof |
| WO2010102533A1 (en) * | 2009-03-10 | 2010-09-16 | 广州迈普再生医学科技有限公司 | Artificial dura mater and manufacturing method thereof |
| CN102698318A (en) * | 2012-03-02 | 2012-10-03 | 首都医科大学附属北京朝阳医院 | Biological-material complex patch |
| CN104414773A (en) * | 2013-08-23 | 2015-03-18 | 深圳迈普再生医学科技有限公司 | Anti-adhesion tissue repair membrane and preparation method thereof |
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