CN105999419A - Bionical type absorbable dura mater patch and preparation method and application thereof - Google Patents
Bionical type absorbable dura mater patch and preparation method and application thereof Download PDFInfo
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- CN105999419A CN105999419A CN201610293457.5A CN201610293457A CN105999419A CN 105999419 A CN105999419 A CN 105999419A CN 201610293457 A CN201610293457 A CN 201610293457A CN 105999419 A CN105999419 A CN 105999419A
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- dura mater
- lubricating layer
- regeneration zone
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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
-
- 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
-
- 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
-
- 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
-
- 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
-
- 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
Abstract
The invention discloses a bionical type absorbable dura mater patch and a preparation method and application thereof. The bionical type absorbable dura mater patch has a two-layer structure, the side making contact with the brain tissue is a lubricating layer which contains natural polymers with a lubricating effect, and the side deviating from the brain tissue is a dura mater regeneration promoting layer in which nanofibers are arranged in a highly-oriented mode. According to the bionical type absorbable dura mater patch, the microscopic structure is completely bionic to that of the natural dura mater, directional crawling of cells can be guided, the brain tissue can be protected against wearing and injuries, and tissue adhesion is prevented; meanwhile, the biocompatibility, the flexibility and the attaching property are good, industrialized production is easy to achieve, and good application prospects are achieved.
Description
Technical field
The invention belongs to biology medical material technical field, be specifically related to a kind of bionic-type can absorb dural patch and
Preparation method and application.
Background technology
Cerebral dura mater is one layer and is positioned at inside skull and connective tissue outside brain, is the natural cover for defense of protection cerebral tissue.
The reasons such as open craniocerebral bone injury, meningioma and other brainpan illness all can cause dura defect, and then causes brain ridge
The generation of liquid leakage.If treatment can cause intracranial infection the most in addition, cause arachnoiditis or meningitis, even develop into brain
The a series of complication threatening patient vitals of abscess and intracranial hemorrhage etc..The most clinically for cerebral dura mater repairing defect
Main Means be mostly to use draw materials autospasy cellular allograft or animal sources corium, pericardium etc. to organize the biological sticking patch that obtains,
Or the non-degradable macromolecular fibre sticking patch such as polyurethane, expanded PTFE.
Natural cerebral dura mater is made up of the periosteal layer in outside and the meninges layer double-layer structure of inner side, and wherein periosteal layer is rich in blood
Pipe, neural and a large amount of collagen fiber, Main Function is to provide mechanics protection for cerebral tissue;Meninges layer is mainly by smoothing
Mesothelial cell forms, and can secrete endogenous hyaluronic acid sodium, it is provided that lubrication, makes cerebral tissue the most frayed injured.But mesh
The meninges sticking patch product of front list marketing is single layer structure, it is impossible to the most simultaneously meet promote defect meninges regeneration and
Prevent the effect that cerebral tissue abrasion is injured.
Additionally, natural cerebral dura mater is a kind of anisotropic material, it is embodied in its micro structure or mechanical characteristic at each
Being not quite similar on direction, its basic component units collagen microfibrils presents the orientations of height in specific region
Characteristic.Research shows, in cerebral dura mater, the collagen microfibrils of distribution presents left and right high degree of symmetry structure along median sagittal plane,
In temporo district, the left and right sides until in superior sagittal sinus region the collagen fiber of distribution be height-oriented arrangement, simultaneously in volume side and
Dorsal part also has collagen fiber (Malinin et.al., the Quantification of that there is height-oriented arrangement inside subregion
the collagen fiber architecture of human cranial dura mater,J.Anat.,1998,192:99-106).But
Various dural patch in clinical practice the most are isotropic material, the most bionical natural
Cerebral dura mater micro structure, therefore it can not fully meet reparation requirement as dural patch.
Chinese invention patent ZL 200910037736.5, invention entitled: " a kind of nanometer people possessing multiple functional layer
Work cerebral dura mater and preparation method thereof ", Authorization Notice No. CN 101507661 B, disclose one and there is at least two merit
The artificial dura mater of ergosphere, by face cerebripetal hydrophobicity anti electrospinning layer and the cerebripetal hydrophilic nano cell of the back of the body
Shelf layer forms.The fibrous membrane that wherein hydrophobicity antiblocking layers is obtained through electrospinning by hydrophobic polymer is constituted, hydrophilic
Cytoskeleton layer is made up of the fibrous membrane obtained through electrospinning after hydrophobic polymer composite hydrophilic macromolecule.Implement at it
In example, antiblocking layers selects hydrophobic PLLA and 6-caprolactone, and both ratios are 50:50;Cytoskeleton layer
Selecting Polyethylene Glycol and chondroitin sulfate, both mass ratioes are 70:30, and finally this nano artificial cerebral dura mater is by above-mentioned two-layer
It is composited.But this artificial dura mater has a disadvantage in that (1) have employed hydrophobicity electrospinning layer towards brain side,
Without Natural hydrophilic macromolecule;And in natural cerebral dura mater towards in the meninges layer of brain side containing in hyaluronate sodium etc.
Source property greasing substance, therefore this artificial dura mater fails to carry out bionical to meninges layer composition;(2) brain side is dorsad
The cytoskeleton layer of isotropic, its interior hydrophilic macromolecule is lack of alignment;And natural cerebral dura mater periosteal layer temporo district
And the collagen microfibrils in volume side, posterior components region is height-oriented arrangement, therefore this artificial dura mater fails to periosteum
Rotating fields carries out bionical.
Therefore, the most also do not have one can complete bionical natural cerebral dura mater structure, simultaneously preparation process simple,
Artificial hard brain (ridge) the film patching material that industrialization prospect is wide.
Summary of the invention
It is an object of the invention to, from bionical natural cerebral dura mater structure, provide one to have anisotropic microstructure knot for clinic
Structure and natural double-layer structure, pliability and attaching stitching good, resistance to, histocompatibility and mechanical strength are good, fall
Solve speed moderate and in vivo Wholly-degradable absorb, can remarkably promote cerebral dura mater regeneration and prevention tissue adhesion, be prone to
Cut out, preserve the absorbable dural patch that Clinical practice is simple to operate simultaneously.
It is a further object of the present invention to provide preparation method and the application of this absorbable dural patch.
Bionic-type artificial dura mater sticking patch provided by the present invention, described artificial dura mater sticking patch has double-decker, by
Lubricating layer and rush cerebral dura mater regeneration zone composition;
Wherein, contacting side with cerebral tissue is lubricating layer;
Side is deviated from for promoting cerebral dura mater regeneration zone with cerebral tissue;
Described lubricating layer and rush cerebral dura mater regeneration zone are constituted by nanofiber, and the nanofiber within described lubricating layer
Having lubrication, the nanofiber within described rush cerebral dura mater regeneration zone is oriented in arrangement;
Constitute the nanofiber of described lubricating layer for preparing with materials A and material B for raw material;
Constitute the oriented nanofibers of described rush meninges regeneration zone for preparing with materials A and material C for raw material;
Described materials A is degradable synthesising biological macromolecular material;
Described material B is native biopolymer;
Described material C is that hydrophilic synthesizes macromolecule.
In above-mentioned artificial dura mater sticking patch, described materials A is selected from polylactic acid, polycaprolactone, polyglycolic acid, poly-right
Dioxanone, PTMC, Polyethylene Glycol, poly butyric ester, poly-hydroxyl valerate, polybutadiene
The copolymer of one or more in acid butanediol ester and polyurethane;
Wherein, described polylactic acid concretely Poly-L-lactic acid;
More specifically, described materials A is selected from polylactic-co-glycolic acid, Poly-L-lactic acid, polylactic acid-own interior
Ester copolymer, PTMC;Wherein, the weight average molecular weight of described polylactic-co-glycolic acid can be
120000;The weight average molecular weight of described Poly-L-lactic acid can be 5 ten thousand to 50 ten thousand, preferably 300,000;Described polylactic acid-oneself
The weight average molecular weight of lactone copolymers can be 5 ten thousand to 50 ten thousand, preferably 300,000;The weight of described PTMC
Average molecular weight can be 5 ten thousand to 50 ten thousand, preferably 150,000;
Described material B is selected from hyaluronate sodium, carboxymethyl chitosan, sodium carboxymethyl cellulose, chondroitin sulfate, changes
At least one in property cellulose, modification of chitosan, alginic acid, collagen protein and fibrin;
Wherein, the relative molecular weight of described carboxymethyl chitosan concretely 5 ten thousand to 50 ten thousand, preferably 200,000;
Described material C selected from Polyethylene Glycol, polypropylene glycol, polyvinylpyrrolidone, polyacrylamide, polyvinyl alcohol,
At least one in polyethylene glycol oxide and carbomer;
Wherein, the weight average molecular weight of described polyvinylpyrrolidone can be 5 ten thousand to 50 ten thousand, preferably 300,000;Described poly-
The weight average molecular weight of ethylene glycol can be 5000 to 50000, preferably 10,000;The weight average molecular weight of described carbomer can be 2
Ten thousand to 10 ten thousand, preferably 50,000;The weight average molecular weight of described polyacrylamide can be 2 ten thousand to 10 ten thousand, preferably 50,000;
It is also preferred that the left materials A of the present invention selects polylactic-co-glycolic acid, material B selects hyaluronate sodium,
Material C selects polyvinylpyrrolidone.
Described materials A is 99:1-70:30 with the weight ratio of material B, concretely 95:5 or 96:4 or 97:3;
Preferably 95:5;
Described materials A is 99:1-80:20, concretely 90:10 or 95:5 with the weight ratio of material C;Preferably
90:10;
The nanofiber constituting described lubricating layer concretely passes through electrospinning process with materials A and material B for raw material
Prepare;
The oriented nanofibers constituting described rush meninges regeneration zone concretely passes through quiet with materials A and material C for raw material
Electrical spinning method prepares;
The thickness of described lubricating layer is 0.05-1.5 millimeter, concretely 0.15 millimeter, 0.2 millimeter or 0.25 millimeter;
A diameter of 100-1000 nanometer of nanofiber, between fiber, aperture is 300-3000 nanometer.
The thickness of described rush meninges regeneration zone is 0.05-0.5 millimeter, concretely 0.05 millimeter;Promote cerebral dura mater regeneration zone
Internal nanofiber is height-oriented arrangement, and a diameter of 100-1000 nanometer, between fiber, aperture is that 300-3000 receives
Rice.
Lubricating layer of the present invention is internal contains the natural polymer with lubrication, with natural cerebral dura mater mesothelial cell
The endogenous hyaluronic acid sodium effect of secretion is similar to, and cerebral tissue can be protected from abrasion.Meanwhile, multiple in this lubricating layer
The aperture of condensating fiber is much smaller than fibroblastic average-size, effectively prevents fibroblast to move into inside lubricating layer,
Therefore well prevent and the generation of cerebral tissue adhesion.
Hydrophilic macromolecule composite nano fiber within rush meninges regeneration zone of the present invention is height-oriented arrangement.One
Aspect, the hydrophilic surface promoting regeneration zone is conducive to adhesion and the propagation of cell;On the other hand, with natural cerebral dura mater temporo
The composite nano fiber of the arrangement mode of collagen microfibrils in district, is conducive to guiding cell to climb along nanofiber orientation
OK, this remarkably promotes effect to final dural regeneration effect.With isotropic lack of alignment nano fibrous membrane phase
Ratio, the fiber arranged film of anisotropy orientation has at aspects such as defect dural reparation speed and regeneration cerebral dura mater thickness
Significant advantage.
Present invention also offers a kind of method preparing described artificial dura mater sticking patch, the method comprises the steps:
1) prepare lubricating layer electrostatic spinning solution respectively and promote meninges regeneration zone electrostatic spinning solution, being designated as spinning respectively
Liquid a and spinning liquid b;
Wherein, described spinning liquid a is for be made up of described materials A, material B and spin solvent;
Described spinning liquid b is for be made up of described materials A, material C and spin solvent;
2) by step 1) after gained spinning liquid a carries out electrospinning, obtain described lubricating layer;
3) by step 1) gained spinning liquid b is in step 2) carry out electrospinning on gained lubricating layer, obtain the hard brain of described rush
Film regeneration zone, then be vacuum dried, obtain described artificial dura mater sticking patch.
The step 1 of said method) in, described materials A is 99:1-70:30 with the weight ratio of material B, concretely
95:5 or 96:4 or 97:3;Preferably 95:5;
Described materials A is 99:1-80:20, concretely 90:10 or 95:5 with the weight ratio of material C;Preferably
90:10;
In described spinning liquid a and spinning liquid b, high molecular gross weight percentage composition is 1-20%, and preferably 10%;
Described solvent selected from for acetone, dimethylformamide, dimethyl acetylamide, oxolane, dichloromethane, three
In chloromethanes, deionized water, 1,4-dioxane, hexafluoroisopropanol, ethanol, dimethyl sulfoxide and trifluoroacetic acid
At least one;
Described solvent concretely hexafluoroisopropanol, dichloromethane, chloroform, deionized water, by dimethyl formyl
Amine and the mixed solution of oxolane composition;Wherein, the described mixing being made up of dimethylformamide and oxolane is molten
In liquid, the volume ratio of dimethylformamide and oxolane is 4:1;The preferred hexafluoroisopropanol of described solvent;
Described step 2) and step 3) in eiectrospinning steps, the supply flow rate of spinning liquid is 0.1-20 ml/hour,
Concretely 1 ml/hour, 1.5 mls/hour, 2 mls/hour, 2.5 mls/hour or 3 mls/hour;
High pressure generation end is 3 centimetres-30 centimetres with the distance between collection device, concretely 10 centimetres, 12.5
Centimetre or 15 centimetres;
The voltage of high tension generator is 0.1-40 kilovolt, concretely 12.5 kilovolts or 15 kilovolts;
Collecting substrate and be cylinder, diameter is 2-20 centimetre, concretely 8 centimetres or 10 centimetres;
Wherein step 2) in, the rotating speed of described cylinder is 100-1000 rev/min;Step 3) in, turning of described cylinder
Speed is 1000-5000 rev/min, concretely 3000 revs/min or 3000-5000 rev/min.
In described vacuum drying step, the temperature being dried is 25-50 DEG C, preferably 37 DEG C;Time is 24-72h, preferably
48h;Vacuum is-0.1MPa-0.1MPa, preferably-0.1MPa;
Concrete, described step 2) eiectrospinning steps specifically can carry out in accordance with the following steps: first by step 1) gained spins
Silk liquid a loads Electrospun liquid supplying device;By flow pump regulation and control Electrospun liquid supply flow rate be 0.1-20 milliliter/
Hour;Regulation high pressure generation end is 3 centimetres-30 centimetres with the distance between collection device;Given by high tension generator
Electro-spinning process provides high pressure, can regulate and control between 0.1-40 kilovolt;By rotating speed be 100-1000 rev/min, a diameter of
The cylinder of 2-20 centimetre is connected with earth terminal, as the collection substrate of electro-spinning process;Obtain after collecting on a rotating drum
Must have the thickness lubricating layer fibrous membrane at 0.05-1.5 millimeter.
Described step 3) eiectrospinning steps specifically can carry out in accordance with the following steps: first by step 1) gained spinning liquid b dress
Entering Electrospun liquid supplying device, supply flow rate is 0.1-20 ml/hour;High pressure generation end with between collection device away from
From for 3 centimetres-30 centimetres;High pressure regulates and controls between 0.1-40 kilovolt;It is 1000-5000 rev/min, diameter by rotating speed
For the cylinder of 2-20 centimetre as the collection substrate of electro-spinning process;Have on the rotation cylinder of lubricating layer in surface deposition and receive
Collection obtains the thickness rush regeneration zone fibrous membrane at 0.05-0.5 millimeter.
Above-mentioned steps 2) and 3) in, it is also preferred that the left supply flow rate is set as 3 mls/hour, high pressure generation end is with receiving
Distance between acquisition means is set as 10 centimetres, and high pressure is set as 15 kilovolts, step 2) in speed setting be 100
Rev/min, step 3) in speed setting be 3000 revs/min, diameter of cylinder is 8 centimetres, and lubricating layer thickness is 0.2
Millimeter, promoting regeneration zone thickness is 0.05 millimeter.
It addition, the artificial dura mater sticking patch that the invention described above provides is preparing cerebral dura mater or the product of dural repairing
In application, fall within protection scope of the present invention.
The bionic-type double-layer nanometer fibrous membrane that the present invention provides is used as dural repairment material, has the advantages that
1, the complete bionical natural cerebral dura mater of microstructure, has rush cerebral dura mater regeneration zone and lubricating layer double-decker, its
The internal nanofiber of middle rush meninges regeneration zone is height-oriented arrangement, and lubricating layer contains the natural polymer with lubrication
Son.
2, promote the orientation fiber bootable fibroblast orientation within meninges regeneration zone to creep, hydrophilic surface simultaneously
Be conducive to attaching and the propagation of cell, be more beneficial for the regeneration of defect cerebral dura mater;Lubricating layer both can protect cerebral tissue from mill
Damage injured, it is possible to prevent tissue adhesion.
3, biocompatibility is good, does not cause inflammatory reaction after implanting.
4, the most slowly degrade after implanting, finally can degradable and absorption.
5, pliability and attaching property are good, can realize exempting to sew up fixing in Clinical practice.
6, product composition and preparation technology are simple, and product quality is easily controllable, can realize the industry of high-efficiency and low-cost
Metaplasia is produced.
Therefore, the bionic-type artificial dura mater sticking patch that the present invention provides is the novel doctor of a kind of novel structure, superior performance
With biomaterial, show good application prospect repairing dura defect field.
Accompanying drawing explanation
Fig. 1 is the bionic-type dural structural representation of bilayer degradable artificial.
Fig. 2 is the microscopic appearance that bionic-type bilayer degradable artificial is dural, wherein, is a) unordered in lubricating layer
Fiber arranged microscopic appearance;B) for the microscopic appearance of orientations fiber in rush meninges regeneration zone.Scale is 2 microns.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is further elaborated, but the present invention is not limited to following example.Institute
Method of stating is conventional method if no special instructions.Described raw material the most all can obtain from open commercial sources
?.
Embodiment 1:
Being dissolved in hexafluoroisopropanol by the polylactic-co-glycolic acid that weight average molecular weight is 120,000, concentration is 0.1
Grams per milliliter;Being dissolved in deionized water by the hyaluronate sodium that relative molecular weight is 1,200,000, concentration is 0.06 grams per milliliter;
The solution of stable homogeneous is formed after being stirred at room temperature respectively.Afterwards two kinds of solution are the most uniformly mixed,
Volume ratio is 95:5, is spinning liquid a.
This mixed solution is inserted in syringe, at syringe needle, connects high voltage power supply.Solution supply flow rate controls
3 mls/hour, applying voltage is 15 kilovolts, and high-pressure side is 15 centimetres with the distance of earth terminal, uses a diameter of 8
Centimetre rotation cylinder as collection device, rotating speed is 100 revs/min.Spinning can collect thickness at 0.2 milli after 5 hours
Lubricating layer fibrous membrane (Fig. 2 a) of rice left and right lack of alignment.
It is the polyvinyl pyrrole of 300,000 by polylactic-co-glycolic acid and weight average molecular weight that weight average molecular weight is 120,000
Alkanone is dissolved in hexafluoroisopropanol, and both mass ratioes are 90:10, and solution total concentration is 0.1 grams per milliliter, under room temperature
Form the solution of stable homogeneous after stirring, be spinning liquid b.
Solution supply flow rate controls at 1 ml/hour, and applying voltage is 15 kilovolts, and high-pressure side is with the distance of earth terminal
Being 15 centimetres, use deposition to have the rotation cylinder of lubricating layer fibrous membrane as collection device, rotating speed is 3000 revs/min.
Spinning can collect thickness rush regeneration zone fibrous membrane (Fig. 2 b) in 0.05 millimeter orientations after 1 hour.
To finally collect the bionic-type double-layer nanometer fibrous membrane obtained 37 DEG C of vacuum drying ovens (vacuum is-0.1MPa)
In be dried 48 hours, after taking-up, sterilizing being cut into as required has the artificial dura mater benefit of given shape and size
Sheet, obtains the bionic-type adsorbable artificial dural patch that the present invention provides.
Embodiment 2:
The Poly-L-lactic acid that weight average molecular weight is 300,000 being dissolved in dichloromethane, concentration is 0.08 grams per milliliter;Will
Relative molecular weight be 200,000 carboxymethyl chitosan be dissolved in deionized water, concentration is 0.02 grams per milliliter.Molten by two kinds
Liquid the most uniformly mixes, and volume ratio is 95:5, is spinning liquid a.
Solution supply flow rate controls at 1 ml/hour, apply voltage be 12.5 kilovolts, high-pressure side with earth terminal away from
From for 10 centimetres, using the rotation cylinder of a diameter of 8 centimetres as collection device, rotating speed is 100 revs/min.Spinning 6
The thickness lubricating layer fibrous membrane in 0.15 millimeter lack of alignment can be collected after hour.
Poly-L-lactic acid that weight average molecular weight is 300,000 and Polyethylene Glycol that weight average molecular weight is 10,000 are dissolved in dichloro
In methane, both mass ratioes are 90:10, and solution total concentration is 0.08 grams per milliliter, is spinning liquid b.
Solution supply flow rate controls at 2.5 mls/hour, apply voltage be 12.5 kilovolts, high-pressure side with earth terminal away from
From for 10 centimetres, deposition is used to have the rotation cylinder of lubricating layer fibrous membrane as collection device, rotating speed is 3000 turns/
Point.Spinning can collect the thickness rush regeneration zone fibrous membrane in 0.05 millimeter orientations after 1 hour.
It is dried finally collecting the double-layer nanometer fibrous membrane obtained in 37 DEG C of vacuum drying ovens (vacuum is-0.1MPa)
48 hours, after taking-up, sterilizing preserved, and obtains the bionic-type adsorbable artificial dural patch that the present invention provides.
Embodiment 3:
Polylactic acid-caprolactone copolymer that weight average molecular weight is 300,000 is dissolved in dimethylformamide and oxolane
In mixed solution (volume ratio is 4:1), concentration is 0.12 grams per milliliter;Sodium carboxymethyl cellulose is dissolved in deionized water
In, concentration is 0.01 grams per milliliter.After two kinds of solution are the most uniformly mixed, volume ratio is 97:3, is
Spinning liquid a.
Solution supply flow rate controls at 1.5 mls/hour, apply voltage be 15 kilovolts, high-pressure side with earth terminal away from
From for 12.5 centimetres, using the rotation cylinder of a diameter of 8 centimetres as collection device, rotating speed is 100 revs/min.Spinning
The thickness lubricating layer fibrous membrane in 0.25 millimeter lack of alignment can be collected after 7 hours.
Polylactic acid-caprolactone copolymer that weight average molecular weight is 300,000 and carbomer that weight average molecular weight is 50,000 are dissolved
In the mixed solution (volume ratio is 4:1) of dimethylformamide and oxolane, both mass ratioes are 95:5, molten
Liquid total concentration is 0.08 grams per milliliter, forms the solution of stable homogeneous, be spinning liquid b under room temperature after stirring.
Solution supply flow rate controls at 1.5 mls/hour, apply voltage be 12.5 kilovolts, high-pressure side with earth terminal away from
From for 10 centimetres, deposition is used to have the rotation cylinder of lubricating layer fibrous membrane as collection device, rotating speed is 3000 turns/
Point.Spinning can collect the thickness rush regeneration zone fibrous membrane in 0.05 millimeter orientations after 1 hour.
It is dried finally collecting the double-layer nanometer fibrous membrane obtained in 37 DEG C of vacuum drying ovens (vacuum is-0.1MPa)
48 hours, after taking-up, sterilizing preserved, and obtains the bionic-type adsorbable artificial dural patch that the present invention provides.
Embodiment 4:
The PTMC that weight average molecular weight is 150,000 is dissolved in chloroform, concentration is 0.15 gram/in the least
Rise;Being dissolved in deionized water by chondroitin sulfate, concentration is 0.015 grams per milliliter.After by two kinds of solution in high-speed stirred
Lower uniformly mixing, volume ratio is 96:4, is spinning liquid a.
Solution supply flow rate controls at 2 mls/hour, apply voltage be 12.5 kilovolts, high-pressure side with earth terminal away from
From for 10 centimetres, using the rotation cylinder of a diameter of 10 centimetres as collection device, rotating speed is 100 revs/min.Spinning
The thickness lubricating layer fibrous membrane in 0.2 millimeter lack of alignment can be collected after 5 hours.
By molten to PTMC that weight average molecular weight is 150,000 and polyacrylamide that weight average molecular weight is 50,000
Solution is in chloroform, and both mass ratioes are 95:5, and solution total concentration is 0.1 grams per milliliter, shape after stirring under room temperature
Become the solution of stable homogeneous, be spinning liquid b.
Solution supply flow rate controls at 1 ml/hour, apply voltage be 12.5 kilovolts, high-pressure side with earth terminal away from
From for 10 centimetres, deposition is used to have the rotation cylinder of lubricating layer fibrous membrane as collection device, rotating speed is 3000 turns/
Point.Spinning can collect the thickness rush regeneration zone fibrous membrane in 0.05 millimeter orientations after 1 hour.
It is dried finally collecting the double-layer nanometer fibrous membrane obtained in 37 DEG C of vacuum drying ovens (vacuum is-0.1MPa)
48 hours, after taking-up, sterilizing preserved, and obtains the bionic-type adsorbable artificial dural patch that the present invention provides.
Above-described embodiment 1-4 gained, obtains in the bionic-type adsorbable artificial dural patch that the present invention provides, lubrication
A diameter of 100-1000 nanometer of nanofiber in Ceng, between fiber, aperture is 300-3000 nanometer;Promote meninges regeneration zone
Internal nanofiber is height-oriented arrangement, and a diameter of 100-1000 nanometer, between fiber, aperture is that 300-3000 receives
Rice.
Embodiment 5:
Using the new zealand rabbit 20 of healthy adult, at 19 monthly ages, body weight is between 2.3 and 3.1 kilograms, and male and female are not
Limit.Auricular vein injects 3% pentobarbital sodium (30 mg/kg) anesthesia.Along head median incision longitudinal incision head
Skin, successively separates to cranial periosteum, and the symmetrical circular bone of diameter about 1.2 centimetres is prepared in miniature abrasive drilling in bilateral calvarium portion
Window, prepares 10 × 10mm under operating microscope2Size dura defect.
Bionic-type artificial dura mater sticking patch embodiment 1-4 any embodiment prepared is cut into 13 × 13mm2Size,
Being attached to dura defect district, right side, left side is left intact as blank.Artificial dura mater sticking patch has been implanted
Bi Hou, sews up skin of head.After implanting 6 months, animal is put to death, takes out dural patch and surrounding tissue,
Observe its exterior appearance, dural reconstruciton situation, detected whether inflammatory reaction and whether sticked together with surrounding tissue.
Postoperative laboratory animal list cage is raised, and maintains ambient temperature feedstuff of regularly throwing something and feeding.
Postoperative all of experimental rabbit is kept fit, and does not has the Deviant Behavioies such as obvious epilepsy to occur.Wound healing is good,
Operative site is without cyst and bulging, without cerebrospinal leak.Additionally, artificial dura mater sticking patch generation obvious degradation, with surrounding
Tissue is without adhesion, and implant site has one layer of newborn class cerebral dura mater connective tissue to generate.
The ultimate principle of the present invention, principal character and advantages of the present invention have more than been shown and described.The technology of the industry
Personnel are it should be appreciated that the present invention is not restricted to the described embodiments, and described in above-described embodiment and description is to say
The principle of the bright present invention, the present invention also has various changes and modifications without departing from the spirit and scope of the present invention,
These changes and improvements both fall within scope of the claimed invention.Claimed scope is by appended right
Claim and equivalent thereof define.
Claims (9)
1. a bionic-type adsorbable artificial dural patch, it is characterised in that: described artificial dura mater sticking patch has
Double-decker, is made up of lubricating layer and rush cerebral dura mater regeneration zone;
Wherein, contacting side with cerebral tissue is lubricating layer;
Side is deviated from for promoting cerebral dura mater regeneration zone with cerebral tissue;
Described lubricating layer and rush cerebral dura mater regeneration zone are constituted by nanofiber, receiving within described rush cerebral dura mater regeneration zone
Rice fiber is oriented in arrangement;
Constitute the nanofiber of described lubricating layer for preparing with materials A and material B for raw material;
Constitute the oriented nanofibers of described rush meninges regeneration zone for preparing with materials A and material C for raw material;
Described materials A is degradable synthesising biological macromolecular material;
Described material B is native biopolymer;
Described material C is that hydrophilic synthesizes macromolecule.
Artificial dura mater sticking patch the most according to claim 1, it is characterised in that: described materials A is selected from poly-breast
Acid, polycaprolactone, polyglycolic acid, PPDO, PTMC, Polyethylene Glycol, poly-hydroxyl
The copolymer of one or more in butyrate, poly-hydroxyl valerate, poly butylene succinate and polyurethane;
Described material B selected from hyaluronate sodium, chondroitin sulfate, modified cellulose, modification of chitosan, alginic acid,
At least one in collagen protein and fibrin;
Described material C selected from Polyethylene Glycol, polypropylene glycol, polyvinylpyrrolidone, polyacrylamide, polyvinyl alcohol,
At least one in polyethylene glycol oxide and carbomer.
Artificial dura mater sticking patch the most according to claim 1 and 2, it is characterised in that: the thickness of described lubricating layer
Degree is 0.05-1.5 millimeter;
The thickness of described rush meninges regeneration zone is 0.05-0.5 millimeter.
4. according to described artificial dura mater sticking patch arbitrary in claim 1-3, it is characterised in that: described materials A
It is 99:1-70:30, preferably 95:5 with the weight ratio of material B;
Described materials A is 99:1-80:20, preferably 90:10 with the weight ratio of material C.
5. prepare a method for arbitrary described artificial dura mater sticking patch in claim 1-4, comprise the steps:
1) prepare lubricating layer electrostatic spinning solution respectively and promote meninges regeneration zone electrostatic spinning solution, being designated as spinning respectively
Liquid a and spinning liquid b;
Wherein, described spinning liquid a is for be made up of described materials A, material B and spin solvent;
Described spinning liquid b is for be made up of described materials A, material C and spin solvent;
2) by step 1) after gained spinning liquid a carries out electrospinning, obtain described lubricating layer;
3) by step 1) gained spinning liquid b is in step 2) carry out electrospinning on gained lubricating layer, obtain the hard brain of described rush
Film regeneration zone, then be vacuum dried, obtain described artificial dura mater sticking patch.
Method the most according to claim 5, it is characterised in that: described step 1) in, materials A and material B
Weight ratio be 99:1-70:30;
Described materials A is 99:1-80:20 with the weight ratio of material C;
In described spinning liquid a and spinning liquid b, high molecular gross weight percentage composition is 1-20%;
Described solvent selected from for acetone, dimethylformamide, dimethyl acetylamide, oxolane, dichloromethane, three
In chloromethanes, deionized water, 1,4-dioxane, hexafluoroisopropanol, ethanol, dimethyl sulfoxide and trifluoroacetic acid
At least one.
7. according to the method described in claim 5 or 6, it is characterised in that: described step 2) and step 3) electrospinning
In step, the supply flow rate of spinning liquid is 0.1-20 ml/hour;
High pressure generation end is 3 centimetres-30 centimetres with the distance between collection device;
The voltage of high tension generator is 0.1-40 kilovolt;
Collecting substrate and be cylinder, diameter is 2-20 centimetre;
Wherein said step 2) in, the rotating speed of described cylinder is 100-1000 rev/min;
Described step 3) in, the rotating speed of described cylinder is 1000-5000 rev/min.
8. according to described method arbitrary in claim 5-7, it is characterised in that: in described vacuum drying step, dry
Dry temperature is 25-50 DEG C, and the time is 24-72h, and vacuum is-0.1MPa-0.1MPa.
9. in claim 1-5 arbitrary described artificial dura mater sticking patch in preparing cerebral dura mater or pachymeninx repair products
Application.
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