CN106943625A - A kind of preparation method of electrostatic spinning cornea repair material and application - Google Patents
A kind of preparation method of electrostatic spinning cornea repair material and application Download PDFInfo
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- CN106943625A CN106943625A CN201710067821.0A CN201710067821A CN106943625A CN 106943625 A CN106943625 A CN 106943625A CN 201710067821 A CN201710067821 A CN 201710067821A CN 106943625 A CN106943625 A CN 106943625A
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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
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
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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
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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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
- A61L27/14—Macromolecular materials
- A61L27/26—Mixtures of macromolecular compounds
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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
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- D—TEXTILES; PAPER
- D04—BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
- D04H—MAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL; FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING ; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION
- D04H1/00—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
- D04H1/70—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres
- D04H1/72—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged
- D04H1/728—Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged by electro-spinning
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
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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
- A61L2430/16—Materials or treatment for tissue regeneration for reconstruction of eye parts, e.g. intraocular lens, cornea
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- Oral & Maxillofacial Surgery (AREA)
- Animal Behavior & Ethology (AREA)
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Abstract
The present invention relates to a kind of preparation method of Electrospun cornea repair material, it is comprised the concrete steps that：（1）Prepare spinning solution；（2）Electrospun solution functionalization；（3）Electrostatic spinning process prepares cornea repair material.Method of the present invention technique is simple, and production efficiency is high, surface texture is controllable, reproducible, is suitable for the application of different demands；Simultaneously based on electrospun material specificity structure, available for bio-medical material, drug loading and medicine controlled releasing association area.
Description
Technical field
The invention belongs to biomedical materials field, it is related to a kind of preparation method of Electrospun cornea repair material, specifically
It is related to a kind of cornea repair material that multiple topological structure is built by electrostatic spinning process and preparation method thereof.
Background technology
Eyeball is a kind of complicated and accurate optical system, is related to the optical principle of complexity, mainly by dioptric conducting system
With photosensitive imaging system composition.Wherein, cornea is first of path that ambient enters intraocular, is also that cornea tissue is used for supporting
The first line of defence of imperial external world's harmful substance invasion, the optometry function to human eye plays an important role.Cornea tissue complexity
Sandwich construction plays special protective effect together with scleral tissue to its hetero-organization of fine intraocular and material.
Keratonosus is one of main diseases causing blindness of China, and current China there are about 4,000,000 because keratonosus causes the trouble of blinding
Person.As the technologies such as corneal restoration and transplantation reach its maturity, in the urgent need to both having high bioactivity, high-biocompatibility, again
Have the repair materials of cornea physiological function concurrently.
The structure of natural human cornea and performance are to prepare cornea repair material " goldstandard ", and particularly cornea has special
Layer structure, it is ensured that the transparency of cornea, and make it have the oxygen flow and ion permeable performance of height, so as to maintain cornea
Normal vision and physiological function.Cornea repair material must have the mechanical property and light same or similar with cornea tissue
Learn performance.
People are entered using various natural and synthesis macromolecular material, autologous organisms material etc. by various methods in recent years
Row biomimetic modification and modification, to prepare the carrier that biocompatibility is good, injured corneal tissue can be promoted to regenerate and repair.Cause
And, a kind of good biocompatibility is found by the various bionic methods such as composition, structure and surface, and cornea vision can be recovered as early as possible
Regeneration with physiological function has turned into the focus that people study with repair materials.That studies at present is used for cornea reconstruction and reparation
Material is generally natural polymer, such as chitosan, hyaluronic acid, alginate, collagen, gelatin, cellulose.Due to this kind of high score
Sub- material has excellent biocompatibility, nontoxicity, degradability, can promotion organization cytothesis, while having good
Optical property, becomes corneal restoration and the ideal material substituted.
Electrostatic spinning is a kind of short-cut method for directly preparing superfine fibre, and its device configuration is simple, mainly by high pressure
Power supply, syringe pump, spinning head, collection device are constituted.High molecular weight species available for electrostatic spinning are various, can not only obtain
Micro-, the nanofiber of single solute, can also obtain a variety of solutes and be mixed with obtained mixing micro nanometer fiber etc..Due to logical
Cross the fiber surface area that electrostatic spinning obtains big, different arrangements can also be obtained by the parameters for adjusting electrostatic spinning process
Mode, different topology structure, the fiber of different surfaces structure, can meet the various demands in application process.The present invention is based on
Cornea physiological function and relationship between structure, by the bionical of composition, structure and surface, prepare with high bioactivity and
The cornea repair material of function, finally realizes the New Reclaiming Material that structure and performance match with cornea tissue.
The content of the invention
It is an object of the invention to provide a kind of appearance structure is controllable, good biocompatibility, it is easy to effectively promote to repair and subtract
The electrostatic spinning cornea repair material of few scar.
Another object of the present invention is to provide the preparation method of above-mentioned cornea repair material.
It is still another object of the present invention to provide the application of above-mentioned cornea repair material.
The purpose of the present invention is achieved through the following technical solutions：
A kind of preparation method of electrostatic spinning cornea repair material, is concretely comprised the following steps：
(1) spinning solution is prepared：Macromolecular material is added in organic solvent and dissolved, mechanical agitation, the range of speeds is 100
~700r/min, 2~8h of mixing time, are made spinning solution；
(2) Electrospun solution functionalization：Add medicine and arrive step 1) in spinning solution, mechanical agitation is obtained to being well mixed
To the Electrospun solution containing functional drug；
(3) electrostatic spinning：Electrospun solution is placed in injector for medical purpose, the injection that top connection spout diameter is 0.4mm
Syringe needle, the distance between syringe needle and collection device is 10~25cm, 1~5mL/h of solution flow rate, the Static Spinning under 10~20kV voltages
Silk, produces electrostatic spinning cornea repair material.
It is preferred that, the medicine of addition and the mass ratio of macromolecular material are 1：(10~100).
It is preferred that, collection device is flat board or roller.
It is preferred that, macromolecular material is 1 with organic solvent mass ratio:(5~20).
It is preferred that, organic solvent be DMF, methyl acetate, tetrahydrofuran, DMA,
At least one in chloroform, dichloromethane, methylisobutylketone, methyl cyanide, ethanol, acetic acid, petroleum ether, hexafluoroisopropanol or acetone
Kind.
It is preferred that, macromolecular material be Chitosan-phospholipid complex, collagen, gelatin, polyvinyl alcohol, PLA, gather oneself in
Ester, cellulose and its derivates, polymethyl methacrylate, polyethylene terephthalate, polyurethane, makrolon with
And at least one in polyalcohols and long-chain fat acids.
It is preferred that, medicine is cephazoline, vancomycin, clindamycin, benzyl penicillin, cefotaxime, ceftriaxone, appropriate
Obramycin, quinolones, chloramphenicol, gentamicin, Polymyxin B sulfate, amikacin, ACV, iodoxuridine, ancitabine, arabinose
At least one in adenosine.
Compared with prior art, the invention has the advantages that and beneficial effect：
(1) present invention regulates and controls the structure and performance of formed cornea repair material, Ke Yishi by electrostatic spinning process
Now from microcosmic to macro adjustments and controls, the transformation of various structures, the integration of specific functionalized design and a variety of functions；
(2) preparation process technique of the invention is simple, reproducible, and production efficiency is high, be suitable for bio-medical material system
The popularization of Preparation Method；
(3) cornea repair material of the invention can be used for drug loading, medicine controlled releasing and tissue damage to repair association area.
Brief description of the drawings
The electrostatic spinning collagen-based materials flying-spot microscope image of Fig. 1 random fibers arrangement.
The electrostatic spinning collagen-based materials contact angle of Fig. 2 random fibers arrangement.
Fig. 3 fiber crossovers are orientated (A) and the electrostatic spinning poly-lactic acid material of mono-oriented (B).
Fig. 4 nano-celluloses strengthen collagen electrospun material and the mechanical performance of conventional pure collagen-based materials.
Fig. 5 electrostatic spinning process combines cast film-forming process and prepares compound double membrane sectional view.
The repairing effect that Fig. 6 cornea repair material zooperies are changed over time.
Embodiment
The present invention is further elaborated for specific examples below, but not as a limitation of the invention.
Embodiment 1
1) by 3.0g collagenolysises in 25mL hexafluoroisopropanols, mechanical agitation 8h, the rotating speed of stirring is 100r/min, system
Obtain electrostatic spinning liquid；
2) solution is placed in injection device, voltage 15kV, spinning flow velocity 5mL/h, spinning head to receive roller away from
From for 15cm, using flat board reception device, electrostatic spinning obtains collagem membrane；
3) organic solvent produces the electrostatic spinning cornea repair material of about 10 microns of thickness at room temperature after volatilizing naturally.
Flying-spot microscope observation is it can be seen that its microstructure fiber is in random arrangement (Fig. 1).Contact angle test result surface
The collagem membrane has good hydrophily (Fig. 2), meets the application requirement of cornea repair material.
Embodiment 2
1) 1.0g PLAs and 0.01g TOBs are dissolved in 5mL tetrahydrofurans, mechanical agitation 2h, turn of stirring
Speed is 700r/min, and the quiet Electrospun liquid containing medicine is made；
2) solution is placed in injection device, voltage 20kV, spinning flow velocity 1mL/h, spinning head to receive roller away from
From for 20cm, using roller reception device, drum rotation speed is 3000r/min, and electrostatic spinning obtains polylactic acid membrane；
3) organic solvent volatilizees and produces the electrostatic spinning cornea repair material of carrying medicament naturally at room temperature.
Flying-spot microscope observation is it can be seen that its microstructure fiber is in regular orientations, and fibers parallel degree of alignment is high
(Fig. 3).
Embodiment 3
1) 5.0g collagens and 0.05g nano-celluloses are added in the acetic acid solution that concentration is 1.5% and prepare 5% concentration
Collagen solution, mechanical agitation 4h, the rotating speed of stirring is 300r/min, after being well mixed by solution injection from molding jig, system
Obtain collagen/nano-cellulose mixed solution；
2) collagen/nano-cellulose film is obtained by solution injection from molding jig, after drying naturally at room temperature standby.By 2.0g
Gelatin and 2.0g collagenolysises are in 12mL hexafluoroisopropanols, mechanical agitation 6h, and the rotating speed of stirring is 400r/min, is made compound
Electrostatic spinning liquid；
3) solution is placed in injection device, voltage 20kV, spinning flow velocity 2mL/h, using flat board reception device, will make
Collagem membrane invest in reception device, organic solvent is produced after volatilizing naturally and received under electrostatic spinning room temperature directly on collagem membrane
The enhanced composite collagen electrostatic spinning cornea repair material of rice cellulose.
As shown in the table, resulting repair materials have good mechanical performance (figure compared with conventional pure collagen-based materials
4)。
Embodiment 4
1) 1.0g collagens are added to the collagen solution that 1% concentration is prepared in the acetic acid solution that concentration is 0.5%, machinery is stirred
4h is mixed, the rotating speed of stirring is 300r/min, after being well mixed solution injection is obtained into glue from molding jig after drying naturally at room temperature
Former film is standby；
2) 0.3g gelatin and 0.03g cephazolines are dissolved in 6mL hexafluoroisopropanols, mechanical agitation 3h, turn of stirring
Speed is 400r/min, and electrostatic spinning liquid is made.Solution is placed in injection device, voltage 20kV, spinning flow velocity 1mL/h, sprayed
Silk head invests obtained collagem membrane in reception device, the Static Spinning directly on collagem membrane to the distance of roller is received for 15cm
Silk；
3) organic solvent produces the composite electrostatic spinning cornea repair material of carrying medicament at room temperature after volatilizing naturally.Scanning
It is good (Fig. 5) that the contact of composite section can be seen in micro- sem observation；In addition, selection new zealand white rabbit eye cornea wound is
Animal experimental model, cuts off a part of normal cornea and manufactures an exposed surface of a wound, by prepared collagen corneal repair materials first
Be cut to surface of a wound size, after being soaked through physiological saline, transplant in corneal injury region and suture, taken pictures by routine observation and
OCT testing results show that the material has good repairing effect (Fig. 6).
Claims (7)
1. a kind of preparation method of electrostatic spinning cornea repair material, is concretely comprised the following steps：
（1）Prepare spinning solution：Macromolecular material is added in organic solvent and dissolved, mechanical agitation, the range of speeds is 100~700
R/min, the h of mixing time 2~8, are made spinning solution；
（2）Electrospun solution functionalization：Medicine is added to step 1）In spinning solution, mechanical agitation is contained to well mixed
The Electrospun solution of functional property medicine；
（3）Electrostatic spinning：Electrospun solution is placed in injector for medical purpose, the injection syringe needle that top connection spout diameter is 0.4mm,
Distance between syringe needle and collection device is 10~25cm, the mL/h of solution flow rate 1~5, the electrostatic spinning under 10~20kV voltages,
Produce electrostatic spinning cornea repair material.
2. the preparation method of electrostatic spinning cornea repair material according to claim 1, it is characterised in that：The medicine of addition and
The mass ratio of macromolecular material is 1：（10~100）.
3. the preparation method of electrostatic spinning cornea repair material according to claim 1, it is characterised in that：Described collection dress
It is set to flat board or roller.
4. the preparation method of electrostatic spinning cornea repair material according to claim 1, it is characterised in that：The macromolecule material
Material is 1 with organic solvent mass ratio:（5 ~ 20）.
5. the preparation method of electrostatic spinning cornea repair material according to claim 1, it is characterised in that：The organic solvent
For N,N-dimethylformamide, methyl acetate, tetrahydrofuran, DMAC N,N' dimethyl acetamide, chloroform, dichloromethane, methyl tert-butyl
At least one in ketone, methyl cyanide, ethanol, acetic acid, petroleum ether, hexafluoroisopropanol or acetone.
6. the preparation method of electrostatic spinning cornea repair material according to claim 1, it is characterised in that：The macromolecule material
Expect for Chitosan-phospholipid complex, collagen, gelatin, polyvinyl alcohol, PLA, polycaprolactone, cellulose and its derivates, poly- first
Base methyl acrylate, polyethylene terephthalate, polyurethane, makrolon and polyalcohols and long-chain fat acids
In at least one.
7. the preparation method of electrostatic spinning cornea repair material according to claim 1, it is characterised in that：The medicine is head
Spore oxazoline, vancomycin, clindamycin, benzyl penicillin, cefotaxime, ceftriaxone, TOB, quinolones, chloramphenicol,
At least one in gentamicin, Polymyxin B sulfate, amikacin, ACV, iodoxuridine, ancitabine, arabinosy ladenosine.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108796632A (en) * | 2018-06-27 | 2018-11-13 | 南通纺织丝绸产业技术研究院 | It is used to prepare the electrospinning process of ordered fiber |
| CN109125808A (en) * | 2018-09-21 | 2019-01-04 | 陕西慧康生物科技有限责任公司 | A kind of biodegradable collagen-based cornea substitute and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101695585A (en) * | 2009-10-27 | 2010-04-21 | 吉林大学 | Degradation controlled tissue engineering comea fibrous scaffold and preparation method thereof |
| CN102580166A (en) * | 2012-02-27 | 2012-07-18 | 浙江大学 | Medical bionic transparent film implanting material, and preparation method and application of material |
| CN103046225A (en) * | 2012-01-19 | 2013-04-17 | 苏州达普生物技术有限公司 | Preparation method of collagen membrane |
| CN103603138A (en) * | 2013-11-15 | 2014-02-26 | 无锡中科光远生物材料有限公司 | Preparation method of PLGA fibrous coat used for corneal tissue transplant |
-
2017
- 2017-02-07 CN CN201710067821.0A patent/CN106943625A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101695585A (en) * | 2009-10-27 | 2010-04-21 | 吉林大学 | Degradation controlled tissue engineering comea fibrous scaffold and preparation method thereof |
| CN103046225A (en) * | 2012-01-19 | 2013-04-17 | 苏州达普生物技术有限公司 | Preparation method of collagen membrane |
| CN102580166A (en) * | 2012-02-27 | 2012-07-18 | 浙江大学 | Medical bionic transparent film implanting material, and preparation method and application of material |
| CN103603138A (en) * | 2013-11-15 | 2014-02-26 | 无锡中科光远生物材料有限公司 | Preparation method of PLGA fibrous coat used for corneal tissue transplant |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108796632A (en) * | 2018-06-27 | 2018-11-13 | 南通纺织丝绸产业技术研究院 | It is used to prepare the electrospinning process of ordered fiber |
| CN109125808A (en) * | 2018-09-21 | 2019-01-04 | 陕西慧康生物科技有限责任公司 | A kind of biodegradable collagen-based cornea substitute and preparation method thereof |
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