CN104998297B - One kind is poly-（L lactide co ε caprolactones）Nano-fiber nerve conduit and preparation method - Google Patents
One kind is poly-（L lactide co ε caprolactones）Nano-fiber nerve conduit and preparation method Download PDFInfo
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- CN104998297B CN104998297B CN201410150694.7A CN201410150694A CN104998297B CN 104998297 B CN104998297 B CN 104998297B CN 201410150694 A CN201410150694 A CN 201410150694A CN 104998297 B CN104998297 B CN 104998297B
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Abstract
It is poly- the invention discloses one kind（L lactide co ε caprolactones）Nano-fiber nerve conduit and preparation method, preparation method include：（1）Will be poly-（L lactide co ε caprolactones）It is dissolved in tetrahydrofuran and N, the in the mixed solvent of N dimethylformamides；（2）Nanofiber is received in metal bar immersion gelatin solution, taking-up is dried, in metal bar outer layer one layer of gelatin film of formation；（3）Gathered（L lactide co ε caprolactones）/ tetrahydrofuran/N, the electrostatic spinning of N dimethyl formamide solutions receives nanofiber with the metal bar for being coated with gelatin film；（4）After electrostatic spinning terminates, metal bar is immersed in warm water and dissolves gelatin, you can nerve trachea is removed.The nerve trachea of the present invention has a good biocompatibility and mechanical strength, and tube wall has abundant micropore, beneficial to the exchange of nutriment, and nerve trachea degradation time matches with the autologous nerve recovery time；Preparation method of the present invention is simple, free from environmental pollution, high financial profit.
Description
Technical field
The invention belongs to biomedical materials field, and in particular to poly- to one kind（L- lactide-co- 6-caprolactones）Nanometer
Fiber nerve conduit and preparation method.
Background technology
Peripheral nerve injury can cause the decline or forfeiture of patient perceivable's function or motor function, and severe patient can cause paralysis
Paralysis.According to statistics, China is annual because the peripheral nerve defection that traffic accident, industrial injury, athletic injury, surgical operation etc. are caused
Case just have more than 100 ten thousand.Clinically repairing the method for neurologic defect at present mainly has end end sewing, nerve autograft
Three kinds of method and artificial nerve catheter ridge method.End sewing is held due to causing to significantly affect on microcirculation in nerve, newborn god
Few through of poor quality, quantity, repairing effect is undesirable.Though nerve autograft is clinical repair neurologic defect " goldstandard ",
There is many complication and drawback in the measure of this " robbing Peter to pay Paul ", such as area's neurological disorder, neural neoplasia, also
It is difficult to reach preferable therapeutic effect.Artificial nerve catheter ridge method is a kind of reparation nerve fast-developing over nearly 30 years
The method of defect, by artificial nerve catheter, the broken ends of fractured bone of Bridging nerve two builds neural autogenous repairing environment.
Mainly include nondegradable material and the class of biodegradation material two currently used for the material of artificial nerve catheter.
Nondegradable material mainly has silicone, polyethylene, polytetrafluoroethylene (PTFE) etc., and this kind of material has good mechanical property and life
Thing inertia, but the non-degradable in human body, are present in human body after the completion of CO2 laser weld as foreign matter, easily cause inflammation or
Pressuring nerve is, it is necessary to which operation taking-up again, causes secondary injury, clinical practice is restricted.Biodegradable material includes again
The synthetic material such as the natural biologic materials such as collagen, fibroin albumen, chitosan and PLA, polyglycolic acid, polycaprolactone two
Class, natural biologic material has a good biocompatibility, but mechanical property is poor, it is necessary to improve intensity by being crosslinked, but
Cross-linking reagent cytotoxicity used is larger, and the control of the material of biological source its immunogenicity is a difficult point；Manually
Synthetic material biocompatibility has also been proven, but single material property is often difficult to the need for meeting nerve trachea
Will, the toughness of such as PLA and polyglycolic acid is poor, pliable in vivo, and degradation time is short, and increases its molecular weight
Its fragility and hardness increase can be caused again, polycaprolactone pliability is good, but is metabolized slowly in vivo, and these make facing for they
Bed application is restricted.
Preferable artificial nerve catheter material should have good biocompatibility and mechanical strength, and degradation time
The need for CO2 laser weld being met, and existence time is not long in vivo.It is poly-（L- lactide-co- 6-caprolactones）It is by L-
The degradable high polymer material that lactide and 6-caprolactone copolymerization are obtained, its final catabolite be H2O and CO2, to human body without
Evil, and by controlling the molecular weight of polymer and the molar content of L- lactides and 6-caprolactone, can obtain elastic and soft
Good toughness, the material that degradation time matches with neurotization time.
The existing multiple patents of nerve trachea are prepared by electrostatic spinning technique to be related to, Chinese patent CN 101579246A are public
A kind of artificial silk fibroin nano-fiber nerve conduit and preparation method thereof has been driven, fibroin albumen nanometer is prepared by electrostatic spinning
Fiber, collects fibroin fiber with roller and obtains nerve trachea；Chinese patent CN 101543645A disclose a kind of gather in oneself
Ester PCL static spinning nerve conduits and its preparation and application, with chloroform/methanol mixed solvent dissolving PCL, through electrostatic spinning
Prepare nerve trachea；The nerve trachea prepared by electrostatic spinning has abundant micropore, and beneficial to mass exchange, and nanofiber is sharp
In the tactophily of nerve cell.But nanofiber is directly received with metal bar, after conduit is molded on metal bar, it is difficult to
Separated from metal bar, and easily cause the destruction of nerve trachea internal structure, have impact on its application effect.
The content of the invention
To solve the limitation of existing nerve trachea material, and caused by directly receiving nanofiber using metal bar
Pipe difficult problem is taken, it is poly- the invention provides one kind（L- lactide-co- 6-caprolactones）Nano-fiber nerve conduit and preparation side
Method, prepared nerve trachea has good biocompatibility and mechanical strength, and degradation time is appropriate, and by metal
One layer of gelatin film is formed on rod, passes through water-soluble removing gelatin film after conduit is formed, in that context it may be convenient to take nerve trachea
Under, maintain the integrality of nerve trachea structure.
The present invention's is poly-（L- lactide-co- 6-caprolactones）Nano-fiber nerve conduit and preparation method include following step
Suddenly：
（1）Will be poly-（L- lactide-co- 6-caprolactones）The mixing dissolved with tetrahydrofuran and N,N-dimethylformamide is molten
In agent, the solution that concentration is 0.05 ~ 0.2 g/ml is configured to；It is poly-（L- lactide-co- 6-caprolactones）Molecular weight for 100,000 ~
The molar ratio of 500000, L- lactide and 6-caprolactone is 80/20 ~ 50/50, is preferably gathered（L- lactide-co- 6-caprolactones）
Molecular weight be that the molar ratio of 300,000, L- lactides and 6-caprolactone is 70/30；Tetrahydrofuran and N,N-dimethylformamide
Volume ratio be 70/30 ~ 40/60, it is preferred that the volume ratio of tetrahydrofuran and DMF be 50/50；It is preferred that
, the concentration of polymer is 0.1g/ml；
（2）Metal bar will be received to immerse in 0.01 ~ 0.1 g/ml gelatin solution, taking-up is dried, in metal bar surface shape
Into one layer of gelatin film；It is preferred that, the concentration of gelatin solution is 0.05g/ml；
（3）By step（1）The solution of preparation carries out electrostatic spinning, with step（2）The metal for being covered with gelatin film prepared
Rod receives nanofiber, and collecting nanofibers form seamless conduit on metal bar；The condition of the electrostatic spinning is：Voltage 8
~ 20KV, spinning speed is 0.5 ~ 3ml/h, and it is 10 ~ 20cm to receive distance；It is preferred that, voltage 10KV, spinning speed is 1ml/h,
It is 15cm to receive distance；
（4）After electrostatic spinning terminates, metal bar is placed in 30 ~ 50 DEG C of warm water, makes Gelatin, you can by nerve trachea
Removed from metal bar.
It is provided by the present invention poly-（L- lactide-co- 6-caprolactones）Nano-fiber nerve catheter length is 10 ~ 100mm,
Internal diameter is 1 ~ 10mm, and pipe thickness is 0.2 ~ 2mm；According to different defects the nerve of different specification size can be selected to lead
Pipe.
Beneficial effects of the present invention：
（1）Prepared by the present invention poly-（L- lactide-co- 6-caprolactones）Nano-fiber nerve conduit good biocompatibility,
With good crushing resistance and pliability, while there is tube wall abundant micropore to be exchanged beneficial to nutriment, nanofiber is adapted to
The tactophily of nerve fibre.
（2）Prepared nerve trachea has different specifications, is adapted to the neurologic defect for repairing different parts, matching
Property it is high.
（3）Preparation method of the present invention is simple, environmentally safe, obtained nerve trachea structural integrity, is adapted to industrialization
Production.
Brief description of the drawings
Fig. 1 is the metal bar for being covered with gelatin；
Fig. 2 is poly- for the different size of preparation（L- lactide-co- 6-caprolactones）Nano-fiber nerve conduit；
Fig. 3 is the stereoscan photograph of nerve trachea.
Embodiment
With reference to specific embodiment, the present invention is expanded on further.It should be understood that these embodiments are merely to illustrate the present invention
Rather than limitation the scope of the present invention.In addition, it is to be understood that after the content of the invention lectured has been read, people in the art
Member can make various changes or modifications to the present invention, and these equivalent form of values equally fall within the application appended claims and limited
Scope.
Embodiment 1
（1）0.5g is weighed to gather（L- lactide-co- 6-caprolactones）（Molecular weight 100,000, L- lactides and 6-caprolactone rub
You are than being 80/20）, it is dissolved in the in the mixed solvent of 4ml tetrahydrofurans and DMF, tetrahydrofuran and N, N- bis-
The volume ratio of NMF is 70/30, is configured to the polymer solution that concentration is 0.125g/ml；
（2）By in a diameter of 2mm metal bar immersion concentration 0.02g/ml gelatin solution, taking-up is dried, in metal bar
Outer layer formation gelatin film；
（3）Spinning parameter is set, electrostatic spinning is carried out, spinning voltage is 10KV, and spinning speed is 2ml/h, receives distance
For 10cm;
（4）Metal bar is removed after spinning 1h, is placed in 30 DEG C of water, dissolves the gelatin film being overlying on metal bar,
Nerve trachea is removed, prepared nerve trachea internal diameter is 2mm, and length is 5cm, and pipe thickness is 0.3mm.
Embodiment 2
（1）1g is weighed to gather（L- lactide-co- 6-caprolactones）（Mole of molecular weight 300,000, L- lactides and 6-caprolactone
Than for 70/30）, it is dissolved in the in the mixed solvent of 10ml tetrahydrofurans and DMF, tetrahydrofuran and N, N- bis-
The volume ratio of NMF is 50/50, is configured to the polymer solution that concentration is 0.1g/ml；
（2）By in a diameter of 5mm metal bar immersion concentration 0.05g/ml gelatin solution, taking-up is dried, in metal bar
Outer layer formation gelatin film；
（3）Set spinning parameter, carry out electrostatic spinning, spinning voltage is 15KV, and spinning speed is 0.8ml/h, receive away from
From for 15cm；
（4）Metal bar is removed after spinning 5h, is placed in 40 DEG C of water, dissolves the gelatin film being overlying on metal bar,
Nerve trachea is removed, prepared nerve trachea internal diameter is 5mm, and length is 10cm, and pipe thickness is 0.5mm.
Embodiment 3
（1）2g is weighed to gather（L- lactide-co- 6-caprolactones）（Mole of molecular weight 500,000, L- lactides and 6-caprolactone
Than for 50/50）, it is dissolved in the in the mixed solvent of 15ml tetrahydrofurans and DMF, tetrahydrofuran and N, N- bis-
The volume ratio of NMF is 60/40, is configured to the polymer solution that concentration is 0.13g/ml；
（2）By in a diameter of 10mm metal bar immersion concentration 0.1g/ml gelatin solution, taking-up is dried, in metal bar
Outer layer formation gelatin film；
（3）Spinning parameter is set, electrostatic spinning is carried out, spinning voltage is 20KV, and spinning speed is 2ml/h, receives distance
For 20cm；
（4）Metal bar is removed after spinning 6h, is placed in 50 DEG C of water, dissolves the gelatin film being overlying on metal bar,
Nerve trachea is removed, prepared nerve trachea internal diameter is 10mm, and length is 8cm, and pipe thickness is 1mm.
Claims (5)
1. a kind of preparation method of poly- (L- lactide-co- 6-caprolactones) nano-fiber nerve conduit, comprises the following steps：
(1) poly- (L- lactide-co- 6-caprolactones) is dissolved in the mixed solvent of tetrahydrofuran and N,N-dimethylformamide
In, it is configured to the solution that concentration is 0.05~0.2g/mL；
(2) metal bar will be received to immerse in 0.01~0.1g/mL gelatin solution, taking-up is dried, and one is formed on metal bar surface
Layer gelatin film；
(3) solution for preparing step (1) carries out electrostatic spinning, is connect with the metal bar for being covered with gelatin film prepared by step (2)
By nanofiber, collecting nanofibers form seamless conduit on metal bar；
(4) after electrostatic spinning terminates, metal bar is placed in 30~50 DEG C of warm water, makes Gelatin, you can by nerve trachea from
Removed on metal bar.
2. the preparation method of poly- (L- lactide-co- 6-caprolactones) nano-fiber nerve conduit according to claim 1,
Characterized in that, poly- (L- lactide-co- 6-caprolactones) molecular weight is 100,000~500,000, in copolymer L- lactides and
The molar ratio of 6-caprolactone is 80/20~50/50；
3. the preparation method of poly- (L- lactide-co- 6-caprolactones) nano-fiber nerve conduit according to claim 1,
Characterized in that, the mixed solvent of the tetrahydrofuran and DMF, tetrahydrofuran and N, N- dimethyl formyl
The volume ratio of amine is 70/30~40/60.
4. the preparation method of poly- (L- lactide-co- 6-caprolactones) nano-fiber nerve conduit according to claim 1,
Characterized in that, the condition of the electrostatic spinning is：8~20KV of voltage, spinning speed is 0.5~3mL/h, and it is 10 to receive distance
~20cm.
5. the preparation method of poly- (L- lactide-co- 6-caprolactones) nano-fiber nerve conduit according to claim 1,
Characterized in that, the nerve trachea length is 10~100mm, internal diameter is 1~10mm, and pipe thickness is 0.2~2mm.
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| CN109847104B (en) * | 2019-03-07 | 2022-05-03 | 宁波光远致信生物科技有限公司 | Nerve repair membrane and preparation method and application thereof |
| CN109938875A (en) * | 2019-03-07 | 2019-06-28 | 宁波光远致信生物科技有限公司 | A kind of nerve prosthesis and its preparation method and application |
| CN113117130B (en) * | 2021-01-13 | 2022-05-10 | 海南建科药业有限公司 | Surface treatment method for medical operation line |
| WO2023108469A1 (en) * | 2021-12-15 | 2023-06-22 | 深圳先进技术研究院 | Tubular nanofiber material and preparation method therefor |
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| CN101653624A (en) * | 2009-09-18 | 2010-02-24 | 福建师范大学 | Preparation method of composite nanometer fiber small-diameter intravascular tissue engineering stent material |
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