CN1216652C - Nervous duct and membrane with fixed nerve regeneration promoting agent with surface modified by plasma and their preparations - Google Patents
Nervous duct and membrane with fixed nerve regeneration promoting agent with surface modified by plasma and their preparations Download PDFInfo
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- CN1216652C CN1216652C CN 03115939 CN03115939A CN1216652C CN 1216652 C CN1216652 C CN 1216652C CN 03115939 CN03115939 CN 03115939 CN 03115939 A CN03115939 A CN 03115939A CN 1216652 C CN1216652 C CN 1216652C
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Abstract
The present invention relates to a nerve conduit or a membrane of an immobilizing nerve regeneration accelerating agent by plasma surface modification, which is mainly characterized in that the surface of the conduit or the membrane is provided with one layer of polymer coating layer which is formed by the surface polymerization modification of plasma and comprises an active group used for immobilized reaction of the next step, the nerve regeneration accelerating agent is then chemically bonded and fixed to the surface of the conduit or the membrane by a covalent bond, and fibers, nonwoven fabric or a spongy material filler which is parallel with a conduit axis is also inserted in the middle in the conduit so that the present invention is formed. Because the nerve conduit and the membrane of the present invention are manufactured by adopting a unique method of plasma surface modification and immobilization of the nerve regeneration accelerating agent, the nerve regeneration accelerating agent can be focused inside the conduit and on the surface of a conduit wall so as to exert functions. Nerve cells are induced to grow by contacting the wall without diffusing to other positions of an organism along with the outflow and the inflow of body fluid so as to exert functions with a longtime effect during nerve regeneration and promote the improvement of a nerve regeneration repairing function. The membrane can likewise be used for rapidly cultivating nerve cells outside a body.
Description
Technical field
The present invention relates to the nerve trachea of plasma surface modification immobilizing neuranagenesis promoter or film and preparation method thereof, nerve trachea can the implantable bioartificial body in the repair deficiency nerve, the film material can externally be used for the cultivation of neurocyte.
Background technology
Nervous system is the topmost organ of human body, and it is controlling the sense organ motor function of human body.Neural in a single day damaged, usually mean the sensation at some position of human body, the forfeiture of motor function, cause great misery to the patient.But up to the present, the reconstruction of the reparation of damaged nerve and function is still a human emphasis and a difficult problem of paying close attention to.
At present, the clinical repair of damaged nerve is mainly taked to transplant from body, allogeneic nerve; Adventitia, bundle film coincide; The medicine auxiliary treatment at nerve trachea bridge joint art, injured nerve position, electromagnetism auxiliary treatment etc.Nerve autograft is the most effective at present neural restorative procedure, soon patient's fibular nerve takes off one section and is transplanted to the defect that needs, but it has increased the number of times and the difficulty of operation, causes that patient's autologous nerve takes out the position afunction, has problems such as the source is limited simultaneously.And allogeneic nerve is transplanted the problem with immunologic rejection.Adventitia and bundle film anastomosis are directly will damage or the stitching that undergos surgery of the neural near end of dialysis and body end far away, has good efficacy to damaging slight or short damaged neural reparation the intermittently, but because nerve does not stretch function, the regeneration that the tension force that stitching produces can affect the nerves, also powerless to the neurologic defect reparation of long pause.Nerve trachea bridge joint art is to utilize the neural certain Regeneration and Repair ability (1mm/ days) that has, near end at damaged nerve is put up a bridge by conduit with body end far away, induce nerve to regenerate along duct direction, simultaneously, build a microenvironment that helps the performance of neuranagenesis function, can promote the Regeneration and Repair of damaged nerve.It is the research focus that present neuranagenesis is repaired.
Nerve trachea bridge joint art is from the research to the catheter-based material, turn to the research of conduit micro structure, simultaneously, combine with molecular biotechnology, by adsorbing or filling various neuranagenesis promoter, promote that the Regeneration and Repair of the damaged nerve of long pause is current development trend.The nerve trachea host material trends towards making collagen, polylactic acid, poly (glycolide-co-lactide), chitosan of apparatus biocompatibility and absorbability etc. at present.The United States Patent (USP) at the beginning of the nineties " US4963146 " is the blank of present all kinds of absorptive nervous catheters.It has biocompatibility and absorbability, semi permeability, can carry out the transmission and the metabolism of nutrient substance by tube wall; Have and sew up mechanical strength and the performance required with motion; Also include neuranagenesis promoter such as glucose albumen, outer skin growth factor, nerve growth factor, human body laminine simultaneously; Japan Patent JP[31] 162397 (Chinese patent CN1304296A) improvement conduit micro structure, simultaneously with coating conduit fibrous materials such as laminines, promote the Regeneration and Repair of cat, monkey than the long pause neurologic defect.
All kinds of neuranagenesis promoter have mostly been used in the research of above-mentioned nerve trachea.As neurocyte trophic factors (NGF) ciliary neurotrophic factor (CNTF) or fibroblast growth factor (FGF), people's laminine (laminine), fibronectin (fibronection) or the like.Although its detailed mechanism is not clear, find that all nerve growth is had definite facilitation.But in above-mentioned nerve trachea is used, these neuranagenesis promoter mostly adopt the mode of physical absorption to import catheter interior or tube material surface, because the nerve trachea tube wall must be a semipermeable system, help the discharge that nutrient substance enters catheter interior and metabolite in the body fluid, therefore, under the effect of body fluid, the nerve growth promoter of these physical absorptions just sees through tube wall easily and flows out in early days, cause the diffusion in vivo of nerve growth promoter, the growth promoter that affects the nerves concentrates in the pipe and plays a role, and may cause the bad reflection of body simultaneously.Therefore a kind of new nerve trachea or the development of film are individual very important research project.
Summary of the invention
Based on the application present situation of above-mentioned nerve growth promoter in nerve trachea, the nerve trachea of plasma surface modification immobilizing neuranagenesis promoter of the present invention and film and preparation method thereof have been proposed.The nerve trachea or the film characteristics of plasma surface modification immobilizing neuranagenesis promoter of the present invention are: it is pipe or the film of being made by biological absorbable and degradable material, there is one deck to modify the polymer coating that goes on foot the active group of immobilized reactant as back one that contains that forms by the plasma surface polymerization on its surface, by covalent bond neuranagenesis promoter chemical bonding is fixed on the surface of conduit or film again, also be inserted with the fiber parallel in the middle of in conduit, implant such as non-woven fabrics or spongy material and forming with tubular axis.Porosity after the filling is 90-99%.
The nerve trachea of plasma surface modification immobilizing neuranagenesis promoter of the present invention or the preparation method of film comprise the following steps:
1. biological absorbable and degradable material is become conduit or film
With biological absorbable and degradable material such as collagen, polylactic acid, poly (glycolide-co-lactide) (PGLA) etc., preferred PGLA, molecular weight is 10-50 ten thousand, conventional melt spinning is made the long filament of fiber number 0.8-2.8 gram/bag, be woven into pipe by the garden weave again, outer tube diameter 0.8-5.0mm, pipe thickness 0.05-0.5mm, be inserted with fiber, non-woven fabrics or spongy material implants such as the collagen parallel with tubular axis, polylactic acid, poly (glycolide-co-lactide) in the middle of in the pipe, filling the back porosity in the pipe is 90-99%.Perhaps be hot pressed into thin film by fusion method, thin film is thick to be 0.02-0.05mm, or the fusion method film forming is at the sheet glass that can be used for cell culture.
2. plasma surface is modified
The conduit of above-mentioned making is cut into the length of 2-5cm.Conduit or thin film that needs are handled and fiber, non-woven fabrics or the spongy material that need be filled into conduit place the reactor of the plasma of frequency 20KHz-13.56MHz, reactor can carry out impulse modulation, discharge is intermittently carried out between "on" and "off", pulse ratio (time of " opening " is divided by the temporal summation of " opening " and " pass ") is 1%-99%, and the time range of " opening " is 1ms-50ms.Reactor electrodes is a capacitance coupling type.Be evacuated to base vacuum degree 3.5 * 10
-2Pa, the monomer such as the aminoacid that will contain amino, carboxyl: for example alanine, glycine, lysine, acrylamide, vinyl acetic acid or acrylic acid are made into the aqueous solution of concentration 10% to 100%, import reactor by non-polymerization gas bubblings such as argon, helium, neon, nitrogen.Regulating effusion meter control gas flow is 5-150sccm, vacuum ranges 5-300Pa, and discharge power 2W-260W, polymerization time 0.1hr-5hr takes out behind the discharge polymerization, and conduit or film surface form the one layer of polymeric coating.Infrared survey is the result show, by the regulating impulse ratio, can keep amino, carboxyl in original monomer structure in the polymer more, and the reservation amount is looked monomeric species, polymerizing condition and changed.For example, under vinyl acetic acid polymerization situation, at peak power 20W, vacuum 35Pa, under the argon flow amount 120sccm condition, change to 10% with pulse ratio from 100%, x-ray photoelectron spectroscopy (XPS) measurement result shows that the content of oxygen in the vinyl acetic acid polymerization modified membrane changes to 17% from 13%.The amino that is kept, carboxyl are participated in follow-up immobilized reactant as essential group.
3. the immobilized reactant of neuranagenesis promoter
Through epoxy hexane or disinfection by ultraviolet light, placing concentration then is the PBS solution that the carbodiimide class catalyst of 1-50% is made into the conduit of above-mentioned polymerization modified or film, takes out after room temperature reaction 20-100 minute, and superfluous catalyst is with twice of PBS solution flushing.Put into the PBS solution of the neuranagenesis promoter albumen of concentration (30-300ng/ml) such as ciliary neurotrophic factor (CNTF), nerve growth factor (NGF), Brain Derived Neurotrophic Factor (BDNF) etc. then, the volume ratio of solution and pending material was at least 1: 1, reaction 15-40hr takes out under the 2-10 ℃ of condition, PBS solution flushing three times.Concentration by Elisa method mensuration immobilization neuranagenesis promoter for example, adopts R﹠amp; The DNT-00 human body of D company-CNTF Elisa quantification kit, to fix the film of neuranagenesis accelerant C NTF as the embedded antibody that combines CNTF, the immunoreation of antibody (anti-CNTF β-Lac Bovis seu Bubali glycosidase) Yu CNTF by CNTF, by the reaction and the photometering of anti-CNTF β-Lac Bovis seu Bubali glucosides zymolyte, record and fixed CNTF neuranagenesis promoter on the film effectively again.The concentration of immobilization neuranagenesis promoter can be 12-41ng/cm
2Owing to having only neuranagenesis promoter in reaction, to be detected, promote the factor so fixed neuranagenesis on this measurement shows film effectively with the membrance chemistry bonding.Be fixed with neuranagenesis and promote the nerve trachea of the factor and nerve trachea and the neural culture membrane that film is plasma surface modification immobilizing neuranagenesis promoter of the present invention.
Behind the nerve trachea and packing material combination through above-mentioned preparation method acquisition, the Regeneration and Repair that can be used for damaged nerve in the body, because catheter surface contains immobilized neuranagenesis promoter, promote neuronic growth promoter, improved the nerve signal transmission speed of regenerating nerve, the sectional area and the quantity of stage casing neural axon widely.
The film that obtains through above-mentioned preparation method can be used for various external neuronal cell cultures, because immobilized neuranagenesis promoter is contained on the film surface, has accelerated neurocyte widely and has pasted the speed that an ancient piece of jade, round, flat and with a hole in its centre is grown, and shortens the cell culture time.
Plasma surface modification immobilizing neuranagenesis promoter method of the present invention, mainly be at first to modify by plasma surface, obtain to carry out next step Activity of Chemical Reaction group at the nerve trachea material surface, again by carbodiimide class biocatalyzer, at low temperatures, the neuranagenesis that will have protein structure by covalent bond promotes that the factor is chemically bound in the nerve trachea material surface, and this method has the following advantages:
1. radio frequency continuous wave plasma polymerization resulting polymers contains more cross-linked structure, and COOH, NH in the former monomer
2, functional group such as CHO intactly keeps than difficulty.By radio frequency plasma is carried out impulse modulation, discharge is intermittently carried out between "on" and "off", be in discharge " open " stage, plasma reaction is carried out according to conventional plasma reaction, is mainly the generation stage of spike and more cross-linked structure; Be in discharge " pass " stage, plasma reaction has the pattern of free radical or ionic polymerization reaction, is mainly the chain growth polymerization stage; Reaction conditions such as control impuls ratio, power can be controlled the active group that the more amino of reservation, carboxyl etc. can carry out next step immobilized reactant, to satisfy the requirement of subsequent fixed reaction.
2. the pulsed radiofrequency plasma modification is a kind of material surface method of modifying, only influences the degree of depth of material surface several thousand dusts, thereby only influential to the surface property of tube material, can not influence other ontological property of material.
3. by carbodiimide class biocatalyzer, the immobilization polycondensation reaction can be finished at low temperatures, and the neuranagenesis that will have protein structure by covalent bond promotes that the factor is chemically bound in the nerve trachea material surface.Because immobilized reactant carries out at low temperature, neuranagenesis is promoted that the bioactive influence of the factor is also less.
4. because neuranagenesis promotes that the factor is fixed on the nerve trachea material surface by covalent bond, thereby can concentrate on catheter interior packing material surface or tube wall surface plays a role, induce the adherent growth of neurocyte, can not flow into other positions that are diffused into body with the outflow of body fluid, thereby during neuranagenesis, play a role longer, promote the raising of the neural repair function of nerve trachea.
Description of drawings
Fig. 1 is the infrared spectrogram of plasma discharge polymer poly lysine (a) and monomer whose (b).
Fig. 2 is C in the plasma discharge polymer poly ethylene acetic acid
1sElectronic energy spectrum.The a-e pulse ratio is respectively 1%, 5%, 10%, 60%, 100% (discharge power 20W) f pulse ratio 10% (discharge power 200W)
Fig. 3 is the culture experiment result of fetus optic cell (12 week) on external film
A. on the slide of Mus tail Jiao Bao quilt (2 days)
B. on the slide of Mus tail Jiao Bao quilt (8 days)
C. on the PGLA diaphragm of modifying through plasma (2 days)
D. on the PGLA diaphragm of modifying through plasma (8 days)
Fig. 4 is the SABC result of the test that neurogliocyte (GFAP is positive to be neurogliocyte) and neuronal cell (NF is positive to be neuronal cell) carry out on external film.
A. on the slide of Mus tail Jiao Bao quilt (GFAP-6 days)
B. on the slide of Mus tail Jiao Bao quilt (NF-12 days)
C. on the PGLA film that plasma is modified (GFAP-6 days)
D. on the PGLA film that plasma is modified (NF-12 days)
Fig. 5 is nerve trachea of the present invention carries out damaged nerve in the rat body a Regeneration and Repair test sketch map.
The specific embodiment
The preparation of embodiment 1 lysine plasma surface modified coatings film
The PGLA of molecular weight 200,000 is melted on the sheet glass, is cooled to uniformly transparent film.Insert 13.56MHz, diameter 10cm, in the glass plasma reactor of long 55cm, electrode is a capacitance coupling type.Be evacuated to vacuum 3.5 * 10
-2Pa, the lysine solution of the concentration 30% that feeding prepares imports reactor by argon.Regulating effusion meter control gas flow is 100sccm, vacuum 50Pa, the regulating impulse ratio is 80%, the interval of " opening " is 3ms, power 40w, power-on discharge polymerization 3hr gets polylysine coating PGLA film, the infrared spectrum of lysine coating has kept amino acid whose amide I (1620cm as shown in Figure 1 preferably in the polymerization modified membrane
-1The C=O of place stretching vibration peak), amide II (1520cm
-1The N-H of place deformation vibration peak), amide III gene (1351cm
-1The C-N of place stretching vibration peak).
The preparation of embodiment 2 vinyl acetic acid plasma surface modified coatings films
The PGLA of molecular weight 200,000 is melted on the sheet glass, is cooled to uniformly transparent film.Insert 13.56MHz, diameter 10cm, in the glass plasma reactor of long 55cm, electrode is a capacitance coupling type.Be evacuated to vacuum 3.5 * 10
-2Pa feeds vinyl acetic acid solution, imports reactor by argon.Regulating effusion meter control gas flow is 30sccm, vacuum ranges 120Pa, and power 20w, power-on discharge polymerization 2hr, regulating impulse is than being 100-1%, the interval of " opening " is 10ms, gets polyvinyl acetic acid modified coatings PGLA film.The XPS spectrum of vinyl acetic acid coating as shown in Figure 2, the C in C-C, C-O, the C=O functional group
1sAtomic binding energy is respectively 284.6eV, 286.0eV, 287.6eV.From Fig. 2 as seen, when regulating impulse than changing to 1% from 100,, the C that links to each other with oxygen
1s(C-O, C=O) intensity and the C that links to each other with carbon
1s(C-C) strength ratio increases, and the increase of modifying oxygen-containing functional group in the polymeric membrane is described.From its wide scanning spectrum and O
1sMeticulous analysis of spectrum learns, when regulating impulse than changing to 1% from 100, the content of oxygen changes to 13%, [O from 17%
1s]/[C
1s] than changing to 0.16 from 0.21.
The immobilized reactant of embodiment 3 neuranagenesis accelerant C NTF on film
The PGLA film that the lysine plasma coating that embodiment 1 is made is modified is made into carbodiimide class biocatalyzer the PBS solution of 20% concentration through the room temperature oxirane disinfection.Neuranagenesis promotes factor CNTF (ciliary neurotrophic factor) to be made into concentration 50ng/ml PBS aqueous solution.The PGLA film places carbodiimide class solution 30min, takes out back sterile distilled water flushing, inserts in the CNTF solution again, and the volume ratio of solution and pending material is 2: 1,4 ℃ of reaction 32hr.It is stand-by with PBS solution flushing three times to take out the back.The Elisa method records that fixed CNTF concentration is 13ng/cm on the film
2
Carry out external neuronal cell cultures test on the embodiment 4 neural culture membranes
Get the fetus eyeball of 12 week artificial abortion in age, separate and obtain retina cell, blow and beat gently repeatedly to cell with pasteur pipet and to disperse, evenly be inoculated on the film that embodiment 3 obtains then respectively and on the slide of Mus tail Jiao Bao quilt, then postvaccinal thin film is placed 24 orifice plates, with the DMEM/F12 culture medium culturing that contains 15% hyclone, changed liquid 1 time in per 2 days.Carry out the fetal retinal cell culture.Observe both growth differences every day with inverted microscope.Experimental result shows that retinal neuronal cell speed of growth on the PGLA film of plasma modification immobilizing CNTF is accelerated, and after 2 days, retinal neuronal cell has been climbed full diaphragm.The speed of growth obviously is better than Mus tail Jiao Bao by the speed of growth on the slide, referring to Fig. 3.
Among Fig. 3 among c and Fig. 3 d be that the fetus optic cell is at the growing state of two days and eight days on the PGLA thin film of plasma modification immobilizing, the slide fetus optic cell that b is respectively Mus tail Jiao Bao quilt among a and Fig. 3 among Fig. 3 is at the growing state of two days and eight days.As seen from Figure 3, promptly observe a large amount of fetus optic cell adherent growth two days later on the PGLA of plasma modification immobilizing thin film, the speed of growth was fast than the diaphragm of Mus tail gel coating, had been paved with whole membrane surface fully by the 8th day.
Embodiment 5 neural culture membranes carry out the SABC test of external neurogliocyte (GFAP) and neuronal cell (NF)
The PGLA of molecular weight 450,000 is melted on the sheet glass, and the cooling back forms uniformly transparent film.With 1 * 1cm
216 on diaphragm, insert in the plasma reactor of frequency 20KHz, diameter 10cm, long 55cm, electrode is a capacitance coupling type.Be evacuated to vacuum 3.5 * 10
-2Pa, the lysine solution of the concentration 50% that feeding prepares imports reactor by argon.Regulating effusion meter control gas flow is 170sccm, vacuum ranges 30Pa, and the regulating impulse ratio is 10%, the interval of " opening " is 10ms, power 80w, power-on discharge polymerization 1hr..Obtain the PGLA film that plasma coating is modified.
The PGLA film that above-mentioned plasma coating is modified is through the room temperature oxirane disinfection, and the carbodiimide biocatalyzer is made into the PBS solution of 38% concentration, and the PGLA film is placed carbodiimide solution 88min, takes out back sterile distilled water flushing.Insert CNTF concentration 130ng/ml PBS aqueous solution, the volume ratio of solution and pending material is 1: 1.5 ℃ of reaction 20hr.It is stand-by with PBS solution flushing three times to take out the back.The Elisa method records that fixed CNTF is 20ng/cm2 on the film.Get the fetus eyeball of 14 week artificial abortion in age then, separate to obtain retina cell, according to the condition inoculation identical, cultivate with the foregoing description 4, the slide that also has Mus tail Jiao Bao quilt of inoculated and cultured simultaneously.Stop cell culture simultaneously, carry out the immunohistochemical experiment of GFAP and NF,, judge astrocyte and neuronal cell growth promoter situation by the quality and quantity of the positive cell that occurs.Among Fig. 4 among a and Fig. 4 b be respectively GFAP and NF positive cell growing state on the sheet glass of Mus tail Jiao Bao quilt, among Fig. 4 among c and Fig. 4 d be respectively GFAP and NF positive cell growing state on the PGLA film of plasma modified coatings. find on the PGLA film of plasma modified coatings that GFAP and NF positive cell number are many on the sheet glass than Mus tail Jiao Bao quilt.Illustrate under the situation of cultivating two days that the sheet glass epineural cell growth promoter of Mus tail Jiao Bao quilt is not as the PGLA film of plasma modified coatings, the PGLA film that the plasma modified coatings also is described has promoted the growth promoter of neuronal cell effectively.
Embodiment 6 uses nerve trachea to carry out the Regeneration and Repair test of damaged nerve in the rat body
Get PGLA and make the experimental procedure of the PGLA fiber of filling usefulness in long conduit of 2cm and the pipe by embodiment 1 and 3, carry out the plasma modification immobilizing and make the PGLA nerve trachea, this PGLA nerve trachea is implanted the damaged femoral nerve of rats with left 1.5cm place, be experimental group.The right side is the matched group (not shown), adopts the PGLA nerve trachea of handling without any coating.Every group of 6 rat.Cover connection bridge joint.1 month observation period.Viewing duration is watched local wound healing and foot and is had or not ulcer.Find that all rat wound I phases heal.In two weeks of postoperative, the rat foot begins to occur ulcer.Right side matched group foot ulcers occurrence rate is apparently higher than left side experimental group (P＜0.05), and difference has the significance meaning.Observation period is measured muscle compound action potential (CMAP) maximum amplitude, incubation period and calculates nerve conduction velocity when finishing.And dissect the NE conduit, and observe the general form of nerve trachea, find that nerve trachea is attached at muscle surface, tube wall is complete, and the neurocele two ends are connected with the sciatic nerve two ends, the impassivity neoplasia.Nerve trachea branch stage casing, section two parts far away are drawn materials, are dyeed then, observing the nerve trachea tube wall changes, nervous tissue's reproduction condition, and adopt image analysis system to calculate myelinated nerve fiber number, myelinated nerve fiber average diameter and myelinated nerve fiber sectional area, and carry out statistical procedures.Result such as table 1 and shown in Figure 5.Compare with the matched group of coating not, the nerve conduction velocity of the experimental group of coating, stage casing neural axon number, stage casing nerve fiber area all improve a lot.Explanation has good facilitation through the nerve trachea of pulse plasma surface modification immobilizing to the reparation of damaged nerve.
The nerve of back one month matched group of table 1 operation and experimental group relatively
| Matched group | Experimental group | The P value | |
| Conduction velocity (m/s) stage casing neural axon number is (individual/mm 2) stage casing nerve fiber area (mm 2) | 0 962±422 12.77±7.24 | 17.13±11.26 2384±796 39.66±11.35 | P＜0.05 P＜0.05 P＜0.05 |
Claims (15)
1, a kind of nerve trachea or film of plasma surface modification immobilizing neuranagenesis promoter, it is characterized in that it being conduit or the film of making by biological absorbable and degradable material, there is one deck to modify the polymer coating that goes on foot the active group of immobilized reactant as back one that contains that forms by the plasma surface polymerization on its surface, by covalent bond neuranagenesis promoter chemical bonding is fixed on the surface of conduit or film again, also is inserted with the fiber of also handling parallel in the middle of in conduit with tubular axis through this modification immobilizing, non-woven fabrics or spongy material implant and form.
2, nerve trachea as claimed in claim 1 or film is characterized in that described biological absorbable and degradable material is collagen, polylactic acid or poly (glycolide-co-lactide), and molecular weight is 10-50 ten thousand.
3, nerve trachea as claimed in claim 1 or film is characterized in that described polymer coating is the polymer coating that is formed by the monomer polymerization that contains amino, carboxyl.
4, nerve trachea as claimed in claim 3 or film is characterized in that the described monomer that contains amino, carboxyl is aminoacid, acrylamide, vinyl acetic acid or acrylic acid.
5, nerve trachea as claimed in claim 4 or film is characterized in that described aminoacid is alanine, glycine or lysine.
6, nerve trachea as claimed in claim 1 or film is characterized in that described neuranagenesis promoter is ciliary neurotrophic factor, nerve growth factor or Brain Derived Neurotrophic Factor.
7, nerve trachea as claimed in claim 1 or film is characterized in that described filler fiber is collagen, polylactic acid or poly (glycolide-co-lactide) fiber.
8, nerve trachea as claimed in claim 1 or film is characterized in that filling the back porosity in the described conduit is 90-99%.
9. the conduit of a plasma surface modification immobilizing neuranagenesis promoter or the preparation method of film is characterized in that this method comprises the following steps:
1). biological absorbable and degradable material is become conduit or film
The outer tube diameter of conduit is 0.8-5.0mm, and pipe thickness is 0.05-0.5mm, the middle fiber parallel, non-woven fabrics or the spongy material implant of being inserted with in the conduit with tubular axis, and filling the back porosity in the pipe is 90-99%; Thickness is 0.02-0.05mm;
2). plasma surface is modified
It is the reactor of the plasma of 20KHz-13.56MHz that conduit and implant or film are placed frequency, reactor is carried out impulse modulation, pulse ratio is 1-99%, the time of discharge " opening " is 1-50ms, to contain concentration that amino, carboxylic monomer is made into by non-polymerization gas is that the aqueous solution of 10-100% imports in the reactor, gas flow is 5-150sccm, vacuum is 5-300Pa, discharge power 2-260W, polymerization time 0.1-5hr, discharge polymerization rear tube or film surface form the one layer of polymeric coating;
3). the immobilized reactant of neuranagenesis promoter
With the conduit of polymerization modified or film and the reaction of carbodiimide class catalyst room temperature 20-100 minute, again with neuranagenesis promoter in 2-10 ℃, reaction 15-40hr carries out immobilization.
10, preparation method as claimed in claim 9 is characterized in that described biological absorbable and degradable material is collagen, polylactic acid or poly (glycolide-co-lactide), and molecular weight is 10-50 ten thousand.
11, preparation method as claimed in claim 9 is characterized in that described filler fiber is collagen, polylactic acid or poly (glycolide-co-lactide) fiber.
12, preparation method as claimed in claim 9 is characterized in that described non-polymerization gas is argon, helium, neon or nitrogen.
13, preparation method as claimed in claim 9 is characterized in that the described monomer that contains amino, carboxyl is aminoacid, acrylamide, vinyl acetic acid or acrylic acid.
14, preparation method as claimed in claim 13 is characterized in that described aminoacid is alanine, glycine or lysine.
15, preparation method as claimed in claim 9 is characterized in that described neuranagenesis promoter is ciliary neurotrophic factor, nerve growth factor or Brain Derived Neurotrophic Factor.
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| CN 03115939 CN1216652C (en) | 2003-03-21 | 2003-03-21 | Nervous duct and membrane with fixed nerve regeneration promoting agent with surface modified by plasma and their preparations |
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| CN 03115939 CN1216652C (en) | 2003-03-21 | 2003-03-21 | Nervous duct and membrane with fixed nerve regeneration promoting agent with surface modified by plasma and their preparations |
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| US7858142B2 (en) | 2006-10-17 | 2010-12-28 | Henrich Cheng | Laminin-modified conduit for nerve regeneration and methods of manufacturing the conduit and regenerating nerves using the conduit |
| CN102337211B (en) * | 2011-08-25 | 2013-04-17 | 中国科学院深圳先进技术研究院 | Cell culture device |
| CN110152507B (en) * | 2019-06-06 | 2021-07-27 | 闽江学院 | Preparation method of self-cleaning polymer porous membrane with surface grafted with mixed polymer brush |
| CN110665066B (en) * | 2019-09-17 | 2021-07-02 | 南通大学 | Preparation method of nerve regeneration nanofiber containing activating factors |
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