A kind of nerve rehabilitating tube and preparation method thereof
Technical field
The present invention relates to implantable medical device and biology medical material technical field, be specifically related to a kind of neural
Repair conduit and preparation method thereof.
Background technology
Nerve injury is the most common, especially peripheral nerve injury.Current clinical commonly used autologous nerve moves
Plant or epineurium, perineurium are sewed up and repaired, but donor nerve source is limited, and is required to
Carry out sewing up and easily occur that Sensory nerve fibre invades with misconnection and the broken ends of fractured bone scar tissue of Motor nerve fibre
Etc. problem.According to the neural renewal theory that selects the most confirmed by numerous scholars, employing artificial neuron
Sheath pipe carries out Peripheral nerve repair and becomes a preferable alternative method, and it carries mainly by broken ends of fractured bone slot milling
Selective property regenerative space induced damage neuranagenesis.
But the biological nondegradable material of the many employings of the nerve repair material of prior art is made, it is generally required to
Employing second operation is removed.And the existing commonly used single layer structure of nerve rehabilitating tube, preparation side
Method is single, causes nerve rehabilitating tube limited performance, or can only meet requirement of strength but material relatively difficult to achieve
Transmission, or easily realize material transmission but intensity difference.
Summary of the invention
The present invention provides a kind of nerve rehabilitating tube and preparation method thereof, to solve cannot accomplish in prior art
Should ensure that nerve rehabilitating tube can be conducive to transport and the inducing nerve cell regeneration of trophic factors, also
Need to ensure the technical problem that nerve rehabilitating tube has certain intensity.
The nerve rehabilitating tube of the present invention, including: internal layer and the outer layer being located at described inner layer outer wall;In described
Layer is prepared by one or more composites in collagen, Chitosan-phospholipid complex, and described outer layer is by glue
One or more composites in former, chitosan, fibroin albumen and derivant thereof prepare.
Further, a diameter of required of described nerve rehabilitating tube repairs neural 1.1 1.5 times, described god
The pipe thickness of repaired conduit is 0.5 2.0mm.
Further, described internal layer contains the medicative seed cell of tool, and described seed cell is selected from: god
One or many in stem cell, medulla mesenchyma cell, embryonic stem cell, Schwann cell, Olfactory essheathing cell
Kind.
Further, described internal layer contains the medicative cytokine of tool, and described cytokine is selected from: god
One or more in somatomedin, neurotrophic factor, basic fibroblast growth factor.
Further, described internal layer uses freeze-drying to be prepared, and described outer layer uses method of electrostatic spinning to carry out
Preparation.
The preparation method of the nerve rehabilitating tube that the present invention provides, including:
One or more in employing water dissolution collagen, chitosan, fibroin albumen and derivant thereof are configured to
First solution, utilizes described first solution and uses metal bar to dip method to be formed after coating at metal bar outer wall,
Carry out lyophilization molding and prepare the internal layer of nerve rehabilitating tube, or, the first solution is injected artificial neuron
Sheath pipe mold is with the internal layer of prepared nerve rehabilitating tube;
Organic solvent dissolving fibroin albumen, chitosan, collagen protein is used to be configured to the second solution, by outer wall
The metal bar with described nerve rehabilitating tube internal layer loads cylinder collection device, utilizes described second solution also
Electrostatic spinning is used to prepare the outer layer of described nerve rehabilitating tube.
Further, prepare after nerve rehabilitating tube completes, also include:
Medicative for tool seed cell is injected into described nerve rehabilitating tube internal layer, and formation comprises compound
The nerve rehabilitating tube of seed cell;Wherein, described seed cell is selected from: fill between neural stem cell, bone marrow
One or more in cell plastid, embryonic stem cell, Schwann cell, Olfactory essheathing cell.
Further, prepare after nerve rehabilitating tube completes, also include:
Medicative for tool cytokine is injected into described nerve rehabilitating tube internal layer, and formation comprises compound
The nerve rehabilitating tube of cytokine;Wherein, described cytokine is selected from: nerve growth factor, neural battalion
Support one or more in the factor, basic fibroblast growth factor.
Further, the step of the internal layer preparing nerve rehabilitating tube also includes:
In the first solution, add porogen, form pore space structure with the internal layer at nerve rehabilitating tube.
A kind of nerve rehabilitating tube that the present invention provides and preparation method thereof, nerve rehabilitating tube can be repaiied very well
Multiple nerve injury, has good biocompatibility, in vivo can be with natural degradation, and CO2 laser weld is led simultaneously
Pipe uses double layer design, and endothecium structure is conducive to the growth of neurocyte orthoselection and somatomedin transport,
Layer structure contributes to strengthening nerve rehabilitating tube intensity.
Accompanying drawing explanation
For the technical scheme being illustrated more clearly that in the embodiment of the present invention, institute in embodiment being described below
The accompanying drawing used is needed to be briefly described, it should be apparent that, the accompanying drawing in describing below is the one of the present invention
A little embodiments, for those of ordinary skill in the art, on the premise of not paying creative work,
Other accompanying drawing can also be obtained according to these accompanying drawings:
Fig. 1 is the perspective view of the nerve rehabilitating tube of the embodiment of the present invention one;
Fig. 2 is the side cross sectional views of the nerve rehabilitating tube of the embodiment of the present invention one.
Detailed description of the invention:
For making the purpose of the embodiment of the present invention, technical scheme and advantage clearer, below in conjunction with the present invention
Accompanying drawing in embodiment, is clearly and completely described the technical scheme in the embodiment of the present invention, it is clear that
Described embodiment is a part of embodiment of the present invention rather than whole embodiments.Based in the present invention
Embodiment, those of ordinary skill in the art obtained under not making creative work premise all its
His embodiment, broadly falls into the scope of protection of the invention.
Embodiment one
Fig. 1 is the perspective view of the nerve rehabilitating tube of the embodiment of the present invention one, and Fig. 2 is that the present invention is real
Executing the side cross sectional views of the nerve rehabilitating tube of example one, as depicted in figs. 1 and 2, the nerve of the present invention is repaiied
Multiple conduit 100, including: internal layer 110 and the outer layer 120 being located at described internal layer 110 outer wall;Described internal layer 110 by
One or more composites in collagen, Chitosan-phospholipid complex prepare, described outer layer 120 by collagen,
One or more composites in chitosan, fibroin albumen and derivant thereof prepare.The outer wall of internal layer 110
Fitting tightly with the inwall of outer layer 120, the inwall of internal layer 110 constitutes hollow structure 130.
Except passing through layer materials and internal structure difference thereof at interior outer double-layer structure, it is ensured that nutrient substance
Do not run off and promote the orthoselection growth of nerve fiber, ectonexine preparation technology and outer layer simultaneously
Material selects different to play the effect of reinforcement material intensity.
Further, a diameter of required repair nerve 1.1 1.5 times of described nerve rehabilitating tube, preferably 1.2
Times, the pipe thickness of described nerve rehabilitating tube is 0.5 2.0mm.Described internal layer uses freeze-drying to enter
Row preparation, described outer layer uses method of electrostatic spinning to be prepared.
Described internal layer 110 is containing having medicative seed cell, and described seed cell is selected from: nerve trunk is thin
One or more in born of the same parents, medulla mesenchyma cell, embryonic stem cell, Schwann cell, Olfactory essheathing cell;Or
Person, described internal layer 110 is containing having medicative cytokine, and described cytokine is selected from: nerve growth
One or more in the factor, neurotrophic factor, basic fibroblast growth factor.
Embodiment two
The preparation method of the nerve rehabilitating tube of the embodiment of the present invention two, including:
Step S201, use the one in water dissolution collagen, chitosan, fibroin albumen and derivant thereof or
Various configurations becomes the first solution, utilizes described first solution and uses metal bar to dip method in metal bar outer wall shape
After becoming the coating of thickness about 10 200 μm, carry out lyophilization molding and prepare the internal layer of nerve rehabilitating tube.This
Locate preferred collagen aqueous solution as the first solution.
Step S202, uses that organic solvent dissolves fibroin albumen, chitosan, that collagen protein is configured to second is molten
Liquid, the metal bar that outer wall has described nerve rehabilitating tube internal layer loads cylinder collection device, utilizes described
Second solution also uses electrostatic spinning to prepare the outer layer of described nerve rehabilitating tube.Preferred fibroin albumen six herein
Fluorine aqueous isopropanol is as the second solution.
Step S203, is injected into having medicative seed cell in the nerve rehabilitating tube prepared
Layer, forms the nerve rehabilitating tube comprising compound seed cell;Wherein, described seed cell is selected from: neural
One or more in stem cell, medulla mesenchyma cell, embryonic stem cell, Schwann cell, Olfactory essheathing cell.
Embodiment three
The preparation method of the nerve rehabilitating tube of the embodiment of the present invention three includes:
Step S301, boils natural silk mass fraction 0.05% sodium carbonate liquor 20-30 minute, repeats
Obtain pure fibroin fiber three times, be dissolved in 80 degrees Celsius of stirring and dissolving in lithium bromide ethanol solution, thoroughly
Analysis becomes regenerated silk fibroin film after drying.
Step S302, is dissolved in obtained for step S301 fibroin protein film formic acid and is configured to the first solution, directly
After connecing employing optional and smooth outer surface the metal bar of diameter uniformly dipping the first solution, evaporation of solvent or
Person uses lyophilization to remove solvent to obtain the endothecium structure of nerve rehabilitating tube.
Step S303, uses that organic solvent dissolves fibroin albumen, chitosan, that collagen protein is configured to second is molten
Liquid, the metal bar after directly step S302 being processed is transferred to the cylinder collection device of high-voltage electrostatic spinning device
On, utilize the second solution to carry out the preparation of nerve rehabilitating tube outer layer, drum apparatus rotary speed is preferably
20r/min, point-to-point speed is preferably 12cm/s.
Embodiment four
The preparation method of the nerve rehabilitating tube of the embodiment of the present invention four includes:
Step S401, configures 2% chitosan aqueous solution, as the first solution.
Step S402, injects specific artificial nerve sheath pipe mold by step S401 gained suspension, puts into-80 DEG C
Pre-freeze 48 hours, postlyophilization remove this mould and i.e. can get nerve rehabilitating tube internal layer.
Step S403, uses that organic solvent dissolves fibroin albumen, chitosan, that collagen protein is configured to second is molten
Liquid, utilizes the second solution to carry out the preparation of nerve trachea outer layer.
Embodiment five
The preparation method of the nerve rehabilitating tube of the embodiment of the present invention five includes:
Step S501, adds a certain amount of porogen (such as, salt ion in collagen solution (containing acid)
Deng), pre-freeze molding-80 DEG C of lyophilizing 8 hours more in a particular mold, carry out after ion filter drains saline solution,
Lyophilizing obtains nerve rehabilitating tube internal layer again;Obtained nerve rehabilitating tube internal layer is placed on chi supporting with it
On very little smooth iron staff and fix.Realize CO2 laser weld by the ratio granular size controlling interpolation saline solution to lead
The pore space structure size of pipe and how many regulation and control.
Step S502, boils natural silk mass fraction 0.05% sodium carbonate liquor 20-30 minute, repeats
Obtain pure fibroin fiber three times, be dissolved in lithium bromide ethanol solution, stir molten at 80 degrees celsius
Solving, dialysis becomes regenerated silk fibroin film after drying.
In the first solution, add porogen, mix homogeneously, after internal layer I is prepared in lyophilizing, use ion filter drip
Method removes this porogen, and lyophilizing obtains final internal layer II again
Step S503, is dissolved in formic acid by obtained for step S502 fibroin protein film, obtained by step S601
The iron staff containing nerve rehabilitating tube internal layer be contained on electrostatic spinning catching device, by method of electrostatic spinning former
Carry out the spinning of outer layer on the basis of having internal layer, thus obtain the fibroin albumen artificial neuron that ectonexine structure is different
Repairing conduit, drum apparatus rotary speed is preferably 20r/min, and point-to-point speed is preferably 12cm/s.
Step S504, is injected into Schwann cell in step S503 in prepared nerve rehabilitating tube, is formed
Comprise the nerve rehabilitating tube of compound seed cell.
Embodiment six
The preparation method of the nerve rehabilitating tube of the embodiment of the present invention six includes:
Step S601, adds a certain amount of porogen (such as, salt ion in collagen solution (containing acid)
Deng) pre-freeze molding-80 DEG C of lyophilizing 8 hours more in a particular mold, carry out after ion filter drains saline solution,
Lyophilizing obtains nerve rehabilitating tube internal layer again;Obtained nerve rehabilitating tube internal layer is placed on supporting with it
On the smooth iron staff of size and fix.
Step S602, natural silk mass fraction 0.05% sodium carbonate liquor boils 20-30 minute, repeats three
The pure fibroin fiber of secondary acquisition, is dissolved in lithium bromide ethanol solution, stirring and dissolving at 80 degrees celsius,
Dialysis becomes regenerated silk fibroin film after drying.
Step S603, is dissolved in formic acid by obtained for step S602 fibroin protein film, obtained by step S701
The iron staff containing nerve rehabilitating tube internal layer be contained on electrostatic spinning catching device, by method of electrostatic spinning former
Carry out the spinning of outer layer on the basis of having internal layer, thus obtain the fibroin albumen artificial neuron that ectonexine structure is different
Repairing conduit, drum apparatus rotary speed is preferably 20r/min, and point-to-point speed is preferably 12cm/s.
Last it is noted that various embodiments above is only in order to illustrate technical scheme, it is not intended to limit;
Although being described in detail the present invention with reference to foregoing embodiments, those of ordinary skill in the art should
Work as understanding: the technical scheme described in foregoing embodiments still can be modified by it, or to wherein
Some or all of technical characteristic carries out equivalent;And these amendments or replacement, do not make relevant art
The essence of scheme departs from the scope of various embodiments of the present invention technical scheme.