CN117731840A - Fiber-based directional diversion nerve conduit and preparation method and application thereof - Google Patents
Fiber-based directional diversion nerve conduit and preparation method and application thereof Download PDFInfo
- Publication number
- CN117731840A CN117731840A CN202311764640.5A CN202311764640A CN117731840A CN 117731840 A CN117731840 A CN 117731840A CN 202311764640 A CN202311764640 A CN 202311764640A CN 117731840 A CN117731840 A CN 117731840A
- Authority
- CN
- China
- Prior art keywords
- fiber
- nerve conduit
- based directional
- nerve
- hydrophilic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000835 fiber Substances 0.000 title claims abstract description 126
- 210000005036 nerve Anatomy 0.000 title claims abstract description 98
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 239000002105 nanoparticle Substances 0.000 claims abstract description 29
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 28
- 239000004480 active ingredient Substances 0.000 claims abstract description 25
- 239000012528 membrane Substances 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 9
- 239000000243 solution Substances 0.000 claims description 74
- 239000010410 layer Substances 0.000 claims description 41
- 229920001410 Microfiber Polymers 0.000 claims description 24
- 239000012792 core layer Substances 0.000 claims description 19
- 229920001600 hydrophobic polymer Polymers 0.000 claims description 18
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 16
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical compound OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 claims description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 14
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 claims description 12
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 claims description 12
- 229960003987 melatonin Drugs 0.000 claims description 12
- 239000004626 polylactic acid Substances 0.000 claims description 12
- 238000002156 mixing Methods 0.000 claims description 11
- 238000010041 electrostatic spinning Methods 0.000 claims description 10
- 125000005456 glyceride group Chemical group 0.000 claims description 10
- 229920001610 polycaprolactone Polymers 0.000 claims description 10
- 239000004632 polycaprolactone Substances 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- 229920003169 water-soluble polymer Polymers 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 9
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 9
- 238000006116 polymerization reaction Methods 0.000 claims description 9
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 9
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 9
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 229920001577 copolymer Polymers 0.000 claims description 8
- 235000011187 glycerol Nutrition 0.000 claims description 8
- 108010041308 Endothelial Growth Factors Proteins 0.000 claims description 7
- 108010025020 Nerve Growth Factor Proteins 0.000 claims description 7
- 239000002202 Polyethylene glycol Substances 0.000 claims description 7
- 238000000151 deposition Methods 0.000 claims description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims description 7
- 102000015336 Nerve Growth Factor Human genes 0.000 claims description 6
- 239000012530 fluid Substances 0.000 claims description 6
- 238000011068 loading method Methods 0.000 claims description 6
- 229940053128 nerve growth factor Drugs 0.000 claims description 6
- 210000000578 peripheral nerve Anatomy 0.000 claims description 6
- 230000007547 defect Effects 0.000 claims description 5
- 230000009977 dual effect Effects 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- 239000007853 buffer solution Substances 0.000 claims description 3
- 239000003658 microfiber Substances 0.000 claims description 2
- 239000007943 implant Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 8
- 210000000416 exudates and transudate Anatomy 0.000 abstract description 6
- 230000002757 inflammatory effect Effects 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 4
- 230000035755 proliferation Effects 0.000 abstract description 3
- 230000007774 longterm Effects 0.000 abstract description 2
- 230000005012 migration Effects 0.000 abstract description 2
- 238000013508 migration Methods 0.000 abstract description 2
- 230000002950 deficient Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 238000009987 spinning Methods 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- 230000015556 catabolic process Effects 0.000 description 12
- 238000006731 degradation reaction Methods 0.000 description 12
- 229920003023 plastic Polymers 0.000 description 11
- 239000004033 plastic Substances 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 230000007613 environmental effect Effects 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 230000008439 repair process Effects 0.000 description 7
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 5
- 208000010886 Peripheral nerve injury Diseases 0.000 description 5
- 229920000954 Polyglycolide Polymers 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000004633 polyglycolic acid Substances 0.000 description 5
- 230000008929 regeneration Effects 0.000 description 5
- 238000011069 regeneration method Methods 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 206010052428 Wound Diseases 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000007590 electrostatic spraying Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000002513 implantation Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 239000003517 fume Substances 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 231100000241 scar Toxicity 0.000 description 3
- 238000002791 soaking Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 2
- 238000001523 electrospinning Methods 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 229920001477 hydrophilic polymer Polymers 0.000 description 2
- 230000005660 hydrophilic surface Effects 0.000 description 2
- 230000005661 hydrophobic surface Effects 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000010146 3D printing Methods 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 208000037922 refractory disease Diseases 0.000 description 1
- 238000001223 reverse osmosis Methods 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
Landscapes
- Materials For Medical Uses (AREA)
Abstract
The invention provides a fiber-based directional diversion nerve conduit, and a preparation method and application thereof, and relates to the technical field of medical instruments. The fiber-based directional diversion nerve conduit provided by the invention has a double-layer structure, and a hydrophobic superfine fiber membrane and a hydrophilic superfine fiber membrane are sequentially arranged from inside to outside; the hydrophobic superfine fiber membrane is loaded with nano particles for encapsulating active ingredients among fibers. The invention can solve the problems of slow repairing process, untimely treatment of inflammatory effusion and the like of the traditional nerve conduit, realize slow release of active ingredients and exert long-term effects thereof, promote adhesion, proliferation and migration of cells along the axial direction of the conduit, timely transport and discharge wound exudates in damaged nerves as required, and improve the treatment effect of the nerve conduit on defective nerves.
Description
Technical Field
The invention relates to the technical field of medical instruments, in particular to a fiber-based directional diversion nerve conduit, a preparation method and application thereof.
Background
Peripheral nerve injury is a clinically high-onset refractory disease, the incidence rate of which rises year by year, and the number of new cases is up to 100 thousands. Among them, severe peripheral nerve injuries, such as peripheral nerve defects, can cause motor and sensory dysfunction in patients, and it is difficult to maintain normal life and work. At present, the autologous nerve transplantation is still a gold standard for treating peripheral nerve defects, but has the limitations of limited donor, mismatching in size, damage to donor areas and the like, and greatly limits the large-scale clinical application. The artificial nerve conduit is a tubular bracket prepared from fiber, fabric, hydrogel and the like, and is expected to be used as an artificial implantation material to replace a nerve autograft to repair damaged nerves.
By the bionic nerve structure, morphology, chemistry and biological clues are integrated into nerve conduit manufacture, and nerve repair and regeneration can be promoted. As disclosed in patent CN202110086162.1, a nerve conduit with a three-layer structure and a preparation method thereof are disclosed, wherein the inner layer is an oriented fiber film, the middle layer is deposited with electrospun particles loaded with growth factors, and the outer layer is a random fiber film, so as to promote cell migration, proliferation, differentiation and axon extension; however, the three-layer fiber membrane cannot form a tubular structure by a one-step method, and needs to be curled into a tube by using an additional adhesive, and the bonding part is easy to crack and break. Patent CN202210207175.4 discloses a melatonin nerve conduit and a preparation method thereof, which is characterized in that melatonin suspension or melatonin is added into biodegradable materials, the melatonin nerve conduit is obtained through 3D printing or electrostatic spinning equipment, the maturity of regenerated nerves and the number of acting nerve fibers are improved, but the direct loading of melatonin is easy to cause the rapid drug release period, and the action time and effect of active ingredients are limited.
In addition, the development of inflammation after peripheral nerve injury also has a key role in nerve regeneration. After nerve injury, barriers are broken, lymphocytes and antibodies invade nerve tissues to trigger inflammatory reaction, so that a complex microenvironment containing various components such as inflammatory mediators, nutrients, microvascular changes, proliferation cells and the like is formed, and the nerve repair process is greatly influenced. If the nerve conduit can timely remove and transfer the exudates of the fracture wound, inflammatory reaction at the early stage of peripheral nerve injury can be inhibited to a certain extent, and recovery of nerve morphology and functionality is promoted; simultaneously, the external fibroblast is prevented from entering the catheter along with the tissue fluid, so that excessive fibroblast is prevented from easily fibrozing peripheral nerves and forming scars at suture positions, and the nerve functions are prevented from being influenced. However, the existing nerve conduit can only be used as a mechanical channel for nerve regeneration to seal the damaged nerve in the tube, prevents invasion of external cells, simultaneously blocks transfer of internal exudates to the outside, and is difficult to realize accurate regulation and control of the nerve repair microenvironment.
Disclosure of Invention
The invention aims to provide a fiber-based directional diversion nerve conduit and a preparation method and application thereof, and the invention can solve the problems of slow repair process, untimely treatment of inflammatory effusion and the like of the traditional nerve conduit, realize slow release of active components and exert long-term effects thereof, promote adhesion, proliferation and migration of cells along the axial direction of the conduit, timely transport and discharge wound exudates in damaged nerves as required, and improve the treatment effect of the nerve conduit on the damaged nerves.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a fiber-based directional diversion nerve conduit which has a double-layer structure, and a hydrophobic superfine fiber membrane and a hydrophilic superfine fiber membrane are sequentially arranged from inside to outside; the hydrophobic superfine fiber membrane is loaded with nano particles for encapsulating active ingredients among fibers.
Preferably, the fibers of the hydrophobic microfiber film have a dual orientation structure; the dual orientation structure is specifically: the grooves on the surface of the single fiber are oriented, and the plurality of fibers are axially aligned and oriented.
Preferably, the thickness of the hydrophobic ultrafine fiber film is 30-80 μm.
Preferably, the fibers in the hydrophilic ultrafine fibrous membrane are randomly arranged.
Preferably, the hydrophilic ultrafine fiber film has a thickness of 250 to 350 μm.
Preferably, the fiber-based directional diversion nerve conduit has an inner diameter of 1.5-2 mm, an outer diameter of 1.8-2.4 mm and a length of 8-15 mm.
The invention provides a preparation method of the fiber-based directional diversion nerve conduit, which comprises the following steps:
mixing a first degradable hydrophobic polymer, a water-soluble polymer and a first solvent to obtain a solution A;
dissolving polylactic acid-glycolic acid copolymer in acetone to obtain a shell solution B; dissolving the active ingredient in PBS buffer solution to obtain a nuclear layer solution C;
mixing sebacic acid and glycerin, and performing polymerization reaction to obtain hydrophilic polysebacic acid glyceride;
mixing the hydrophilic polysebacic acid glyceride, a second degradable hydrophobic polymer and a second solvent to obtain a solution D;
forming superfine fiber films which are arranged along the axial orientation on the surface of a receiving device through electrostatic spinning; synchronously loading nanoparticles encapsulating active ingredients on the fibers by the shell layer solution B and the core layer solution C to obtain an oriented superfine fiber film loaded with the nanoparticles;
depositing hydrophilic superfine fiber films which are randomly arranged on the surface of the oriented superfine fiber films loaded with the nano particles by electrostatic spinning to form a nerve conduit with a double-layer structure;
and washing the nerve conduit with water, and removing the receiving device to obtain the fiber-based directional diversion nerve conduit.
Preferably, the first and second degradable hydrophobic polymers independently comprise one or more of polylactic acid, polycaprolactone, and polylactide-caprolactone copolymers;
the water-soluble polymer comprises one or more of polyvinylpyrrolidone and polyethylene glycol.
Preferably, the active ingredient comprises one or more of nerve growth factor, endothelial growth factor and melatonin.
The invention provides an application of the fiber-based directional diversion nerve conduit prepared by the technical scheme or the preparation method of the technical scheme in preparing peripheral nerve defect implantation materials.
The invention provides a fiber-based directional diversion nerve conduit, which utilizes the wettability difference formed by a hydrophilic superfine fiber film with high degradation rate and a hydrophobic superfine fiber film with low degradation rate to endow the nerve conduit with controllable directional diversion characteristics, the diversion function of the nerve conduit is gradually weakened along with the rapid degradation of the hydrophilic fiber, inflammatory exudation in the conduit can be led to the outside in the initial stage of nerve healing, meanwhile, scar tissue invasion outside the conduit is blocked, and the active ingredients required in the nerve growth process are reserved in the conduit cavity in the later stage so as to promote nerve regeneration and vascularization, realize the effective regulation and control of the nerve repair microenvironment and improve the treatment effect on peripheral nerve injury.
Compared with the prior art, the fiber-based directional diversion nerve conduit provided by the invention has the following advantages:
the wettability difference formed by the hydrophobic superfine fiber and the hydrophilic superfine fiber is utilized to endow the nerve conduit with directional diversion characteristics, and the controllable adjustment of diversion effect aging is realized based on the degradation rate difference of the hydrophobic superfine fiber and the hydrophilic superfine fiber. The method can direct inflammatory exudates inside the fractured nerve out of the lumen at the initial stage of the catheter implantation and inhibit scar tissue outside the tube from penetrating into the lumen. The hydrophilic fiber gradually changes from hydrophilic to hydrophobic along with the rapid degradation of the hydrophilic polymer in the middle and later stages, the flow guiding function of the nerve conduit gradually weakens, and the nutrient substances and active ingredients required in the lumen in the nerve growth process are reserved.
As a preferable scheme, the hydrophobic superfine fiber of the inner layer has a double orientation structure (single fiber surface groove orientation, and multiple fibers are arranged in parallel), and the physical structure is utilized to induce nerve cells and endothelial cells to directionally migrate from the orifice of the nerve conduit to the middle part of the conduit; nanoparticles for encapsulating active ingredients such as nerve growth factor, endothelial growth factor, melatonin and the like are synchronously sprayed on the surface of the hydrophobic superfine fiber through coaxial electrostatic spraying, so that the half life and stability of the active ingredients are prolonged, and nerve repair and regeneration are promoted for a long time.
As a preferable scheme, the outer layer of the nerve conduit takes a synthetic hydrophilic polymer with high degradation rate and a synthetic hydrophobic polymer with low degradation rate as raw materials, and the hydrophilic superfine fiber film is formed by electrostatic spinning after being mixed according to a certain proportion, wherein the hydrophobic polymer is an inner layer hydrophobic superfine fiber raw material, so that layering phenomenon caused by incompatibility of two components can be avoided when the conduit is formed, and the phenomenon that the nerve growth cannot be supported due to structural collapse of a middle-late material caused by all rapid degradation of the hydrophilic fiber film can be prevented, and the integral structural stability of the conduit is improved.
Drawings
FIG. 1 is a schematic illustration of a process for preparing a fiber-based directional guiding nerve conduit;
FIG. 2 is a scanning electron microscope image of the fiber-based directional guiding nerve conduit prepared in example 1;
fig. 3 is a graph showing the actual directional flow guiding effect of the fiber-based directional flow guiding nerve conduit prepared in example 1, wherein the fiber-based directional flow guiding nerve conduit is shown in the dashed line.
Detailed Description
The invention provides a fiber-based directional diversion nerve conduit which has a double-layer structure, and a hydrophobic superfine fiber membrane and a hydrophilic superfine fiber membrane are sequentially arranged from inside to outside; the hydrophobic superfine fiber membrane is loaded with nano particles for encapsulating active ingredients among fibers.
In the present invention, the fibers of the hydrophobic ultrafine fiber film preferably have a double-oriented structure; the dual orientation structure is specifically: the grooves on the surface of the single fiber are oriented, and the plurality of fibers are axially aligned and oriented. In the present invention, the thickness of the hydrophobic ultrafine fiber film is preferably 30 to 80. Mu.m, more preferably 40 to 50. Mu.m. In the present invention, the diameter of the individual fibers in the hydrophobic ultrafine fiber film is preferably between 1 and 4 μm; the size of the grooves is preferably one fifth of the diameter of the individual fibers.
In the present invention, the hydrophobic ultrafine fibrous membrane is interfiber-loaded with nanoparticles encapsulating an active ingredient. In the present invention, the diameter of the nanoparticle is preferably 50 to 800nm. In the present invention, the active ingredient preferably includes one or more of nerve growth factor, endothelial growth factor and melatonin.
In the present invention, the fibers in the hydrophilic ultrafine fiber film are preferably arranged randomly. In the present invention, the thickness of the hydrophilic ultrafine fiber film is preferably 250 to 350. Mu.m, more preferably 250 to 300. Mu.m. In the present invention, the diameter of the fibers in the hydrophilic ultrafine fiber film is preferably 500nm to 2. Mu.m.
In the invention, the inner diameter of the fiber-based directional diversion nerve conduit is preferably 1.5-2 mm, the outer diameter is preferably 1.8-2.4 mm, and the length is preferably 8-15 mm.
The invention provides a preparation method of the fiber-based directional diversion nerve conduit, which comprises the following steps:
mixing a first degradable hydrophobic polymer, a water-soluble polymer and a first solvent to obtain a solution A;
dissolving polylactic acid-glycolic acid copolymer in acetone to obtain a shell solution B; dissolving the active ingredient in PBS buffer solution to obtain a nuclear layer solution C;
mixing sebacic acid and glycerin, and performing polymerization reaction to obtain hydrophilic polysebacic acid glyceride;
mixing the hydrophilic polysebacic acid glyceride, a second degradable hydrophobic polymer and a second solvent to obtain a solution D;
forming superfine fiber films which are arranged along the axial orientation on the surface of a receiving device through electrostatic spinning; synchronously loading nanoparticles encapsulating active ingredients on the fibers by the shell layer solution B and the core layer solution C to obtain an oriented superfine fiber film loaded with the nanoparticles;
depositing hydrophilic superfine fiber films which are randomly arranged on the surface of the oriented superfine fiber films loaded with the nano particles by electrostatic spinning to form a nerve conduit with a double-layer structure;
and washing the nerve conduit with water, and removing the receiving device to obtain the fiber-based directional diversion nerve conduit.
The invention mixes the first degradable hydrophobic polymer, the water-soluble polymer and the first solvent to obtain solution A. In the present invention, the first degradable hydrophobic polymer preferably includes one or more of polylactic acid (PLA), polycaprolactone (PCL) and polylactide-caprolactone copolymer (PLCL). In the present invention, the molecular weight of the PLA is preferably 10 to 60 ten thousand, more preferably 30 ten thousand; the molecular weight of the PCL is preferably 1 to 10 ten thousand, more preferably 8 ten thousand; the molecular weight of the PLCL is preferably 10 to 60 ten thousand, more preferably 25 ten thousand. In the present invention, the water-soluble polymer preferably includes one or more of polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG). In the present invention, the molecular weight of PVP is preferably 30 to 130 ten thousand, more preferably 60 ten thousand; the molecular weight of the PEG is preferably 0.2 to 2 ten thousand, more preferably 1 ten thousand. In the present invention, the mass ratio of the first degradable hydrophobic polymer to the water-soluble polymer is preferably 1 to 2:1 to 2, more preferably 1:1 to 2. In the present invention, the first solvent preferably includes one or more of hexafluoroisopropanol, trifluoroethanol, N dimethylformamide and dichloromethane, more preferably a mixed solvent of N, N dimethylformamide and dichloromethane. In a specific embodiment of the present invention, the volume ratio of N, N dimethylformamide to dichloromethane in the mixed solvent of N, N dimethylformamide and dichloromethane is 1:3. in the present invention, the mixing is preferably performed under room temperature conditions. In the present invention, the total concentration of the first degradable hydrophobic polymer and the water-soluble polymer in the solution A is preferably 10 to 30% (w/v), more preferably 15 to 18% (w/v).
In the invention, polylactic acid-glycolic acid copolymer (PLGA) is dissolved in acetone to obtain a shell solution B; the active ingredient was dissolved in PBS buffer to give core layer solution C. In the present invention, the molar ratio of polylactic acid (PLA) to polyglycolic acid (PGA) in the PLGA is preferably 30 to 70:30 to 70, more preferably 50:50. In the present invention, the mass volume concentration (w/v) of the shell solution B is preferably 2 to 8%, more preferably 5%. In the present invention, the active ingredient preferably includes one or more of nerve growth factor, endothelial growth factor and melatonin. In the present invention, the pH of the PBS buffer is preferably 7.4. In the present invention, the concentration of the core layer solution C is preferably 500 to 1000ng/mL.
The invention mixes sebacic acid and glycerin, and carries out polymerization reaction to obtain hydrophilic polysebacic acid glyceride (PGS). In the present invention, the molar ratio of sebacic acid to glycerin is preferably 1:1. In the present invention, the polymerization reaction preferably includes: heating to the temperature of the polymerization reaction under the protection of nitrogen to carry out the polymerization reaction, keeping the temperature unchanged, continuing the vacuumizing reaction, and then cooling to the room temperature. In the present invention, the temperature of the polymerization reaction is preferably 120 to 150 ℃, more preferably 130 ℃. In the present invention, the polymerization reaction is carried out under the nitrogen protection for a period of time of preferably 12 to 36 hours, more preferably 24 hours. In the invention, the time of the vacuumizing reaction is preferably 12-72 h, more preferably 24h; the vacuum degree of the vacuuming reaction is preferably 10 -12 Pa. The invention firstly carries out reaction under nitrogen atmosphere, and then the vacuumizing reaction is used for improving the esterification degree.
After the hydrophilic polysebacic acid glyceride is obtained, the hydrophilic polysebacic acid glyceride is mixed with a second degradable hydrophobic polymer and a second solvent to obtain a solution D. In the present invention, the second degradable hydrophobic polymer preferably includes one or more of polylactic acid (PLA), polycaprolactone (PCL) and polylactide-caprolactone copolymer (PLCL). In the present invention, the molecular weight of the PLA is preferably 10 to 60 ten thousand, more preferably 30 ten thousand; the molecular weight of the PCL is preferably 1 to 10 ten thousand, more preferably 8 ten thousand; the molecular weight of the PLCL is preferably 10 to 60 ten thousand, more preferably 25 ten thousand. In the present invention, the mass ratio of the hydrophilic polysebacic glyceride to the second degradable hydrophobic polymer is preferably 5 to 9:1 to 5, more preferably 7 to 8:2 to 3. In the present invention, the second solvent preferably includes one or more of hexafluoroisopropanol, N dimethylformamide and methylene chloride. In the present invention, the mixing is preferably performed under room temperature conditions. In the present invention, the total mass volume concentration (w/v) of the hydrophilic polyglycerine sebacate and the second degradable hydrophobic polymer in the solution D is preferably 10 to 20%, more preferably 15 to 20%.
After the solution A, the shell layer solution B and the core layer solution C are obtained, forming an ultrafine fiber film which is arranged along the axial orientation on the surface of a receiving device through electrostatic spinning by the solution A; and synchronously loading nanoparticles encapsulating active ingredients on the fibers by the shell layer solution B and the core layer solution C to obtain the oriented ultrafine fiber film loaded with the nanoparticles. In the present invention, the receiving means is preferably a plastic rod. In the present invention, the plastic rod preferably has a diameter of 1.5 to 2mm. In the present invention, the shell layer solution B and the core layer solution C preferably spray nanoparticles encapsulating the active ingredient simultaneously on the surface of the fiber by coaxial electrostatic spraying.
In the present invention, the spinning process parameters of the solution a for forming the ultrafine fiber film aligned in the axial direction on the surface of the receiving device by electrospinning preferably include: the propulsion speed is 1.5mL/h; the receiving distance is 12cm; the working voltage is 15kV; the ambient humidity is 30-60%; the spinning time is 5-15 min. In the present invention, in the process of loading the nanoparticles encapsulating the active ingredient on the fiber with the shell layer solution B and the core layer solution C, the spinning process parameters preferably include: the propelling speed of the shell layer solution B is 0.8mL/h, and the propelling speed of the core layer solution C is 0.3mL/h; the receiving distance is 10cm; the working voltage is 15kV; the ambient humidity is 30-60%; the spinning time is 5-15 min.
After the solution D and the nanoparticle-loaded oriented superfine fiber film are obtained, the hydrophilic superfine fiber film which is randomly arranged is deposited on the surface of the nanoparticle-loaded oriented superfine fiber film by electrostatic spinning to form the nerve conduit with a double-layer structure.
In the present invention, the spinning process parameters of the solution D for depositing the randomly arranged hydrophilic ultrafine fiber film on the surface of the oriented ultrafine fiber film loaded with the nanoparticles by electrospinning preferably include: the propulsion speed is 2mL/h; the receiving distance is 12cm; the working voltage is 15kV; the ambient humidity is 30-60%; the spinning time is 30-40 min.
After the nerve conduit with the double-layer structure is obtained, the nerve conduit is washed by water, and then a receiving device is removed, so that the fiber-based directional diversion nerve conduit is obtained. In the present invention, the water washing is preferably performed under stirring. The invention dissolves the water-soluble polymer in the axial orientation arrangement fiber by water washing, and forms an orientation groove structure on the surface of the hydrophobic fiber.
The present invention preferably dries the resulting material overnight in a hood chamber Wen Biguang after removal of the receiving device to yield a fiber-based directional fluid guiding nerve conduit.
In the invention, the degradation rate of the hydrophobic superfine fiber is low; the PGS of the hydrophilic component in the hydrophilic superfine fiber can be rapidly degraded within 1 month, the degradation rate is high, and the hydrophilic fiber gradually changes from hydrophilic to hydrophobic along with the degradation of the hydrophilic component. The guiding function of the directional guiding nerve conduit gradually fails along with the degradation of PGS.
The invention provides an application of the fiber-based directional diversion nerve conduit prepared by the technical scheme or the preparation method of the technical scheme in preparing peripheral nerve defect implantation materials.
The technical solutions of the present invention will be clearly and completely described in the following in connection with the embodiments of the present invention. It will be apparent that the described embodiments are only some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1
Synthesis of PGS: weighing 0.1mol of sebacic acid and 0.1mol of glycerin respectively, putting into a three-necked bottle, continuously introducing nitrogen, heating for 24 hours at 130 ℃, keeping the temperature unchanged, continuously vacuumizing for reaction for 24 hours, and cooling to room temperature to obtain the hydrophilic PGS.
PLCL (molecular weight 25 ten thousand) and PVP (molecular weight 60 ten thousand) were mixed at a mass ratio of 1:1, dissolved in N, N dimethylformamide and methylene chloride (v/v=1/3) at a concentration of 18% (w/v), and stirred at room temperature for 12 hours to obtain solution A.
PLGA (PLA: PGA molar ratio of 50:50) is dissolved in acetone at a concentration of 5% (w/v) to prepare a shell solution B of coaxial electrostatic spraying; nerve growth factor was dissolved in PBS buffer (pH 7.4) at a concentration of 500ng/mL, to which 10vol% aqueous Bovine Serum Albumin (BSA) 1mg/mL was added to maintain its biological activity, to prepare a concentric electrosprayed core layer solution C.
The hydrophilic PGS and PLCL (molecular weight 25 ten thousand) were mixed at a mass ratio of 7:3, dissolved in hexafluoroisopropanol at a concentration of 15% (w/v), and stirred at room temperature for 12 hours to give solution D.
As shown in FIG. 1, a plastic rod with the diameter of 2mm is taken as a receiving device, a component 1 (filled with a solution A) is spun for 5min at a pushing speed of 1.5mL/h, a receiving distance of 12cm, a working voltage of 15kV and an environmental humidity of 50% as spinning process parameters, and a superfine fiber film which is arranged along the axial orientation is formed on the surface of the plastic rod, wherein the thickness is 50 mu m; the component 2 (two injectors are respectively filled into the shell layer solution B and the core layer solution C) synchronously loads nano particles for encapsulating nerve growth factors on axially oriented fibers at the advancing speed of the shell layer solution B of 0.8mL/h, the advancing speed of the core layer solution C of 0.3mL/h, the receiving distance of 10cm, the working voltage of 15kV and the environmental humidity of 50% as spinning process parameters for 5min. And then closing the assembly 2, filling the solution D into the assembly 1, spinning for 30min at a propulsion speed of 2mL/h, a receiving distance of 12cm, a working voltage of 15kV and an environmental humidity of 50% as spinning technological parameters, and depositing a layer of hydrophilic ultrafine fiber film with a thickness of 250 mu m on the surface of the oriented ultrafine fiber film loaded with the nano particles.
And (3) fully stirring and soaking the obtained tubular stent in deionized water, completely dissolving PVP, then extracting the nerve conduit from the plastic rod, and drying the tubular stent in a fume hood in dark overnight to obtain the fiber-based directional diversion nerve conduit.
Example 2
Synthesis of PGS: weighing 0.1mol of sebacic acid and 0.1mol of glycerin respectively, putting into a three-necked bottle, continuously introducing nitrogen, heating for 24 hours at 120 ℃, keeping the temperature unchanged, continuously vacuumizing for reaction for 24 hours, and cooling to room temperature to obtain the hydrophilic PGS.
PLA (molecular weight: 30 ten thousand) and PVP (molecular weight: 60 ten thousand) were mixed at a mass ratio of 1:1, and dissolved in N, N dimethylformamide and methylene chloride (v/v=1/3) at a concentration of 15% (w/v), and stirred at room temperature for 12 hours to obtain a solution A.
PLGA (PLA: PGA molar ratio of 50:50) is dissolved in acetone at a concentration of 5% (w/v) to prepare a shell solution B of coaxial electrostatic spraying; endothelial growth factor (VEGF-A) was dissolved in PBS buffer (pH 7.4) at Sub>A concentration of 500ng/mL, and 10vol% aqueous BSA solution (1 mg/mL) was added thereto to maintain its bioactivity, to prepare an on-axis electrosprayed core layer solution C.
The hydrophilic PGS and PLA (molecular weight: 30 ten thousand) were mixed at a mass ratio of 8:2, dissolved in hexafluoroisopropanol at a concentration of 20% (w/v), and stirred at room temperature for 12 hours to obtain solution D.
As shown in FIG. 1, a plastic rod with the diameter of 2mm is taken as a receiving device, a component 1 (filled with a solution A) is spun for 5min at a pushing speed of 1.5mL/h, a receiving distance of 12cm, a working voltage of 15kV and an environmental humidity of 50% as spinning process parameters, and a superfine fiber film which is arranged along the axial orientation is formed on the surface of the plastic rod, wherein the thickness is 40 mu m; the assembly 2 (two injectors are respectively filled into the shell layer solution B and the core layer solution C) synchronously loads the nano particles for encapsulating the endothelial growth factors on the axially oriented fibers by taking the shell layer solution B propulsion speed of 0.8mL/h, the core layer solution C propulsion speed of 0.3mL/h, the receiving distance of 10cm, the working voltage of 15kV and the environmental humidity of 50% as spinning process parameters and spinning for 5min. And then closing the assembly 2, filling the solution D into the assembly 1, spinning for 40min at a propulsion speed of 2mL/h, a receiving distance of 12cm, a working voltage of 15kV and an environmental humidity of 50% as spinning technological parameters, and depositing a layer of hydrophilic ultrafine fiber film with a thickness of 300 mu m on the surface of the oriented ultrafine fiber film loaded with the nano particles.
And (3) fully stirring and soaking the obtained tubular stent in deionized water, completely dissolving PVP, then extracting the nerve conduit from the plastic rod, and drying the tubular stent in a fume hood in dark overnight to obtain the fiber-based directional diversion nerve conduit.
Example 3
Synthesis of PGS: weighing 0.1mol of sebacic acid and 0.1mol of glycerin respectively, putting into a three-necked bottle, continuously introducing nitrogen, heating for 24 hours at 130 ℃, keeping the temperature unchanged, continuously vacuumizing for reaction for 24 hours, and cooling to room temperature to obtain the hydrophilic PGS.
PCL (molecular weight 8 ten thousand) and PEG (molecular weight 1 ten thousand) were mixed at a mass ratio of 1:2, dissolved in trifluoroethanol at a concentration of 30% (w/v), and stirred at room temperature for 12 hours to obtain a solution A.
PLGA (PLA: PGA molar ratio of 50:50) was dissolved in acetone at a concentration of 8% (w/v) to prepare a shell solution B of coaxial electrostatic spray; melatonin was dissolved in PBS buffer (pH 7.4) at a concentration of 1000ng/mL to prepare a concentric electrosprayed core layer solution C.
The hydrophilic PGS and PCL (molecular weight: 8 ten thousand) were mixed at a mass ratio of 5:5, dissolved in hexafluoroisopropanol at a concentration of 20% (w/v), and stirred at room temperature for 12 hours to obtain solution D.
As shown in FIG. 1, a plastic rod with the diameter of 1.5mm is taken as a receiving device, a component 1 (filled with a solution A) is spun for 15min at a pushing speed of 1.5mL/h, a receiving distance of 12cm, a working voltage of 15kV and an environmental humidity of 60% as spinning process parameters, and a superfine fiber film which is arranged along the axial orientation is formed on the surface of the plastic rod, wherein the thickness is 80 mu m; the component 2 (two injectors are respectively filled in the shell layer solution B and the core layer solution C) synchronously loads and encapsulates the melatonin nanoparticles on the axially oriented fibers at the advancing speed of the shell layer solution B of 0.8mL/h, the advancing speed of the core layer solution C of 0.3mL/h, the receiving distance of 10cm, the working voltage of 15kV and the environmental humidity of 60% as spinning process parameters for 15min. And then closing the assembly 2, filling the solution D into the assembly 1, spinning for 30min at a propulsion speed of 2mL/h, a receiving distance of 12cm, a working voltage of 15kV and an environmental humidity of 60% as spinning technological parameters, and depositing a layer of hydrophilic ultrafine fiber film with a thickness of 270 mu m on the surface of the oriented ultrafine fiber film loaded with the nano particles.
And (3) fully stirring and soaking the obtained tubular stent in deionized water, completely dissolving out PEG, and then extracting the nerve conduit from the plastic rod, and drying the tubular stent in a fume hood in dark place overnight to obtain the fiber-based directional diversion nerve conduit.
Test case
Fig. 2 is a scanning electron microscope image of the fiber-based directional guiding nerve conduit prepared in example 1. As can be seen from fig. 2, the fiber-based directional guiding nerve conduit prepared by the present invention has a double-layer structure, wherein the hydrophobic PLCL fibers of the inner layer are aligned along the axial direction, and the PLCL/PGS fibers of the outer layer are randomly aligned.
Characterization of directional flow conductivity of nerve conduit: a wound exudation simulation liquid (fetal bovine serum dyed with red ink) of 2mL was applied over the fiber-based directional fluid-guiding nerve conduit prepared in example 1 (white tubular stent in yellow frame in the figure), and the liquid-permeable material was observed, and if the liquid was able to penetrate from the hydrophobic surface (PLCL as an example) to the hydrophilic surface but not from the hydrophilic surface (PGS/PLCL as an example) to the hydrophobic surface, the conduit material was proved to have a directional fluid-guiding function. The actual flow guiding effect is shown in fig. 3, and 2mL of wound exudates can penetrate from the hydrophobic layer to the hydrophilic layer within 10min without reverse osmosis, and the directional flow guiding rate is 0.2mL/min. The structure of the fiber-based directional guiding nerve conduits prepared in examples 2 to 3 was similar to example 1, and the guiding effect obtained was similar to example 1.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (10)
1. The fiber-based directional diversion nerve conduit is characterized by having a double-layer structure, and sequentially comprising a hydrophobic superfine fiber membrane and a hydrophilic superfine fiber membrane from inside to outside; the hydrophobic superfine fiber membrane is loaded with nano particles for encapsulating active ingredients among fibers.
2. The fiber-based directional fluid guiding nerve conduit of claim 1, wherein the fibers of the hydrophobic ultra-fine fiber membrane have a dual orientation structure; the dual orientation structure is specifically: the grooves on the surface of the single fiber are oriented, and the plurality of fibers are axially aligned and oriented.
3. The fiber-based directional fluid guiding nerve conduit according to claim 1 or 2, wherein the thickness of the hydrophobic ultra-fine fiber membrane is 30-80 μm.
4. The fiber-based directional fluid guiding nerve conduit of claim 1, wherein the fibers in the hydrophilic microfiber membrane are randomly arranged.
5. The fiber-based directional fluid guiding nerve conduit of claim 1 or 4, wherein the hydrophilic ultrafine fiber membrane has a thickness of 250-350 μm.
6. The fiber-based directional and guiding nerve conduit according to claim 1, wherein the fiber-based directional and guiding nerve conduit has an inner diameter of 1.5-2 mm, an outer diameter of 1.8-2.4 mm, and a length of 8-15 mm.
7. The method for preparing the fiber-based directional diversion nerve conduit of any one of claims 1-6, comprising the following steps:
mixing a first degradable hydrophobic polymer, a water-soluble polymer and a first solvent to obtain a solution A;
dissolving polylactic acid-glycolic acid copolymer in acetone to obtain a shell solution B; dissolving the active ingredient in PBS buffer solution to obtain a nuclear layer solution C;
mixing sebacic acid and glycerin, and performing polymerization reaction to obtain hydrophilic polysebacic acid glyceride;
mixing the hydrophilic polysebacic acid glyceride, a second degradable hydrophobic polymer and a second solvent to obtain a solution D;
forming superfine fiber films which are arranged along the axial orientation on the surface of a receiving device through electrostatic spinning; synchronously loading nanoparticles encapsulating active ingredients on the fibers by the shell layer solution B and the core layer solution C to obtain an oriented superfine fiber film loaded with the nanoparticles;
depositing hydrophilic superfine fiber films which are randomly arranged on the surface of the oriented superfine fiber films loaded with the nano particles by electrostatic spinning to form a nerve conduit with a double-layer structure;
and washing the nerve conduit with water, and removing the receiving device to obtain the fiber-based directional diversion nerve conduit.
8. The method of preparing according to claim 7, wherein the first and second degradable hydrophobic polymers independently comprise one or more of polylactic acid, polycaprolactone, and polylactide-caprolactone copolymer;
the water-soluble polymer comprises one or more of polyvinylpyrrolidone and polyethylene glycol.
9. The method of claim 7, wherein the active ingredient comprises one or more of nerve growth factor, endothelial growth factor, and melatonin.
10. Use of a fiber-based directional guiding nerve conduit according to any one of claims 1 to 6 or a fiber-based directional guiding nerve conduit prepared by a preparation method according to any one of claims 7 to 9 for preparing a peripheral nerve defect implant material.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311764640.5A CN117731840A (en) | 2023-12-21 | 2023-12-21 | Fiber-based directional diversion nerve conduit and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311764640.5A CN117731840A (en) | 2023-12-21 | 2023-12-21 | Fiber-based directional diversion nerve conduit and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117731840A true CN117731840A (en) | 2024-03-22 |
Family
ID=90278995
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311764640.5A Pending CN117731840A (en) | 2023-12-21 | 2023-12-21 | Fiber-based directional diversion nerve conduit and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117731840A (en) |
-
2023
- 2023-12-21 CN CN202311764640.5A patent/CN117731840A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20200384159A1 (en) | Electrospinning with sacrificial template for patterning fibrous constructs | |
| US11946164B2 (en) | Nanofiber structures and methods of use thereof | |
| US6858222B2 (en) | Fabrication of drug loaded biodegradable polymer fibers | |
| CN103006359A (en) | Bionic three-dimensional tissue engineering scaffold and preparation method thereof | |
| US20050161857A1 (en) | Polymeric fibre and method for making same | |
| US20060085063A1 (en) | Nano- and micro-scale engineering of polymeric scaffolds for vascular tissue engineering | |
| MX2011009282A (en) | Artificial dura mater and manufacturing method thereof. | |
| CN1733311A (en) | The preparation method of the nanofiber of a kind of packaging medicine or somatomedin | |
| JP2006525446A (en) | Drug-release biodegradable fiber for therapeutic drug delivery | |
| KR20080091827A (en) | Biomimetic scaffolds | |
| US11801328B2 (en) | Electrospun nanofibers and membrane | |
| WO2016192733A1 (en) | Conduit for regeneration of biological material | |
| CN105079874A (en) | Method for preparing small-diameter artificial blood vessels on basis of nanotechnologies | |
| CN105536055A (en) | Shape memory type high-elasticity activity nano-fiber stent and application thereof | |
| CN109381732A (en) | Electrostatic spinning dressing, preparation method and the application of growth factor-loaded micromolecular inhibitor | |
| AU2019352788A1 (en) | Membrane | |
| CN111068110A (en) | 3D printing degradable composite stent, preparation method thereof and loading composite stent | |
| CN111265721B (en) | Preparation method of electrostatic spinning double-layer artificial blood vessels with different diameters | |
| CN1267590C (en) | Preparing method for growth factor slow-releasing system for tissue repair | |
| CN111214708A (en) | Composite film carrying biological active factor PLA/PLGA/CS and preparation method thereof | |
| CN107349473B (en) | Degradable polylactic acid/fibroin/chitosan composite nerve conduit and preparation method thereof | |
| CN116171170A (en) | Fiber composite material | |
| CN117731840A (en) | Fiber-based directional diversion nerve conduit and preparation method and application thereof | |
| He et al. | Electrospraying and electrospinning for nanobiomaterial fabrication | |
| CN114808276B (en) | Preparation method of nerve conduit with three-layer structure and nerve conduit |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |