CN114957588A - Bioabsorbable nerve scaffold and preparation method thereof - Google Patents

Bioabsorbable nerve scaffold and preparation method thereof Download PDF

Info

Publication number
CN114957588A
CN114957588A CN202210739148.1A CN202210739148A CN114957588A CN 114957588 A CN114957588 A CN 114957588A CN 202210739148 A CN202210739148 A CN 202210739148A CN 114957588 A CN114957588 A CN 114957588A
Authority
CN
China
Prior art keywords
block molecules
magnetic
prepolymer
hydrophobic block
stirring
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.)
Granted
Application number
CN202210739148.1A
Other languages
Chinese (zh)
Other versions
CN114957588B (en
Inventor
蓝志元
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ruiju Regeneration Xiamen Medical Technology Co ltd
Original Assignee
Ruiju Regeneration Xiamen Medical Technology Co ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Ruiju Regeneration Xiamen Medical Technology Co ltd filed Critical Ruiju Regeneration Xiamen Medical Technology Co ltd
Priority to CN202210739148.1A priority Critical patent/CN114957588B/en
Publication of CN114957588A publication Critical patent/CN114957588A/en
Application granted granted Critical
Publication of CN114957588B publication Critical patent/CN114957588B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40—High-molecular-weight compounds
    • C08G18/48—Polyethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/08—Carbon ; Graphite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/08—Processes
    • C08G18/10—Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
    • C08G18/12—Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step using two or more compounds having active hydrogen in the first polymerisation step
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40—High-molecular-weight compounds
    • C08G18/4009—Two or more macromolecular compounds not provided for in one single group of groups C08G18/42 - C08G18/64
    • C08G18/4018—Mixtures of compounds of group C08G18/42 with compounds of group C08G18/48
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40—High-molecular-weight compounds
    • C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40—High-molecular-weight compounds
    • C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
    • C08G18/4202—Two or more polyesters of different physical or chemical nature
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40—High-molecular-weight compounds
    • C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
    • C08G18/4266—Polycondensates having carboxylic or carbonic ester groups in the main chain prepared from hydroxycarboxylic acids and/or lactones
    • C08G18/4269—Lactones
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40—High-molecular-weight compounds
    • C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
    • C08G18/4266—Polycondensates having carboxylic or carbonic ester groups in the main chain prepared from hydroxycarboxylic acids and/or lactones
    • C08G18/4269—Lactones
    • C08G18/4277—Caprolactone and/or substituted caprolactone
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40—High-molecular-weight compounds
    • C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
    • C08G18/4266—Polycondensates having carboxylic or carbonic ester groups in the main chain prepared from hydroxycarboxylic acids and/or lactones
    • C08G18/428—Lactides
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
    • C08G83/002—Dendritic macromolecules
    • C08G83/005—Hyperbranched macromolecules
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/02—Elements
    • C08K3/04—Carbon
    • C08K3/041—Carbon nanotubes
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K9/00—Use of pretreated ingredients
    • C08K9/10—Encapsulated ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/32—Materials or treatment for tissue regeneration for nerve reconstruction
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K2201/00—Specific properties of additives
    • C08K2201/011—Nanostructured additives

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Veterinary Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Nanotechnology (AREA)
  • Polyurethanes Or Polyureas (AREA)

Abstract

The invention provides a bioabsorbable nerve scaffold and a preparation method thereof, which takes hydrophilic block molecules, hydrophobic block molecules, prepolymer containing isocyanate functional groups and magnetic nano materials as raw materials and is processed into a hollow tubular structure by blending. The nerve scaffold can be gradually degraded in human tissues, and has good mechanical properties and good nerve repair effect. The hydrophilic block molecules are polyester polyol or polyether polyol, the hydrophobic block molecules are polylactic acid, polyglycolide or polycaprolactone and are obtained by packaging the polylactic acid, the polyglycolide or the polycaprolactone through hydroxyl end groups, and the prepolymer is obtained by reacting the hydrophilic block molecules, the hydrophobic block molecules and isocyanate. The main structure of the invention is obtained by polymerization reaction of hydrophilic block molecules, hydrophobic block molecules and isocyanate, has good mechanical property, can be gradually degraded in human tissues, promotes nerve regeneration and plays a role in nerve repair.

Description

Bioabsorbable nerve scaffold and preparation method thereof
Technical Field
The invention relates to the technical field of medical stent materials, in particular to a bioabsorbable nerve stent and a preparation method thereof.
Background
The nervous system injury mainly comprises spinal cord injury, brain injury, peripheral nerve injury and the like, once the nervous system is diseased, the recovery degree is limited, the treatment effect is not good enough, and serious sequelae are still always remained after treatment. Therefore, implanting the nerve scaffold to replace the completely damaged tissue and promote the regeneration of nerve tissue becomes a common clinical treatment means for treating the nervous system injury at present.
The development of neural scaffolds goes through the following three major stages:
1. autologous venous vessels, amniotic membranes, etc. are used to bridge defective nerves, primarily because these biological grafts contain basement membranes similar to those of schwann cells.
2. Non-degradable materials such as polyethylene, polyvinyl chloride and the like are used, a microenvironment is artificially provided for nerve regeneration, and after repair is completed, the materials need to be taken out through secondary operations, so that secondary damage is easily caused.
3. The material which can be absorbed by biology is adopted to provide a temporary microenvironment for nerve regeneration, and the material can be degraded automatically after nerve repair is finished, and finally absorbed by human body or discharged out of the body.
The use of bioabsorbable nerve scaffold materials is the most preferred choice, both in terms of therapeutic efficacy and patient pain.
For example, collagen is a commonly used bioabsorbable nerve scaffold material, which has good degradability, biocompatibility, low immunity and repairability, and can promote axon regeneration of dorsal root ganglia. However, in the production process of collagen, it is usually necessary to dissolve in acetic acid, and if a solid collagen material is to be obtained, an alkaline solution is usually necessary to neutralize the acetic acid, and salts generated after neutralization are mixed in the solution, and thus it is necessary to remove the salts by dialysis, and therefore, the production method of the collagen material currently used is complicated and expensive. Compared with collagen, synthetic high molecular polymers have natural cost advantages.
Patent CN104645409B discloses a polylactic acid nerve scaffold and a preparation method thereof, comprising a scaffold membrane material and degradable metal wires wrapped by the scaffold membrane material, wherein the degradable metal wires are distributed along the transverse direction and the longitudinal direction of the scaffold, and the main component of the scaffold membrane material is polylactic acid. The mechanical property of the nerve scaffold is relatively poor, and the nerve repair effect is not good enough.
Disclosure of Invention
The invention aims to provide a bioabsorbable nerve scaffold and a preparation method thereof, which have good mechanical properties and good nerve repair effect.
In order to achieve the purpose, the invention is realized by the following scheme:
a method for preparing a bioabsorbable nerve scaffold comprises the steps of taking hydrophilic block molecules, hydrophobic block molecules, prepolymer containing isocyanate functional groups and magnetic nano materials as raw materials, blending and processing the raw materials into a hollow tubular structure to obtain the bioabsorbable nerve scaffold; the hydrophilic block molecules are polyester polyol or polyether polyol, the hydrophobic block molecules are polylactic acid, polyglycolide or polycaprolactone and are obtained by packaging hydroxyl end groups, and the prepolymer is obtained by reacting the hydrophilic block molecules, the hydrophobic block molecules and isocyanate; the magnetic nano material is prepared by the following method:
(A) firstly, ferric chloride, sodium acetate and hexamethylene diamine are used as raw materials to prepare amino magnetic nanospheres, and then the amino magnetic nanospheres are mixed with methyl acrylate and hexamethylene diamine for reaction to obtain amino hyperbranched magnetic nanospheres;
(B) and then reacting the amino hyperbranched magnetic nanospheres, the chitosan-coated carbon nanotubes and polylactic acid to obtain the magnetic nano material.
Preferably, the method for preparing the hollow tubular structure is any one selected from melt extrusion, 3D printing or melt spinning.
Further preferably, the melt extrusion temperature is 120-260 ℃, further preferably 150-220 ℃, further preferably 170-200 ℃; the treatment time is 30-40 minutes.
Further preferably, the specific method of 3D printing is: the powder is flatly paved on a workbench of a 3D printer, the set temperature is 100 ℃, the laser power is 60W, the scanning interval is 0.2mm, the powder paving thickness is 0.12mm, and the scanning speed is 7.3 m/s.
Further preferably, the melt spinning process conditions are as follows: the temperature is 170-180 ℃, the stretching multiple of the spinning nozzle is 2-4 times, and the heat setting temperature is 50-60 ℃.
Preferably, the inner diameter of the hollow tubular structure is 1-5 mm, and further preferably 1.5-3 mm; the thickness is 0.2 to 1mm, and more preferably 0.3 to 0.6 mm.
Preferably, the hydrophobic block molecules are prepared by the following method in parts by weight: mixing 1 part of polylactic acid, polyglycolide or polycaprolactone with 1.2-1.3 parts of glycol, heating to 130-140 ℃ under the condition of 0.5-0.6 MPa, stirring for 2-3 hours under heat preservation, heating to 150-160 ℃, stirring for 5-7 hours under heat preservation, cooling and crushing to obtain the hydrophobic block molecule.
Preferably, the prepolymer is prepared by the following method in parts by weight: firstly, hydrophilic block molecules, hydrophobic block molecules, isocyanate, ethylenediamine and ferric acetylacetonate according to a molar ratio of 1: 0.3-0.5: 8-10: 1-2: 0.005-0.008, adding the mixture into N, N-dimethylformamide which is 5-7 times of the total weight of the mixture, stirring and reacting for 2-3 hours at 65-75 ℃ under the protection of nitrogen, and removing the N, N-dimethylformamide to obtain the prepolymer.
Preferably, the prepolymer has a molecular weight of 100 to 5000g/mol, more preferably 200 to 2000g/mol, and even more preferably 300 to 1000 g/mol.
Preferably, the prepolymer contains 1 to 20% by weight of isocyanate functional groups, and more preferably 3 to 12% by weight.
Preferably, the isocyanate is selected from any one of diphenylmethane diisocyanate, 2, 4-toluene diisocyanate, p-phenylene diisocyanate or hexamethylene diisocyanate.
Preferably, in the step (a), the preparation method of the amino-magnetic nanosphere comprises the following steps: adding 1 part of ferric chloride, 3-4 parts of sodium acetate and 4-5 parts of hexamethylenediamine into 12-15 parts of ethylene glycol, stirring and reacting for 7-9 hours at 160-180 ℃, naturally cooling to room temperature, centrifuging, washing and drying to obtain the product.
Preferably, in the step (a), the preparation method of the amino hyperbranched magnetic nanospheres comprises the following steps: firstly, mixing and stirring 1 part of amino magnetic nanosphere, 0.3-0.4 part of absolute ethyl alcohol and 0.15-0.25 part of methyl acrylate for 5-7 hours, then adding 0.15-0.25 part of ethylenediamine, stirring and reacting for 4-6 hours at 50-60 ℃, centrifuging, washing and drying to obtain the amino hyperbranched magnetic nanosphere.
Preferably, the specific method of step (B) is as follows, in parts by weight: adding 1 part of amino hyperbranched magnetic nanosphere and 0.1-0.2 part of chitosan coated carbon nanotube into 5-7 parts of chloroform, uniformly dispersing by ultrasonic waves, adding 2.2-2.5 parts of polylactic acid, stirring and reacting for 25-30 hours, and removing the chloroform by reduced pressure distillation to obtain the magnetic nano material.
Preferably, in the step (B), the chitosan-coated carbon nanotubes are prepared by the following method in parts by weight: firstly, adding 0.1 part of chitosan into 100-110 parts of acetic acid solution with mass concentration of 1%, uniformly stirring and dispersing to obtain chitosan acetic acid solution, then adding 0.01-0.02 part of carbon nano tube into the chitosan acetic acid solution, uniformly dispersing by ultrasonic waves, adjusting the pH value to be 7-8, dropwise adding glutaraldehyde aqueous solution with mass concentration of 1% while stirring, continuously stirring for 70-80 minutes after the dropwise adding is finished, centrifuging, washing, and drying to obtain the chitosan acetic acid.
More preferably, the stirring speed is 300 to 500 rpm.
The invention also claims a bioabsorbable nerve scaffold obtained by the preparation method.
Compared with the prior art, the invention has the beneficial effects that:
(1) the invention takes hydrophilic block molecules, hydrophobic block molecules, prepolymer containing isocyanate functional groups and magnetic nano materials as raw materials, and the raw materials are blended and processed into the bioabsorbable nerve scaffold with a hollow tubular structure. The nerve scaffold can be gradually degraded in human tissues, has good mechanical properties and good nerve repair effect;
(2) the hydrophilic block molecule is polyester polyol or polyether polyol, the hydrophobic block molecule is polylactic acid, polyglycolide or polycaprolactone which is obtained by packaging hydroxyl end groups, and the prepolymer is obtained by reacting the hydrophilic block molecule and the hydrophobic block molecule with isocyanate. The main structure of the invention is obtained by polymerization reaction of hydrophilic block molecules, hydrophobic block molecules and isocyanate, has good mechanical property, can be gradually degraded in human tissues, promotes nerve regeneration, and plays a role in nerve repair;
(3) the technical key point of the invention is to introduce a magnetic nano material, which is prepared by the following method: firstly, ferric chloride, sodium acetate and hexamethylene diamine are used as raw materials to prepare amino magnetic nanospheres, and then the amino magnetic nanospheres are mixed with methyl acrylate and hexamethylene diamine for reaction to obtain amino hyperbranched magnetic nanospheres; then reacting the amino hyperbranched magnetic nanospheres, the carbon nanotubes coated by the chitosan and polylactic acid to obtain the nano-composite material. The magnetic nano material has magnetism, and can induce and accelerate nerve regeneration and improve nerve repair effect under the influence of a micro magnetic field in a human body. The magnetic nano material has a nano size, and the nano material induces and promotes degradation along with the degradation of the nerve scaffold. In addition, the magnetic nano material has good mechanical property, and is beneficial to improving the mechanical property of the nerve scaffold. In addition, the polylactic acid is introduced into the magnetic nano material, so that the dispersity and the compatibility in a system are effectively improved, and the mechanical property of a product is further improved.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A method for preparing a bioabsorbable nerve scaffold comprises the steps of taking hydrophilic block molecules, hydrophobic block molecules, prepolymer containing isocyanate functional groups and magnetic nano materials as raw materials, blending and processing the raw materials into a hollow tubular structure to obtain the bioabsorbable nerve scaffold; the hydrophilic block molecules are polyester polyol or polyether polyol, the hydrophobic block molecules are polylactic acid, polyglycolide or polycaprolactone and are obtained by packaging hydroxyl end groups, and the prepolymer is obtained by reacting the hydrophilic block molecules, the hydrophobic block molecules and isocyanate; the magnetic nano material is prepared by the following method:
(A) firstly, ferric chloride, sodium acetate and hexamethylene diamine are used as raw materials to prepare amino magnetic nanospheres, and then the amino magnetic nanospheres are mixed with methyl acrylate and hexamethylene diamine for reaction to obtain amino hyperbranched magnetic nanospheres;
(B) and then reacting the amino hyperbranched magnetic nanospheres, the chitosan-coated carbon nanotubes and polylactic acid to obtain the magnetic nano material.
The processing method is melt extrusion, and the temperature of the melt extrusion is 170 ℃; the treatment time was 40 minutes.
The inner diameter of the hollow tubular structure is 1.5 mm; the thickness is 0.6 mm.
The preparation method of the hydrophobic block molecule comprises the following steps: mixing 1g of polylactic acid, polyglycolide or polycaprolactone with 1.2g of glycol, heating to 130 ℃ under the condition of 0.6MPa, stirring for 3 hours under heat preservation, heating to 150 ℃, stirring for 7 hours under heat preservation, cooling and crushing to obtain the hydrophobic block molecule.
The prepolymer was prepared as follows: firstly, mixing a hydrophilic block molecule, a hydrophobic block molecule, isocyanate, ethylenediamine and iron acetylacetonate according to a molar ratio of 1: 0.3: 10: 1: 0.008, adding into N, N-dimethylformamide with 5 times of the total weight of the raw materials, stirring and reacting at 75 ℃ for 2 hours under the protection of nitrogen, and removing the N, N-dimethylformamide to obtain the prepolymer.
The molecular weight of the prepolymer was 1000 g/mol.
The prepolymer contained 3% by weight of isocyanate functional groups.
The isocyanate is diphenylmethane diisocyanate.
In the step (A), the preparation method of the amino magnetic nanospheres comprises the following steps: adding 1g of ferric chloride, 4g of sodium acetate and 4g of hexamethylenediamine into 15g of ethylene glycol, stirring and reacting for 9 hours at 160 ℃, naturally cooling to room temperature, centrifuging, washing and drying to obtain the product.
In the step (A), the preparation method of the amino hyperbranched magnetic nanospheres comprises the following steps: firstly, mixing and stirring 1g of amino magnetic nanospheres, 0.3g of absolute ethyl alcohol and 0.25g of methyl acrylate for 5 hours, then adding 0.25g of ethylenediamine, stirring and reacting for 6 hours at 50 ℃, centrifuging, washing and drying to obtain the amino hyperbranched magnetic nanospheres.
The specific method of step (B) is as follows: firstly, 1g of amino hyperbranched magnetic nanospheres and 0.1g of chitosan-coated carbon nanotubes are added into 7g of chloroform, uniformly dispersed by ultrasonic waves, then 2.2g of polylactic acid is added, stirred and reacted for 30 hours, and the chloroform is removed by reduced pressure distillation, thus obtaining the magnetic nano material.
In the step (B), the chitosan-coated carbon nanotube is prepared by the following method: firstly, 0.1g of chitosan is added into 100g of acetic acid solution with the mass concentration of 1%, the mixture is stirred and dispersed uniformly to obtain chitosan acetic acid solution, then 0.02g of carbon nano tube is added into the chitosan acetic acid solution, the mixture is dispersed uniformly by ultrasonic waves, the pH value is adjusted to be 7, glutaraldehyde aqueous solution with the mass concentration of 1% is dripped while stirring, the mixture is continuously stirred for 80 minutes after the dripping is finished, and the chitosan acetic acid solution is obtained by centrifugation, washing and drying. The stirring rate was 300 rpm.
Example 2
A method for preparing a bioabsorbable nerve scaffold comprises the steps of taking hydrophilic block molecules, hydrophobic block molecules, prepolymer containing isocyanate functional groups and magnetic nano materials as raw materials, blending and processing the raw materials into a hollow tubular structure to obtain the bioabsorbable nerve scaffold; the hydrophilic block molecules are polyester polyol or polyether polyol, the hydrophobic block molecules are polylactic acid, polyglycolide or polycaprolactone and are obtained by packaging hydroxyl end groups, and the prepolymer is obtained by reacting the hydrophilic block molecules, the hydrophobic block molecules and isocyanate; the magnetic nano material is prepared by the following method:
(A) firstly, ferric chloride, sodium acetate and hexamethylene diamine are used as raw materials to prepare amino magnetic nanospheres, and then the amino magnetic nanospheres are mixed with methyl acrylate and hexamethylene diamine for reaction to obtain amino hyperbranched magnetic nanospheres;
(B) and then reacting the amino hyperbranched magnetic nanospheres, the chitosan-coated carbon nanotubes and polylactic acid to obtain the magnetic nano material.
The processing method is 3D printing, and the specific method of the 3D printing is as follows: the powder is flatly paved on a workbench of a 3D printer, the set temperature is 100 ℃, the laser power is 60W, the scanning interval is 0.2mm, the powder paving thickness is 0.12mm, and the scanning speed is 7.3 m/s.
The inner diameter of the hollow tubular structure is 3 mm; the thickness is 0.3 mm.
The preparation method of the hydrophobic block molecule comprises the following steps: mixing 1g of polylactic acid, polyglycolide or polycaprolactone with 1.3g of glycol, heating to 140 ℃ under the condition of 0.5MPa, keeping the temperature and stirring for 2 hours, then heating to 160 ℃, keeping the temperature and stirring for 5 hours, cooling and crushing to obtain the hydrophobic block molecule.
The prepolymer was prepared as follows: firstly, hydrophilic block molecules, hydrophobic block molecules, isocyanate, ethylenediamine and ferric acetylacetonate according to a molar ratio of 1: 0.5: 8: 2: 0.005, adding the mixture into N, N-dimethylformamide with the weight 7 times of the total weight of the mixture, stirring and reacting for 3 hours at 65 ℃ under the protection of nitrogen, and removing the N, N-dimethylformamide to obtain the prepolymer.
The molecular weight of the prepolymer was 300 g/mol.
The prepolymer contained 12% by weight of isocyanate functional groups.
The isocyanate is 2, 4-toluene diisocyanate.
In the step (A), the preparation method of the amino magnetic nanospheres comprises the following steps: adding 1g of ferric chloride, 3g of sodium acetate and 5g of hexamethylenediamine into 12g of ethylene glycol, stirring and reacting for 7 hours at 180 ℃, naturally cooling to room temperature, centrifuging, washing and drying to obtain the product.
In the step (A), the preparation method of the amino hyperbranched magnetic nanospheres comprises the following steps: firstly, 1g of amino magnetic nanosphere, 0.4g of absolute ethyl alcohol and 0.15g of methyl acrylate are mixed and stirred for 7 hours, then 0.15g of ethylenediamine is added, stirring reaction is carried out for 4 hours at 60 ℃, centrifugation, washing and drying are carried out, and the amino hyperbranched magnetic nanosphere is obtained.
The specific method of step (B) is as follows: firstly, adding 1g of amino hyperbranched magnetic nanospheres and 0.2g of chitosan-coated carbon nanotubes into 5g of chloroform, uniformly dispersing by ultrasonic waves, then adding 2.5g of polylactic acid, stirring for reacting for 25 hours, and removing the chloroform by reduced pressure distillation to obtain the magnetic nanomaterial.
In the step (B), the chitosan-coated carbon nanotube is prepared by the following method: firstly, adding 0.1g of chitosan into 110g of acetic acid solution with the mass concentration of 1%, uniformly stirring and dispersing to obtain chitosan acetic acid solution, then adding 0.01g of carbon nano tube into the chitosan acetic acid solution, uniformly dispersing by ultrasonic waves, adjusting the pH value to 8, dropwise adding glutaraldehyde aqueous solution with the mass concentration of 1% while stirring, continuously stirring for 70 minutes after the dropwise adding is finished, centrifuging, washing and drying to obtain the chitosan acetic acid. The stirring rate was 500 rpm.
Example 3
A method for preparing a bioabsorbable nerve scaffold comprises the steps of taking hydrophilic block molecules, hydrophobic block molecules, prepolymer containing isocyanate functional groups and magnetic nano materials as raw materials, blending and processing the raw materials into a hollow tubular structure to obtain the bioabsorbable nerve scaffold; the hydrophilic block molecules are polyester polyol or polyether polyol, the hydrophobic block molecules are polylactic acid, polyglycolide or polycaprolactone and are obtained by packaging hydroxyl end groups, and the prepolymer is obtained by reacting the hydrophilic block molecules, the hydrophobic block molecules and isocyanate; the magnetic nano material is prepared by the following method:
(A) firstly, ferric chloride, sodium acetate and hexamethylene diamine are used as raw materials to prepare amino magnetic nanospheres, and then the amino magnetic nanospheres are mixed with methyl acrylate and hexamethylene diamine for reaction to obtain amino hyperbranched magnetic nanospheres;
(B) and then reacting the amino hyperbranched magnetic nanospheres, the chitosan-coated carbon nanotubes and polylactic acid to obtain the magnetic nano material.
The processing method is melt spinning, and the process conditions of the melt spinning are as follows: the temperature is 175 ℃, the stretch ratio of the spinneret is 3 times, and the heat setting temperature is 55 ℃.
The inner diameter of the hollow tubular structure is 2 mm; the thickness is 0.4 mm.
The preparation method of the hydrophobic block molecule comprises the following steps: mixing 1g of polylactic acid, polyglycolide or polycaprolactone with 1.25g of glycol, heating to 135 ℃ under the condition of 0.55MPa, stirring for 2.5 hours under heat preservation, heating to 155 ℃, stirring for 6 hours under heat preservation, cooling and crushing to obtain the hydrophobic block molecules.
The prepolymer was prepared as follows: firstly, hydrophilic block molecules, hydrophobic block molecules, isocyanate, ethylenediamine and ferric acetylacetonate according to a molar ratio of 1: 0.4: 9: 1.5: 0.006, adding into N, N-dimethylformamide 6 times of the total weight of the two, stirring and reacting at 70 ℃ for 2.5 hours under the protection of nitrogen, and removing the N, N-dimethylformamide to obtain the prepolymer.
The molecular weight of the prepolymer was 800 g/mol.
The prepolymer contained isocyanate functional groups in an amount of 9% by weight.
The isocyanate is p-phenylene diisocyanate.
In the step (A), the preparation method of the amino magnetic nanospheres comprises the following steps: adding 1g of ferric chloride, 3.5g of sodium acetate and 4.5g of hexamethylenediamine into 13g of ethylene glycol, stirring and reacting for 8 hours at 170 ℃, naturally cooling to room temperature, centrifuging, washing and drying to obtain the product.
In the step (A), the preparation method of the amino hyperbranched magnetic nanospheres comprises the following steps: firstly, mixing and stirring 1g of amino magnetic nanospheres, 0.35g of absolute ethyl alcohol and 0.2g of methyl acrylate for 6 hours, then adding 0.2g of ethylenediamine, stirring and reacting for 5 hours at 55 ℃, centrifuging, washing and drying to obtain the amino hyperbranched magnetic nanospheres.
The specific method of step (B) is as follows: firstly, 1g of amino hyperbranched magnetic nanospheres and 0.15g of chitosan-coated carbon nanotubes are added into 6g of chloroform, uniformly dispersed by ultrasonic waves, then 2.4g of polylactic acid is added, stirred and reacted for 28 hours, and the chloroform is removed by reduced pressure distillation, thus obtaining the magnetic nano material.
In the step (B), the chitosan-coated carbon nanotube is prepared by the following method: firstly, adding 0.1g of chitosan into 105g of acetic acid solution with mass concentration of 1%, uniformly stirring and dispersing to obtain chitosan acetic acid solution, then adding 0.015g of carbon nano tube into the chitosan acetic acid solution, uniformly dispersing by ultrasonic waves, adjusting the pH value to be 7.5, dropwise adding glutaraldehyde aqueous solution with mass concentration of 1% while stirring, continuously stirring for 75 minutes after dropwise adding is finished, centrifuging, washing and drying to obtain the chitosan acetic acid solution. The stirring rate was 400 rpm.
Comparative example 1
A method for preparing a bioabsorbable nerve scaffold comprises the steps of taking hydrophilic block molecules, hydrophobic block molecules, prepolymer containing isocyanate functional groups and magnetic nano materials as raw materials, blending and processing the raw materials into a hollow tubular structure to obtain the bioabsorbable nerve scaffold; the hydrophilic block molecules are polyester polyol or polyether polyol, the hydrophobic block molecules are polylactic acid, polyglycolide or polycaprolactone and are obtained by packaging hydroxyl end groups, and the prepolymer is obtained by reacting the hydrophilic block molecules, the hydrophobic block molecules and isocyanate; the magnetic nano material is prepared by the following method:
(A) firstly, ferric chloride, sodium acetate and hexamethylene diamine are taken as raw materials to prepare the amino magnetic nanospheres;
(B) then, the amino magnetic nanospheres, the carbon nanotubes coated by the chitosan and the polylactic acid react to obtain the magnetic nano material.
The processing method is melt extrusion, and the temperature of the melt extrusion is 170 ℃; the treatment time was 40 minutes.
The inner diameter of the hollow tubular structure is 1.5 mm; the thickness is 0.6 mm.
The preparation method of the hydrophobic block molecule comprises the following steps: mixing 1g of polylactic acid, polyglycolide or polycaprolactone with 1.2g of glycol, heating to 130 ℃ under the condition of 0.6MPa, stirring for 3 hours under heat preservation, heating to 150 ℃, stirring for 7 hours under heat preservation, cooling and crushing to obtain the hydrophobic block molecule.
The prepolymer was prepared as follows: firstly, hydrophilic block molecules, hydrophobic block molecules, isocyanate, ethylenediamine and ferric acetylacetonate according to a molar ratio of 1: 0.3: 10: 1: 0.008, adding into N, N-dimethylformamide with 5 times of the total weight of the raw materials, stirring and reacting at 75 ℃ for 2 hours under the protection of nitrogen, and removing the N, N-dimethylformamide to obtain the prepolymer.
The molecular weight of the prepolymer was 1000 g/mol.
The prepolymer contained 3% by weight of isocyanate functional groups.
The isocyanate is diphenylmethane diisocyanate.
In the step (A), the preparation method of the amino magnetic nanospheres comprises the following steps: adding 1g of ferric chloride, 4g of sodium acetate and 4g of hexamethylenediamine into 15g of ethylene glycol, stirring and reacting for 9 hours at 160 ℃, naturally cooling to room temperature, centrifuging, washing and drying to obtain the product.
The specific method of step (B) is as follows: firstly, 1g of amino magnetic nanospheres and 0.1g of chitosan coated carbon nanotubes are added into 7g of chloroform, dispersed uniformly by ultrasonic waves, then 2.2g of polylactic acid is added, stirred and reacted for 30 hours, and the chloroform is removed by reduced pressure distillation, thus obtaining the magnetic nano material.
In the step (B), the chitosan-coated carbon nanotube is prepared by the following method: firstly, 0.1g of chitosan is added into 100g of acetic acid solution with the mass concentration of 1%, the mixture is stirred and dispersed uniformly to obtain chitosan acetic acid solution, then 0.02g of carbon nano tube is added into the chitosan acetic acid solution, the mixture is dispersed uniformly by ultrasonic waves, the pH value is adjusted to be 7, glutaraldehyde aqueous solution with the mass concentration of 1% is dripped while stirring, the mixture is continuously stirred for 80 minutes after the dripping is finished, and the chitosan acetic acid solution is obtained by centrifugation, washing and drying. The stirring rate was 300 rpm.
Comparative example 2
A method for preparing a bioabsorbable nerve scaffold comprises the steps of taking hydrophilic block molecules, hydrophobic block molecules, prepolymer containing isocyanate functional groups and magnetic nano materials as raw materials, blending and processing the raw materials into a hollow tubular structure to obtain the bioabsorbable nerve scaffold; the hydrophilic block molecules are polyester polyol or polyether polyol, the hydrophobic block molecules are polylactic acid, polyglycolide or polycaprolactone and are obtained by packaging hydroxyl end groups, and the prepolymer is obtained by reacting the hydrophilic block molecules, the hydrophobic block molecules and isocyanate; the magnetic nano material is prepared by the following method: firstly, ferric chloride, sodium acetate and hexamethylene diamine are used as raw materials to prepare the amino magnetic nanospheres, and then the amino magnetic nanospheres are mixed with methyl acrylate and hexamethylene diamine for reaction to obtain the magnetic nano material.
The processing method is melt extrusion, and the temperature of the melt extrusion is 170 ℃; the treatment time was 40 minutes.
The inner diameter of the hollow tubular structure is 1.5 mm; the thickness is 0.6 mm.
The preparation method of the hydrophobic block molecule comprises the following steps: mixing 1g of polylactic acid, polyglycolide or polycaprolactone with 1.2g of glycol, heating to 130 ℃ under the condition of 0.6MPa, stirring for 3 hours under heat preservation, heating to 150 ℃, stirring for 7 hours under heat preservation, cooling and crushing to obtain the hydrophobic block molecule.
The prepolymer was prepared as follows: firstly, hydrophilic block molecules, hydrophobic block molecules, isocyanate, ethylenediamine and ferric acetylacetonate according to a molar ratio of 1: 0.3: 10: 1: 0.008, adding into N, N-dimethylformamide with 5 times of the total weight of the raw materials, stirring and reacting at 75 ℃ for 2 hours under the protection of nitrogen, and removing the N, N-dimethylformamide to obtain the prepolymer.
The molecular weight of the prepolymer was 1000 g/mol.
The prepolymer contained 3% by weight of isocyanate functional groups.
The isocyanate is diphenylmethane diisocyanate.
In the step (A), the preparation method of the amino magnetic nanospheres comprises the following steps: adding 1g of ferric chloride, 4g of sodium acetate and 4g of hexamethylenediamine into 15g of ethylene glycol, stirring and reacting for 9 hours at 160 ℃, naturally cooling to room temperature, centrifuging, washing and drying to obtain the product.
In the step (A), the preparation method of the magnetic nano material comprises the following steps: firstly, 1g of amino magnetic nanosphere, 0.3g of absolute ethyl alcohol and 0.25g of methyl acrylate are mixed and stirred for 5 hours, then 0.25g of ethylenediamine is added, the mixture is stirred and reacted for 6 hours at the temperature of 50 ℃, and the mixture is centrifuged, washed and dried to obtain the amino magnetic nanosphere.
Comparative example 3
A method for preparing a bioabsorbable nerve scaffold comprises the steps of taking hydrophilic block molecules, hydrophobic block molecules, prepolymer containing isocyanate functional groups and magnetic nano materials as raw materials, blending and processing the raw materials into a hollow tubular structure to obtain the bioabsorbable nerve scaffold; the hydrophilic block molecules are polyester polyol or polyether polyol, the hydrophobic block molecules are polylactic acid, polyglycolide or polycaprolactone which are packaged by hydroxyl end groups, and the prepolymer is obtained by reacting the hydrophilic block molecules, the hydrophobic block molecules and isocyanate; the magnetic nano material is prepared by the following method:
(A) firstly, ferric chloride, sodium acetate and hexamethylene diamine are used as raw materials to prepare amino magnetic nanospheres, and then the amino magnetic nanospheres are mixed with methyl acrylate and hexamethylene diamine for reaction to obtain amino hyperbranched magnetic nanospheres;
(B) and then reacting the amino hyperbranched magnetic nanospheres with polylactic acid to obtain the magnetic nano material.
The processing method is melt extrusion, and the temperature of the melt extrusion is 170 ℃; the treatment time was 40 minutes.
The inner diameter of the hollow tubular structure is 1.5 mm; the thickness is 0.6 mm.
The preparation method of the hydrophobic block molecule comprises the following steps: mixing 1g of polylactic acid, polyglycolide or polycaprolactone with 1.2g of glycol, heating to 130 ℃ under the condition of 0.6MPa, stirring for 3 hours under heat preservation, heating to 150 ℃, stirring for 7 hours under heat preservation, cooling and crushing to obtain the hydrophobic block molecule.
The prepolymer was prepared as follows: firstly, hydrophilic block molecules, hydrophobic block molecules, isocyanate, ethylenediamine and ferric acetylacetonate according to a molar ratio of 1: 0.3: 10: 1: 0.008, adding into N, N-dimethylformamide with 5 times of the total weight of the raw materials, stirring and reacting at 75 ℃ for 2 hours under the protection of nitrogen, and removing the N, N-dimethylformamide to obtain the prepolymer.
The molecular weight of the prepolymer was 1000 g/mol.
The prepolymer contained 3% by weight of isocyanate functional groups.
The isocyanate is diphenylmethane diisocyanate.
In the step (A), the preparation method of the amino magnetic nanospheres comprises the following steps: adding 1g of ferric chloride, 4g of sodium acetate and 4g of hexamethylenediamine into 15g of ethylene glycol, stirring and reacting for 9 hours at 160 ℃, naturally cooling to room temperature, centrifuging, washing and drying to obtain the product.
In the step (A), the preparation method of the amino hyperbranched magnetic nanospheres comprises the following steps: firstly, mixing and stirring 1g of amino magnetic nanospheres, 0.3g of absolute ethyl alcohol and 0.25g of methyl acrylate for 5 hours, then adding 0.25g of ethylenediamine, stirring and reacting for 6 hours at 50 ℃, centrifuging, washing and drying to obtain the amino hyperbranched magnetic nanospheres.
The specific method of step (B) is as follows: firstly, 1g of amino hyperbranched magnetic nanospheres are added into 7g of chloroform, the mixture is uniformly dispersed by ultrasonic waves, then 2.2g of polylactic acid is added, the mixture is stirred and reacts for 30 hours, and the chloroform is removed by reduced pressure distillation, so that the magnetic nano material is obtained.
Comparative example 4
A method for preparing a bioabsorbable nerve scaffold comprises the steps of taking hydrophilic block molecules, hydrophobic block molecules, prepolymer containing isocyanate functional groups and magnetic nano materials as raw materials, blending and processing the raw materials into a hollow tubular structure to obtain the bioabsorbable nerve scaffold; the hydrophilic block molecules are polyester polyol or polyether polyol, the hydrophobic block molecules are polylactic acid, polyglycolide or polycaprolactone and are obtained by packaging hydroxyl end groups, and the prepolymer is obtained by reacting the hydrophilic block molecules, the hydrophobic block molecules and isocyanate; the magnetic nano material is prepared by the following method:
(A) firstly, ferric chloride, sodium acetate and hexamethylene diamine are used as raw materials to prepare amino magnetic nanospheres, and then the amino magnetic nanospheres are mixed with methyl acrylate and hexamethylene diamine for reaction to obtain amino hyperbranched magnetic nanospheres;
(B) and then mixing the amino hyperbranched magnetic nanospheres and the chitosan-coated carbon nanotubes to obtain the magnetic nano material.
The processing method is melt extrusion, and the temperature of the melt extrusion is 170 ℃; the treatment time was 40 minutes.
The inner diameter of the hollow tubular structure is 1.5 mm; the thickness is 0.6 mm.
The preparation method of the hydrophobic block molecule comprises the following steps: mixing 1g of polylactic acid, polyglycolide or polycaprolactone with 1.2g of glycol, heating to 130 ℃ under the condition of 0.6MPa, stirring for 3 hours under heat preservation, heating to 150 ℃, stirring for 7 hours under heat preservation, cooling and crushing to obtain the hydrophobic block molecule.
The prepolymer was prepared as follows: firstly, hydrophilic block molecules, hydrophobic block molecules, isocyanate, ethylenediamine and ferric acetylacetonate according to a molar ratio of 1: 0.3: 10: 1: 0.008, adding into N, N-dimethylformamide with 5 times of the total weight of the raw materials, stirring and reacting at 75 ℃ for 2 hours under the protection of nitrogen, and removing the N, N-dimethylformamide to obtain the prepolymer.
The molecular weight of the prepolymer was 1000 g/mol.
The prepolymer contained 3% by weight of isocyanate functional groups.
The isocyanate is diphenylmethane diisocyanate.
In the step (A), the preparation method of the amino magnetic nanospheres comprises the following steps: adding 1g of ferric chloride, 4g of sodium acetate and 4g of hexamethylenediamine into 15g of ethylene glycol, stirring and reacting for 9 hours at 160 ℃, naturally cooling to room temperature, centrifuging, washing and drying to obtain the product.
In the step (A), the preparation method of the amino hyperbranched magnetic nanospheres comprises the following steps: firstly, 1g of amino magnetic nanosphere, 0.3g of absolute ethyl alcohol and 0.25g of methyl acrylate are mixed and stirred for 5 hours, then 0.25g of ethylenediamine is added, stirring reaction is carried out for 6 hours at 50 ℃, centrifugation, washing and drying are carried out, and the amino hyperbranched magnetic nanosphere is obtained.
The specific method of step (B) is as follows: adding 1g of amino hyperbranched magnetic nanospheres and 0.1g of chitosan-coated carbon nanotubes into 7g of chloroform, uniformly dispersing by ultrasonic waves, and removing the chloroform by reduced pressure distillation to obtain the magnetic nanomaterial.
Comparative example 5
A method for preparing a bioabsorbable nerve scaffold comprises the steps of taking hydrophilic block molecules, hydrophobic block molecules and prepolymers containing isocyanate functional groups as raw materials, blending and processing the raw materials into a hollow tubular structure; the hydrophilic block molecules are polyester polyol or polyether polyol, the hydrophobic block molecules are polylactic acid, polyglycolide or polycaprolactone which are packaged by hydroxyl end groups, and the prepolymer is obtained by reacting the hydrophilic block molecules, the hydrophobic block molecules and isocyanate.
The processing method is melt extrusion, and the temperature of the melt extrusion is 170 ℃; the treatment time was 40 minutes.
The inner diameter of the hollow tubular structure is 1.5 mm; the thickness is 0.6 mm.
The preparation method of the hydrophobic block molecule comprises the following steps: mixing 1g of polylactic acid, polyglycolide or polycaprolactone with 1.2g of glycol, heating to 130 ℃ under the condition of 0.6MPa, stirring for 3 hours under heat preservation, heating to 150 ℃, stirring for 7 hours under heat preservation, cooling and crushing to obtain the hydrophobic block molecule.
The prepolymer was prepared as follows: firstly, mixing a hydrophilic block molecule, a hydrophobic block molecule, isocyanate, ethylenediamine and iron acetylacetonate according to a molar ratio of 1: 0.3: 10: 1: 0.008, adding into N, N-dimethylformamide with 5 times of the total weight of the raw materials, stirring and reacting at 75 ℃ for 2 hours under the protection of nitrogen, and removing the N, N-dimethylformamide to obtain the prepolymer.
The molecular weight of the prepolymer was 1000 g/mol.
The prepolymer contained 3% by weight of isocyanate functional groups.
The isocyanate is diphenylmethane diisocyanate.
The nerve scaffolds obtained in examples 1 to 3 and comparative examples 1 to 5 were subjected to a performance test.
1. Mechanical properties:
the mechanical property test method comprises the following steps: the tensile strength was measured by a universal tester, and the elongation at a loading strength of 0.5kg/cm was measured. The test results are shown in Table 2.
TABLE 2 mechanical Property test results
Tensile Strength (MPa) Elongation (%)
Example 1 8.45 530.1
Example 2 8.28 519.3
Example 3 8.34 535.7
Comparative example 1 7.52 440.3
Comparative example 2 7.03 319.1
Comparative example 3 7.08 338.5
Comparative example 4 7.15 422.4
Comparative example 5 6.02 220.3
As is clear from Table 2, the neural scaffolds obtained in examples 1 to 3 have high tensile strength, high elongation and excellent mechanical properties.
Comparative example 1 replaces the amino hyperbranched magnetic nanospheres with the amino magnetic nanospheres, comparative example 2 replaces the magnetic nanomaterials with the amino hyperbranched magnetic nanospheres, comparative example 3 omits the chitosan-coated carbon nanotubes when preparing the magnetic nanomaterials, comparative example 4 omits polylactic acid when preparing the magnetic nanomaterials, and comparative example 5 omits the magnetic nanomaterials, so that the mechanical properties of the obtained nerve scaffold are obviously poor, and the surface modification and the compounding with the carbon nanotubes of the magnetic nanomaterials are synergistic to achieve the enhancement effect and improve the mechanical properties of the product.
3. Nerve repair effect
10 newborn SD rats (1-2 days, purchased from Nanjing Junceae bioengineering Co., Ltd.) were subjected to sciatic nerve isolation, nerve tissue cutting, digestion and centrifugation, and then subjected to differential adherence method for purification and culture of Schwann cells. And carrying out fluorescent double-staining identification on S-100 and DAPI immune cells of the Schwann cells of the third generation to determine that the concentration of the seed cells is 99%. Then the disinfected nerve scaffold is cut into a cylinder with the length of 5mm and the diameter of 2mm, the cylinder is put into a 96-well plate, and the seed cells are arranged according to the proportion of 1 multiplied by 10 5 Density per well in combination with nerve scaffold. After 24 hours, the cells were subjected to pulsed electromagnetic field (0.1mT, 50Hz) for 24 hours for cell proliferation and adhesion. The results are shown in Table 3.
TABLE 3 examination of nerve repair Effect
Proliferation Rate (%) Adhesion Rate (%)
Example 1 96.9 99.3
Example 2 95.8 98.5
Example 3 97.3 99.2
Comparative example 1 87.3 92.1
Comparative example 2 84.9 90.1
Comparative example 3 89.5 93.6
Comparative example 4 90.1 91.1
Comparative example 5 80.7 82.5
As can be seen from Table 3, the neural scaffolds obtained in examples 1 to 3 can significantly promote nerve regeneration and have good nerve repair effects.
Comparative example 1 replaces the amino hyperbranched magnetic nanospheres with the amino magnetic nanospheres, comparative example 2 replaces the magnetic nanomaterials with the amino hyperbranched magnetic nanospheres, comparative example 3 omits the chitosan-coated carbon nanotubes when preparing the magnetic nanomaterials, comparative example 4 omits the polylactic acid when preparing the magnetic nanomaterials, and comparative example 5 omits the magnetic nanomaterials, and the nerve repair effect of the obtained nerve scaffold is obviously poor, which indicates that the specific composition of the magnetic materials synergistically promotes nerve regeneration, thereby improving the nerve repair effect.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
Furthermore, it should be understood that although the present description refers to embodiments, not every embodiment may contain only a single embodiment, and such description is for clarity only, and those skilled in the art should integrate the description, and the embodiments may be combined as appropriate to form other embodiments understood by those skilled in the art.

Claims (10)

1. A method for preparing a bioabsorbable nerve scaffold is characterized in that hydrophilic block molecules, hydrophobic block molecules, prepolymers containing isocyanate functional groups and magnetic nano materials are used as raw materials and are blended to prepare a hollow tubular structure; the hydrophilic block molecules are polyester polyol or polyether polyol, the hydrophobic block molecules are polylactic acid, polyglycolide or polycaprolactone and are obtained by packaging hydroxyl end groups, and the prepolymer is obtained by reacting the hydrophilic block molecules, the hydrophobic block molecules and isocyanate; the magnetic nano material is prepared by the following method:
(A) preparing amino magnetic nanospheres from ferric chloride, sodium acetate and hexamethylene diamine as raw materials, and then mixing and reacting the amino magnetic nanospheres with methyl acrylate and hexamethylene diamine to obtain amino hyperbranched magnetic nanospheres;
(B) and (2) reacting the amino hyperbranched magnetic nanospheres prepared in the step (1), the chitosan-coated carbon nanotubes and polylactic acid to obtain the magnetic nanomaterial.
2. The method of manufacturing according to claim 1, wherein the method of manufacturing the hollow tubular structure is any one selected from melt extrusion, 3D printing, or melt spinning.
3. The method according to claim 1, wherein the hollow tubular structure has an inner diameter of 1 to 5mm, preferably 1.5 to 3 mm; the thickness is 0.2 to 1mm, and more preferably 0.3 to 0.6 mm.
4. The method according to claim 1, wherein the hydrophobic block molecule is prepared by the following method in parts by weight: mixing 1 part of polylactic acid, polyglycolide or polycaprolactone with 1.2-1.3 parts of glycol, heating to 130-140 ℃ under the condition of 0.5-0.6 MPa, stirring for 2-3 hours under heat preservation, heating to 150-160 ℃, stirring for 5-7 hours under heat preservation, cooling and crushing to obtain the hydrophobic block molecule.
5. The method according to claim 1, wherein the prepolymer is prepared by the following method in parts by weight: firstly, hydrophilic block molecules, hydrophobic block molecules, isocyanate, ethylenediamine and ferric acetylacetonate according to a molar ratio of 1: 0.3-0.5: 8-10: 1-2: 0.005-0.008, adding the mixture into N, N-dimethylformamide which is 5-7 times of the total weight of the mixture, stirring and reacting for 2-3 hours at 65-75 ℃ under the protection of nitrogen, and removing the N, N-dimethylformamide to obtain the prepolymer.
6. The method according to claim 1, wherein the prepolymer has a molecular weight of 100 to 5000g/mol, more preferably 200 to 2000g/mol, and still more preferably 300 to 1000 g/mol.
7. The process according to claim 1, wherein the prepolymer contains 1 to 20% by weight of isocyanate functional groups, more preferably 3 to 12% by weight.
8. The method according to claim 1, wherein the isocyanate is any one selected from the group consisting of diphenylmethane diisocyanate, 2, 4-tolylene diisocyanate, p-phenylene diisocyanate, and hexamethylene diisocyanate.
9. The method according to claim 1, wherein the amino-magnetic nanospheres are prepared in step (a) by the following method in parts by weight: adding 1 part of ferric chloride, 3-4 parts of sodium acetate and 4-5 parts of hexamethylenediamine into 12-15 parts of ethylene glycol, stirring and reacting for 7-9 hours at 160-180 ℃, naturally cooling to room temperature, centrifuging, washing and drying to obtain the product.
10. A bioabsorbable neural scaffold prepared by the method of any one of claims 1 to 9.
CN202210739148.1A 2022-06-28 2022-06-28 Bioabsorbable nerve scaffold and preparation method thereof Active CN114957588B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202210739148.1A CN114957588B (en) 2022-06-28 2022-06-28 Bioabsorbable nerve scaffold and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210739148.1A CN114957588B (en) 2022-06-28 2022-06-28 Bioabsorbable nerve scaffold and preparation method thereof

Publications (2)

Publication Number Publication Date
CN114957588A true CN114957588A (en) 2022-08-30
CN114957588B CN114957588B (en) 2023-10-24

Family

ID=82966346

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210739148.1A Active CN114957588B (en) 2022-06-28 2022-06-28 Bioabsorbable nerve scaffold and preparation method thereof

Country Status (1)

Country Link
CN (1) CN114957588B (en)

Citations (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995003356A1 (en) * 1993-07-23 1995-02-02 Massachusetts Institute Of Technology Nanoparticles and microparticles of non-linear hydrophilic-hydrophobic multiblock copolymers
CN102977319A (en) * 2012-12-17 2013-03-20 中国科学院长春应用化学研究所 Degradable polylactic acid diblock copolymer, preparation method and application to modified polylactic acid
US20130344159A1 (en) * 2011-03-09 2013-12-26 Occlugel Implantable swellable bio-resorbable polymer
CN103897133A (en) * 2012-12-27 2014-07-02 深圳先进技术研究院 Polyurethane material and preparation method thereof
CN104744661A (en) * 2015-03-03 2015-07-01 宁波市医疗中心李惠利医院 Hydrophilic degradable segmented polyurethane as well as preparation method and application thereof
KR20160031682A (en) * 2014-09-12 2016-03-23 단국대학교 천안캠퍼스 산학협력단 Method for preparing magnetic scaffold including nanoparticle with functionalized surface for bone regeneration and a magnetic scaffold obtained thereby
CN105693969A (en) * 2016-02-24 2016-06-22 佳化化学科技发展（上海）有限公司 Polyether composition and polyurethane elastomer prepared from same
CN106336496A (en) * 2016-08-25 2017-01-18 中国电子科技集团公司第四十六研究所 Modified polylactic acid material for 3D printing, and preparation method thereof
CN106935882A (en) * 2017-04-14 2017-07-07 湖北工程学院 A kind of compound proton exchange membrane and preparation method thereof
CN107213879A (en) * 2017-06-05 2017-09-29 西安交通大学 Hyperbranched chlorogenic acid molecular engram magnetic nano-balls of a kind of amino and its preparation method and application
CN108976370A (en) * 2018-06-27 2018-12-11 滁州环球聚氨酯科技有限公司 A kind of hydrophobic fire-retardant method for preparing polyurethane elastic body
CN109627413A (en) * 2018-12-07 2019-04-16 上海应用技术大学 A kind of high abrasion polyurethane material and preparation method thereof
CN110078884A (en) * 2019-04-19 2019-08-02 广东大盈新材料科技有限公司 A kind of inorganic nano material modified polyurethane resin and preparation method thereof
CN110354314A (en) * 2019-07-30 2019-10-22 东南大学 A kind of magnetic enhancement is mutually modified medical composite material bone repairing support and manufacturing method
CN110354313A (en) * 2019-07-30 2019-10-22 东南大学 A kind of magnetic enhancement phase modified composite material and preparation method thereof
CN110527065A (en) * 2019-08-12 2019-12-03 黎明化工研究设计院有限责任公司 A kind of high performance polyurethane damping material and its one-step preppn process
CN110801536A (en) * 2018-07-18 2020-02-18 中南大学 Organic-coated magnetic nanoparticle composite bone scaffold and preparation method thereof
CN111378262A (en) * 2020-04-16 2020-07-07 孝感市易生新材料有限公司 Polylactic acid-based thermoplastic polyurethane modified polylactic acid composite material, preparation method thereof and application thereof in 3D printing consumables
CN111393834A (en) * 2020-04-21 2020-07-10 东莞市雄林新材料科技股份有限公司 TPU (thermoplastic polyurethane) -based biomedical 3D printing material and preparation method thereof
CN113861641A (en) * 2021-09-29 2021-12-31 合肥工业大学 Sulfonic acid ionic liquid element-containing polyurethane modified carbon nanotube/PLA/PBAT composite material
CN113968954A (en) * 2021-12-13 2022-01-25 福建汇得新材料有限公司 Degradable thermoplastic polyurethane elastomer and preparation method and application thereof

Patent Citations (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995003356A1 (en) * 1993-07-23 1995-02-02 Massachusetts Institute Of Technology Nanoparticles and microparticles of non-linear hydrophilic-hydrophobic multiblock copolymers
US20130344159A1 (en) * 2011-03-09 2013-12-26 Occlugel Implantable swellable bio-resorbable polymer
CN102977319A (en) * 2012-12-17 2013-03-20 中国科学院长春应用化学研究所 Degradable polylactic acid diblock copolymer, preparation method and application to modified polylactic acid
CN103897133A (en) * 2012-12-27 2014-07-02 深圳先进技术研究院 Polyurethane material and preparation method thereof
KR20160031682A (en) * 2014-09-12 2016-03-23 단국대학교 천안캠퍼스 산학협력단 Method for preparing magnetic scaffold including nanoparticle with functionalized surface for bone regeneration and a magnetic scaffold obtained thereby
CN104744661A (en) * 2015-03-03 2015-07-01 宁波市医疗中心李惠利医院 Hydrophilic degradable segmented polyurethane as well as preparation method and application thereof
CN105693969A (en) * 2016-02-24 2016-06-22 佳化化学科技发展（上海）有限公司 Polyether composition and polyurethane elastomer prepared from same
CN106336496A (en) * 2016-08-25 2017-01-18 中国电子科技集团公司第四十六研究所 Modified polylactic acid material for 3D printing, and preparation method thereof
CN106935882A (en) * 2017-04-14 2017-07-07 湖北工程学院 A kind of compound proton exchange membrane and preparation method thereof
CN107213879A (en) * 2017-06-05 2017-09-29 西安交通大学 Hyperbranched chlorogenic acid molecular engram magnetic nano-balls of a kind of amino and its preparation method and application
CN108976370A (en) * 2018-06-27 2018-12-11 滁州环球聚氨酯科技有限公司 A kind of hydrophobic fire-retardant method for preparing polyurethane elastic body
CN110801536A (en) * 2018-07-18 2020-02-18 中南大学 Organic-coated magnetic nanoparticle composite bone scaffold and preparation method thereof
CN109627413A (en) * 2018-12-07 2019-04-16 上海应用技术大学 A kind of high abrasion polyurethane material and preparation method thereof
CN110078884A (en) * 2019-04-19 2019-08-02 广东大盈新材料科技有限公司 A kind of inorganic nano material modified polyurethane resin and preparation method thereof
CN110354314A (en) * 2019-07-30 2019-10-22 东南大学 A kind of magnetic enhancement is mutually modified medical composite material bone repairing support and manufacturing method
CN110354313A (en) * 2019-07-30 2019-10-22 东南大学 A kind of magnetic enhancement phase modified composite material and preparation method thereof
CN110527065A (en) * 2019-08-12 2019-12-03 黎明化工研究设计院有限责任公司 A kind of high performance polyurethane damping material and its one-step preppn process
CN111378262A (en) * 2020-04-16 2020-07-07 孝感市易生新材料有限公司 Polylactic acid-based thermoplastic polyurethane modified polylactic acid composite material, preparation method thereof and application thereof in 3D printing consumables
CN111393834A (en) * 2020-04-21 2020-07-10 东莞市雄林新材料科技股份有限公司 TPU (thermoplastic polyurethane) -based biomedical 3D printing material and preparation method thereof
CN113861641A (en) * 2021-09-29 2021-12-31 合肥工业大学 Sulfonic acid ionic liquid element-containing polyurethane modified carbon nanotube/PLA/PBAT composite material
CN113968954A (en) * 2021-12-13 2022-01-25 福建汇得新材料有限公司 Degradable thermoplastic polyurethane elastomer and preparation method and application thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
罗锋;李洁华;谭鸿;傅强;: "生物可降解医用聚氨酯及其应用", 高分子通报, no. 10, pages 132 - 142 *

Also Published As

Publication number Publication date
CN114957588B (en) 2023-10-24

Similar Documents

Publication Publication Date Title
Amiryaghoubi et al. Injectable thermosensitive hybrid hydrogel containing graphene oxide and chitosan as dental pulp stem cells scaffold for bone tissue engineering
AU773826B2 (en) Hyaluronic acid gel composition, process for producing the same, and medical material containing the same
JP4704506B2 (en) Organic-inorganic composite hydrogel and method for producing the same
CN114272433A (en) Gelatin-based biomedical adhesive and preparation method thereof
KR101604584B1 (en) Composite comprising hydroxyapatite, chitosan or its derivative, and catechol or its derivative and use thereof
CN110585485A (en) Novel bamboo fiber/hydroxyapatite/chitosan composite membrane and preparation method thereof
CN110152055A (en) The functional drug that alginic acid amination derivative/bacteria cellulose nanocomposite gel is constructed is sustained medical dressing
CN114262455B (en) Starch/epsilon-polylysine/poly (L-lactic acid) double-crosslinking material and preparation method and application thereof
AU767426B2 (en) A film for medical use, consisting of linear block polymers of polyurethane and a method for the production of such film
CN114957588B (en) Bioabsorbable nerve scaffold and preparation method thereof
CN109851744B (en) Degradable polyurethane biomaterial and preparation method and application thereof
KR102046263B1 (en) Process Of Producing Regenerated Protain Fiber Having Excellent Water-fastness
JP5684111B2 (en) Thermoplastic paste for repairing living tissue
CN107375999A (en) A kind of lipid-loweringing sterilization suture and preparation method thereof
CN115501390B (en) Skin beautifying compound injection and preparation method thereof
JP2009513290A (en) Scleral buckling band and manufacturing method thereof
CN110755683B (en) Silicon-based elastic nanofiber bone repair material and preparation method and application thereof
CN112662152B (en) Polylactic acid-based degradable composite material, preparation method and application of polylactic acid-based degradable composite material as mulching film
CN111172623B (en) Biodegradable fiber and preparation method thereof
CN115252909B (en) Medical degradable composite material and preparation method thereof
KR20130134447A (en) New nanofiber membrane and manufacturing method thereof
CN115109274A (en) Natural polysaccharide hydrogel and preparation method and application thereof
KR20210061130A (en) Method for preparing collagen mat and collagen mat prepared therefrom
CN112794998A (en) Polycaprolactone implant material and preparation method thereof, fiber, patch and preparation method thereof
CN115634314B (en) Unsupported bone repair gel microsphere and preparation method thereof

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
GR01 Patent grant
GR01 Patent grant