CN117797324A - Plastic filling bracket for cartilage repair and preparation method thereof - Google Patents
Plastic filling bracket for cartilage repair and preparation method thereof Download PDFInfo
- Publication number
- CN117797324A CN117797324A CN202211211915.8A CN202211211915A CN117797324A CN 117797324 A CN117797324 A CN 117797324A CN 202211211915 A CN202211211915 A CN 202211211915A CN 117797324 A CN117797324 A CN 117797324A
- Authority
- CN
- China
- Prior art keywords
- repair layer
- subchondral bone
- bone repair
- layer
- cartilage
- 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
- 230000008439 repair process Effects 0.000 title claims abstract description 240
- 210000000845 cartilage Anatomy 0.000 title claims abstract description 119
- 238000011049 filling Methods 0.000 title claims abstract description 20
- 229920003023 plastic Polymers 0.000 title abstract description 11
- 239000004033 plastic Substances 0.000 title abstract description 11
- 238000002360 preparation method Methods 0.000 title abstract description 10
- 210000005065 subchondral bone plate Anatomy 0.000 claims abstract description 135
- 239000011148 porous material Substances 0.000 claims abstract description 30
- 239000000835 fiber Substances 0.000 claims abstract description 28
- 238000004108 freeze drying Methods 0.000 claims abstract description 26
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims abstract description 20
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 20
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 20
- 235000015097 nutrients Nutrition 0.000 claims abstract description 15
- 229920006237 degradable polymer Polymers 0.000 claims abstract description 13
- 239000002861 polymer material Substances 0.000 claims abstract description 11
- 230000000717 retained effect Effects 0.000 claims abstract description 3
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 35
- 239000004626 polylactic acid Substances 0.000 claims description 35
- 229920001610 polycaprolactone Polymers 0.000 claims description 30
- 239000004632 polycaprolactone Substances 0.000 claims description 30
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 20
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 238000010521 absorption reaction Methods 0.000 claims description 16
- 238000010146 3D printing Methods 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 11
- 241001465754 Metazoa Species 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 8
- 230000006835 compression Effects 0.000 claims description 7
- 238000007906 compression Methods 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 102000008186 Collagen Human genes 0.000 claims description 6
- 108010035532 Collagen Proteins 0.000 claims description 6
- 230000005540 biological transmission Effects 0.000 claims description 6
- 229920001436 collagen Polymers 0.000 claims description 6
- 238000010041 electrostatic spinning Methods 0.000 claims description 6
- 230000001413 cellular effect Effects 0.000 claims description 5
- 230000009286 beneficial effect Effects 0.000 claims description 4
- 238000001523 electrospinning Methods 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 6
- 230000002349 favourable effect Effects 0.000 abstract description 2
- 239000000499 gel Substances 0.000 description 33
- 239000000243 solution Substances 0.000 description 31
- 230000015556 catabolic process Effects 0.000 description 14
- 238000006731 degradation reaction Methods 0.000 description 14
- 210000000988 bone and bone Anatomy 0.000 description 12
- 230000007547 defect Effects 0.000 description 12
- 210000001612 chondrocyte Anatomy 0.000 description 8
- 235000016709 nutrition Nutrition 0.000 description 7
- 230000035764 nutrition Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 206010007710 Cartilage injury Diseases 0.000 description 6
- 239000012634 fragment Substances 0.000 description 5
- 239000002510 pyrogen Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 108091005804 Peptidases Proteins 0.000 description 4
- 239000004365 Protease Substances 0.000 description 4
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 4
- 210000001188 articular cartilage Anatomy 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 4
- 238000002386 leaching Methods 0.000 description 4
- 238000002054 transplantation Methods 0.000 description 4
- 241000283977 Oryctolagus Species 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000007639 printing Methods 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 239000012085 test solution Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000036760 body temperature Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 230000003848 cartilage regeneration Effects 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000000593 degrading effect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000000968 fibrocartilage Anatomy 0.000 description 2
- 229940015043 glyoxal Drugs 0.000 description 2
- 210000003035 hyaline cartilage Anatomy 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- 229920002749 Bacterial cellulose Polymers 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 210000001361 achilles tendon Anatomy 0.000 description 1
- 239000002390 adhesive tape Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 239000005016 bacterial cellulose Substances 0.000 description 1
- 239000003462 bioceramic Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 238000001804 debridement Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000005553 drilling Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000002121 nanofiber Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000004537 potential cytotoxicity Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000011046 pyrogen test Methods 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- 238000004626 scanning electron microscopy Methods 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000009966 trimming Methods 0.000 description 1
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61L27/20—Polysaccharides
-
- 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
- A61L27/12—Phosphorus-containing materials, e.g. apatite
-
- 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
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
-
- 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
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- 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
- A61L27/56—Porous materials, e.g. foams or sponges
-
- 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
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/23—Carbohydrates
- A61L2300/236—Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
-
- 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
- A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Dermatology (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Dispersion Chemistry (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Prostheses (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention discloses a plastic filling bracket for cartilage repair and a preparation method thereof, wherein the bracket comprises the following components: the cartilage repair layer is of a honeycomb porous structure formed by stacking degradable polymer fibers, the cartilage repair layer is freeze-dried sponge, a gel layer is formed by pouring a gel solution onto the cartilage repair layer, and the gel layer is formed by freeze-drying, wherein the gel solution contains hyaluronic acid and degradable high polymer material nano short fibers; the gel solution is partially filled into pores of a porous structure of the subchondral bone repair layer, and is retained in the pores after freeze drying, so that the subchondral bone repair layer and the subchondral bone repair layer are interconnected, a channel which is favorable for conveying nutrient substances from the subchondral bone repair layer to the subchondral bone repair layer is formed in the repair process, and sufficient supporting strength can be formed to avoid deformation of the subchondral bone repair layer.
Description
Technical Field
The invention relates to a cartilage injury repair material, in particular to a plastic filling bracket for cartilage repair and a preparation method thereof.
Background
Articular cartilage, also called hyaline cartilage, is a dense connective tissue, and plays an important role in absorbing impact force of bones on joint surfaces, reducing friction force between bones, and the like. However, problems such as excessive exercise, aging, excessive obesity, etc. in daily life of people easily cause cartilage damage. Since there are no blood vessels, lymph and nervous systems in the articular cartilage, only a single kind of cells, namely chondrocytes, the growth environment of the chondrocytes is limited, so that the cartilage is difficult to repair by itself after being damaged, even if the cartilage is damaged slightly, progressive degeneration can occur, arthritis is developed, and great pain is caused to patients. Thus, the treatment of cartilage damage is currently a major challenge.
The early repair of articular cartilage is mostly realized by adopting joint debridement, and the method is to resect damaged articular cartilage tissue under an arthroscope, remove worn fragments, relieve pain of patients caused by cartilage defect, but have no effect of repairing cartilage in histology. With the development of tissue engineering, autologous chondrocyte transplantation, bone marrow stimulation, cartilage transplantation, etc. have appeared as cartilage injury repair means. Autologous chondrocyte transplantation treatment refers to a method of taking out normal cartilage tissue from an autologous secondary part of a patient to culture in vitro, multiplying to obtain a sufficient number of chondrocytes, and transplanting the chondrocytes to a cartilage defect site, wherein the cultured new chondrocyte state is similar to the natural cartilage state, but secondary operation is required and the supply area is limited. Bone marrow stimulation refers to a method for drilling holes in bones to bleed the bottom of cartilage defects, stimulating fibrocartilage formation and helping cartilage healing, and the newly generated cartilage at cartilage injuries is fibrocartilage, so that the mechanical properties of hyaline cartilage are difficult to achieve. Cartilage transplantation is limited by the problems of insufficient autologous donor, rejection of foreign bodies and the like.
Based on the problems, a plurality of degradable cartilage repair stent materials are sequentially formed by adding components such as gelatin, bacterial cellulose, modified chitosan, stem cells, growth factors and the like, and play a certain role in cartilage repair, but the materials are fast in degradation speed, short in nutrition supply time, and the cartilage cannot provide nutrition, so that the repair effect is not similar; on the other hand, the defects of the cartilage are usually accompanied with the defects of the subchondral bone, and the defects have different shapes, so that the existing repairing material has slow repairing and insufficient supporting strength on the subchondral bone, and can not meet the personalized difference requirements.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides a plastic filling bracket for cartilage repair and a preparation method thereof, so as to improve the nutrition conveying problem in the cartilage repair process.
In a first aspect of the present invention, the present invention provides a plastically-filled scaffold for cartilage repair comprising:
a subchondral bone repair layer having a cellular porous structure formed by stacking degradable polymer fibers;
the cartilage repair layer is freeze-dried sponge, is formed by pouring a gel solution onto the subchondral bone repair layer and freeze-drying, and the gel solution contains hyaluronic acid and degradable high polymer material nano short fibers;
the gel solution is partially filled into the pores of the porous structure of the subchondral bone repair layer, and is retained in the pores after freeze drying, so that the subchondral bone repair layer and the subchondral bone repair layer are interconnected, and a channel which is beneficial to the transmission of nutrients from the subchondral bone repair layer to the subchondral bone repair layer is formed in the repair process.
In some embodiments of the invention, the degradable polymer in the subchondral bone repair layer comprises a polycaprolactone-polylactic acid copolymer.
In some embodiments of the invention, the subchondral bone repair layer is prepared by 3D printing, and the receiving medium for the 3D printing is a hydrochloric acid solution of hydroxyapatite, so that the subchondral bone repair layer forms a rough surface modified by the hydroxyapatite.
In some embodiments of the invention, the porosity of the porous structure of the subchondral bone repair layer is interpenetrating with the porosity of the subchondral bone repair layer formed by lyophilization, the subchondral bone repair layer having a pore size of 50-100 μm and the cartilage repair layer having a pore size of 100-500 μm.
In some embodiments of the invention, the subchondral bone repair layer has a modulus of elasticity in compression of greater than 52Mpa.
In some embodiments of the invention, the degradable polymer material nano short fiber is formed by crushing a combination of animal collagen and polycaprolactone after forming a film by an electrostatic spinning process.
In some embodiments of the invention, the water absorption capacity of the cartilage repair layer is 14-16 and the water absorption capacity of the subchondral bone repair layer is 5-6.
In some embodiments of the invention, the subchondral bone repair layer has a tapered structure at a surface facing away from the cartilage repair layer.
In some embodiments of the invention, the polycaprolactone-polylactic acid copolymer has a molar ratio of polycaprolactone to polylactic acid of 45:55 to 70:30.
In another aspect, the present invention also provides a method of preparing a filled scaffold for repairing cartilage damage, the method comprising the steps of:
forming a subchondral bone repair layer comprising: preparing polycaprolactone/polylactic acid copolymer fibers by 3D printing, and stacking the fibers layer by layer to form a subchondral bone repair layer with a honeycomb porous structure;
forming a cartilage repair layer comprising: placing the formed subchondral bone repair layer in a freeze drying mould, pouring a gel solution containing hyaluronic acid and degradable high polymer material nanometer short fibers into the freeze drying mould, forming a gel layer on the subchondral bone repair layer, filling the gel solution into the porous structure of the subchondral bone repair layer, and then freeze drying to obtain the filling bracket.
In some embodiments of the invention, the receiving medium for 3D printing is a hydrochloric acid solution of hydroxyapatite, such that the subchondral bone repair layer forms a surface modified with hydroxyapatite.
In some embodiments of the invention, the polycaprolactone-polylactic acid copolymer has a molar ratio of polycaprolactone to polylactic acid of 45:55 to 70:30.
In some embodiments of the invention, the degradable polymer material nano short fiber is formed by crushing a combination of animal collagen and polycaprolactone after forming a film by an electrostatic spinning process.
In some embodiments of the invention, the hyaluronic acid has a weight average molecular weight of 80KD to 220KD.
In addition, the invention also provides application of the plastic filling stent in repairing cartilage defect, which comprises the following steps:
a) Removing surrounding fibrotic tissue from the damaged cartilage and subchondral layer;
b) Cutting the cartilage repair scaffold according to the shape of damaged tissues;
c) After trimming is completed, the scaffold is inserted into the damaged tissue.
Compared with the prior art, the invention has the following beneficial effects:
in the plastic filling bracket, the gel solution for forming the cartilage repair layer is partially filled into the porous structure of the subchondral bone repair layer, and nutrient components hyaluronic acid and degradable polymer material nanometer short fibers contained in the gel solution are reserved in pores after freeze drying, so that the cartilage repair layer and the subchondral bone repair layer are interconnected, the cartilage repair layer is partially fused in the subchondral bone repair bracket, and the pores of the upper layer and the lower layer are mutually communicated. In the cartilage repair process, the cartilage repair layer can continuously absorb nutrition from the subchondral bone layer, so that better transmission of cartilage tissue repair nutrition substances is realized, and therefore, the cartilage tissue regeneration difficulty is reduced.
On the other hand, in the cartilage repair process, the subchondral bone repair layer can provide enough supporting strength while continuously conveying nutrient substances to the cartilage repair layer, so that the cartilage repair layer is prevented from deforming, and the degradation rate can be adjusted through the material design of the subchondral bone repair layer, so that the subchondral bone repair layer meets the requirements of supporting and nutrient conveying in the cartilage repair process, and is suitable for cartilage repair of people of different ages. When the degradable polymer of the subchondral bone repair layer is polycaprolactone-polylactic acid copolymer, the degradation rate and the supporting strength of the polymer can be controlled by adjusting the ratio of polycaprolactone to polylactic acid, so that the conveying speed of nutrient substances and the supporting of the subchondral bone repair layer can be controlled.
The plastic filling bracket has good plasticity, can be cut randomly, and is flexible and convenient to use in cooperation with arthroscope operation.
The plastic filling stent does not need secondary operation, wherein hyaluronic acid becomes a nutrient component in cartilage and subchondral bone repair, and the degradable material is degraded along with cartilage regeneration.
Drawings
Fig. 1A shows SEM microtopography of cartilage repair layers in a plastically-filled scaffold of example 1 of the present invention.
Fig. 1B shows SEM microtopography of subchondral bone repair layers in a plastically-filled stent of example 1 of the present invention.
Fig. 1C shows the SEM micro morphology of the subchondral bone repair layer of example 1 of the present invention when the plastically-filled stent is in an incompletely lyophilized state.
Fig. 2A shows SEM microtopography of cartilage repair layers in a plastically-filled scaffold of example 2 of the present invention.
Fig. 2B shows SEM microtopography of subchondral bone repair layers in a plastically-filled stent of example 2 of the present invention.
Fig. 2C shows the SEM micro morphology of the subchondral bone repair layer of example 2 of the present invention when the plastically-filled stent is in an incompletely lyophilized state.
Fig. 3A shows SEM micro morphology of the cartilage repair layer in the plastically-filled scaffold of example 3 of the present invention.
Fig. 3B shows SEM microtopography of subchondral bone repair layers in a plastically-filled stent of example 3 of the present invention.
Fig. 3C shows the SEM micro morphology of the subchondral bone repair layer of example 3 of the present invention when the plastically-filled stent is in an incompletely lyophilized state.
Fig. 4A shows SEM micro morphology of the cartilage repair layer in the plastically-filled scaffold of example 4 of the present invention.
Fig. 4B shows SEM microtopography of subchondral bone repair layer in a plastically-filled stent of example 4 of the present invention.
Fig. 4C shows the SEM micro morphology of the subchondral bone repair layer of example 4 of the present invention when the plastically-filled stent is in an incompletely lyophilized state.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, various aspects related to the present invention will be described in detail with reference to the following specific embodiments, but these specific embodiments are only for illustrating the present invention, and do not limit the scope and spirit of the present invention in any way.
In order to complete the support of the cartilage repair layer and the nutrition transmission required by cartilage repair, the subchondral bone repair layer of the plastic filling bracket has a honeycomb porous structure formed by stacking degradable polymer fibers, the degradable polymer can be selected to have good biocompatibility and degrading performance meeting the requirements of cartilage repair period, in the specific embodiment of the invention, polycaprolactone-polylactic acid copolymer is selected as the material of the subchondral bone repair layer, the mechanical property and degrading performance of the subchondral bone repair layer can be further regulated by changing the ratio of polycaprolactone and polylactic acid in the copolymer, and the requirement of cartilage repair is further met, wherein the molar ratio of polycaprolactone to polylactic acid in the polycaprolactone-polylactic acid copolymer is preferably 45:55 to 70:30, and numerical values in the molar ratio range are respectively selected in the specific embodiment described later.
The subchondral bone repair layer in the invention is preferably formed into a honeycomb porous structure formed by stacking degradable polymer fibers by adopting a 3D printing technology, and the porous structure should meet the strength requirement of supporting the subchondral bone repair layer. In addition, through the selection of 3D printing medium, can carry out the modification treatment to the surface of the lower bone repair layer that the 3D printing formed, in the concrete embodiment of the invention, select the hydroxyapatite solution that has osteogenesis activity as printing medium, form the rough surface that is modified by hydroxyapatite at the lower bone repair layer, be favorable to the restoration of subchondral bone. Wherein the hydroxyapatite is selected from bioceramic bone or animal extracted bone or a combination thereof.
The cartilage repair layer is formed by pouring a gel solution into the subchondral bone repair layer to form a gel layer and freeze-drying the gel layer, wherein the gel solution contains hyaluronic acid and degradable high polymer material nano short fibers, and the degradable high polymer material preferably comprises animal collagen and polycaprolactone. The invention can adjust the fluidity of the gel solution by micro-crosslinking by using a crosslinking agent (such as glyoxal), so that the fluidity is suitable for forming a cartilage repair layer on the lower bone repair layer, and partial gel can be filled into the pores of the lower bone repair layer, so that the upper repair layer and the lower repair layer are interconnected by filling the gel into the through holes. The fluidity of the gel solution may also be regulated by other means known in the art. The nanometer short fiber in the cartilage repair layer is preferably made by electrostatic spinning, can also be made by other processes known in the art, and is crushed after film formation according to the use requirement to obtain the nanometer short fiber with proper size.
The pore diameter of the porous structure of the subchondral bone repair layer is smaller than that of the cartilage repair layer, the relative compactness of the subchondral bone repair layer enables the subchondral bone repair layer to have enough supporting strength, the pore diameter of the cartilage repair layer meets the requirements of adhesion, climbing and the like of chondrocytes, and the pore diameter of the subchondral bone repair layer is similar to that of a conventional cartilage repair bracket. In a specific embodiment of the present invention, the subchondral bone repair layer has a pore size in the range of 50-100 μm and the cartilage repair layer has a pore size in the range of 100-500 μm.
The molecular weight of the hyaluronic acid contained in the gel solution is selected to be in a proper range as a nutrient for cartilage repair, and in the specific embodiment of the invention, the weight average molecular weight of the hyaluronic acid is 80 KD-220 KD, the fluidity of the gel is affected by the too high molecular weight, and the formation of the freeze-dried sponge formed by freeze-drying the gel layer is affected by the too low molecular weight. In the cartilage repair process, hyaluronic acid filled in the pores of the lower bone repair layer is transported from the lower bone repair layer to the cartilage repair layer through the interpenetrated pores, thereby promoting cartilage repair. In order to improve the transmission of nutrients, the water absorption of the cartilage repair layer is higher than that of the subchondral bone repair layer, and in the specific embodiment of the invention, the water absorption rate of the cartilage repair layer is 14-16, and the water absorption rate of the subchondral bone repair layer is 5-6, so that the continuous transmission of nutrients from the subchondral bone repair layer with lower water absorption rate to the cartilage repair layer with higher water absorption rate is facilitated in the cartilage repair process.
In addition, according to the actual situation of the subchondral bone defect, the invention can form the surface corresponding to the subchondral bone defect on the surface of the subchondral bone layer facing away from the cartilage repair layer through 3D printing. For example, a roughened surface may be formed on the surface of the subchondral bone layer facing away from the cartilage repair layer that is adapted to contact the subchondral bone defect cavity to be repaired. In addition, depending on the condition of the subchondral bone defect to be repaired, a tapered structure may also be formed on the surface of the subchondral bone repair layer facing away from the cartilage repair layer.
Example 1
The preparation method of the filling bracket of the embodiment is as follows:
1. preparation of subchondral bone repair layer
The subchondral bone repair layer of this embodiment is prepared by adopting a 3D printing technology, the polycaprolactone-polylactic acid copolymer fiber formed by melt extrusion is stacked layer by layer at different angles to form a bracket with a cellular porous structure, wherein the polycaprolactone-polylactic acid copolymer is obtained by market, the molar ratio of polycaprolactone to polylactic acid in the copolymer is 68/32, the intrinsic viscosity is 1.7-2.6dL/g, 3%wt of hydrochloric acid aqueous solution of hydroxyapatite biological ceramic particles (with the particle size of 0.25-1 mm) is adopted as a receiving medium for printing the bracket, the bracket is printed in the receiving medium, the temperature of the receiving solution is set to be 50-80 ℃, the receiving solution is cooled to 25 ℃ after printing is completed, then the bracket is taken out, the bracket is washed to be neutral by using a hydrochloride buffer solution, and then is placed in a vacuum oven at 45 ℃ for drying for 4-24 hours, and the polycaprolactone-polylactic acid copolymer fiber bracket with the surface modified by hydroxyapatite is provided with the cellular porous structure, the pore size is 50-100 μm, and the size is about 3cm.
2. Preparation of cartilage repair layer
The cartilage repair layer in this example is a freeze-dried sponge containing Polycaprolactone (PCL) electrostatic nanofibers, which connects the cartilage repair layer and the subchondral bone repair layer by way of gel filling using the cellular porous structure of the subchondral bone repair layer. Therefore, in the cartilage repair process, nutrition can be continuously absorbed through the subchondral bone repair layer and tissues, and cartilage repair is promoted. The cartilage repair layer in this example was prepared as follows:
2.1 preparation of PCL nanometer staple Using Electrostatic spinning
Dissolving natural collagen and PCL extracted from bovine Achilles tendon in chloroform, and performing electrostatic spinning according to a receiving distance of 10-20cm, a voltage of 15-20kv, a solution flow rate of 0.5-1ml/h, and a receiving device as a directional fiber yarn-grafting device to obtain a biomembrane capable of guiding cartilage regeneration. And crushing the obtained electrospun biomembrane to obtain the PCL nanometer short fiber.
2.2 preparation of cartilage repair layer
And (3) selecting hyaluronic acid with the weight average molecular weight of 80-120KD, preparing 125g of aqueous solution of hyaluronic acid with the weight percentage concentration of 2.5%, adding 0.06g of glyoxal, stirring at 60 ℃ until the hyaluronic acid is fully dissolved, immediately adding 0.6g of broken electrostatic PCL nano short fibers prepared in the step (2.1), and continuing stirring for 5 minutes to uniformly disperse the broken electrostatic PCL nano short fibers to form gel solution.
And (3) placing the subchondral bone repair layer formed by 3D printing on the lower layer of a freeze-drying mold, after fixing, pouring the gel solution prepared in the step (2.2) into the freeze-drying mold to form a gel layer, ensuring that the pores of the subchondral bone repair layer are filled with gel, and then performing freeze-drying for 34 hours to obtain the cartilage repair plastic filling bracket. Wherein the cartilage repair layer has a thickness of about 5mm.
3. Sterilization of stent
And (3) filling the cartilage repair filling support obtained according to the steps into a bubble cap and a white card paper box, and performing irradiation sterilization by using a dosage of 18-24kGy to obtain a finished product.
Example 2
Example 2 differs from example 1 in that: the molar ratio of polycaprolactone to polylactic acid in the polycaprolactone-polylactic acid copolymer for forming the subchondral bone repair layer is 66/34, the hydroxyapatite used for modifying the surface of the subchondral bone repair layer is extracted from animals, and the weight average molecular weight of hyaluronic acid contained in gel for forming the subchondral bone repair layer is 100-180KD.
Example 3
Example 3 differs from example 1 in that: the polycaprolactone-polylactic acid copolymer forming the subchondral bone repair layer has a molar ratio of 58/42 of polycaprolactone to polylactic acid, and the hyaluronic acid contained in the gel forming the subchondral bone repair layer has a weight average molecular weight of 140-200KD.
Example 4
Example 4 differs from example 1 in that: the molar ratio of polycaprolactone to polylactic acid in the polycaprolactone-polylactic acid copolymer for forming the subchondral bone repair layer is 47/53, the hydroxyapatite used for surface modification of the subchondral bone repair layer is extracted from animals, and the gel for forming the subchondral bone repair layer is hyaluronic acid with weight average molecular weight of 180-220 KD.
The molar ratios of hydroxyapatite, hyaluronic acid molecular weight and polycaprolactone/polylactic acid used in examples 1-4 are summarized in Table 1 below.
TABLE 1
The physicochemical properties of the cartilage repair scaffolds obtained in examples 1 to 4 were examined as follows.
1. SEM observations of examples 1-4 are as follows:
in order to observe the microscopic morphology of the cartilage repair scaffolds prepared in examples 1 to 4, appropriate amounts of the scaffold samples of examples 1 to 4 were cut according to the size of the loading device, fixed on a conductive adhesive tape, and the microscopic structures inside the samples were observed by SEM scanning electron microscopy, and the SEM morphologies of the cartilage repair layer and the subchondral bone repair layer of each example were observed, respectively.
1.1 SEM characterization of cartilage repair layers
SEM microtopography of cartilage repair layers of the scaffold samples of examples 1-4 are shown in fig. 1A, 2A, 3A and 4A, respectively.
1.2 SEM characterization of subchondral bone repair layer
SEM microtopography of subchondral bone repair layers of the scaffold samples of examples 1-4 are shown in fig. 1B, 2B, 3B, and 4B.
1.3 SEM characterization of subchondral bone repair layer during lyophilization (not completely lyophilized state)
In order to clearly observe that the gel solution for forming the cartilage repair layer is filled into the porous structure of the subchondral bone repair layer, after the gel for forming the cartilage repair layer is poured into the freeze-drying mold to form the gel layer, sampling is carried out in the freeze-drying process to observe microscopic morphology, in the embodiment 1-4, the subchondral bone repair layer is respectively sampled about 20 hours after freeze-drying, at this time, the sample is in a state of incomplete freeze-drying, the SEM microscopic morphology of the subchondral bone repair layer of the bracket sample of the embodiment 1-4 is as shown in fig. 1C, fig. 2C, fig. 3C and fig. 4C, from these figures, a part of the unvaporized gel solution is still reserved in the porous structure of the subchondral bone repair layer with a slower drying speed, the gel solution for forming the cartilage repair layer is filled into the pores of the porous structure of the subchondral bone repair layer, the cartilage repair layer and the subchondral bone repair layer are interconnected, the cartilage repair layer is partially fused in the subchondral bone repair bracket, the pores of the upper layer and the lower layer are mutually communicated, and the moisture in the pores of the complete transparent nutrient substances are reserved after the gel solution is evaporated.
As can be seen from the SEM microcosmic morphology, the pores formed by freeze drying in the cartilage repair layer are mutually communicated with the pores of the subchondral bone repair layer, which is beneficial to the migration of cells and the transportation of nutrient substances and the like.
The pore diameter of the subchondral bone repair layer is between 50 and 100 mu m, and is more compact than that of the subchondral bone repair layer, so that the subchondral bone repair layer can provide better mechanical strength.
The aperture of the cartilage repair layer is between 100 and 500 mu m, and the cartilage repair layer is in an elastic spongy shape, so that the cartilage repair layer has plasticity, is more comfortable for user experience, and can be cut as required.
2. Modulus of elasticity under compression
The cartilage repair layer and the subchondral bone repair layer of each of the scaffolds of examples 1 to 4 were cut as two test samples, compressive load was applied to the end surfaces of the test samples in the main axis direction at a deformation rate of (1.+ -. 0.5)% per minute, respectively, and compressive deformation within the specific limits was measured, and the ratio of the increase in compressive stress to the corresponding increase in compressive strain was the compressive elastic modulus. The compressive elastic modulus of the cartilage repair layer and subchondral bone repair layer of each of the scaffolds of examples 1 to 4 was thus obtained as shown in Table 2 below.
TABLE 2
| Detecting items | Example 1 | Example 2 | Example 3 | Example 4 |
| Cartilage repair layer compression modulus/Mpa | 5 | 6 | 5 | 5 |
| Subchondral bone repair layer compression modulus/Mpa | 54 | 61 | 57 | 64 |
The compression elastic modulus of the natural bone is generally 52-318Mpa, and as can be seen from table 2, the compression modulus of the subchondral bone repair layer of the scaffold of examples 1-4 can reach more than 52, and the scaffold has good mechanical properties, and can meet the requirement of mechanical support in the cartilage repair process.
3. Water absorption rate
The cartilage repair layer and subchondral bone repair layer of each of the scaffolds of examples 1 to 4 were cut as two test samples, 5 samples were taken for each test sample, their mass was precisely weighed, then immersed in a beaker containing purified water for 1min, the samples were gently held with forceps and lifted out of the water surface, slightly inclined to one side for several seconds, and the mass was precisely weighed again until no liquid was dropped out, and the water absorption capacity was calculated from the mass. The water absorption capacities of the cartilage repair layer and the subchondral bone repair layer of each of the scaffolds of examples 1 to 4 are shown in Table 3 below.
TABLE 3 Table 3
| Detecting items | Example 1 | Example 2 | Example 3 | Example 4 |
| Cartilage repair layer water absorption rate | 14 | 16 | 14 | 15 |
| Subchondral bone repair layer water absorption rate | 5 | 6 | 5 | 5 |
As can be seen from the values of the water absorption ratios shown in table 3, in the scaffold of the present invention, the water absorption ratio of the subchondral bone repair layer is far lower than that of the cartilage repair layer, thereby ensuring that the cartilage repair layer can continuously absorb nutrients from the subchondral bone repair layer and promote cartilage repair.
4. Simulated degradation test
The scaffolds obtained in examples 1 to 4 were sampled using phosphate buffer solution to prepare a protease solution of 2U/ml, the weights of the respective samples were kept uniform, the protease solutions prepared above were added to the samples, respectively, and the samples were placed in a shaking table at 37℃to replace the protease solutions once a day. Degradation of each of the samples of examples 1-4 is shown in Table 4 below.
TABLE 4 Table 4
| Examples | Period of in vitro protease solution degradation |
| Example 1 | The degradation amount can reach 50% after 13 weeks, and only the fragment structure of the hydroxyapatite remains after 24 weeks |
| Example 2 | The degradation amount can reach 50% after 14 weeks, and only the fragment structure of the hydroxyapatite remains after 23 weeks |
| Example 3 | The degradation amount can reach 50% after 11 weeks, and only the fragment structure of the hydroxyapatite remains after 19 weeks |
| Example 4 | The degradation amount can reach 50% after 8 weeks, and only the fragment structure of the hydroxyapatite remains after 15 weeks |
Typically, the cartilage repair cycle is typically 3-6 months, with the cartilage repair cycle increasing as the patient ages.
From table 4, it can be seen that the degradation of each of the scaffolds of examples 1-4 can meet the supply requirements and the support strength requirements of cartilage repair for nutrients throughout the entire cycle of cartilage and subchondral bone repair.
In addition, the polycaprolactone/polylactic acid ratio in the subchondral bone repair layer can be adjusted to meet different degradation period requirements, so that the subchondral bone repair layer can be used for selecting products of patients with different ages.
From examples 1 to 4, it is understood that the degradation rate is accelerated as the molar ratio of polycaprolactone to polylactic acid is decreased, the molar ratio of caprolactone to polylactic acid in example 4 is 47/53, the degradation rate has reached 15 weeks, and further lowering the polycaprolactone/polylactic acid ratio has not satisfied the whole cycle of cartilage repair well, therefore, the polycaprolactone/polylactic acid molar ratio in the polycaprolactone/polylactic acid copolymer in the subchondral bone repair layer of the present invention is preferably in the range of 45:55 to 70:30.
The biological properties of the scaffolds of examples 1-4 were evaluated as follows.
1. Pyrogenic reaction
For the stent sampling of examples 1-4, 3 New Zealand rabbits were used for injection leaching solutions for each example, and test solutions were prepared according to the following procedure: 0.1g sample: 1mL of leaching medium, wherein the leaching medium is 0.9% sodium chloride injection, (37+ -1) DEG C, (72+ -2) hours, test solution is prepared, and the test solution is taken according to the method specified in GB/T16886.11-2011.
The whole process is carried out in an ultra-clean bench in a sterile environment. The test vessel in contact with the sample should be sterile and pyrogen free. The pyrogen is removed by a wet heat sterilization method. The results of the pyrogen examination of examples 1 to 4 are shown in tables 5 to 8, respectively, below.
TABLE 5
TABLE 6
TABLE 7
TABLE 8
12 New Zealand rabbits injected with the sample leaching solution in the pyrogen test have the body temperature rise lower than 0.6 ℃ and the total body temperature rise of each group of New Zealand rabbits is lower than 1.3 ℃; according to the fourth pyrogen examination technical requirement of the Chinese pharmacopoeia 2020 edition, the pyrogen examination of each stent of examples 1 to 4 is judged to be in accordance with the regulations.
2. Cytotoxicity detection
The effect of 100%, 80%, 40% and 20% concentration of the test sample on the relative proliferation rate of mouse fibroblast L929 cells in 24 hours was examined by MTT colorimetric method, and cytotoxicity was evaluated, and the results of the cytotoxicity test for each scaffold of examples 1 to 4 are shown in Table 9 below.
TABLE 9
| Examples | Survival rate |
| Example 1 | 84％ |
| Example 2 | 86％ |
| Example 3 | 79％ |
| Example 4 | 82％ |
Under the experimental conditions, the cell viability of examples 1-4 is greater than 70%, and no potential cytotoxicity is observed
The present invention has been described with reference to specific embodiments, which are merely illustrative, and not intended to limit the scope of the invention, and those skilled in the art can make various modifications, changes or substitutions without departing from the spirit of the invention. Thus, various equivalent changes may be made according to this invention, which still fall within the scope of the invention.
Claims (14)
1. A plastically-filled scaffold for cartilage repair, comprising:
a subchondral bone repair layer having a cellular porous structure formed by stacking degradable polymer fibers;
the cartilage repair layer is freeze-dried sponge, a gel layer is formed by pouring a gel solution onto the subchondral bone repair layer, and the gel layer is formed by freeze-drying, wherein the gel solution contains hyaluronic acid and degradable high polymer material nano short fibers;
the gel solution is partially filled into the pores of the porous structure of the subchondral bone repair layer, and is retained in the pores after freeze drying, so that the subchondral bone repair layer and the subchondral bone repair layer are interconnected, and a channel which is beneficial to the transmission of nutrients from the subchondral bone repair layer to the subchondral bone repair layer is formed in the repair process.
2. The filled scaffold of claim 1, the degradable polymer in the subchondral bone repair layer comprising a polycaprolactone-polylactic acid copolymer.
3. The filled scaffold of claim 2, wherein the subchondral bone repair layer is prepared using 3D printing, and the receiving medium for the 3D printing is a hydrochloric acid solution of hydroxyapatite, such that the subchondral bone repair layer forms a roughened surface modified with the hydroxyapatite.
4. The filled scaffold of claim 1, wherein pores of the porous structure of the subchondral bone repair layer are interpenetrated with pores formed by freeze drying in the subchondral bone repair layer, the pore size of the subchondral bone repair layer is 50-100 μm, and the pore size of the cartilage repair layer is 100-500 μm.
5. The filled scaffold of claim 4, wherein the subchondral bone repair layer has a modulus of elasticity in compression greater than 52Mpa.
6. The filled stent of claim 1, wherein the degradable polymeric material nano-staple fibers are formed by crushing a combination of animal collagen and polycaprolactone after a film is formed by an electrospinning process.
7. The filled scaffold of claim 1, wherein the water absorption rate of the cartilage repair layer is 14-16 and the water absorption rate of the subchondral bone repair layer is 5-6.
8. The filled scaffold of claim 1, wherein the subchondral bone repair layer has a tapered structure at a surface facing away from the cartilage repair layer.
9. The filled stent of claim 2, wherein the molar ratio of polycaprolactone to polylactic acid in the polycaprolactone-polylactic acid copolymer is from 45:55 to 70:30.
10. A method of preparing a plastically-filled scaffold for cartilage repair, comprising the steps of:
forming a subchondral bone repair layer comprising: preparing polycaprolactone-polylactic acid copolymer fibers by 3D printing, and stacking the fibers layer by layer to form a subchondral bone repair layer with a honeycomb porous structure;
forming a cartilage repair layer comprising: placing the formed subchondral bone repair layer in a freeze drying mould, pouring a gel solution containing hyaluronic acid and degradable high polymer material nanometer short fibers into the freeze drying mould, forming a gel layer on the subchondral bone repair layer, filling the gel solution into the porous structure of the subchondral bone repair layer, and then freeze drying to obtain the filling bracket.
11. The method of claim 10, wherein the receiving medium for 3D printing is a hydrochloric acid solution of hydroxyapatite, such that the subchondral bone repair layer forms a surface modified with hydroxyapatite.
12. The method of claim 10, wherein the polycaprolactone-polylactic acid copolymer has a molar ratio of polycaprolactone to polylactic acid of 45:55 to 70:30.
13. The method of claim 10, wherein the degradable polymer material nano-staple fiber is formed by crushing a combination of animal collagen and polycaprolactone after forming a film by an electrostatic spinning process.
14. The method of claim 10, wherein the weight average molecular weight of the hyaluronic acid is 80KD to 220KD.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211211915.8A CN117797324A (en) | 2022-09-30 | 2022-09-30 | Plastic filling bracket for cartilage repair and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211211915.8A CN117797324A (en) | 2022-09-30 | 2022-09-30 | Plastic filling bracket for cartilage repair and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117797324A true CN117797324A (en) | 2024-04-02 |
Family
ID=90428611
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211211915.8A Pending CN117797324A (en) | 2022-09-30 | 2022-09-30 | Plastic filling bracket for cartilage repair and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117797324A (en) |
-
2022
- 2022-09-30 CN CN202211211915.8A patent/CN117797324A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Han et al. | Biohybrid methacrylated gelatin/polyacrylamide hydrogels for cartilage repair | |
| Shen et al. | Engineering a highly biomimetic chitosan-based cartilage scaffold by using short fibers and a cartilage-decellularized matrix | |
| US9192655B2 (en) | System and method for a hydrogel and hydrogel composite for cartilage repair applications | |
| US9421305B2 (en) | Aligned scaffolding system for skeletal muscle regeneration | |
| JP5345573B2 (en) | Biocompatible support scaffold with tissue fragments | |
| EP1835947B1 (en) | A biocompatible material and a prosthetic device made thereof for the replacement, repair and regeneration of meniscus | |
| US20160106548A1 (en) | Cell-nanofiber composite and cell-nanofiber-hydrogel composite amalgam based engineered intervertebral disc | |
| US20130274892A1 (en) | Electrospun Mineralized Chitosan Nanofibers Crosslinked with Genipin for Bone Tissue Engineering | |
| Lin et al. | In vitro and in vivo evaluation of the developed PLGA/HAp/Zein scaffolds for bone-cartilage interface regeneration | |
| KR101472045B1 (en) | Core-shell fibrous cell carrier and composition for regeneration of osseous tissue or cartilage tissue comprising the same | |
| KR20080065606A (en) | A method for cell implantation | |
| JP2004136097A (en) | Biocompatible scaffold device for ligament or tendon repair | |
| Li et al. | Hierarchical porous bacterial cellulose scaffolds with natural biomimetic nanofibrous structure and a cartilage tissue-specific microenvironment for cartilage regeneration and repair | |
| CN110665055B (en) | Sericin/nano-hydroxyapatite tissue engineering bone graft and preparation method and application thereof | |
| Zhang et al. | Application of chitosan with different molecular weights in cartilage tissue engineering | |
| CN108992212B (en) | Bone-cartilage integrated repair scaffold and preparation method thereof | |
| George et al. | Biopolymer-based scaffolds: Development and biomedical applications | |
| Han et al. | Sericin-reinforced dual-crosslinked hydrogel for cartilage defect repair | |
| EP4178634B1 (en) | Integrated core-shell bioactive structure for the regeneration of bone and osteochondral tissues | |
| Wang et al. | Highly resilient and fatigue-resistant poly (4-methyl-ε-caprolactone) porous scaffold fabricated via thiol-yne photo-crosslinking/salt-templating for soft tissue regeneration | |
| Hernández-Rangel et al. | Electrospun chitosan materials and their potential use as scaffolds for bone and cartilage tissue engineering | |
| EP4422709A1 (en) | A pla-collagen scaffold for medical use loaded with cells | |
| CN117797324A (en) | Plastic filling bracket for cartilage repair and preparation method thereof | |
| EP4119169A1 (en) | A construct for articular cartilage regeneration and a method of preparation | |
| Senköylü et al. | Interaction of cultured chondrocytes with chitosan scaffold |
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 |