CN108404214A - A kind of bionical osteochondral composites and preparation method thereof - Google Patents
A kind of bionical osteochondral composites and preparation method thereof Download PDFInfo
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/28—Bones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/30756—Cartilage endoprostheses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
-
- 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
- A61L27/10—Ceramics or glasses
-
- 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
- A61L27/50—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
- A61L27/56—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/28—Bones
- A61F2002/2835—Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30003—Material related properties of the prosthesis or of a coating on the prosthesis
- A61F2002/3006—Properties of materials and coating materials
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- 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
Abstract
The present invention provides a kind of bionical osteochondral composites and preparation method thereof, bionical osteochondral composites include cartilage layers, barrier layer and subchondral bone layer, and the both sides of the barrier layer are connect with the subchondral bone layer and the cartilage layers respectively.A kind of bionical osteochondral composites provided by the invention can be implanted into human body cartilaginous lesion site, barrier layer under cartilage, cartilage and subchondral bone are subjected to integrated reparation, formed can inducing endogenous cell move into but also play the Bionics Bone repair of cartilage body of barrier function.
Description
Technical field
The invention belongs to medical instruments field, it is related to a kind of bionical osteochondral composites and preparation method thereof.
Background technology
Cartilage damage is likely to result in the generation of osteoarthritis, and current research finds that osteoarthritis is sent out in subchondral bone damage
Life also has a major impact.The generation of osteoarthritis can effectively be delayed by clinically thinking to repair cartilage, but articular cartilage damage
When be frequently accompanied by subchondral bone damage, existing treatment means only focus on repair of cartilage, and are often repaired cartilage underlying bony structure
And it is unstable.
It is a kind of repair of cartilage means being usually used in clinic that micro fractures, which repair cartilage, under in defect to cartilage
Bone drilling, guiding stem cell repair cartilage, and the cartilage of formation is often fibrocartilage.It is shown according to Follow-up results,
It was found that the means short term efficacy is good, and long-term results are unsatisfactory, can lead to subchondral bone structural damage.
Autologous Chondrocyte transplanting (ACI) is another common repair of cartilage means, by being derived from autologous patient
Cartilage cell carries out culture amplification, is subsequently implanted required reparation position.Long term follow-up finds that this method is to layer cartilage defects
Curative effect is relatively good, but therapeutic process is complex.
It is loaded into Autologous Chondrocyte transplanting using the collagen scaffold that can induce repair of cartilage to carry out repair of cartilage (MACI)
It is a kind for the treatment of technology newly risen, which can be greatly simplified operation on the basis of ACI, improve safety and have
Effect property.For MACI when applied to repair of cartilage, holder is extremely important, and the material of holder generally uses synthetic material,
Synthetic material has the advantages that machinability is strong, but its biocompatibility is poor, and Clinical practice effect is not ideal enough, such as
Smith&Nephew TRUFITTM, shown according to clinical follow up results, 2 years Clinical Follow-ups of cell bone cartilage frame gone to fail
Rate is 72%, and main cause, which is autogenous cell, can not grow into allogeneic Acellular bone cartilage frame.
Some researches show that, to synthetic material prepare holder handle after, then be transplanted to defect point induction it is endogenous
Property cell move into carry out repair of cartilage, have preferable effect.Wherein, it is no lack of using BMP or micromolecular compound etc. come to branch
Frame is handled, to induce noble cells.Such as micromolecular compound kartongenin can induce repair of cartilage, but it is this kind of
Small molecule is while inducing noble cells, it is also possible to and tendon ligament lesion can be induced so as to cause articular degeneration,
So still in conceptual phase, cannot clinically use.
It can be seen that technology good there are no repairing effect for the injury repair of cartilage at present and that treatment is easy, micro- bone
The long-term treatment result that folding repairs cartilage is undesirable, and Autologous Chondrocyte transplantation treatment process is complex, and self cartilage is thin
The therapeutic effect that born of the same parents transplant (ACI) then extremely relies on its holder used, and holder in the prior art can not meet soft well
Needed for Bone Defect Repari.
Invention content
The object of the present invention is to provide a kind of bionical osteochondral composites and preparation method thereof, to solve the prior art
The problem of repairing effect difference existing for holder needed for middle repair of cartilage.
In order to solve the above technical problems, the present invention provides a kind of bionical osteochondral composites, including cartilage layers, barrier layer
And subchondral bone layer, the both sides of the barrier layer are connect with the subchondral bone layer and the cartilage layers respectively.
Further, the cartilage frame is collagen porous layer, is prepared using natural collagen；The barrier layer is
Micropore biological ceramic layer uses tricalcium phosphate and/or hydroxyapatite to be prepared；The subchondral bone layer is multiporous biological
Ceramic layer uses tricalcium phosphate to be prepared；The aperture in hole is given birth to more than or equal to the micropore on the porous bio-ceramic layer
The aperture in hole on object ceramic layer.
Further, subchondral bone layer connection integrated with the barrier layer, the cartilage layers and the barrier layer
By being coupled or being crosslinked connection.
Further, the burr of the collagen porous layer and pseudopodium stretch into the micropore biological ceramic layer inside and with institute
State the connection of micropore biological ceramic layer.
Further, which is characterized in that the cartilage layers include ripe cartilage layers, and the subchondral bone layer includes under cartilage
Bone trabecula layer；The barrier layer includes sequentially connected calcified cartilage layer, articulamentum and subcartilaginous osseous lamella layer；The maturation cartilage
Layer is connect with the calcified cartilage layer, and the subcartilaginous osseous lamella layer is connect with the cartilaginous trabecula layer.
Further, the ripe cartilage layers are porous collagen maturation cartilage layers, and collagen is used to be prepared；The calcium
Cartilage layer is collagen calcified layer, and collagen composite tricalcium phosphate is used to be prepared；The subcartilaginous osseous lamella layer is made pottery for micropore
Enamel coating uses tricalcium phosphate or hydroxylapatite ceramic to build to obtain；The subchondral bone girder layer is gradient porous biology
Ceramic layer has several holes thereon, and the aperture in several holes is along the direction gradient close to the micropore compact substance ceramic layer
Successively decrease, and the aperture in the hole on the gradient porous bioceramic layer is more than the aperture in the hole on the micropore ceramics layer；Institute
It is composite collagen articulamentum to state articulamentum, and collagen is used to be prepared.
Further, connecting between the porous collagen maturation cartilage layers and the collagen calcified layer, the collagen calcium
Change connecting between layer and the composite collagen articulamentum, the company between the composite collagen articulamentum and the micropore ceramics layer
It connects, the connection between the micropore ceramics layer and the gradient porous bioceramic layer, is all made of coupling or crosslinked mode connects
It connects.
Further, the burr or pseudopodium of the collagen calcified layer stretch into the micropore biological ceramic layer inside and with institute
State the connection of micropore biological ceramic layer.
A kind of a kind of preparation method of bionical osteochondral composites as described above, includes the following steps：It is prepared into respectively
To the cartilage layers and the subchondral bone layer；It is prepared on the side of the subchondral bone layer and forms the barrier layer；By institute
It states cartilage layers to connect with the barrier layer, obtains the bionical osteochondral composites.
Further, the preparation method of the cartilage layers includes：Using CAD and Solid Freeform
Collagen is prepared into collagen scaffold by method；The cartilage for being built different layerings on the collagen scaffold using laser cutting technique is fallen into
Nest；By the holder being prepared according to the hierarchical ar-rangement of cartilaginous tissue, is handled, obtained using frost forging casting and crosslinked method
To the cartilage layers, porosity 10-50%, aperture is 10-100 microns.
Further, the subchondral bone layer is prepared using porous ceramics manufacture craft, porosity 40-80%,
Aperture is 100-800 microns；The barrier layer is using ceramic capillary preparation process on the side of the subchondral bone layer
It is formed, porosity 0.5-40%, aperture is 0.1-15 microns.
A kind of preparation method of bionical osteochondral composites, includes the following steps：The ripe cartilage layers, institute are prepared respectively
State calcified cartilage layer, the subcartilaginous osseous lamella layer and the subchondral bone girder layer；Described in coupling or crosslinking Treatment connection
The ripe cartilage layers and calcified cartilage layer, the subcartilaginous osseous lamella layer and subchondral bone girder layer；Utilize collagen solution
As adhesive, the calcified cartilage layer is connected with the subcartilaginous osseous lamella layer, the calcified cartilage layer after connection and institute
It is the articulamentum to state the collagen layer between subcartilaginous osseous lamella layer.
Further, the ripe cartilage layers are porous collagen maturation cartilage layers, the porous collagen maturation cartilage layers
Preparation method includes：Auxiliary agent and collagen are prepared into mixed solution；Mixed solution is crosslinked using crosslinking agent, is crosslinked
Solution afterwards；The solution after the crosslinking is handled using CAD and frost curing process, is obtained porous
Collagen maturation cartilage layers, porosity 10-50%, aperture are 10-100 microns.
Further, it is sub- to be selected from 2- (N- morpholines) ethanesulfonic acid monohydrate, sodium chloride, N- maloyls for the auxiliary agent
One or more combinations in amine, dimethylaminopropyl ethyl carbamide and sodium alginate；The collagen is I types and/or II
Collagen Type VI；The crosslinking agent is adipic dihydrazide.
Further, the calcified cartilage layer is collagen calcified layer, and the preparation method of the collagen calcified layer includes：By phosphorus
Sour tricalcium is blended with collagen solution, and drying and forming-film obtains the collagen calcified layer.
Further, the subcartilaginous osseous lamella layer is micropore ceramics layer, and the preparation method of the micropore ceramics layer includes：It will
The micropore ceramics layer, the micropore pottery is prepared through high temperature sintering in the powder slurries of tricalcium phosphate and/or hydroxyapatite
The porosity of enamel coating is 0.5-40%, and aperture is 0.1-15 microns.
Further, the subchondral bone girder layer is gradient porous bioceramic layer, the gradient porous bioceramic
Layer preparation method include：According to the structure design organic formwork of subchondral bone girder layer；Using organic formwork method, described in setting
The gradient porous bioceramic layer, the gradient porous pottery is prepared in the size and accumulation mode of microballoon in organic formwork
The porosity of enamel coating is 40-80%, and aperture is 100-800 microns.
Compared with prior art, the present invention provides a kind of bionical osteochondral composites and preparation method thereof, the complexs
It can be implanted into human body cartilaginous lesion site, barrier layer under cartilage, cartilage and subchondral bone are subjected to integrated reparation, formation can
Inducing endogenous cell moves into and can play the Bionics Bone repair of cartilage body of barrier function.Wherein, barrier layer can prevent joint
Liquid leaks and blocks blood vessel and nerve to grow into cartilage, and the structure of subchondral bone layer can be very good to meet vascularization and osteanagenesis
It is required that.Moreover, complex is combined into one by coupling and/or crosslinked method, and stretched by the burr or pseudopodium of collagen
Increase contact surface in the porous structure of ceramics, while being formed the collagen being solidificated in hole using the small interior big structure of the mouth of ball
The effect of " being difficult to extricate oneself ", reaches and effect is firmly fixed.
Also, in the complex of the five-layer structure in the present invention, gradient porous ceramics device is cellular, and distribution of pores is equal
Even, multiple-layer stacked, aperture arranges in gradient from top to bottom, is interconnected between gap, cell and tissue can be guided to grow into, simultaneously
Enough blood supply nutrition can be obtained by vascularization, make new life's to organize the formation of corresponding function.
In addition, the complex of the present invention is collagen and ceramic structure, after stem cell and ceramic device are compound on the surface thereof
It is close to attach and assemble growth into ceramic composite hole, it can be good at being attached to ceramic device hole inner wall and be filled
The stretching, extension divided, since bleeding and flushing cause cell loss when can be effectively prevented from cell-device complex application.Also, it should
Complex can reach reconstruction using the configuration and intensity of ceramics and act on, it is made to play filling, support, again in diseased region
Effect is built and guides, this is especially even more important to bone structure position, is suitably applied the injury repair of cartilage.
Description of the drawings
Fig. 1 is a kind of schematic diagram of cartilage structure.
Fig. 2 is a kind of structural schematic diagram for bionical osteochondral composites that one embodiment of the invention provides；
Fig. 3 is a kind of structural schematic diagram for bionical osteochondral composites that another embodiment of the present invention provides.
Wherein, 1- cartilage layers；2- barrier layers；3- subchondral bone layers；21- calcified cartilage layers；22- articulamentums；Under 23- cartilages
Bone plate layer.
Specific implementation mode
Below in conjunction with the drawings and specific embodiments to a kind of bionical osteochondral composites proposed by the present invention and its preparation side
Method is described in further detail.According to following explanation and claims, advantages and features of the invention will become apparent from.It needs to illustrate
, attached drawing is all made of very simplified form and uses non-accurate ratio, only to it is convenient, lucidly aid in illustrating this
The purpose of inventive embodiments.
Inventor has carried out detailed in-depth study to the structure of articular cartilage, finds articular cartilage rich in collagen, albumen
The connection of glycan and cartilage cell, articular cartilage and subchondral bone is a kind of labyrinth, as shown in Figure 1, connection structure master
To include loose under ripe cartilage (NCC), calcified cartilage (CC), damp line (Tidemark, Tm), subcartilaginous osseous lamella (SBP) and cartilage
The table shallow-layer of matter bone (STB), articular cartilage provides nutrition by joint fluid, and deep layer needs the tissue fluid of subchondral bone to permeate confession
It supports.
The study found that have " barrier " between articular cartilage and subchondral bone, the calcified cartilage and cartilage connected by damp line
Sending down the fishbone board group at.It is somebody's turn to do " barrier " and had both stopped that the blood vessel of subchondral bone and nerve grew into articular cartilage, and joint fluid is prevented to leak
Into articular cartilage, while ensureing that the tissue fluid in subchondral bone is soft by the deep layer of nutrition supply articular cartilage through barrier again
Bone.If subchondral bone cyst, bone defect, micro- bone split, osteonecrosis may occur for the barrier breakdown, and articular surface is caused to collapse
It falls into.Therefore, the treatment of articular cartilage damage will not only carry out bone and cartilage integration reparation and it is necessary to focus on articular cartilage with
The reparation of " barrier " between subchondral bone.
Based on this, the present invention provides under a kind of bionical osteochondral composites, including cartilage layers 1, barrier layer 2 and cartilage
The both sides of osteoplaque 3, the barrier layer 2 are connect with the subchondral bone layer 3 and the cartilage layers 1 respectively.The complex can plant
Enter human body cartilaginous lesion site, barrier layer under cartilage, cartilage and subchondral bone is subjected to integrated reparation, formation both can induce interior
Property cell in source moves into and can play the Bionics Bone repair of cartilage body of barrier function.
Structure, thickness and the size of bionical osteochondral composites are vital, will significantly affect its mechanical property, life
Object feature and clinical efficacy.By the further investigation to normal human's articular cartilage form and structure, complex can be specified
Each layer thickness, and can suitably being adjusted according to material characteristics and performance, compound volume morphing and size according to its whether carry cell,
Cartilage itself repair ability and operation method determine.
As a kind of realization method of the present invention, in one embodiment of this invention, the cartilage layers 1 are that collagen is porous
Layer, is prepared using natural collagen；The barrier layer 2 is micropore biological ceramic layer, uses tricalcium phosphate and/or hydroxyl
Apatite is prepared；The subchondral bone layer 3 is porous bio-ceramic layer, and tricalcium phosphate is used to be prepared；It is described more
The aperture in hole is more than or equal to the aperture in hole on the micropore biological ceramic layer on the biological ceramic layer of hole.The subchondral bone layer 3 with
The barrier layer 2 can be integrated connection, and the cartilage layers 1 are connect with the barrier layer 2 by coupling or crosslinked mode.
Also, the burr and pseudopodium of the collagen porous layer can stretch into the inside of the micropore biological ceramic layer and be given birth to the micropore
Object ceramic layer connects.The bionical osteochondral composites of three-decker can coordinate matrix inducing self-body chondrocyte cell transplantation.
Specifically, the preparation method of the bionical cartilage complex of three-decker includes the following steps in the present embodiment：Point
The cartilage layers 1 and the subchondral bone layer 3 are not prepared；It prepares to form the screen in one end of the subchondral bone layer 3
Barrier layer 2；The cartilage layers 1 are connect with the barrier layer 2, obtain the bionical osteochondral composites.
Wherein, when prepared by the cartilage layers 1, using the collagen scaffold that can induce repair of cartilage in MACI, in conjunction with liquid nitrogen ice
The porous structure collagen layer of endogenous cell cartilage differentiation can be promoted by freezing technology and layer assembly method structure, specific next
It says, the preparation method of porous collagen cartilage layers includes：It will be natural using the method for CAD and Solid Freeform
Collagen solution is prepared into the good collagen scaffold of structural arrangement through chemistry and special ice freeze techniques curing process.By detecting glue
Fibrinogen orientation, collagen membrane aperture, water absorption and swelling rate etc. can determine collagem membrane mechanical strength, and can measure the life of collagem membrane
Object degradation rate determines that collagen degradation connects each other with what its mechanical property changed, to which satisfactory collagen be prepared
Holder.
Then, the cartilage cavities of different layerings is built on the collagen scaffold using laser cutting technique；It will be prepared into
The holder arrived is freezed using frost forging casting such as liquid nitrogen at technique and crosslinked method according to the hierarchical ar-rangement of cartilaginous tissue
Reason, obtains the cartilage layers 1, porosity 10-50%, and aperture is 10-100 microns.
There is the cartilage cavities of the layered structure and different layerings of cartilaginous tissue by the cartilage layers that this method is prepared
No matter form accomplishes fully bionical from physical property and biological nature.It can be by microscope, scanning electron microscopic observation detection most
The pattern and structure of whole cartilage layers holder measure porosity, hole connectivity and the hole of cartilage layers holder by micro-CT etc.
Diameter is distributed.Different crosslinking conditions, which are measured, by dynamic test machine obtains the mechanical property of holder.Pass through weighing and ratiometer method
The water absorption and swelling performance and degradation rate of the cartilage layers holder that different crosslinking conditions obtain can be measured.
When preparing the subchondral bone layer 3, since subchondral bone layer 3 is porous bio-ceramic layer, it may be used porous
Ceramic preparation method is prepared, and accumulates the organic framework that more contact point principles prepare porous structure using sphere, is then perfused
Ceramic slurries, are dried to base, are sintered at high temperature into ceramics, precisely prepare the subchondral bone layer 3 with porous structure, and porosity is
40-80%, aperture are 100-800 microns.
The barrier layer 2 then equally uses ceramic capillary preparation process shape on the side of the subchondral bone layer 3
At forming controllable thin uniform layer micropore dense ceramic layers on subchondral bone layer 3, pass through diameter of particle, concentration of slurry, sintering
Temperature and pore creating material are next adjusted and controlled, and in the present embodiment, the porosity of barrier layer 2 is 0.5-40%, and aperture is that 0.1-15 is micro-
Rice.The ceramic layer of different micro-structures and different thickness to simulate joint fluid nutritional ingredient permeability, to blood vessel and nerve growth
Barrier effect all have an impact, can monitor nutrient permeation and vascular endothelial cell growth bioreactor system by establishing one
System, using this system, will observe whether to have have vascularization trend in barrier layer 2, to repair of cartilage ability and
Mechanical Property of Ceramics is evaluated.
Since barrier layer 2 and subchondral bone layer 3 have formed integration during ceramic post sintering, it is only necessary to by collagen cartilage layers
It is attached by crosslinking method and barrier layer 2, can judge connection effect and influence factor by tearing strength.In addition,
The burr and pseudopodium of the porous cartilage layers of collagen can stretch into the inside of the micropore biological ceramic layer and make pottery with the micropore biological
Enamel coating connection, burr and pseudopodium, which stretch into ceramic porous structure, can increase contact surface, while small interior big using the mouth of ball
Structure makes cured collagen in hole form the effect of " being difficult to extricate oneself ", achievees the effect that be fixedly secured, enhancing collagen porous layer with
Ceramic layer is connected and fixed effect.
Further, in another embodiment of the present invention, the bionical osteochondral composites can also be five layers of knot
Structure, specifically, in the bionical osteochondral composites, the cartilage layers 1 include ripe cartilage layers, the subchondral bone layer 3
Including subchondral bone girder layer；The barrier layer 2 includes sequentially connected calcified cartilage layer 21, articulamentum 22 and subcartilaginous osseous lamella
Layer 23；The maturation cartilage layers are connect with the calcified cartilage layer 21, the subcartilaginous osseous lamella layer 23 and the cartilaginous trabecula layer
Connection.
Wherein, the ripe cartilage layers are porous collagen maturation cartilage layers, and collagen is used to be prepared；The calcification is soft
Osteoplaque 21 is collagen calcified layer, and collagen composite tricalcium phosphate is used to be prepared；The subcartilaginous osseous lamella layer 23 is made pottery for micropore
Enamel coating uses tricalcium phosphate or hydroxylapatite ceramic to build to obtain；The subchondral bone girder layer is gradient porous biology
Ceramic layer has several holes thereon, and the aperture in several holes is along the direction gradient close to the micropore compact substance ceramic layer
Successively decrease, and the aperture in the hole on the gradient porous bioceramic layer is more than the aperture in the hole on the micropore ceramics layer；Institute
It is composite collagen articulamentum 22 to state articulamentum 22, and collagen is used to be prepared.
Connecting between the porous collagen maturation cartilage layers and the collagen calcified layer, the collagen calcified layer with it is described
Connecting between composite collagen articulamentum 22, the connection between the composite collagen articulamentum 22 and the micropore ceramics layer, institute
The connection between micropore ceramics layer and the gradient porous bioceramic layer is stated, coupling is all made of or crosslinked mode connects.And
And the burr or pseudopodium of the collagen calcified layer can stretch into the micropore biological ceramic layer inside and with the micropore biological
Ceramic layer connects.
Specifically, the preparation method of the bionical cartilage complex of five-layer structure includes the following steps in the present embodiment：Point
The ripe cartilage layers, the calcified cartilage layer 21, the subcartilaginous osseous lamella layer 23 and the subchondral bone girder layer are not prepared；
Using coupling or crosslinking Treatment the connection ripe cartilage layers and the calcified cartilage layer 21, the subcartilaginous osseous lamella layer 23 and institute
State subchondral bone girder layer；Using collagen solution as adhesive, by the calcified cartilage layer 21 and the subcartilaginous osseous lamella layer
23 connections, the collagen layer between the calcified cartilage layer 21 and the subcartilaginous osseous lamella layer 23 after connection are the articulamentum
22。
Wherein, the ripe cartilage layers are porous collagen maturation cartilage layers, the preparation of the porous collagen maturation cartilage layers
Method includes：Auxiliary agent and collagen are prepared into mixed solution；Mixed solution is crosslinked using crosslinking agent, after being crosslinked
Solution；The solution after the crosslinking is handled using CAD and frost curing process, obtains porous collagen
Ripe cartilage layers, porosity 10-50%, aperture are 10-100 microns.It is different by studying double bond grafting rate, macromonomer
With when concentration, water absorption and swelling rate etc. to the affecting parameters of mechanical strength, and the biodegradation rate of composite construction collagen is combined,
It obtains collagen degradation to connect each other with what its mechanical property changed, to which suitable porous collagen maturation cartilage layers be prepared.
In the above scheme, the auxiliary agent is selected from 2- (N- morpholines) ethanesulfonic acid monohydrate, sodium chloride, N- maloyls
One or more combinations in imines, dimethylaminopropyl ethyl carbamide and sodium alginate；The collagen be I types and/or
II Collagen Type VIs；The crosslinking agent is adipic dihydrazide.
When preparing calcified cartilage layer 21, since the calcified cartilage layer 21 is collagen calcified layer, the collagen calcified layer
Preparation method may include：Tricalcium phosphate is blended with collagen solution, drying and forming-film obtains the evenly dispersed organic/inorganic of powder
Hydridization collagem membrane, the hydridization compact substance collagen calcified cartilage layer 21 are the required calcified cartilage layer 21 of the present invention.
The subcartilaginous osseous lamella layer 23 is micropore ceramics layer, and the preparation method of the micropore ceramics layer includes：By tricresyl phosphate
The micropore ceramics with dense micro-hole structure are prepared through high temperature sintering in the powder slurries of calcium and/or hydroxyapatite
Layer, in the present embodiment, the porosity of the micropore ceramics layer is 0.5-40%, and aperture is 0.1-15 microns.
In the present embodiment, the subchondral bone girder layer is gradient porous bioceramic layer, based on to natural bone tissue
The understanding and understanding of structure prepare intercommunicating pore knot by multistage package technique with the controllable organic micro-spheres architecture template of three-dimensional structure
The controllable calcium phosphate gradient porous ceramics of structure build the subchondral bone girder layer.By regulating and controlling Microsphere Size, heap in template
The regulation and control such as product mode porosity, pore size, distribution and aperture connected ratio etc., by assigning material lower end larger aperture size
With porosity so as to fit the adherency, growth and differentiation of osteocyte；It is smaller (close to cartilaginous areas) by assigning material upper end
Structure makes it effectively inhibit relevant cell behavior and blood vessel to cartilage.It realizes with this configuration and linked groups' cell is being repaired
Biology performance regulates and controls in body, and advantageous microenvironment is provided for bone cartilage integration reparation.Specifically, the gradient porous biology
The preparation method of ceramic layer includes：According to the structure design organic formwork of subchondral bone girder layer；Using organic formwork method, setting
The gradient porous bioceramic layer, the micropore pottery is prepared in the size and accumulation mode of microballoon in the organic formwork
The porosity of enamel coating is 40-80%, and aperture is 100-800 microns.
Specifically, gradient porous bioceramic layer of the invention can be completed by following technological process：
1) holder makes：According to shape of product and size, corresponding mold is made, passes through layered arrangement different-grain diameter PMMA
Particle makes holder.Set of molds is two cylinders of nested type size, small cylinder mould diameter 20mm, cylinder and bottom wall thickness
0.1mm, high 20mm, cylinder and bottom are uniformly distributed micropore, and micropore size is less than the aperture of PMMA particles used, and bolt is arranged at top
Body.Big cylinder is entity, and diameter 30mm, cylinder and bottom wall thickness 5mm, high 25mm, both size cylinder molds gap are straight
Diameter is about 10mm.In small cylinder by multilayer PMMA particles from small to large, be arranged under the overlay constitute from bottom to up, share 6 layers.Successively
Weigh suitable PMMA particles with measuring cup, die hole poured by funnel, spread from bottom to up aperture be 100 microns, it is 200 micro-
Rice, 300 microns, 400 microns, 500 microns, 600 microns of PMMA particles, thickness is 2 millimeters；It completes upper back and bolt is added
Body is put into big cylinder；In 22-30 DEG C of room temperature, 75% acetone is slowly injected in the gap of size cylinder mold, acetone
Particle is slowly infiltrated from the bottom to top, need to submerge particle.Body uniform pressurization simultaneously；Acetone stops 2.5-5 minutes in gap, takes
Body is removed, is rinsed with purified water, reaches and is adhesively fixed；Small cylinder mold is inverted in purified water, fixed-type branch is made
Frame deviates from mold, is used in combination in purified water and rinses；The carrying of holder stainless steel instruments box is put into 50 DEG C of drying in oven, 8-12 is small
When.
2) holder is in the milk：Weigh suitable purified water and tricalcium phosphate powder；They and suitable son of milling are put into stone roller
In grinding jar, capping is tightened nut and is fixed；Grinding mill is put it into, is milled 2 hours；Slurries are obtained, slurries, which are poured into beaker, to be added
Corresponding deal adhesive；Blender is put it into stir 10 minutes.The PMMA holders made neatly are put on gypsum,
Periphery is surrounded with plaster strip, is bonded holder；Slurries are poured on the PMMA stent covers enclosed, slurries is kept to submerge organic framework；
It stands until the moisture of slurries is absorbed by plasterboard；After slurries are solid, you can the plaster strip for removing out periphery, by solid ceramic blank
Body is peeled away, with the gauze for being soaked with purified water that the repairing of ceramic body surface is smooth, is stored with stainless steel instruments box；It is placed in electric heating
Air dry oven dries 50 DEG C, 8-12 hours.
3) ceramic blank-body exhaust glue and sintering：Ceramic body is positioned in sintering tank, and is put into draft glue discharging furnace；According to technique item
Relevant parameter is arranged in part, starts draft glue discharging furnace and exhaust blower；Drained ceramic body is put into sintering furnace；It is set according to process conditions
Relevant parameter is set, sintering furnace and exhaust blower are started；After the completion of sintering, the ceramics sintered into are taken out in 1000-1200 DEG C of furnace temperature
Product sterilizes, and obtains the gradient porous bioceramic layer that can directly use.
After completing the preparation to the ripe cartilage layers, calcified cartilage layer, subcartilaginous osseous lamella layer and subchondral bone girder layer,
Compound connection is carried out by successively assemble method.Since each fabrication of cartilage structure sheaf is mainly made of collagen and calcium phosphate ceramic,
Hydrogen bond and Van der Waals force interaction can be formed between them.Each layer is soaked using collagen solution as adhesive, it is dry through room temperature
Dry step can be obtained double replica bone cartilage repair materials of the biomimetic features containing multilayer.The burr or puppet of collagen can stretch into ceramics completely
Porous structure in and increase contact surface, in hole collagen solidification after with ceramics formed cross structure reach secured effect.
The present invention provides a kind of bionical osteochondral composites and preparation method thereof, which can be implanted into human body cartilage
Barrier layer under cartilage, cartilage and subchondral bone are carried out integrated reparation by damage location, formation can inducing endogenous cell move
Enter and can play the Bionics Bone repair of cartilage body of barrier function.Wherein, barrier layer can prevent joint fluid from leaking and blocking blood vessel
Cartilage is grown into nerve, the structure of subchondral bone layer can be very good the requirement for meeting vascularization and osteanagenesis.Moreover, complex
It is combined into one by coupling and/or crosslinked method, and is stretched into the porous structure of ceramics by the burr of collagen or pseudopodium
And increase contact surface, while the collagen being solidificated in hole being formed to the effect of " being difficult to extricate oneself " using the small interior big structure of the mouth of ball
Fruit reaches and effect is firmly fixed.
Also, in the complex of the five-layer structure in the present invention, gradient porous ceramics device is cellular, and distribution of pores is equal
Even, multiple-layer stacked, aperture arranges in gradient from top to bottom, is interconnected between gap, cell and tissue can be guided to grow into, simultaneously
Enough blood supply nutrition can be obtained by vascularization, make new life's to organize the formation of corresponding function.
In addition, the complex of the present invention is collagen and ceramic structure, after stem cell and ceramic device are compound on the surface thereof
It is close to attach and assemble growth into ceramic composite hole, it can be good at being attached to ceramic device hole inner wall and be filled
The stretching, extension divided, since bleeding and flushing cause cell loss when can be effectively prevented from cell-device complex application.Also, it should
Complex can reach reconstruction using the configuration and intensity of ceramics and act on, it is made to play filling, support, again in diseased region
Effect is built and guides, this is especially even more important to bone structure position, is suitably applied the injury repair of cartilage.
Foregoing description is only the description to present pre-ferred embodiments, not to any restriction of the scope of the invention, this hair
Any change, the modification that the those of ordinary skill in bright field does according to the disclosure above content, belong to the protection of claims
Range.
Claims (10)
1. a kind of bionical osteochondral composites, which is characterized in that including cartilage layers, barrier layer and subchondral bone layer, the screen
The both sides of barrier layer are connect with the subchondral bone layer and the cartilage layers respectively.
2. a kind of bionical osteochondral composites according to claim 1, which is characterized in that the cartilage frame is that collagen is more
Aperture layer is prepared using natural collagen；
The barrier layer is micropore biological ceramic layer, and tricalcium phosphate and/or hydroxyapatite is used to be prepared；
The subchondral bone layer is porous bio-ceramic layer, and tricalcium phosphate is used to be prepared；
The aperture in hole is more than or equal to the aperture in hole on the micropore biological ceramic layer on the porous bio-ceramic layer.
3. a kind of bionical osteochondral composites according to claim 2, which is characterized in that the subchondral bone layer with it is described
Barrier layer integration connects, and the cartilage layers are connect with the barrier layer by being coupled or being crosslinked；The hair of the collagen porous layer
Thorn and pseudopodium stretch into the inside of the micropore biological ceramic layer and are connect with the micropore biological ceramic layer.
4. a kind of bionical osteochondral composites according to claim 1, which is characterized in that it is characterized in that, the cartilage
Layer includes ripe cartilage layers, and the subchondral bone layer includes subchondral bone girder layer；
The barrier layer includes sequentially connected calcified cartilage layer, articulamentum and subcartilaginous osseous lamella layer；
The maturation cartilage layers are connect with the calcified cartilage layer, and the subcartilaginous osseous lamella layer is connect with the cartilaginous trabecula layer.
5. a kind of bionical osteochondral composites according to claim 4, which is characterized in that the maturation cartilage layers are porous
Collagen maturation cartilage layers, use collagen to be prepared；
The calcified cartilage layer is collagen calcified layer, and collagen composite tricalcium phosphate is used to be prepared；
The subcartilaginous osseous lamella layer is micropore ceramics layer, and tricalcium phosphate or hydroxylapatite ceramic is used to build to obtain；
The subchondral bone girder layer is gradient porous bioceramic layer, has several holes, the hole in several holes thereon
Diameter successively decreases along the direction gradient close to the micropore compact substance ceramic layer, and the hole in the hole on the gradient porous bioceramic layer
Diameter is more than the aperture in the hole on the micropore ceramics layer；
The articulamentum is composite collagen articulamentum, and collagen is used to be prepared.
6. a kind of bionical osteochondral composites according to claim 5, which is characterized in that the porous collagen maturation cartilage
Layer the collagen calcified layer between connect, the connection between the collagen calcified layer and the composite collagen articulamentum, institute
Connecting between composite collagen articulamentum and the micropore ceramics layer, the micropore ceramics layer and the gradient porous biology is stated to make pottery
Connection between enamel coating, is all made of coupling or crosslinked mode connects；
The burr or pseudopodium of the collagen calcified layer stretch into the inside of the micropore biological ceramic layer and make pottery with the micropore biological
Enamel coating connects.
7. a kind of a kind of preparation method of bionical osteochondral composites as claimed in any one of claims 1-3, feature exist
In including the following steps：
The cartilage layers and the subchondral bone layer are prepared respectively；
It is prepared on the side of the subchondral bone layer and forms the barrier layer；
The cartilage layers are connect with the barrier layer, obtain the bionical osteochondral composites.
8. a kind of preparation method of bionical osteochondral composites according to claim 7, which is characterized in that the cartilage layers
Preparation method include：
Collagen is prepared by collagen scaffold using the method for CAD and Solid Freeform；
The cartilage cavities of different layerings is built on the collagen scaffold using laser cutting technique；
By the holder being prepared according to the hierarchical ar-rangement of cartilaginous tissue, handled using frost forging casting and crosslinked method,
The cartilage layers, porosity 10-50% are obtained, aperture is 10-100 microns；
The subchondral bone layer is prepared using porous ceramics manufacture craft, porosity 40-80%, aperture 100-800
Micron；
The barrier layer is formed using ceramic capillary preparation process on the side of the subchondral bone layer, and porosity is
0.5-40%, aperture are 0.1-15 microns.
9. a kind of a kind of preparation method of bionical osteochondral composites as described in any one of claim 4-6, feature exist
In including the following steps：
The ripe cartilage layers, the calcified cartilage layer, the subcartilaginous osseous lamella layer and the subchondral bone girder are prepared respectively
Layer；
Using coupling or crosslinking Treatment the connection ripe cartilage layers and the calcified cartilage layer, the subcartilaginous osseous lamella layer and institute
State subchondral bone girder layer；
Using collagen solution as adhesive, the calcified cartilage layer is connected with the subcartilaginous osseous lamella layer, the institute after connection
It is the articulamentum to state the collagen layer between calcified cartilage layer and the subcartilaginous osseous lamella layer.
10. a kind of preparation method of bionical osteochondral composites according to claim 9, which is characterized in that the maturation
Cartilage layers are porous collagen maturation cartilage layers, and the preparation method of the porous collagen maturation cartilage layers includes：
Auxiliary agent and collagen are prepared into mixed solution；
Mixed solution is crosslinked using crosslinking agent, the solution after being crosslinked；
Using CAD and frost curing process the solution after the crosslinking is handled, obtain porous collagen at
Ripe cartilage layers, porosity 10-50%, aperture are 10-100 microns；
The calcified cartilage layer is collagen calcified layer, and the preparation method of the collagen calcified layer includes：By tricalcium phosphate and collagen
Solution blending, drying and forming-film obtain the collagen calcified layer；
The subcartilaginous osseous lamella layer is micropore ceramics layer, and the preparation method of the micropore ceramics layer includes：By tricalcium phosphate and/or
The micropore ceramics layer is prepared through high temperature sintering in the powder slurries of hydroxyapatite, and the porosity of the micropore ceramics layer is
0.5-40%, aperture are 0.1-15 microns；
The subchondral bone girder layer is gradient porous bioceramic layer, the preparation method packet of the gradient porous bioceramic layer
It includes：According to the structure design organic formwork of subchondral bone girder layer；
Using organic formwork method, the size and accumulation mode of microballoon in the organic formwork are set, it is more that the gradient is prepared
The porosity of hole biological ceramic layer, the gradient porous ceramics layer is 40-80%, and aperture is 100-800 microns.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109730812A (en) * | 2019-01-31 | 2019-05-10 | 重庆凝骄生物科技有限公司 | A kind of focal cartilage defect repair body |
| CN110368529A (en) * | 2019-08-19 | 2019-10-25 | 江苏地韵医疗科技有限公司 | Cartilage or subchondral bone holostrome recovery support and preparation method thereof |
| CN110652381A (en) * | 2019-10-24 | 2020-01-07 | 深圳兰度生物材料有限公司 | Osteochondral repair scaffold and preparation method thereof |
| CN112535553A (en) * | 2020-12-12 | 2021-03-23 | 山东百多安医疗器械股份有限公司 | Skull repairing plate with composite structure |
| CN113478815A (en) * | 2021-06-30 | 2021-10-08 | 杭州电子科技大学 | 3D printing method of osteochondral scaffold with highly bionic mechanical property |
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Citations (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005000169A2 (en) * | 2003-06-24 | 2005-01-06 | Dr. H. C. Robert Mathys Stiftung | Prosthetic device for cartilage repair |
| EP1547547A1 (en) * | 1994-05-13 | 2005-06-29 | Kensey Nash Corporation | Device and method for in vivo culturing of diverse tissue cells |
| US20070148242A1 (en) * | 2003-02-26 | 2007-06-28 | Zimmer Orthobiologics, Inc | Preparation for repairing cartilage tissue, especially articular cartilage defects |
| CN101020083A (en) * | 2007-03-08 | 2007-08-22 | 中国人民解放军第三军医大学第一附属医院 | Integral engineering rack of interface osteochondro tissue with bionic function |
| CN101032430A (en) * | 2007-04-13 | 2007-09-12 | 中国人民解放军第三军医大学第一附属医院 | Method for preparing integrated frame fabrication of cartilage of tissue-engineered bone having function interface |
| US20080249632A1 (en) * | 2007-02-26 | 2008-10-09 | Biomet Sports Medicine, Inc. | Stable cartilage defect repair plug |
| WO2010114578A1 (en) * | 2009-04-02 | 2010-10-07 | Synvasive Technology, Inc. | Monolithic orthopedic implant with an articular finished surface |
| WO2011094316A2 (en) * | 2010-01-26 | 2011-08-04 | Warsaw Orthopedic, Inc. | Highly compression resistant matrix with porous skeleton |
| CN103463676A (en) * | 2013-08-14 | 2013-12-25 | 西安交通大学 | Bionic bone/cartilage composite scaffold and preparation technology and fixing method thereof |
| CN104117097A (en) * | 2014-08-14 | 2014-10-29 | 天津市天津医院 | Integrated epiphyseal cartilage scaffold with bionic interface structure and preparation method thereof |
| CN104324418A (en) * | 2014-10-27 | 2015-02-04 | 东华大学 | Nanofiber bone cartilage repairing stent for tissue engineering and preparation method thereof |
| CN105312538A (en) * | 2014-07-07 | 2016-02-10 | 陈焕铭 | New method for preparing Nb/TiAl composite material |
| CN105833348A (en) * | 2016-04-19 | 2016-08-10 | 青岛大学附属医院 | Method for preparing hBMSCs/hyaline cartilage particle/calcium alginate gel compound and application thereof |
| CN106659819A (en) * | 2014-07-24 | 2017-05-10 | 维尔纳·恩斯特·路德维格·格奥尔格·米勒 | Printable morphogenetic phase-specific chitosan-calcium-polyphosphate scaffold for bone repair |
| WO2017118863A1 (en) * | 2016-01-08 | 2017-07-13 | Ucl Business Plc | Osteochondral scaffold |
-
2018
- 2018-06-01 CN CN201810559175.4A patent/CN108404214B/en active Active
Patent Citations (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1547547A1 (en) * | 1994-05-13 | 2005-06-29 | Kensey Nash Corporation | Device and method for in vivo culturing of diverse tissue cells |
| US20070148242A1 (en) * | 2003-02-26 | 2007-06-28 | Zimmer Orthobiologics, Inc | Preparation for repairing cartilage tissue, especially articular cartilage defects |
| WO2005000169A2 (en) * | 2003-06-24 | 2005-01-06 | Dr. H. C. Robert Mathys Stiftung | Prosthetic device for cartilage repair |
| US20080249632A1 (en) * | 2007-02-26 | 2008-10-09 | Biomet Sports Medicine, Inc. | Stable cartilage defect repair plug |
| CN101020083A (en) * | 2007-03-08 | 2007-08-22 | 中国人民解放军第三军医大学第一附属医院 | Integral engineering rack of interface osteochondro tissue with bionic function |
| CN101032430A (en) * | 2007-04-13 | 2007-09-12 | 中国人民解放军第三军医大学第一附属医院 | Method for preparing integrated frame fabrication of cartilage of tissue-engineered bone having function interface |
| WO2010114578A1 (en) * | 2009-04-02 | 2010-10-07 | Synvasive Technology, Inc. | Monolithic orthopedic implant with an articular finished surface |
| WO2011094316A2 (en) * | 2010-01-26 | 2011-08-04 | Warsaw Orthopedic, Inc. | Highly compression resistant matrix with porous skeleton |
| CN103463676A (en) * | 2013-08-14 | 2013-12-25 | 西安交通大学 | Bionic bone/cartilage composite scaffold and preparation technology and fixing method thereof |
| CN105312538A (en) * | 2014-07-07 | 2016-02-10 | 陈焕铭 | New method for preparing Nb/TiAl composite material |
| CN106659819A (en) * | 2014-07-24 | 2017-05-10 | 维尔纳·恩斯特·路德维格·格奥尔格·米勒 | Printable morphogenetic phase-specific chitosan-calcium-polyphosphate scaffold for bone repair |
| CN104117097A (en) * | 2014-08-14 | 2014-10-29 | 天津市天津医院 | Integrated epiphyseal cartilage scaffold with bionic interface structure and preparation method thereof |
| CN104324418A (en) * | 2014-10-27 | 2015-02-04 | 东华大学 | Nanofiber bone cartilage repairing stent for tissue engineering and preparation method thereof |
| WO2017118863A1 (en) * | 2016-01-08 | 2017-07-13 | Ucl Business Plc | Osteochondral scaffold |
| CN105833348A (en) * | 2016-04-19 | 2016-08-10 | 青岛大学附属医院 | Method for preparing hBMSCs/hyaline cartilage particle/calcium alginate gel compound and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| FRANCESCO PERDISA等: "One-Step Treatment for Patellar Cartilage Defects With a Cell-Free Osteochondral Scaffold：A Prospective Clinical and MRI Evaluation", 《THE AMERICAN JOURNAL OF SPORTS MEDICINE》 * |
| TOBIAS GOTTERBARM等: "An in vivo study of a growth-factor enhanced, cell free, two-layered collagen–tricalcium phosphate in deep osteochondral defects", 《BIOMATERIALS》 * |
| 陈竹生等: "纳米β-磷酸三钙/Ⅰ、Ⅱ型胶原层状支架复合骨髓间充质干细胞修复膝关节骨软骨缺损", 《中国组织工程研究与临床康复》 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109730812A (en) * | 2019-01-31 | 2019-05-10 | 重庆凝骄生物科技有限公司 | A kind of focal cartilage defect repair body |
| CN109730812B (en) * | 2019-01-31 | 2022-02-08 | 重庆凝骄生物科技有限公司 | Focal cartilage defect prosthesis |
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| CN110652381A (en) * | 2019-10-24 | 2020-01-07 | 深圳兰度生物材料有限公司 | Osteochondral repair scaffold and preparation method thereof |
| CN112535553A (en) * | 2020-12-12 | 2021-03-23 | 山东百多安医疗器械股份有限公司 | Skull repairing plate with composite structure |
| CN112535553B (en) * | 2020-12-12 | 2021-12-07 | 山东百多安医疗器械股份有限公司 | Skull repairing plate with composite structure |
| CN113478815A (en) * | 2021-06-30 | 2021-10-08 | 杭州电子科技大学 | 3D printing method of osteochondral scaffold with highly bionic mechanical property |
| CN114191615A (en) * | 2021-12-21 | 2022-03-18 | 浙江大学 | Multilayer composite material for promoting repair of articular cartilage-calcified layer-subchondral bone and preparation method thereof |
| CN114191615B (en) * | 2021-12-21 | 2022-07-08 | 浙江大学 | Multilayer composite material for promoting repair of articular cartilage-calcified layer-subchondral bone and preparation method thereof |
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