CN100522265C - Integral engineering rack of interface osteochondro tissue with bionic function - Google Patents
Integral engineering rack of interface osteochondro tissue with bionic function Download PDFInfo
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- CN100522265C CN100522265C CNB2007100782649A CN200710078264A CN100522265C CN 100522265 C CN100522265 C CN 100522265C CN B2007100782649 A CNB2007100782649 A CN B2007100782649A CN 200710078264 A CN200710078264 A CN 200710078264A CN 100522265 C CN100522265 C CN 100522265C
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Abstract
The integral engineering rack of interface osteochondro tissue with bionic interface includes from the top to the bottom one cartilage layer, one calcified layer and one bone layer below cartilage connected organically. The cartilage layer consists of type II collagen and chitosan connected in covalent bond; the calcified layer consists of type II collagen and hydroxyapatite connected in covalent bond; the bone layer below cartilage consists of type I collagen and hydroxyapatite connected in covalent bond; and each of the cartilage layer and the bone layer below cartilage has at least one pore of 100-500 micron size. The integral engineering rack of the present invention has excellent biocompatibility, excellent degradability, sufficient mechanical first and bionic interface function.
Description
Technical field
The present invention relates to a kind of tissue engineering bracket that is used to repair the human synovial osteochondral defect, especially have the bionic function integral engineering rack of interface osteochondro tissue.
Background technology
The diarthrosis end osteochondral defect that wound, infection and regression etc. cause is the clinical common disease of orthopaedics, often shows as intractable pain, joint movement disorder, but severe patient lost-motion function.According to statistics, the sickness rate of U.S.'s ossa articularia cartilage defect is about 1.5 ‰～3 ‰, and China is its 5～6 times.Because articular cartilage does not have blood vessel, nerve and lymphsystem, diameter surpasses the osteochondral defect of 2mm～4mm and almost can not repair fully.All there is open defect in existing Therapeutic Method, and is difficult to make it really to reach the nature reparative regeneration.Joint debridement art respite symptom can not stop course of disease development; Arthrodesis, excision-arthroplasty are seriously lost function of joint; There are problems such as bone dissolving at a specified future date and prosthetic loosening in artificial joint replacement; Arthroscope sending down the fishbone cartilage piece transplantation, autotransplantation cause that then there are drawbacks such as rejection and potential communicate illness in damaged and limited, the heteroplastic transplantation of originating for the district.Developing rapidly of tissue engineering technique is for the Regeneration and Repair of ossa articularia cartilage defect provides New Policy.
Both at home and abroad the structure research of osteochondro tissue is paid attention to day by day.Construction strategy commonly used can be divided into 2 classes: (1) divides layer building: dividing layer building is the construction strategy that researcher adopts at first, promptly make up cartilage and osseous tissue respectively, with modes such as absorbable thread stitching or fibrin glue bonds both are bonded into an integral body then, external continuation is cultivated a period of time or is not cultivated the repair deficiency that directly implants.Schaefer etc. are inoculated in poly-Acetic acid, hydroxy-, bimol. cyclic ester (PGA) non-woven fiber network structure cartilage with the chondrocyte in new born bovine condyle of femur source, the osteoblast in ulna periosteum source are inoculated in mixture (80: 20) the structure subchondral bone of polylactide-poly-glycolide copolymer (PLGA) and Polyethylene Glycol (PEG); Both are by promoting into cartilage and 1 week or 4 weeks of skeletonization condition single culture, with absorbable thread the outer continuation of both suture bodies was cultivated for 4 weeks altogether then, morphologic detection shows that both are in conjunction with having formed osteochondro tissue, zoopery shows subchondral bone and host bone integration on every side well, but the cartilage that makes up is not good enough with host's cartilage integration on every side.The poly-ethanol fat (PEGDA) of the two acrylic acids of utilizations such as Alhadlaq makes up cartilage and osseous tissue respectively, adopt the uv photopolymerization method that the timbering material of two kinds of tissues is aggregated into then and be used for experiment in the body after as a whole, detect in 12 weeks of postoperative and find have cartilage sample or osteoid tissue to form, but do not form damp line structure between tissue at respective regions; Domestic Cao Yi woods, Hu Yunyu etc. have similar research; (2) one makes up: the identical or different integrated bone cartilage compound rest of prepared composition and structure at first, inoculate into the cartilage seed cell in the cartilage zone then, skeletonization zone inoculation or do not inoculate the skeletonization seed cell, the structure osteochondro tissue.Guoping Chen etc. makes cartilage frame with collagen sponge, and polylactide-poly-glycolide copolymer (PLGA) and collagen formation bone support are connected by collagen sponge between two-layer; Then Canis familiaris L. MSCs is inoculated in the two-phase support, implants in one week of In vitro culture and repair Canis familiaris L. knee joint osteochondral defect, 4 months histology results of postoperative show that repair tissue forms cartilage and bone respectively, but mechanical performance is relatively poor.The integrated bone cartilage compound rest that usefulness TheriFormTM 3 D-printing fabrication techniques such as Sherwood are made of heterogeneity, cartilage portion be by D, and L-PLGA/l-PLA constitutes, and porosity 90% is column, in channels interleaved is arranged; Osseous part is made of L-PLGA/TCP, and porosity 55% is cloverleaf (four-leaf clover) shape, changes in gradient at cartilage and bone junctional area material and porosity.Cartilage frame inoculation chondrocyte, osseous part is 6 weeks of inoculating cell In vitro culture not, and the groupization detection shows has cartilaginous part to have cartilage to form, and the osseous part mechanical property is similar to the fresh spongy bone intensity of people.Domestic king meets army, Zhang Renji etc. correlational study.Adopt tissue engineering technique to reproduce single bone of cell component or extensively success of cartilaginous tissue acquisition, the part achievement has entered clinical practice.The research of reproducing of through engineering approaches osteochondro tissue starts to walk a little later, but progress is swift and violent, has obtained phasic results from making up Preliminary Feasibility Exploration to animal experiment study; Reproducing that liver mass defective, graft and host integrate not good enough and lack corresponding mechanical function is the main bottleneck that limits its clinical practice.
The human synovial osteochondro tissue is the very complicated functional organization of The Nomenclature Composition and Structure of Complexes, ideal through engineering approaches bone cartilage complex construction strategy is not that the cartilage that will reproduce and osseous tissue are sewed up simply or be bonded together, and it is the decision key of success that the integrated three-dimensional support with function interface makes up.Therefore, the imagination that makes up bionic function interface (calcification layer structure) certainly will solve reproduces liver mass defective, graft and host and integrates problems such as not good enough, this be because: (1) can be securely fixed in cartilage on the subchondral bone by bionical calcification layer particular interface structure, the back cartilage that prevents to implant breaks away from body from subchondral bone, thereby helps graft and host's integration of interface.(2) osteochondro tissue that utilizes calcification layer compact structure to make to implant becomes the cartilage microenvironment as what the host was divided into oxygen and nutritious skeletonization microenvironment, oxygen and malnutrition naturally, prevent to implant cell and move with becoming between the cartilage support, promote the specific region cell to utilize separately microenvironment to specific direction propagation, differentiation at skeletonization.
Former studies adopts traditional methods such as lamination, fusion cast and fiber bonding to make bone cartilage compound rest more, and complex process, repeated relatively poor is difficult to realize industrialization production; And the three-dimensional rack regular shape of making is a rectangle or cylindrical often, is difficult to satisfy the changeable osteochondral defect of shape.The 3 D-printing technology is ripe gradually and on probation in single organization's engineering bone and cartilage structure in recent years, adopt this technology not only can realize the integrated manufacturing of bone cartilage compound rest, simultaneously can also make its specific anatomical profile and interior spatial structure with clinical needs, more superior is can be with cell inoculation in the support porous when preparing support.Timbering material is selected and modified is another key factor of preparation bone cartilage compound rest, and ideal timbering material should have excellent biological compatibility, is beneficial to cell adhesion, hypertrophy and differentiation; The degradable absorbability can make by artificial regulatory that the cambium speed of growth is complementary in its degraded and absorbed speed and the body; The favorable mechanical characteristic can satisfy the mechanics requirement of implant site.
The osteochondro tissue that prior art makes up lacks ideal function interface; Exist and to reproduce liver mass defective, graft and host and integrate not good enough and problem such as mechanical strength is relatively poor, can not satisfy clinical repair ossa articularia cartilage defect needs.
Summary of the invention
The osteochondro tissue that the present invention is directed to the prior art structure lacks ideal function interface; Exist and to reproduce liver mass defective, graft and host and integrate not good enough and problem such as mechanical strength is relatively poor, a kind of osteochondro tissue integral engineering rack that has excellent biological compatibility, controlled degradation and sufficient mechanical strength and have the bionic function interface is provided.Adopt support of the present invention can construct the compound repair tissue of through engineering approaches bone cartilage that can meet clinical needs in conjunction with seed cell technology of preparing, two-phase gel inoculation technique and piece of tissue In vitro culture technology.
Technical scheme of the present invention:
Has the bionic function integral engineering rack of interface osteochondro tissue, it is characterized in that: this support is made up of cartilage layers, calcification layer and subchondral bone layer three part from top to bottom, each layer has different constituent and interior spatial structure, closely connects by the special The Nomenclature Composition and Structure of Complexes of calcification layer between each layer.(1) cartilage layers is made up of II Collagen Type VI and chitosan, and II Collagen Type VI weight ratio is 80%～90%, the chitosan weight ratio is 10%～20%; Upper surface is smooth, lower surface is wavy and the upper surface calcification layer and is complementary, wave height be 50 μ m～80 μ m, ripple wide be 200 μ m～300 μ m; Thickness is 3mm～5mm; Porosity is 85%～90%, the aperture is that 100 μ m～150 μ m, hole passband are 100%; (2) the calcification layer is made up of II Collagen Type VI and hydroxyapatite, and II Collagen Type VI weight ratio is 60%～70%, the hydroxyapatite weight ratio is 30%～40%; Upper surface is wavy and is complementary with lower surface cartilage layers; Lower surface be rough and uneven in surface broach shape and subchondral bone upper surface mutually anchor close, it is coniform that broach is, the awl height is that 250 μ m～300 μ m, cone bottom diameter are 200 μ m～250 μ m; Thickness is 50 μ m～350 μ m, compact structure.(3) the subchondral bone layer is made up of type i collagen and hydroxyapatite, and the type i collagen weight ratio is 70%～80%, the hydroxyapatite weight ratio is 20%～30%; Upper surface be rough and uneven in surface broach shape and calcification layer lower surface mutually anchor close; Lower surface is also that the utilization of broach shape implants and the firm anchor in host interface closes, awl high for 1mm～2mm, cone bottom diameter be 2mm～3mm; Thickness is 8mm～10mm; Porosity is 55%～60%, the aperture is that 200 μ m～500 μ m, hole passband are 100%.
The present invention adopt the 3 D-printing technology according to bionics principle development have a function interface osteochondro tissue integral engineering rack, have following characteristics:
1, structure-functional characteristics: (1) cartilage layers support has the interior spatial structure of suitable chondrocyte proliferation, differentiation; (2) subchondral bone layer support has the interior spatial structure of suitable osteoblastic proliferation, differentiation; (3) utilize the scraggly interfacial structure of calcification layer to increase connection area and bonding strength between support, the firm earth anchor of cartilage frame is combined on the subchondral bone, be beneficial to after implanting that stress disperses between tissue, prevent layering between tissue.Utilize calcification layer compact texture stop to implant cell and move with becoming between the cartilage support at skeletonization, the cell that is beneficial to the specific region utilizes separately microenvironment to specific direction propagation, differentiation, thus the integration of interface between reinforcement graft and the host.
2, form--functional characteristics (1) selects for use II Collagen Type VI and chitosan as the cartilage layers timbering material, and the one side biomimetic material has excellent biological compatibility and is beneficial to chondrocyte adhesion, hypertrophy and differentiation; Can regulate and control the degradation speed and the mechanical strength of cartilage frame on the other hand by the proportion of composing of control II Collagen Type VI and chitosan; (2) select for use type i collagen and hydroxyapatite as subchondral bone layer timbering material, help osteoblast adhesion, hypertrophy and differentiation on the one hand; Can increase the mechanical strength of support on the other hand; (3) select for use II Collagen Type VI and hydroxyapatite as calcification layer timbering material, the interface is formed have the II Collagen Type VI identical simultaneously and identical hydroxyapatite with subchondral bone with cartilage, promptly strengthened the bonding strength between tissue, avoided simultaneously because of the different interfacial separation that cause of different tissues retractility with swellability.(4) composition and the ratio by the artificial regulatory biomimetic material, realize the controllability of rack mechanical strength and degraded and absorbed speed, make it have the favorable mechanical characteristic, can bear the stress of normal condition after being transplanted in patient's body, satisfy the mechanics requirement of implant site; The interior cambium speed of growth of its degraded and absorbed speed and host is complementary.
Description of drawings
The present invention is further illustrated below in conjunction with accompanying drawing
Fig. 1 is a supporting structure sketch map of the present invention (analysing and observe);
Fig. 2 is second kind of example structure sketch map of support of the present invention (analysing and observe);
The specific embodiment
In Fig. 1,1-cartilage layers, 2-calcification layer, 3-subchondral bone layer, 4-hole,
Integral engineering rack of the present invention, form by cartilage layers 1, calcification layer 2 and subchondral bone layer 3 from top to bottom, the organic connection between cartilage layers 1 and the calcification layer 2, between calcification layer 2 and the subchondral bone layer 3, cartilage layers 1 closely is connected by calcification layer 2 special The Nomenclature Composition and Structure of Complexes with subchondral bone layer 3, organic each other connection, there is not the boundary line between each layer, just structure, the constituent difference between each layer.The composition material of cartilage layers 1 is medical II Collagen Type VI and chitosan; II Collagen Type VI weight ratio is 80%～90%, the chitosan weight ratio is 10%～20%, and II Collagen Type VI/chitosan connects with the covalent bond form; The composition material of calcification layer 2 is medical II Collagen Type VI and hydroxyapatite, and II Collagen Type VI weight ratio is 60%～70%, and the hydroxyapatite weight ratio is 30%～40%, connects with the covalent bond form between II Collagen Type VI/hydroxyapatite; The composition material of subchondral bone layer 3 is medical type i collagen and hydroxyapatite, and the type i collagen weight ratio is 70%～80%, and the hydroxyapatite weight ratio is 20%～30%, connects with the covalent bond form between type i collagen/hydroxyapatite; The product that the product that hydroxyapatite can adopt Haitai Nano Material Co., Ltd., Nanjing to produce, medical type i collagen and II Collagen Type VI can adopt the Sichuan inscription to allow Science and Technology Ltd. produce; Chitosan can be bought from U.S. sigma company.In cartilage layers 1 and subchondral bone layer 3, all be provided with more than one a plurality of hole 4, the aperture of hole 4 is generally at 100 μ m～500 μ m, generally between 100 μ m～150 μ m, the porosity of its hole 4 is between 85%～90% in the aperture of cartilage layers 1, and the hole passband is 100%; Generally between 200 μ m～500 μ m, the porosity of its hole 4 is 55%～60% in the aperture of subchondral bone layer 3, and the hole passband is 100%.
For can be fully integrated after support is implanted with osteochondral defect periphery host, its configuration design usually and human body osteochondral defect position be complementary, the thickness of cartilage layers 1 is generally 3mm～5mm; The compact structure of calcification layer 2, thickness are generally 50 μ m～350 μ m; The thickness of subchondral bone layer 3 is generally 8mm～10mm, novel part is the joint face of subchondral bone support and host bone is designed to sparse broach shape, this kind structural design has increased the be connected area of graft with host's osseous part, strengthen bonding strength, thereby helped fixedly securing of graft.
In Fig. 2, second kind of example structure of support of the present invention, the shape of the linkage interface between cartilage layers 1 and the calcification layer 2, between calcification layer 2 and the subchondral bone layer 3, the last interface of cartilage layers 1 is the plane, the following interface of cartilage layers 1 is wavy; The last interface of calcification layer 2 (face that is connected with the following interface of cartilage layers 1) be the following interface with cartilage layers 1 match wavy, the following interface of calcification layer 2 (face that is connected with the last interface of subchondral bone layer 3) is the broach shape; The last interface of subchondral bone layer 3 is broach shapes that the following interface with calcification layer 2 matches, and the following interface of subchondral bone layer 3 is the broach shape.The following interface of above-mentioned cartilage layers 1, the last interface of calcification layer 2 wavy can be sine wave shape clocklike, wave height be 50 μ m～80 μ m, ripple wide be 200 μ m～300 μ m; Also can be random wavy; Subchondral bone layer 3 upper surface are rough and uneven in surface broach shape, with the lower surface of calcification layer 2 mutually anchor close, broach can be clocklike coniform, the awl height is that 250 μ m～300 μ m, cone bottom diameter are 200 μ m～250 μ m, also can be random zigzag; The lower surface of subchondral bone layer 3 is sparse broach shape, and close with the firm anchor in host bone interface the back of being convenient to implant, and the awl height is that 1～2mm, cone bottom diameter are 2mm～3mm.
In the reality, the shape at the upper and lower interface of cartilage layers 1, the shape at the upper and lower interface of calcification layer 2, the shape at the upper and lower interface of subchondral bone layer 3 according to actual needs, can have multiple, those skilled in the art enlightens according to this, need not spend performing creative labour and just can obtain.
In the reality, except above-mentioned selected biomimetic material, make through engineering approaches osteochondro tissue integrated bracket and can also select other natural materials and synthetic material for use.(1) the cartilage layers support can select natural material that cell free cartilage matrix material, chitin, calcium alginate, fibrin, hyaluronic acid etc. are arranged; The high-molecular organic material of the synthetic that can select comprises aliphatic polyester [polylactide (PLA), PGA, PLGA etc.
, poly-anhydride, poe, polyethers [PEG, polypropylene glycol (PPG)] etc.; It can also be the new material that above-mentioned natural material and synthetic high-molecular organic material combine and form.(2) natural material that can select of calcification layer and subchondral bone support comprises various through physics, chemically treated natural bone tissue (xenogenesis bone and homogeneous allogenic bone are as potteryization, freeze drying bone, decalcification bone, decalcified bone matrix, deproteinization bone etc.), natural coral and artificial bone of coral etc.; The synthetic material that can select comprises ceramic material, as tricalcium phosphate (TCP), biphase calcium phosphor pottery (BCP), biological active glass ceramic (BGC) etc.; High-molecular organic material is as aliphatic polyester [polylactide (PLA), PGA, PLGA etc.], poly-anhydride, poe, polyethers [PEG, polypropylene glycol (PPG)] etc.; It can also be the new material that above-mentioned natural material and synthetic high-molecular organic material combine and form.Those skilled in the art enlightens according to this, need not spend performing creative labour and just can obtain.
In the reality, II collagen type and chitosan in the composition material of cartilage layers 1, medical II collagen type and hydroxyapatite in the composition material of calcification layer 2, medical type i collagen albumen and hydroxyapatite in the composition material of subchondral bone layer 3, its ratio range is not limited to aforesaid proportion, multiple other proportionings can be arranged, II Collagen Type VI (medical) weight ratio as cartilage layers 1 can reach 99.99%, medical II collagen type weight ratio in the composition material of calcification layer 2 can reach 90% even higher, the composition material type i collagen weight ratio of subchondral bone layer 3 can reach 90% even higher, all can adjust according to actual needs.As select other composites for use, its proportioning is also similar substantially to above-mentioned disclosed ratio, also can adjust according to actual needs.Those skilled in the art enlightens according to this, need not spend performing creative labour and just can obtain.
In the reality, selected biomaterial except above-mentioned connect with the covalent bond form, also available binding agent bonds the medical II Collagen Type VI and the chitosan complex dry powder of cartilage layers 1 during making; Medical II Collagen Type VI with the calcification layer during making is connected with the binding agent bonding with hydroxyapatite complex dry powder; The medical type i collagen of subchondral bone layer is connected with the binding agent bonding with hydroxyapatite complex dry powder; As select for use other composite process identical.Binding agent can be selected existing product for use, as the philharmonic medical agent viscose glue of good fortune of Fualie Science ﹠ Technology Developing Co., Ltd., Beijing's production or the wink health medical agent viscose glue of Beijing wink health development in science and technology company limited production.
The manufacture process of support of the present invention
1, according to the ultrastructure related data of human body natural joint osteochondro tissue and in the past to single organization's engineering cartilage and bone structure result of study, design is also formulated the required relevant parameter of structure bone cartilage compound rest: comprise (the seeing technical scheme of the present invention for details) such as thickness, shape and interior porosity, aperture and hole passbands of each layer support, appliance computer Autocad (CAD) is made osteochondro tissue integrated bracket model then.The computer aided design software (CAD) that the present invention is used; be a kind of prior art, those skilled in the art can design or work out out this design software according to the content that this paper discloses; this design software does not belong to protection scope of the present invention, does not do detailed description at this.
2, determine the constituent and the ratio (seeing technical scheme of the present invention for details) of each layer of support according to bionics principle, obtain medical I type, II Collagen Type VI (Mingrang Biological Science ﹠ Technology Co., Ltd., Sichuan Prov.'s development) from Biomatera Inc.; Chitosan (production of U.S. sigma company) and hydroxyapatite (Haitai Nano Material Co., Ltd., Nanjing's production).Adopt crosslinked, mineralising and spray drying technology that collagen/chitosan, the little aggressiveness dry powder of collagen/hydroxyapatite are modified, made to selected biomaterial, connect with the covalent bond form between collagen/chitosan and the collagen/hydroxyapatite.Its covalent bond form syndeton, method etc., specifically can be called " a kind of each method of composite membrane system that is used for guide tissue regeneration " referring to name, number of patent application is 03150163.X, name is called " preparation method of porous collagen composite nano hydroox apatite artificial bone ", number of patent application is 200510107942.0 Chinese invention patent application documents, and name is called " preparation method that composite vascular is produced plain heparinization collagen/chitosan porous rack ", number of patent application is 200510060749.3, and name is called " collagen-chitosan and silicon rubber bilayer skin regeneration support and preparation method thereof ", number of patent application is 200510061872. Chinese invention patent application documents, discloses collagen/chitosan, the covalent bond form syndeton of collagen/hydroxyapatite.Foregoing does not describe in detail at this not as protection scope of the present invention.
3, the cad model that designs is changed into rapid shaping file format input three-dimensional printer, adopt physics and chemistry cross-linking methods such as ultraviolet, glutaraldehyde that little aggressiveness dry powder is bonded to the osteochondro tissue integral engineering rack with function interface by design under the help of three-dimensional printer.Deionized water rinsing repeatedly after printing is finished, low-temperature freeze drying seals low temperature storage after X-radiation sterilization.With 3 D-printing fabrication techniques support of the present invention, between cartilage layers 1 and the calcification layer 2, do not have the boundary line between calcification layer 2 and the subchondral bone layer 3, structure, the constituent difference between each layer just.The 3 D-printing technology that this preparation process adopts, it is a kind of prior art, can consulting name, to be called " three-dimensional printing formation unit and method ", number of patent application be 200510029726.9 Chinese invention patent application documents, or consulting name, to be called " a kind of printing shaping method of making three-dimensional body and support ", number of patent application be 200610038580.9 Chinese invention patent application documents
4,, adopt methods such as SEM, XRD, FTIR, Experiments of Machanics, degradation test, cell toxicity test, genetic toxicity test that the physicochemical properties such as morphosis, mechanical property, biological safety and degraded and absorbed of support are detected according to the ISO10993 series standard.Testing result proves that osteochondro tissue engineering rack of the present invention has the interior spatial structure and the proportion of composing of designing requirement; Have the favorable tissue compatibility and biological safety, be beneficial to cell adhesion, hypertrophy; Have excellent mechanical intensity, can satisfy the mechanics requirement of implant site; Have the controlled degradation absorbability, can make by artificial regulatory that the cambium speed of growth is complementary in its degraded and absorbed speed and the body.
5, adopt this support in conjunction with seed cell technology of preparing, two-phase gel inoculation technique and piece of tissue In vitro culture technique construction through engineering approaches osteochondro tissue; Large animal (pig) body is implanted into to be repaired experimental result and shows that the through engineering approaches osteochondro tissue that adopts osteochondro tissue engineering rack of the present invention the to make up back that implants is fully integrated with normal surrounding tissue, and degradation time mates substantially with the cambium speed of growth on every side; The repair tissue cartilage portion has biological characteristics, the subchondral bone part of similar natural joint cartilage can within a short period of time and host bone tissue generation synostosis.
Claims (9)
1, has the bionic function integral engineering rack of interface osteochondro tissue, it is characterized in that: be made up of cartilage layers (1), calcification layer (2) and subchondral bone layer (3) from top to bottom, cartilage layers (1) closely is connected with the structure of subchondral bone layer (3) by calcification layer (2); The composition material of cartilage layers (1) is II Collagen Type VI and chitosan, and the composition material of calcification layer (2) is II Collagen Type VI and hydroxyapatite, and the composition material of subchondral bone layer (3) is type i collagen and hydroxyapatite; The II Collagen Type VI of cartilage layers (1) and chitosan complex dry powder form the covalent bond syndeton with binding agent; The II Collagen Type VI of calcification layer (2) and hydroxyapatite complex dry powder form the covalent bond syndeton with binding agent; The type i collagen of subchondral bone layer (3) and hydroxyapatite complex dry powder form the covalent bond syndeton with binding agent; All be provided with more than one hole (4) in cartilage layers (1) and subchondral bone layer (3), the aperture of hole (4) is 100 μ m～500 μ m.
2, according to claim 1 have a bionic function integral engineering rack of interface osteochondro tissue, and it is characterized in that: the II Collagen Type VI weight ratio in the cartilage layers (1) is 80%～90%, and the chitosan weight ratio is 10%～20%.
3, according to claim 1 have a bionic function integral engineering rack of interface osteochondro tissue, and it is characterized in that: in calcification layer (2), II Collagen Type VI weight ratio is 60%～70%, and the hydroxyapatite weight ratio is 30%～40%.
4, according to claim 1 have a bionic function integral engineering rack of interface osteochondro tissue, and it is characterized in that: in subchondral bone layer (3), the type i collagen weight ratio is 70%～80%, and the hydroxyapatite weight ratio is 20%～30%.
5, according to the arbitrary described bionic function integral engineering rack of interface osteochondro tissue that has of claim 1 to 4, it is characterized in that: the last interface of cartilage layers (1) is the plane, the following interface of cartilage layers (1) is wavy, the last interface of calcification layer (2) be the following interface with cartilage layers (1) match wavy, wave height be 50 μ m～80, ripple wide be 200 μ m～300 μ m; The following interface of calcification layer (2) is the broach shape, and the last interface of subchondral bone layer (3) is the broach shape that the following interface with calcification layer (2) matches; Broach is clocklike coniform, and the awl height is that 250 μ m～300 μ m, cone bottom diameter are 200 μ m～250 μ m; The lower surface of subchondral bone layer (3) is the broach shape, and close with the firm anchor in host bone interface the back of being convenient to implant.
6, according to the arbitrary described bionic function integral engineering rack of interface osteochondro tissue that has of claim 1 to 4, it is characterized in that: the aperture of cartilage layers (1) hole (4) is between 100 μ m～150 μ m, the porosity of hole (4) is between 85%～90%, and the hole passband is 100%.
7, according to the arbitrary described bionic function integral engineering rack of interface osteochondro tissue that has of claim 1 to 4, it is characterized in that: the aperture of subchondral bone layer (3) hole (4) is between 150 μ m～500 μ m, the porosity of hole (4) is between 55%～60%, and the hole passband is 100%.
8, according to claim 5 have a bionic function integral engineering rack of interface osteochondro tissue, it is characterized in that: the aperture of cartilage layers (1) hole (4) is between 100 μ m～150 μ m μ m, the porosity of hole (4) is between 85%～90%, and the hole passband is 100%; The aperture of subchondral bone layer (3) hole (4) is between 150 μ m～500 μ m, and the porosity of hole (4) is between 55%～60%, and the hole passband is 100%.
9, according to the arbitrary described bionic function integral engineering rack of interface osteochondro tissue that has of claim 1 to 4, it is characterized in that: the thickness of cartilage layers (1) is 3mm～5mm, the thickness of calcification layer (2) is 50 μ m～350 μ m, and the thickness of subchondral bone layer (3) is 8mm～10mm.
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| CN1386478A (en) * | 2001-05-23 | 2002-12-25 | 中国科学院化学研究所 | Cell scaffold with composite structure for tissue engineering and its preparing process and application |
| WO2005025493A2 (en) * | 2003-07-28 | 2005-03-24 | The Board Of Trustees Of The University Of Illinois | Biological engineering of articular structures containing both cartilage and bone |
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