Specific embodiment
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art willUnderstand, the following example is merely to illustrate the present invention, and is not construed as limiting the scope of the invention.It is not specified in embodiment specificCondition person carries out according to conventional conditions or manufacturer's recommended conditions.Reagents or instruments used without specified manufacturer isThe conventional products that can be obtained by commercially available purchase.
In the description of the present invention, it should be noted that term " first ", " second " etc. are only used for distinguishing description, withoutIt can be interpreted as indication or suggestion relative importance.
Below to bone tissue reparation ink, composition, bracket and the preparation method of the embodiment of the present invention and kit intoRow illustrates.
Some embodiments of the present invention provide a kind of bone tissue reparation ink, including biodegradable material and otherAssistant formation material.
Bone tissue reparation ink includes at least one biodegradable material, and can be provided for bone defect healing wellSubstrate, such as no cytotoxicity, non-immunogenicity or low immunogenicity；Biodegrade can be carried out, and within the relatively short timeReplaced by area of new bone；There is certain structure, the bracket (bone conduction effect) in bone defect area can be played；There is induced osteogenesis effectDeng.
Biodegradable material, including degradable inorganic matter, natural macromolecular material, degradable synthesized polymer material,Different type or same type of composite material etc..
Further, biodegradable material has osteoconductive or osteoinductive.Host can be integrated into various degreeBone, and suitable environment can be provided for seed cell to promote regeneration, it is provided for seed cell and sticks, breaks up, increasingThe condition grown or migrated.
Further, biodegradable material has certain mechanical strength, can be realized stereo stocking；With goodMechanical performance, support performance needed for corresponding bone defect position can be matched.
Further, the degradation of biodegradation material is capable of providing maintenance or promotes the microenvironment of osteocyte vital movement,If catabolite is small molecule compound, including organic acid, monosaccharide (such as glucose), oligosaccharides, amino acid, lipid etc..It is suchCatabolite may participate in the metabolic activity (such as synthetic cell epimatrix) of cell, or be used for synthetic cell epimatrixOr it is converted into the required energy of activity.
Further, degradable inorganic matter, such as: tricalcium phosphate, hydroxyapatite, calcium phosphate, calcium silicates, magnesia,Magnesium hydroxide, magnesium chloride, magnesium carbonate, magnesium phosphate, magnesium silicate, iron oxide, titanium dioxide three-iron, iron hydroxide, iron chloride and carbonic acidStrontium etc., it is similar with the ingredient of natural bone matrix, there is good bio-compatible and osteoconductive, and its rear surface energy that implantsThe cell free zone of a bioactivity is formed, wherein being rich in calcium phosphate, mucopolysaccharide and glycoprotein, the deposition for collagen and bone mine is mentionedControl environment has been supplied, provides support for the realization of cell biological function.Therefore, in certain preferred aspects, it is used forThe biodegradable material of bone tissue reparation ink is prepared as degradable inorganic matter or contains degradable inorganic matter.
Further, natural macromolecular material refers to osteocyte epimatrix or its analog, such as: type i collagen fiber and[amorphous, wherein [amorphous is gel, including some non-collagens, glycoprotein, proteoglycan, polypeptide, carbon waterCompound and lipid etc.；Hydroxy apatites and amorphous calcium phosphate class and some CO32-、C1-、F-、Na+、K+、Mg2+Etc. miscellaneousThe microelements such as matter ion and Sr, Zn, are able to use and simulate the microenvironment of the intracorporal bone tissue of people, and it is thin to be more advantageous to promotionAdherency, the stretching, extension of born of the same parents, growth are proliferated, the foundation that differentiation and cellular informatics are interactive.
Further, degradable synthesized polymer material includes polycaprolactone (PCL), polydioxanone(PPDO), polyacrylic acid and its derivative (such as polymethylacrylic acid, the copolymer of acrylic acid and methacrylic acid), polylactic acid(PLA), polyglycolic acid (PGA), polylactic-co-glycolic acid (PLGA), polyorthoester (POE), polycaprolactone (PCL),Poly butyric ester (PHB), polyaminoacid (polyaminoacid) (such as polylysine), degradability polyurethane, Yi JiqiAny combination.
Further, different type or same type of composite material, including hyaluronic acid (HA)/hydroxyapatiteIt is (HA), de- that extracellular matrix (dEMC)/hydroxyapatite (HA) is compound, collagen (COL)/polycaprolactone (PCL) is compound, collagen(COL)/tricalcium phosphate (TCP), tricalcium phosphate (TCP)/polylactic-co-glycolic acid (PLGA) is compound etc. and its is anyCombination.
Assistant formation material refers to the biomaterial that the building can be assisted body formed with cytocompatibility comprising but notIt is limited to one of bio-dispersant, biological binder, biological lubricants, biological anti-coagulants, crosslinking agent, solvent etc. or a variety of groupsIt closes.
Further, " bio-dispersant ", which refers to, plays peptizaiton, the degradation material with cell and biocompatible,Such as poly amic acid.
Further, " biological lubricants ", which refer to, plays lubricating action, can bone tissue reparation ink flow smoothness, and it is thinThe degradation material of born of the same parents and biocompatible, such as glycerine；
Further, " bioadhesive " refers to, plays adhesive effect, it can be achieved that crosslinking or otherwise realization solidificationDegradable polymer (including but not limited to hyaluronic acid, chitosan, collagen or sodium alginate etc.), such as pass through chlorinationCalcium cross-linked alginate passes through the methacrylate gelatin etc. of photo-crosslinking, biology by the collagen of genipin cross-linkedThe viscosity of binder not only adjustable bioactive ceramics slurry, and the step of its crosslinkable characteristic avoids bracket from being sintered,The preparation process of simplified bracket, while may be implemented to print with cells Synchronous, solving bracket inoculation leads to cell distribution notUniform problem, thus the growth of more advantageous cell, proliferation and differentiation.
Some embodiments of the present invention provide a kind of bone tissue reparation ink-manufacturing method, and its step are as follows:
(1) mixture of one or more biodegradable materials is provided.
(2) mixture of one or more assistant formation materials is provided.
(3) a kind of material prescription 1 is selected from step (1) one or more biodegradable materials, from step (2) one kindOr a kind of formula 2 is selected in a variety of assistant formation materials, and formula 1,2 is slurried, form bone tissue reparation ink.
Further, the biodegradable material in bone tissue reparation ink is hydroxyapatite or tricalcium phosphate, hydroxylIt is about 0:10-10:0, such as 0:10,1:9,2:8,3:7 that apatite and tricalcium phosphate, which repair shared mass ratio in ink in bone group,4:6,5:5,6:4,7:3,8:2,9:1,10:0.The mixture of hydroxyapatite and tricalcium phosphate institute in bone tissue reparation inkAccounting for mass percent is 50%-80%.In certain preferred embodiments, binder is sodium alginate, crosslinking agent be calcium chloride,Lubricant is glycerine, dispersing agent is poly amic acid, wherein quality percentage shared by bone tissue reparation ink assistant formation materialThan for 20%-50%.
Further, the biodegradable material in bone tissue reparation ink is hydroxyapatite or magnesium phosphate, hydroxyl phosphorusIt is about 0:10-10:0, such as 0:10,1:9,2:8,3:7,4:6 that lime stone and magnesium phosphate, which repair shared mass ratio in ink in bone group,5:5,6:4,7:3,8:2,9:1,10:0.The mixture of hydroxyapatite and magnesium phosphate shared quality in bone tissue reparation inkPercentage is 50%-90%.In certain preferred embodiments, binder is collagen, and crosslinking agent is Geniposide, lubricantIt is poly amic acid for glycerine, dispersing agent, wherein mass percent shared by bone tissue reparation ink assistant formation material is10%-50%.
Further, the biodegradable material in bone tissue reparation ink is hydroxyapatite or polylactic acid-glycollic acidCopolymer, it is about 0%-100% that hydroxyapatite, which accounts for the mass percent that bone group is repaired in ink, for example, 0%, 1%, 2%,3%, 4%......98%, 99%, 100%.The mixture of hydroxyapatite and polylactic-co-glycolic acid is in bone tissueRepair ink in shared mass percent be 50%-90%, such as 50%, 51%, 52%......77%, 78%, 79%,80%, 90%.In certain preferred embodiments, binder is methylcellulose, solvent 1,4- dioxane, wherein bone groupKnitting and repairing mass percent shared by ink assistant formation material is 10%-50%.
Further, the biodegradable material in bone tissue reparation ink be tricalcium phosphate or polycaprolactone polymer,It is about 0%-80% that example tricalcium phosphate, which accounts for the mass percent that bone group is repaired in ink, for example, 0%, 1%, 2%, 3%,4%.....78%, 79%, 80%.Polycaprolactone shared mass percent in bone tissue reparation ink is 20%-100%,Such as 20%, 21%, 22%......97%, 98%, 99%, 100%.In certain preferred embodiments, bone tissue reparationInk does not include assistant formation material.
Further, bone tissue reparation ink is including but not limited to following combinations:
Some embodiments of the present invention provide a kind of bone tissue reparation composition, including bone tissue reparation ink, lifeObject active carrier and cell factory, wherein bioactive carrier includes bioactivity hydrogel and bioactie agent.
Bioactivity hydrogel includes: natural bioactive hydrogel, and artificial synthesized biological hydrogel is modifiedBiological hydrogel that biological hydrogel or same type or different kind of material are combined or above-mentioned biological hydrogel it is anyCombination.
Further, natural bioactive hydrogel, including collagen, fibrin, fibroin albumen, chitosan, seaAlginates, starch, hyaluronic acid, laminin, agarose, gelatin, glucan and any combination thereof；
Further, artificial synthesized biological hydrogel, including polyacrylic acid and its derivative, polyvinyl alcohol, polyethyleneBase pyrrolidones, polyethylene glycol oxide and its derivative copolymer, polyphosphazene etc. and any combination thereof form；
Further, biological hydrogel modified, including gelatin modified, modified hyaluronic acid, modifiedChondroitin, such as methacrylate gelatin (GelMA), methacrylate hyaluronic acid (GelHA), methacrylate are softOssein etc. and the combination of its arbitrary form；
Further, the biological hydrogel that same type or different kind of material are combined, including metering system acid gelatinComposite transparent matter acid, Sodium Polyacrylate composite collagen, metering system hyaluromic acid composite collagen etc. are any with itForm is compound；
Bioactie agent refers to during bon e formation, can promote the growth of bone, induces the formation of bone or/and preventsBone-loss plays an active component of beneficial effect, including but not limited to bone morphogenic factor, osteogenin, skeletonizationThe factor, bone-inducing factor, anti-bone resorption agent, growth promoter, antibacterial agent etc..
Further, bone-inducing factor, such as: certain Bone Morphogenetic Protein (bone morphogenetic protein,BMP), growth and differentiation factor (growth and differentiation factor, GDP), intracellular elements LIM mineralising eggWhite -1 (LIM mineralization protein-1, LIM)), osteoprotegerin, RUNX2, transforming growth factor β, at fiber finerThe intracellular growth factor, Bone Morphogenetic Protein and any combination thereof form；
Further, anti-bone resorption agent, be bisphosphonates, such as: zoledronic acid, pamidronic acid, how auspicious phosphonic acids, pa phosphine difficult to understandAcid, alendronic acid, ibandronic acid, Risedronic Acid wait and any combination thereof form.
Further, antibacterial agent, such as silver, copper, phosphonomycin, antibiotic.
It is cell factory, including but not limited to cell solution, celliferous gel, cell suspending liquid, cell concentration object, mostly thinBorn of the same parents' aggregation, multicell, subcellular structure (such as organelle and cell membrane).
Some embodiments of the present invention provide a kind of preparation method of bone tissue reparation composition, and its step are as follows:
(1) preparation of bone tissue reparation ink；
A) mixture of one or more biodegradable materials is provided.
B) mixture of one or more assistant formation materials is provided.
C) a kind of material prescription 1 is selected from the one or more biodegradable materials of step (a), from step (b) one kindOr a kind of formula 2 is selected in a variety of assistant formation materials, and formula 1,2 is slurried, form bone tissue reparation ink.
(2) preparation of cell factory
A) cell frozen is put into 50-100s in 30-37 DEG C of shaking bath pot recover
B) cell is transferred in the centrifuge tube equipped with culture medium, is centrifuged.
C) the supernatant culture solution after abandoning centrifugation is inhaled, appropriate culture medium is added, its final concentration of cells is made to be suitble to requirement of experiment, spare.
(3) preparation of bioactive carrier；
Bioactivity hydrogel is dissolved to suitable concentration using coordinative solvent, then will according to a certain percentage with cultureIt base, bioactie agent and gets cell ready and mixes according to a certain percentage, extremely using buffer and acid-base solution adjustment pH value of solution7.4, it makes spare.
Bone tissue reparation ink, cell factory, the bioactive carrier of above-mentioned preparation collectively constitute as bone tissue reparation groupClose object.
Fig. 1-Fig. 2 is please referred to, some embodiments of the present invention provide a kind of preparation method of bone tissue reparation bracket,The following steps are included:
S1, preparation have biodegradable bone tissue reparation ink.
Specifically, in the present embodiment, using bone tissue reparation ink made from aforementioned embodiments.
The bioactive carrier of S2, preparation package cell.
Specifically, the bioactive carrier for wrapping up cell is by bioactivity hydrogel and bioactie agent, according to bodyProduct is made after mixing than being 1:1.
Further, it is poly- to be selected from collagen solution, the mixed solution of gelatin and sodium alginate or shell for bioactivity hydrogelAny one in sugar juice.
Further, bioactie agent is selected from osteoblast or containing any one in mesenchymal stem cellKind.
Optionally, it can be natural biologic material (example for combining the bioactivity hydrogel of bone tissue reparation compositionSuch as collagen, fibrin, fibroin albumen, chitosan, alginate, starch, hyaluronic acid, laminin, agarose,Gelatin, glucan and any combination thereof), artificial synthesized biological hydrogel (such as polyacrylic acid and its derivative, poly- secondEnol, polyvinylpyrrolidone, polyethylene glycol oxide and its derivative copolymer, polyphosphazene etc. and any combination thereof form),The biological hydrogel that biological hydrogel modified, same type or different kind of material are combined, or any combination thereof.
Optionally, the biodegradable hydrogel for combining bone tissue reparation composition is naturally occurring degradable polyClose object.Preferably, degradable polymer be selected from collagen, fibrin, chitosan, alginate (such as sodium alginate),Starch, hyaluronic acid, laminin, agarose, gelatin, fibroin albumen, glucan and any combination thereof.
Optionally, the biodegradable hydrogel for combining bone tissue reparation composition is degradable poly modifiedClose object, such as gelatin modified, modified hyaluronic acid, modified chondroitin, such as methacrylate gelatin(GelMA), methacrylate hyaluronic acid (GelHA), methacrylate chondroitin etc. and the combination of its arbitrary form.
Optionally, the biodegradable hydrogel for combining bone tissue reparation composition is artificial synthesized degradable polyClose object, such as polyacrylic acid and its derivative, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol oxide and its derivative copolymerizationObject, polyphosphazene etc. and any combination thereof form.
Optionally, the biodegradable hydrogel for combining bone tissue reparation composition is that different kind of material is compoundDegradable polymer, such as the gelatin-compounded hyaluronic acid of methacrylic acid, Sodium Polyacrylate composite collagen, methacrylic acidHyaluronic acid composite collagen etc., it is compound with its arbitrary form.
Optionally, the bioactie agent (such as the bioactivator for promoting bone uptake) of bioactive carrier and its degradationProduct is nontoxic for cell, and/or is non-immunogenic for host, and seed cell can promoted to stick lifeLength induces its directed differentiation, secretes specific proteins.In certain preferred aspects, bioactie agent can be boneInducible factor (such as certain Bone Morphogenetic Protein (bone morphogenetic protein, BMP) and some growth and differentiation factors(growth and differentiation factor, GDP) and some -1 (LIM of intracellular elements lim mineralization proteinMineralization protein-1, LIM)), anti-bone resorption agent (such as anti-phosphonate), growth promoter, antimicrobial(such as silver, copper, phosphonomycin, antibiotic), other biological activities agent and its arbitrary combining form.
Optionally, the bioactie agent in bioactive carrier is bone-inducing factor, such as certain Bone Morphogenetic Protein(bone morphogenetic protein, BMP) and some growth and differentiation factors (growth and differentiationFactor, GDP), some intracellular elements lim mineralization proteins -1 (LIM mineralization protein-1, LIM) andAny combination thereof form.
Optionally, the bioactie agent in bioactive carrier is osteogenic factor, such as osteoprotegerin, RUNX2, conversionGrouth factor beta, fibroblast growth factor, Bone Morphogenetic Protein and any combination thereof form.
Optionally, the bioactive carrier for wrapping up cell is anti-absorbent, and in certain preferred embodiments, anti-absorbent is doublePhosphonates.Diphosphonate inhibits bone-loss preferably as the specific inhibitor of osteoclast.Diphosphonate, choosingFrom zoledronic acid, pamidronic acid, how auspicious phosphonic acids, olpadronic acid, alendronic acid, ibandronic acid, Risedronic Acid, is waited and it is anyCombining form.
Optionally, the degradation of bioactive carrier degradation material is capable of providing maintenance or promotes osteocyte vital movementMicroenvironment, such as nutriment.In certain preferred aspects, catabolite is small molecule compound, such as organic acid,Monosaccharide (such as glucose), oligosaccharides, amino acid, lipid etc..Such catabolite may participate in the metabolic activity of cell(such as synthetic cell epimatrix) for synthetic cell epimatrix or is converted into the required energy of activity.
Microenvironment refers to the environment that cell is grown, it includes element include physical factor, for example space structure, mechanics are strongDegree, temperature, humidity, osmotic pressure etc.；Chemical factor, such as pH value, ion concentration etc.；Biological factor, including cell, cell becauseSon etc..These elements collectively form the environment of cell activities, and to the proliferation of the cell grown in this environment, pointChange, migrate, secretion and metabolism carry out dynamic regulation.
S3, bone tissue reparation bracket is constructed according to preset three-dimensional structure.
Further, building bone tissue reparation bracket be by biometric print, coating, pour or fill in it is any oneKind method is constructed.
In present embodiment, the method for selecting biometric print is constructed.
Specific step is as follows:
1, using biometric print machine, taking bone tissue reparation ink to prepare slurry and bioactive carrier ink (can be mixed thinBorn of the same parents' isochronous printing) it is separately added into barrel 1 and barrel 2.
2, start corresponding function (such as: including but not limited to freezing or/and heat and/or solidify), repaired according to bone tissueThe characteristic of multiple ink slurry and bioactive carrier ink is by material processing to corresponding requirements.
3, corresponding CAD model is imported according to model requirements, and the print parameters of appropriate adjustment biometric print machine are generated and corresponded toRational Path.Start print routine, corresponding bone tissue reparation ink and bioactive carrier group are printed on clean micro slideThe three-dimensional construct of conjunction.
4, the bone tissue reparation sectional shelf-unit printed is infiltrated into a period of time in cross-linking agent solution, causes bracketCrosslinking is complete, to improve the stability of bracket.
CAD model is to check the full bone section image data obtained according to the damage location CBCT of patient, utilize medical imageThe 3-D image that processing software rebuilds patient's bone defect establishes bone model, determines the size, structure and region of bone defect, aThe bone defect healing module of property design and defective region form fit.
Appropriate adjustment print parameters refer to by adjusting print parameters (such as: printing thickness, filling angle, filling spacing, sprayHead temperature, platform temperature) disclose its influence to supporting structure precision and physicochemical property；Design and natural internal structure of bone and propertyThe bioactive ceramics sectional shelf-unit that can be matched.
Further, the formula property according to different bone tissue reparation ink slurries and bioactive carrier ink is also optionalSelect various forms of bracket post processing modes.Specific floor-engaging frame post processing mode includes but is not limited to crosslinking, photocuring, freezes and doDry, coating and any combination thereof form.
Still optionally further, three-dimensional construct is constructed using biometric print, which need to reach 4F criterion design requirement.ItsIn, 4F criterion, including shape demand (Form), i.e., its shape of timbering material has to be completely filled with three-dimensional defect, and can lureLead respective organization regeneration；Performance demand (Function), the i.e. mechanical strength of bracket and performance etc., can be before missing tissues temporarilyWhen play missing tissues substitution effect；Function demand (Formation), material need corresponding bioactivity, can be seedCell provides suitable environment and has promoted regeneration, and the condition sticked, break up, be proliferated or migrated is provided for seed cell.It canImplantable (Fixation) i.e. timbering material can be implanted into human body by surgical procedure, it is desirable that timbering material can be fixed on bone defectIn, and suitable surface is provided and has met fixed demand, and plays expected effect.
Still optionally further, the method for biometric print building bracket can be realized continuous printing (Fig. 3), including following stepRapid: the ink used in print procedure is divided into printed material and supply material, and wherein printed material is in print procedure by materialMaterial is divided into surplus material a1 and printed material b1.
Printed material b1 will complete the printing of object 1；Surplus material a1 is classified into surplus material in continuous print carriageA2 and printed material b2.
Printed material b2 when such as its certain ingredient deficiency, can have supply material c1 supplement completely, then carry out object2 printing.
Surplus material a2 will be divided into surplus material a3 and printing materials b3 again；Printed material b3, not such as its certain ingredientWhen sufficient, there can be supply material c2 supplement complete, then carry out the printing of object 3.
Material is fed in bracket print procedure, when monitoring printing materials deficiency for the first time, material is divided into supplyMaterial c1 and surplus material d1 allows it to complete printing wherein supply material c1 can feed printed material b2；It is monitored when for the second timeWhen printed material deficiency, surplus material d1 is classified into supply material c2 and surplus material d2, wherein supply material c2 can feed and beatMaterial b3 is printed, it is allowed to complete printing；In subsequent print procedure, supply material can successively be followed according to the number of institute's printing objectsRing distribution.
This preparation method can be realized the continuous printing of bracket, and in continuous print procedure, can be adjusted flexibly same batchThe configuration proportion of secondary bracket material therefor, use and ratio adjustment for printed material are able to achieve real time on-line monitoring；Wherein,The ratio that material used in same batch bracket is adjusted flexibly, it is thus understood that two or more material can be achievedPreparation.
Some embodiments of the present invention also provide a kind of bone tissue reparation bracket, using bone tissue reparation branch as the aforementionedThe preparation method of frame is made.
Specifically, which includes multi-layer fiber layer；The parallel setting of multi-layer fiber layer.Each layer of fiberLayer includes supporting structure made of the bioactive carrier of supporting structure made of bone tissue reparation ink and package cell；It either include supporting structure made of bone tissue reparation ink or the bioactivity for wrapping up cell per adjacent two fibre layersSupporting structure made of carrier.
Still optionally further, which includes: the multi-layer fiber layer being fixedly connected sequentially from the bottom to top together, and multilayer is fineThe parallel setting of layer is tieed up, every layer of fibrous layer includes the fiber filament of multiple parallel settings, and the fiber filament of adjacent two layers fibrous layer is handed overMistake setting.
Still optionally further, the bracket, the filametntary stagger angle in adjacent two layers fibrous layer are 180 ° of 0 °≤θ <.The cross sectional shape in the hole that multiple fiber filaments of at least two fibre layers are staggered to form is polygon or round.
Still optionally further, for same material, in same layer fibrous layer, the spacing between two neighboring fiber filament is holeDiameter；In same fiber element, for same material, the aperture in the formed hole of fiber filament in same layer fibrous layer is equal.
In the present embodiment, specifically, referring to figure 4., the bracket, the fiber filament that bone tissue reparation ink is formed are (whiteColor fibre silk) with bioactive carrier (black fiber silk) formed fiber filament constitute a fiber element.As shown in figure 4, boneTissue repair ink fiber filament (white fiber silk) and bioactive carrier fiber filament (black fiber silk) are located at same fibrous layerOr different fibrous layers, same fibrous layer, bioactive carrier fiber filament (black fiber silk) are located at bone tissue reparation ink intervalBetween adjacent fiber silk.Different fibrous layers, bioactive carrier fiber filament (black fiber silk) and bone tissue reparation ink fiberIt is parallel or vertical that silk (white fiber silk) is located at adjacent two layers.For same material, (such as bone tissue reparation ink or biology are livingProperty carrier), the fiber filament in fibrous layer is parallel and non-coplanar with fiber filament in other fibrous layers or parallel co-planar setting.Into oneStep, multiple fiber elements form bone tissue reparation composition for ink three-dimensional rack.
Further, the shape of the bracket is multiedge cylinder, cylindrical body, cartilage model or os osseum model.
Some embodiments of the present invention provide a kind of bone tissue reparation kit comprising bone tissue reparation ink,The combination of one or more of bioactive carrier, bone repair composition, three-dimensional building body support frame or other components etc..
Kit includes at least one biological prosthetic ink.
Three-dimensional building body support frame, is natural structure and cell arrangement model based on construct to be printed in kit.
Other components in kit, including other reagents, explanation needed for container, culture medium, buffer, biometric printBook etc..
Kit can be placed in any suitable packaging, such to include but is not limited to, bottle, tank and flexible package (such asPolyester film or polybag).
Kit can there are many purposes, as bone tissue reparation ink and combinations thereof can be used for cultivating cell (such as withIn the dimensional culture of osteoblast)；Or for cell growth, proliferation, differentiation, secretion or migration；Or for biometric print (such as3D biometric print)；Or for constructing three-dimensional building body support frame (such as three-dimensional construct, tissue precursor, tissue or organ)；Or itsHe applies, and the variation (such as metamorphosis or changes of function) generated as analyzed cellular response stimulation or reagent is used for drugScreening or drug discovery, for treating subject with this need, for study stem cell differentiation, for evaluation factor (for example,Chemical reagent, compound；Physical stimulation, such as radiation or heating) effect to the cell in tissue or tissue, it is used for three-dimensional groupCulture is knitted, for measuring in vivo or in vitro, for being implanted into host, for organizational project or is used for regeneration.
Feature and performance of the invention are described in further detail with reference to embodiments: