CN102940909B - Method for modifying tissue engineering scaffold - Google Patents
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- CN102940909B CN102940909B CN201210509347.XA CN201210509347A CN102940909B CN 102940909 B CN102940909 B CN 102940909B CN 201210509347 A CN201210509347 A CN 201210509347A CN 102940909 B CN102940909 B CN 102940909B
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Abstract
The invention relates to a method for modifying a tissue engineering scaffold by employing a molecule layer-by-layer assembly technology. The method comprises the following steps of: (a) soaking the tissue engineering scaffold in aqueous solution with active ingredients I for 1-8 hours; (b) taking out the tissue engineering scaffold subjected to the step (a) and cleaning excessive active ingredients I; (c) soaking the tissue engineering scaffold subjected to the step (b) in aqueous solution with active ingredients II for 1-8 hours; (d) taking out the tissue engineering scaffold subjected to the step (c) and cleaning excessive active ingredients II; and (e) repeating the steps (a) to (d) for n times, wherein n is more than or equal to 0 and less than or equal to 100. The invention also provides a tissue structure and application of the tissue engineering scaffold. The method is carried out in a normal temperature water system, the active ingredients are assembled in a tissue engineering scaffold network layer by layer through interaction between the active ingredients and the tissue engineering scaffold, the assembled components and layers are adjustable, and the method is simple, practical, high in controllability and low in cleaning cost.
Description
Technical field
The present invention relates to technical field of biological materials, especially a kind of group of molecules packing technique that uses modifies the method for tissue engineering bracket, and the organizational structure of tissue engineering bracket that obtains of the method and application thereof.
background technology
The preparation of biological support is one of important content of tissue engineering research, desirable biological support should possess following characteristic: 1. have good biocompatibility, sticking and providing suitable microenvironment at its surface growth for cell of cell can be promoted, no cytotoxicity when cultivating in vitro, can not cause body inflammatory and rejection when implanting; 2. have 3-D solid structure, internal mutual connects and forms open pore passage structure, sticks space, and be beneficial to the transmission of nutrient substance and metabolite for cell provides enough; 3. there is biodegradability, match with the growth rate of cell, and catabolite is harmless to cell proliferation, easily by organism metabolism or absorption; 4. plasticity is strong, the profile that convenient structure is identical with the histoorgan needing to regenerate, repair; 5. there is the mechanical property adapted with transplanted histoorgan; 6. convenient sterilizing sterilization processing, and do not affect the character of material.
As one of form that biomaterial is applied, hydrogel may be defined as swelling in water and keeps large quantity of moisture, degradable or nondegradable polymer.A large amount of moisture is had owing to being full of in hydrogel network, whole material is possessed a kind of character of fluid, this has the body tissue of large quantity of moisture extremely similar to full, be beneficial to the transmission of nutrient substance and the discharge of products of cellular metabolism, soft moistening surface and organize affinity to greatly reduce the zest of material to surrounding tissue, makes hydrogel have good biocompatibility.Hydrogel is easy to be full of whole irregular defect because of its mobility, and operation wound is very small and be easy to operation, is suitable for most building the lower soft tissue organs of mechanical strength.Material for the preparation of hydrogel has chitosan, alginate, hyaluronic acid, polyvinyl alcohol etc.Wherein, chitosan is chitin deacetylase based products, is alkaline polysaccharide unique in natural polysaccharide; it is by β-(1; 4) glycoside units connects to form, and also randomly with N-acetyl group structure in these glycoside units, thus it has glycosaminoglycan and hyaluronic part feature.Chitosan extensively exists at nature, facility of drawing materials, and biocompatibility is good, biodegradable and catabolite avirulence.
Most of mammalian cell is attached cell, and they must attach in suitable substrate, sprawling could homergy propagation and differentiation.The Main Function of extracellular matrix (extracellular matrix, ECM) is mediates cell attachment.Have polypeptide and the carbohydrate ligands of much cell receptor identification in extracellular matrix, this receptoroid, ligand interaction play a very important role to maintenance cell function tool, can also give the response of cellular environment simultaneously.The premiere feature of extracellular matrix is mediates cell attachment, and most cells lacks that stick will apoptosis or death, and loses and stick related signaling pathway and can make cancerous tumor growth and diffusion.By the method for finishing can in hydrogel network analog cell epimatrix, thus to promote and regulating cell growth and tissue construction.Mainly use the methods such as plasma deposition (polymerization) etching, radiation grafting, wet-chemical reaction, absorption, photoreaction, immobilization to timbering material surface modification at present, to improve the biocompatibility of timbering material, the topological structure on surface is regulated and controled on from nanometer to micro-meter scale, inducing cell behavior or biomineralization, control the rate of release of bioactive substance, prevent protein or cell adhesion and tissue adhesions etc.There is such as organic reagent and remain in these methods, process is complicated, and the weak points such as high cost, limit practical application.
Tissue engineering bracket material is modified for wet-chemical reaction, polylactic acid (PLLA) is placed on ethanol/water solution Partial hydrolysis ester group by Boccafoschi etc., then the carboxyl activated in acid MES solution in support by EDC/NHS reaction connects the amino in bioactive molecule RGD, wherein RGD is the important fragment of cell adhesion azelon Fibronectin (fibronectin), thus at timbering material finishing RGD to strengthen the Adhering capacity of cell at material surface.(Boccafoschi F,Fusaro L,Mosca C,Bosetti M,Chevallier P,Mantovani D,Cannas M.The biologicalresponse of poly(L-lactide)films modified by different biomolecules:Role of the coating strategy.J.Biomed.Mater.Res.Part A,2012,100A,2373-2381.)
The shortcoming that timbering material is modified in above-mentioned wet-chemical reaction is:
1. destroy the activity of bioactive molecule.EDC/NHS reaction is carried out in acid MES solution, and pH=5.6, the avtive spot in this solution on RGD molecule may reduce.
2. the selection of bioactive molecule is limited.The conditional request that modified biological bioactive molecule demand fulfillment EDC/NHS reacts on timbering material, namely must contain carboxylic acid or primary amine groups in reactant molecule.
3. the content of bioactive molecule is uncontrollable.EDC/NHS reaction is violent, cannot the quantity of accurate control connection RGD molecule.React after-poppet material and again cannot carry out EDC/NHS reaction forming RGD molecule.
Laminated assembling technology (Layer-by-Layer assembly technique, LbL) be at first based on polyelectrolyte with positive and negative charge interphase interaction exploitation a kind of Supramolecular self assembly technology, then be extended between hydrogen bond action, hydrophobic interaction and biomolecule that specific recognition effect etc. can as the driving force of LBL self-assembly film, this extends the application potential of this technology in biomaterial preparation and modification greatly, and assembled material relates to functional polyalkylene electrolyte, bioactive molecule, nanoparticle, organic/inorganic microgranule, antibacterial, virus etc.In field of tissue engineering technology, use laminated assembling technology to modify timbering material and there is following advantage: 1. the range of choice of assembling molecule is extensive, bioactive molecule (as protein, polysaccharide, DNA etc.) all contains intermolecular interaction site, may be used for assembling under suitable condition; 2. preparation technology is simple, can realize the design on a molecular scale to supporting structure and function by simply alternately immersion technique; 3. preparation condition is gentle, can carry out in normal-temperature water solution, thus keeps the natural activity of biomolecule, does not affect its physicochemical properties; 4. the matrix material kind be suitable for is many, to the three-dimensional-structure strong adaptability of matrix material, and can realize on the device with complex shape structure and material.By laminated assembling technology, extracellular matrix components is directly fixed on material surface, thus covers one layer of cells epimatrix at material surface, the cell compatibility of material is significantly improved, and this kind of research has become the focus in cell compatibility investigation of materials.Artificial mode is adopted to form material-extracellular matrix composite bed, by selecting specific cells epimatrix (as promoted the hyaluronic acid, chrondroitin, fibronectin splicing variants, collagen etc. of cell adhesion) or class extracellular matrix, improving cell sticking and growth performance at material surface, is a kind of simple effective method.
Summary of the invention
Remain for the organic reagent existed in tissue engineering bracket finishing, process is complicated, the problems such as high cost, the object of the invention is to use laminated assembling technology to modify tissue engineering bracket, there is provided a kind of simple and practical, controllability is strong, and the method for clean low cost modifies tissue engineering bracket.
Modify a method for tissue engineering bracket, comprise the steps:
A. tissue engineering bracket to be dipped in active component I aqueous solution 1 ~ 8 hour;
B. the tissue engineering bracket of completing steps a taken out and wash unnecessary active component I;
C. the tissue engineering bracket of completing steps b to be dipped in active component II aqueous solution 1 ~ 8 hour;
D. the tissue engineering bracket of completing steps c taken out and wash unnecessary active component II;
E. a-d step n time is repeated, 0≤n≤100.
Wherein, be combined with each other by least one active force in electrostatic, hydrogen bond, Van der Waals force, hydrophobic interaction, covalent bond, molecular specificity recognition reaction between described tissue engineering bracket, active component I or active component II.Described active component I and active component II can according to selecting factors such as the extracellular matrix components of the electric charge of modified tissue engineering bracket surface molecular, composition, chemical bond and destination organization.
Preferably, the mass percent of described active component I in its aqueous solution is 0.1 ~ 1wt.%; The mass percent of described active component II in its aqueous solution is 0.1 ~ 1wt.%.
Further, described active component I is at least one in chrondroitin, hyaluronic acid, heparin, mucopolysaccharide, fibronectin splicing variants, laminin; Described active component II is at least one in chitosan, lysine, collagen.
Described tissue engineering bracket comprises hydrogel scaffold, and preferably, described tissue engineering bracket to be cross-linked with each other acquisition hydrogel scaffold by cross-linking agent by gel component.
Further, described gel component is at least one in chitosan, collagen, sodium alginate, potassium alginate, polyvinyl alcohol, polyacrylic acid.
Further, described cross-linking agent is genipin aqueous solution, CaCl
2aqueous solution, BaCl
2aqueous solution, FeCl
3aqueous solution, CrCl
3at least one in aqueous solution, glutaraldehyde water solution, ethylene glycol dimethacrylate aqueous solution.
The present invention also provides by the organizational structure of modifying a kind of tissue engineering bracket that tissue engineering bracket method obtains, and comprise tissue engineering bracket, described tissue engineering bracket is coated with alternately laminated active component I and active component II.This alternatively layered structure can reduce or avoid the loss of active component, active component is fixed on support.
Wherein, be by electrostatic between described tissue engineering bracket, active component I or active component II, hydrogen bond, Van der Waals force, hydrophobic interaction, covalent bond, at least one active force in molecular specificity recognition reaction combines.
Further, described active component I is at least one in chrondroitin, hyaluronic acid, heparin, mucopolysaccharide, sodium alginate, fibronectin splicing variants, laminin.
Further, described active component II is at least one in chitosan, lysine, collagen.
Preferably, described tissue engineering bracket comprises hydrogel scaffold, and described hydrogel scaffold to be cross-linked with each other acquisition by cross-linking agent by gel component.
Further, described gel component is at least one in chitosan, collagen, sodium alginate, potassium alginate, polyvinyl alcohol, polyacrylic acid.
Further, described cross-linking agent is genipin aqueous solution, CaCl
2aqueous solution, BaCl
2aqueous solution, FeCl
2aqueous solution, CrCl
2at least one in aqueous solution, glutaraldehyde water solution, ethylene glycol dimethacrylate aqueous solution.
The present invention also provides the method for modifying of this tissue engineering bracket preparing the application in medical apparatus and instruments, has good biocompatibility.
The present invention carries out in normal-temperature water system, be assembled in tissue engineering bracket network by the interaction between active component and tissue engineering bracket layer by layer by active component, composition and the number of plies of assembling are adjustable, and the method is simple and practical, controllability is strong, clean low cost.
Accompanying drawing explanation
Fig. 1 is the schematic flow sheet that the embodiment of the present invention 1 modifies hydrogel scaffold.
Fig. 2 is the surperficial Zeta potential variation diagram of the embodiment of the present invention 1 hydrogel scaffold difference assembling number of plies.
Fig. 3 is the changes of contents figure that in the embodiment of the present invention 1 hydrogel scaffold, chrondroitin assembles the number of plies with difference.
Fig. 4 a is the scanning electron microscope (SEM) photograph of cell in the embodiment of the present invention 1 hydrogel scaffold, and Fig. 4 b is the partial enlarged drawing of Fig. 4 a.
Fig. 5 is the DNA total amount schematic diagram of the embodiment of the present invention 1 in different incubation time point cell/timbering material.
Detailed description of the invention
Hereafter will by reference to the accompanying drawings and embodiment describe the present invention, its objective is and make those skilled in the art of the present technique be easier to understand enforcement of the present invention and advantage, and can not be construed as limiting the invention.
Unless separately had definition in the description of the present invention, otherwise be all that the conventional definitions usually using according to persons skilled in the art and understand uses at this all technical term.
Embodiment 1
The tissue engineering bracket of the present embodiment is the hydrogel scaffold adopting cross-linking agent and gel component to prepare, and such as, cross-linking agent is genipin aqueous solution, CaCl
2aqueous solution, BaCl
2aqueous solution, FeCl
2aqueous solution, CrCl
2at least one in aqueous solution, glutaraldehyde water solution or ethylene glycol dimethacrylate aqueous solution, gel component is at least one in chitosan, collagen, sodium alginate, potassium alginate, polyvinyl alcohol or polyacrylic acid, and both cross-linking reaction occur and obtain hydrogel scaffold.Concrete preparation method can be see application number: the patent application " hydrogel biological support of biomacromolecule and preparation method thereof " of 201010237869.X.
Preparation 0.2wt.% chrondroitin aqueous solution is as active component I solution; 0.2wt.% chitosan aqueous solution (containing 0.1wt.% acetic acid) is for subsequent use as active component II aqueous solution.Then the method for layer assembly is adopted to modify hydrogel scaffold through the following steps:
The flow process of laminated assembling technology beautify chitosan hydrogel scaffold is shown in Fig. 1.
A. aquagel support is immersed 2h in 0.2wt.% chrondroitin aqueous solution, make hydrogel scaffold can assemble last layer chrondroitin.In immersion process, confirmed by surperficial Zeta potential test result (shown in composition graphs 2): chrondroitin is elecrtonegativity, and chitosan is electropositive, both be combined with each other by electrostatic interaction, just assemble one deck chrondroitin molecule after having assembled at aquagel rack surface.According to different assembling concentration needs, immersion process can proper extension, and the general duration that soaks reaches 8 hours and can ensure that loading completes.
Here is the surperficial Zeta potential test result (see Fig. 2) of modifying hydrogel scaffold in layer assembly process:
By investigating the driving force of the Changeement assembling of chitosan hydrogel scaffold surface Zeta potential in layer assembly process.For test needs, hydrogel scaffold is ground into the gel particle of micron-scale, on surperficial zeta potential instrument, tests the surperficial Zeta potential of gel particle in an assembling process.As shown in Figure 2, chrondroitin molecule is in aqueous in electronegativity, assembling chrondroitin after-poppet surface Zeta potential is negative value, chitosan molecule is in aqueous in electropositivity, assembling chitosan after-poppet surface Zeta potential be on the occasion of, therefore, the driving force of layer assembly is the electrostatic interaction between chrondroitin molecule and chitosan molecule.
B. then the hydrogel scaffold being assembled with chrondroitin is placed in pure water and soaks 1h, wash unnecessary chrondroitin.When being assembled into the chrondroitin molecule of some, due to weakening of electrostatic interaction, electrostatic interaction between chitosan and chrondroitin is the more chrondroitin molecule of not enough assembling, and the now assembling of chrondroitin reaches capacity, and some are assembled unstable chrondroitin and will be washed.
C. the hydrogel scaffold of completing steps b is immersed 2h in 0.2wt.% chitosan aqueous solution, on the hydrogel scaffold being assembled with chrondroitin, assemble one deck chitosan by electrostatic interaction.Encasement polysaccharide on the basis of chrondroitin, can allow active component be fixed on the surface of hydrogel scaffold, reduce or avoid the loss of active component, can also strengthen the adaptability of hydrogel scaffold three-dimensional-structure, and the cell compatibility of material is significantly improved.According to different assembling concentration needs, immersion process can proper extension, and the general duration that soaks reaches 8 hours and can ensure that loading completes.
D. similarly, treat that the electrostatic interaction between chrondroitin and chitosan reaches capacity, the hydrogel scaffold of completing steps c is placed in pure water and soaks 1h, wash unnecessary chitosan.
It is 10 times that the present embodiment repeats above-mentioned steps a ~ d.Can repeatedly above a ~ Step d n time, 0≤n≤100.In regulation and control aquagel support, the content of chrondroitin, obtains the aquagel tissue structure of alternately laminated chrondroitin and chitosan thus on hydrogel scaffold.
Here is the content measuring of chrondroitin in the aquagel tissue structure after modifying:
By EDC/NHS reaction labelling fluorescence molecule Alexa in chrondroitin molecule
555cadaverine (Invitrogen), and carry out above-mentioned assembling process.Fluorophotometer records the concentration of chrondroitin in the Strength co-mputation solution of fluorescence molecule.Relatively before and after assembling chrondroitin, in chrondroitin aqueous solution, the concentration change of chrondroitin calculates the content of chrondroitin in aquagel organizational structure.The changes of contents of assembling chrondroitin in the aquagel tissue structure of different number of plies chrondroitin is shown in Fig. 3.As seen from the figure, the content of chrondroitin in aquagel organizational structure can be regulated and controled by the change of the chrondroitin assembling number of plies.
Here is the cell culture experiments of aquagel tissue structure after modifying.
Human lung cancer cell A549 (human lung fibroblast, HLF) is cultivated, the growing state of cell in timbering material before and after softer ossein assembling in aquagel organizational structure.To cultivate after 10 days cellular morphology in the aquagel organizational structure assembling chrondroitin to characterize and see Fig. 4.As seen from the figure, cell is fully sprawled at rack surface, observes a large amount of cell pseudopodium in population of cells, shows the strong interaction between cell and timbering material.The DNA total amount (Fig. 5) in cell/timbering material is detected at different incubation time point.Under the same terms, more known with the sample of unassembled chrondroitin, more DNA composition (corresponding with cells in sample number) can be detected in the sample assembling chrondroitin, show that the hydrogel scaffold assembling chrondroitin and chitosan can provide better growing environment for cell.
Embodiment 2
Aquagel support as different from Example 1, is immersed 4h in the 1wt.% heparin solution of active component I, hydrogel scaffold assembles heparin, is then placed in pure water 1h and cleans unnecessary heparin by this enforcement; Hydrogel scaffold is immersed 3h in the 0.2wt.% chitosan aqueous solution of active component II and assemble chitosan on support; Then be placed in pure water 1h and clean unnecessary chitosan.The present embodiment repeats above-mentioned steps 30 times.Repeatedly above step, can regulate and control the content of heparin in aquagel support, obtains the aquagel tissue structure of alternately laminated heparin and chitosan on hydrogel scaffold thus.
Embodiment 3
Collagen hydrogel support as different from Example 1, is immersed 2h in the 0.4wt.% chrondroitin aqueous solution of active component I, hydrogel scaffold assembles chrondroitin, is then placed in pure water 1h and cleans unnecessary chrondroitin by this enforcement; Hydrogel scaffold is immersed 5h in the 0.3wt.% collagenic aqueous solution of active component II and assemble collagen on support, be then placed in pure water 1h and clean unnecessary collagen.The present embodiment repeats above-mentioned steps 40 times.Repeatedly above step, can regulate and control the content of chrondroitin in collagen hydrogel support, obtains the aquagel tissue structure of alternately laminated chrondroitin and collagen on hydrogel scaffold thus.
Embodiment 4
Aquagel support as different from Example 1, is immersed 2h in the 0.1wt.% sodium alginate aqueous solution of active component I, hydrogel scaffold assembles sodium alginate, is then placed in pure water 1h and cleans unnecessary sodium alginate by this enforcement; Hydrogel scaffold is immersed 4h in the 1wt.% lysine solution of active component II and assemble lysine on support, be then placed in pure water 1h and clean unnecessary lysine.The present embodiment repeats above-mentioned steps 10 times.Repeatedly above step, can regulate and control the content of lysine in aquagel support.Obtain the aquagel tissue structure of alternately laminated sodium alginate and lysine on hydrogel scaffold thus.
Embodiment 5
Collagen hydrogel support as different from Example 1, is immersed 8h in the 0.3wt.% mucopolysaccharide aqueous solution of active component I, hydrogel scaffold assembles mucopolysaccharide, is then placed in pure water 1h and cleans unnecessary mucopolysaccharide by this enforcement; Support is immersed 3h in the 0.2wt.% lysine solution of active component II and assemble lysine on support, be then placed in pure water 1h and clean unnecessary lysine.
Again described hydrogel scaffold is immersed 3h in the 0.1wt.% sodium alginate aqueous solution of active component I, hydrogel scaffold assembles sodium alginate, is then placed in pure water 1h and cleans unnecessary sodium alginate; Hydrogel scaffold is immersed 8h in the 0.4wt.% lysine solution of active component II and assemble lysine on support, be then placed in pure water 1h and clean unnecessary lysine.
The present embodiment repeats above-mentioned steps 10 times.Repeatedly above step, can regulate and control the content of various component in hydrogel scaffold.Obtain the aquagel tissue structure of alternately laminated mucopolysaccharide, sodium alginate, lysine on hydrogel scaffold thus.
In other embodiments, active component I can also be fibronectin splicing variants or laminin.
In the present invention, active component I and active component II can according to the selecting factors such as electric charge, composition, chemical bond of modified tissue engineering bracket surface molecular.The tissue engineering bracket surface modified in the present invention initial electrically on the occasion of, therefore active component I is selected to show electronegative molecule in aqueous, and active component II is selected to show electropositive molecule in aqueous, such active component I and active component II are on support by electrostatic interaction layer assembly.Similarly, modifying different tissue engineering brackets can by different active forces, such as, can also be also hydrogen bond, Van der Waals force, hydrophobic interaction, covalent bond or molecular specificity recognition reaction etc.In the embodiment of the present invention, the selection of active component I and active component II can not be construed as limiting the invention.
The present invention carries out in normal-temperature water system, be assembled in tissue engineering bracket network by the interaction between active component and tissue engineering bracket layer by layer by active component, composition and the number of plies of assembling are adjustable, and the method is simple and practical, controllability is strong, clean low cost.
By laminated assembling technology, extracellular matrix components is directly fixed on material surface, thus covers one layer of cells epimatrix at material surface, the cell compatibility of material is significantly improved.Artificial mode is adopted to form material-extracellular matrix composite bed, by selecting specific cells epimatrix (as promoted the hyaluronic acid, chrondroitin, fibronectin splicing variants, collagen etc. of cell adhesion) or class extracellular matrix, improving cell sticking and growth performance at material surface, is a kind of method of modifying hydrogel scaffold easily and effectively.Owing to having good cell compatibility, the aquagel tissue structure produced has a wide range of applications preparing in medical apparatus and instruments, such as, hydrogel scaffold can be made into different shapes, as nose in column, people's vessel-like, people's ear, people, people's phalanges shape etc., modify upper extracellular matrix components again, can obtain performance preferably biomaterial be applied in medical field.
Claims (6)
1. modify a method for tissue engineering bracket, it is characterized in that, comprise the steps:
A. tissue engineering bracket to be dipped in active component I aqueous solution 1 ~ 8 hour;
B. the tissue engineering bracket of completing steps a taken out and wash unnecessary active component I;
C. the tissue engineering bracket of completing steps b to be dipped in active component II aqueous solution 1 ~ 8 hour;
D. the tissue engineering bracket of completing steps c taken out and wash unnecessary active component II;
E. a-d step n time is repeated, 0≤n≤100; Described tissue engineering bracket comprises hydrogel scaffold, and described hydrogel scaffold to be cross-linked with each other acquisition by cross-linking agent by gel component; Described gel component is at least one in chitosan, collagen, sodium alginate, potassium alginate, polyvinyl alcohol, polyacrylic acid;
Be combined with each other by least one active force in hydrogen bond, Van der Waals force, hydrophobic interaction, covalent bond, molecular specificity recognition reaction between described tissue engineering bracket, active component I or active component II.
2. modify the method for tissue engineering bracket according to claim 1, it is characterized in that, the mass percent of described active component I in its aqueous solution is 0.1 ~ 1wt.%; The mass percent of described active component II in its aqueous solution is 0.1 ~ 1wt.%.
3. modify the method for tissue engineering bracket according to claim 2, it is characterized in that, described active component I is at least one in chrondroitin, hyaluronic acid, heparin.
4. modify the method for tissue engineering bracket according to claim 2, it is characterized in that, described active component I is at least one in mucopolysaccharide, fibronectin splicing variants, laminin.
5. modify the method for tissue engineering bracket according to claim 2, it is characterized in that, described active component II is at least one in chitosan, lysine, collagen.
6. modify the method for tissue engineering bracket according to claim 1, it is characterized in that, described cross-linking agent is genipin aqueous solution, CaCl
2aqueous solution, BaCl
2aqueous solution, FeCl
3aqueous solution, CrCl
3at least one in aqueous solution, glutaraldehyde water solution, ethylene glycol dimethacrylate aqueous solution.
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| CN106963982A (en) * | 2017-04-24 | 2017-07-21 | 广东医科大学附属医院 | A kind of repair materials adhered to anti-bacteria wet keeping appropriate tissue and its preparation method and application |
| CN109224128B (en) * | 2017-07-11 | 2021-04-30 | 中国科学院苏州纳米技术与纳米仿生研究所 | Slow release system of collagen scaffold loaded with bioactive factors and construction method thereof |
| CN107648680A (en) * | 2017-09-29 | 2018-02-02 | 无锡盛雅生物科技有限公司佛山分公司 | Improve the preparation method of the antimicrobial coating of biocompatibility |
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| CN102335455A (en) * | 2010-07-26 | 2012-02-01 | 中国科学院化学研究所 | Biomacromolecular hydrogel biological stent and preparation method thereof |
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