CN1389481A - Photo-oxidation graft and bioactive factor immobilizing process of preparing cell compatible biological material - Google Patents
Photo-oxidation graft and bioactive factor immobilizing process of preparing cell compatible biological material Download PDFInfo
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- CN1389481A CN1389481A CN 02136032 CN02136032A CN1389481A CN 1389481 A CN1389481 A CN 1389481A CN 02136032 CN02136032 CN 02136032 CN 02136032 A CN02136032 A CN 02136032A CN 1389481 A CN1389481 A CN 1389481A
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Abstract
The invention discloses a method for preparing cell-compatible biomaterial by way of the photo-oxidative graft and the fixation of the biological active gene, which includes: first, under the irradiation of ultraviolet light, oxidize the polymer material in the hydrogen-peroxide solution, to lead the giant molecule hydrogen-peroxide group onto the surface of the polymer material; and then use the giant molecule hydrogen-peroxide group on the surface of the oxidized polymer material as the initiator to initiate the free-group grafting polymeric reaction of the ethenyl monomer containing the active functional group on the surface of the polymer material, which lead the active functional group into the polymer material surface; and then make the polymer material react with the biological active gene to combine the covalent bond onto the surface of the polymer material.
Description
Technical field
The present invention relates to the method that photo-oxidation graft and bioactive factor immobilizing prepare cell compatible biological material.
Background technology
Biomaterial can be defined as directly and the contacted material of physiological environment.In application, biomaterial inevitably contacts with the intravital various cells of people, tissue and organ, therefore requires material to have the good cell consistency.The cell compatibility of biomaterial mainly is meant when biomaterial contacts with tissue can not produce toxic action to the cell in the tissue, and require material surface to help the adhesion of cell, and have and promote sprawling of cell, migration, differentiation are also kept the normal phenotype of cell and the effect of cell normal physiological function (as the function of chondrocyte's secretory protein polysaccharide and II Collagen Type VI).
The polymer materials of synthetic has been widely used in bio-medical field such as artificial organ, organizational project, bone tissue restoration, surgical plastic and medicine controlled releasing etc. owing to have good physical and mechanical properties and workability.The three-dimensional porous rack material that for example utilizes degradable polymer material poly(lactic acid) (PLA), polyglycolic acid (PGA) or its multipolymer (PLGA) to make has been applied to bone tissue engineer and cartilage tissue engineered.Its effect is to provide a three-dimensional environment of depending on for existence for cell.Yet the polymer materials of most synthetic all has stronger hydrophobicity, and its surface also all is chemically inert, and especially cell compatibility is undesirable to cause the biocompatibility of these polymer materialss.Poly(lactic acid) for example there are some researches show because its higher hydrophobicity makes cell very low at its surperficial adhesion rate, and cell is difficult adherent and sprawl in three-dimensional rack, has limited its application prospect as the degradable tissue engineering bracket material greatly.
Summary of the invention
The objective of the invention is to propose the method that photo-oxidation graft and bioactive factor immobilizing prepare cell compatible biological material in order to improve the cell compatibility of artificial-synthetic copolymer's material.
The method for preparing cell compatible biological material that the present invention proposes comprises at first under ultraviolet light irradiation, with polymer materials oxidation in superoxol, to introduce macromole hydrogen peroxide group at surface of polymer material, the macromole hydrogen peroxide group that utilizes the surface of polymer material after the oxidation then is as initiator, causing the vinyl monomer that contains active function groups reacts at the free yl graft polymerization of surface of polymer material, active function groups is incorporated into material surface, react with biologically active factors again, the biologically active factors covalence key is closed in surface of polymer material, give surface of polymer material good cell consistency and biological activity.
The method that photo-oxidation graft that the present invention proposes and bioactive factor immobilizing prepare cell compatible biological material may further comprise the steps:
1) polymer materials being put into concentration is 10～40% superoxol, oxidation under ultraviolet light irradiation, 20～80 ℃ of oxidizing temperatures, 0.1～10 hour time, introduce macromole hydrogen peroxide group at surface of polymer material, deionized water rinsing is removed the free hydrogen peroxide molecule;
2) polymer materials after the oxidation being dipped in concentration is 1～20% to contain in the vinyl monomer of active function groups, remove oxygen and filling nitrogen then, under ultraviolet light irradiation, cause the graft polymerization reaction of vinyl monomer at surface of polymer material, 20～50 ℃ of temperature of reaction, time 20～80min;
Perhaps the polymer materials after the oxidation is dipped in concentration and is in 1～20% the vinyl monomer that contains active function groups, remove oxygen and filling nitrogen, under the ferrous ion existence condition, cause the graft polymerization reaction of vinyl monomer at surface of polymer material, the concentration of ferrous ion is 0.01～0.1M in the monomer, 20～50 ℃ of temperature of reaction, time 20～80min;
Perhaps the polymer materials after the oxidation is dipped in concentration and is in 1～20% the vinyl monomer that contains active function groups, monomer is adsorbed on material surface in advance, then material is taken out, remove oxygen and filling nitrogen, under ultraviolet light irradiation, cause the graft polymerization reaction of vinyl monomer, 20～50 ℃ of temperature of reaction, time 20～80min at surface of polymer material;
3) adopt Methanesulfonyl chloride method or carbodiimide dehydrating condensation method that the biologically active factors covalence key is closed in above-mentioned steps 2) the gained material surface.
Said polymer materials is the two-dimensional films and the three-dimensional porous rack of urethane, poly(lactic acid), polyglycolic acid, polylactic acid-glycolic guanidine-acetic acid, polycaprolactone, polyethylene terephthalate, polyethylene, polymethylmethacrylate, polypropylene and polyvinyl chloride in the invention.
The said vinyl monomer that contains active function groups is acrylamide and the Methacrylamide that contains amido group in the invention, the vinylformic acid and the methacrylic acid that contain carboxyl, the hydroxyethyl methylacrylate, Hydroxyethyl acrylate, Propylene glycol monoacrylate, vinylcarbinol, the allyloxyethanol that contain hydroxyl contain the styrene sulfonic acid of sulfonic acid group and sodium salt thereof, sylvite, ammonium salt etc.
Said biologically active factors is meant collagen, gelatin, chitosan, the chondroitin sulfate with good biocompatibility in the invention; Heparin and r-hirudin with anticoagulation function; Have the fiber adhesion albumen, arginine-glycine-aspartic acid (RGD) sequence peptide section, poly-lysine, the ln that promote cell adhesion and value-added functionality, have the differentiation inducing factor Delicious peptide that promotes cytodifferentiation.
Among the present invention the biologically active factors covalence key is closed in the material surface through graft polymerization reaction, promptly bioactive factor immobilizing can adopt the Methanesulfonyl chloride method to realize or adopt carbodiimide dehydrating condensation method to realize.
The Methanesulfonyl chloride method comprises earlier will be behind graft polymerization reaction, the polymkeric substance that hydroxyl is introduced on the surface is dipped in the diethyl ether solution of Methanesulfonyl chloride, the volumetric concentration of Methanesulfonyl chloride is 1～20%, 10～30 ℃ of temperature of reaction, 0.5～20 hour time, utilize the hydroxyl reaction of Methanesulfonyl chloride and surface of polymer material to make the hydroxyl activation, and then immersion contains in the aqueous solution of biologically active factors, make hydroxyl and the reaction of the amino in the biologically active factors after the activation, the concentration of biologically active factors is 1～100mg/ml, 0～50 ℃ of temperature of reaction, 1～24 hour reaction times.
Carbodiimide dehydrating condensation method comprises earlier will be behind graft polymerization reaction, and the polymkeric substance that carboxyl is introduced on the surface is dipped in the phosphate buffered saline buffer (pH=7.4) of 1-ethyl-3-(the 3-dimethyl amine propyl group) carbodiimide (EDAC) that contains 1～50mg/ml and carries out.Temperature of reaction is 0～400C, and the reaction times is 1～24 hour.Utilize water miscible carbodiimide with activated carboxylic, and then immerse and to contain in the aqueous solution of biologically active factors, the amino in activatory carboxyl and the biologically active factors is reacted, the concentration of biologically active factors is 1～100mg/ml, 0～50 ℃ of temperature of reaction, 1～24 hour reaction times.
Method of the present invention, by chemical modification to material surface, chemically inert polymer surfaces introducing chemical active radical can be originally, make surface of polymer material have good chemically reactive, the biologically active factors that further some is had good cell compatibility or specific function is introduced material surface, thereby give material surface good cell consistency or specific biological activity, the present invention simultaneously is to the not influence of good physical and mechanical properties of polymer materials body.
Description of drawings
C1s and N1s peak among the XPS spectrum figure of the PU film (b) behind the further fixedly gelatin of the PU planar film (a) of Fig. 1 surface grafting polymethyl acrylic acid and its surface.The fixedly employing carbodiimide dehydrating condensation method of gelatin.
PU film (the b of Fig. 2 human vas endotheliocyte behind PU film (a) and surperficial fixedly gelatin, c, d) and the proliferation rate on the polystyrene culture plate (e), wherein fixedly the N1s/C1s area ratio on the PU film surface behind the gelatin is respectively (b) 5.58%, (c) 6.55%, (d) 7.89% cell inoculation density is 15 * 10
4/ ml.Incubation time is 4 days.The fixedly employing carbodiimide dehydrating condensation method of gelatin.
Fig. 3 human vas endotheliocyte is the fixing form on the PU film behind the gelatin on the surface.Wherein the N1s/C1s area ratio on film surface is respectively (a) 5.58%, and (b) 6.55%, (c) 7.89% cell inoculation density is 15 * 10
4/ ml.Incubation time is 4 days.The fixedly employing carbodiimide dehydrating condensation method of gelatin.
C1s and N1s peak among the XPS spectrum figure of the PU film (b) behind the PU planar film (a) of Fig. 4 surface grafting polymethyl acrylic acid and the further fixedly RGD in its surface.The fixedly employing carbodiimide dehydrating condensation method of RGD.
Fig. 5 human vas endotheliocyte is the fixing form on the PU film behind the RGD on the surface.Cell inoculation density is 15 * 10
4/ ml.Incubation time is 4 days.The fixedly employing carbodiimide dehydrating condensation method of RGD.
The ATR spectrogram of PLLA film before and after the fixing different biologically active factorss in Fig. 6 surface.Wherein a is unmodified PLLA film, and b is the fixedly PLLA film of gelatin of surface, and c is the fixedly PLLA film of collagen of surface, and d is the PLLA film of surperficial set casing glycan.I-acyl ammonia I; II-acyl ammonia II.The fixedly employing carbodiimide dehydrating condensation method of biologically active factors.
C1S peak before and after the fixing different biologically active factorss in Fig. 7 surface among the PLLA film XPS spectrum figure.Wherein a is unmodified PLLA film, and b is the fixedly PLLA film of gelatin of surface, and c is the fixedly PLLA film of collagen of surface, and d is the PLLA film of surperficial set casing glycan.(I)C-C；(II)C-O；(III)C(＝O)-NH；(IV)C(＝O)-O。The fixedly employing carbodiimide dehydrating condensation method of biologically active factors.
The laser confocal microscope photo of Fig. 8 a chondrocyte on unmodified PLLA film.FDA dyeing.
The laser confocal microscope photo of Fig. 8 b chondrocyte on the PLLA film behind the fixing collagen.FDA dyeing.The fixedly employing carbodiimide dehydrating condensation method of collagen.
The chondrocyte is in its surperficial adhesion rate, proliferation rate and cytoactive before and after the fixing different biologically active factors in Fig. 9 PLLA film surface.Wherein a is the polystyrene culture plate, and b is unmodified PLLA film, and c is the fixedly PLLA film of gelatin of surface, and d is the fixedly PLLA film of collagen of surface, and e is the PLLA film of surperficial set casing glycan.The fixedly employing carbodiimide dehydrating condensation method of biologically active factors.
The XPS spectrum figure of PLLA film behind the surperficial fixedly gelatin of Figure 10.The fixedly employing Methanesulfonyl chloride method of gelatin.
Embodiment
With the oxidation 8 hours in superoxol (30v%) of urethane (PU) planar film, temperature is 50 ℃, and oxidation is carried out under UV-light, and UV-light is provided by the high voltage mercury lamp of 250W.With a large amount of deionized water rinsings of PU planar film after the oxidation, be dipped in after the vacuum-drying in the test tube that fills methacrylic acid (MAA) aqueous solution (10v%) and placed 2 hours, MAA is adsorbed in PU planar film surface in advance.Film is taken out, be positioned in the quartzy polymerizing pipe, except that causing the graft polymerization reaction of MAA on PU film surface by UV-light behind the oxygen and filling nitrogen, UV-light is still provided by the high voltage mercury lamp of 250W, and the grafting time is 1 hour, and temperature is 50 ℃.Then the PU planar film is dipped in the phosphate buffered saline buffer (pH=7.4) of 1-ethyl-3-(the 3-dimethyl amine propyl group) carbodiimide (EDAC) that contains 10mg/ml, is reflected at and carried out under 0 ℃ 4 hours, the carboxyl on PU planar film surface, reaction back is activated.With phosphate buffered liquor (10mg/ml) reaction of PU planar film and gelatin, be reflected at and carried out under 0 ℃ 24 hours again.Gelatin is covalently bonded to material surface.C before and after the modification among the XPS spectrum figure
1SAnd N
1SThe variation at peak has proved the existing of PU film surface gelatin (see Table 1 and Fig. 1).Cell cultures result show the surface fixedly the PU film behind the gelatin consistency of human vas endotheliocyte is obviously improved (seeing Fig. 2 and Fig. 3)
The N1s/C1s area ratio on PU film (PU-g-PMAA-b-Gelatin) surface behind the further fixedly gelatin in urethane (PU) planar film (PU-g-PMAA) of table 1 surface grafting polymethyl acrylic acid (PMAA) and surface.The fixedly employing carbodiimide dehydrating condensation method of gelatin
Table 1
Grafting density (* 10
-2Mg/cm
2) 4.97 14.29 21.56
The N1s/C1s area is than (%, PU-g-PMAA) 2.45 2.22 2.05
The N1s/C1s area is than (%, PU-g-PMAA-g-Gelatin) 5.58 6.55 7.89
Embodiment 2
According to the method for embodiment 1, change gelatin solution into contain 10mg/ml arginine-glycine-aspartic acid tripeptide sequence (RGD) phosphate buffered saline buffer, other condition is constant, with the RGD covalent linkage with in PU planar film surface.C before and after the modification among the XPS spectrum figure
1SAnd N
1SThe variation at peak has proved the existing of PU film surface RGD (see Table 2 and Fig. 4).Cell cultures result show the surface fixedly the PU film behind the RGD consistency of human vas endotheliocyte is obviously improved (see Table 3 and Fig. 5)
The N1s/C1s area ratio on PU film (PU-g-PMAA-g-RGD) surface behind the PU film (PU-g-PMAA) of table 2 surface grafting PMAA and the further fixedly RGD in its surface.The fixedly employing carbodiimide dehydrating condensation method of RGD
Table 2
Sample P U-g-PMAA PU-g-PMAA-g-RGD
The N1s/C1s area is than (%) 2.05 5.49
Table 3 human vas endotheliocyte is in the adhesion rate and the cytoactive (with respect to the tissue culture polystyrene) on PU-g-PMAA-RGD and contrast PU surface.Cell inoculation density 15 * 10
4/ ml.Cultivate respectively and measure cell adhesion rate and appreciation rate after 12 hours and 4 days.
Table 3
Sample P U PU-g-RGD
Cell adhesion rate 54.8 ± 5.0 125.0 ± 3.5
Cytoactive (%) 31.5 ± 4.0 115.2 ± 5.0
Embodiment 3
With the oxidation 40 minutes in superoxol (30v%) of PLLA planar film, temperature is 50 ℃, and oxidation is carried out under UV-light, and UV-light is provided by the high-pressure mercury of 250W.With a large amount of deionized water rinsings of PLLA film after the oxidation, be dipped in after the vacuum-drying in the quartzy polymerizing pipe that fills methacrylic acid (MAA) aqueous solution (10v%), remove oxygen and filling nitrogen, cause the graft polymerization reaction of MAA by UV-light on PLLA film surface.The grafting time is 1 hour, and temperature is 50 ℃, and UV-light is still provided by the high-pressure mercury of 250W.Then, planar film is dipped in the phosphate buffered saline buffer (pH=7.4) that contains 10mg/ml EDAC, is reflected at and carried out under 0 ℃ 4 hours, the carboxyl on PLLA planar film surface, reaction back is activated.With PLLA planar film and acetum (pH=3) reaction that contains 4mg/ml collagen, be reflected at and carried out under 0 ℃ 24 hours again.The collagen macromole is covalently bonded to material surface.Material surface is by the coated collagen of physics and be covalently bonded between the collagen of material surface stronger interaction is arranged, thereby also can improve the collagen content of material surface greatly at the material surface stable existence.C among ATR spectrogram before and after the modification and the XPS spectrum figure
1SThe variation at peak has proved exist (the seeing Fig. 6 and Fig. 7) of PLLA film surface collagen.Cell cultures result show after this method modification the PLLA planar film to chondrocyte's consistency obviously improve (see Fig. 8 a, Fig. 8 b, Fig. 9).Profit uses the same method and also gelatin and chitosan can be fixed on PLLA film surface, improves its consistency to the chondrocyte (seeing Fig. 6 and Fig. 7 and Fig. 9)
Embodiment 4
With the oxidation 40 minutes in superoxol (30v%) of PLLA planar film, temperature is 50 ℃, and oxidation is carried out under UV-light, and UV-light is provided by the high-pressure mercury of 250W.With a large amount of deionized water rinsings of PLLA film after the oxidation, be dipped in after the vacuum-drying in the quartzy polymerizing pipe that fills hydroxyethyl methylacrylate (HEMA) aqueous solution (5v%), except that causing the graft polymerization reaction of HEMA by UV-light behind the oxygen and filling nitrogen on PLLA film surface.The grafting time is 1 hour, and temperature is 50 ℃, and UV-light is still provided by the high-pressure mercury of 250W.Then, the PLLA film behind the grafting PHEMA is dipped in the ether that contains the 10mg/ml Methanesulfonyl chloride, 25 ℃ were reacted 2 hours down, and the hydroxyl on PLLA planar film surface is activated.With PLLA planar film and the phosphate buffered saline buffer reaction that contains the 4mg/ml gelatin, be reflected at and carried out under 30 ℃ 24 hours then.Gelatin is by covalent linkage with in PLLA planar film surface.N among the XPS spectrum figure after the modification
1SThe appearance at peak has proved the exist (see figure 10) of gelatin on PLLA film surface.
Claims (6)
1. photo-oxidation graft and bioactive factor immobilizing prepare the method for cell compatible biological material, it is characterized in that may further comprise the steps:
1) polymer materials being put into concentration is 10～40% superoxol, oxidation under ultraviolet light irradiation, 20～80 ℃ of oxidizing temperatures, 0.1～10 hour time, introduce macromole hydrogen peroxide group at surface of polymer material, deionized water rinsing is removed the free hydrogen peroxide molecule;
2) polymer materials after the oxidation being dipped in concentration is 1～20% to contain in the vinyl monomer of active function groups, remove oxygen and filling nitrogen then, under ultraviolet light irradiation, cause the graft polymerization reaction of vinyl monomer at surface of polymer material, 20～50 ℃ of temperature of reaction, time 20～80min;
Perhaps the polymer materials after the oxidation is dipped in concentration and is in 1～20% the vinyl monomer that contains active function groups, remove oxygen and filling nitrogen, under the ferrous ion existence condition, the concentration of ferrous ion is 0.01～0.1M in the monomer, cause the graft polymerization reaction of vinyl monomer at surface of polymer material, 20～50 ℃ of temperature of reaction, time 20～80min;
Perhaps the polymer materials after the oxidation is dipped in concentration and is in 1～20% the vinyl monomer that contains active function groups and kept 1～10 hour, monomer is adsorbed on material surface in advance, then material is taken out, remove oxygen and filling nitrogen, under ultraviolet light irradiation, cause the graft polymerization reaction of vinyl monomer, 20～50 ℃ of temperature of reaction, time 20～80min at surface of polymer material;
3) adopt Methanesulfonyl chloride method or carbodiimide dehydrating condensation method that the biologically active factors covalence key is closed in above-mentioned steps 2) the gained material surface.
2. the method for preparing cell compatible biological material by described photo-oxidation graft of claim 1 and bioactive factor immobilizing is characterized in that said polymer materials is the two-dimensional films and the three-dimensional porous rack of urethane, poly(lactic acid), polyglycolic acid, polylactic acid-glycolic guanidine-acetic acid, polycaprolactone, polyethylene terephthalate, polyethylene, polymethylmethacrylate, polypropylene and polyvinyl chloride.
3. the method for preparing cell compatible biological material by described photo-oxidation graft of claim 1 and bioactive factor immobilizing, it is characterized in that the said vinyl monomer that contains active function groups is acrylamide and the Methacrylamide that contains amido group, the vinylformic acid and the methacrylic acid that contain carboxyl, the hydroxyethyl methylacrylate, Hydroxyethyl acrylate, Propylene glycol monoacrylate, vinylcarbinol, the allyloxyethanol that contain hydroxyl contain the styrene sulfonic acid of sulfonic acid group and sodium salt thereof, sylvite, ammonium salt etc.
4. the method for preparing cell compatible biological material by described photo-oxidation graft of claim 1 and bioactive factor immobilizing is characterized in that said biologically active factors is meant collagen, gelatin, chitosan, the chondroitin sulfate with good biocompatibility; Heparin and r-hirudin with anticoagulation function, have the fiber adhesion albumen, arginine-glycine-aspartic acid sequence peptide section, poly-lysine, the ln that promote cell adhesion and propagation function, have the differentiation inducing factor Delicious peptide of promotion cytodifferentiation etc.
5. the method for preparing cell compatible biological material by described photo-oxidation graft of claim 1 and bioactive factor immobilizing, it is characterized in that said Methanesulfonyl chloride method comprises that the polymkeric substance that will introduce hydroxyl earlier through the graft polymerization reaction rear surface is dipped in the diethyl ether solution of Methanesulfonyl chloride, the volumetric concentration of Methanesulfonyl chloride is 1～20%, 10～30 ℃ of temperature of reaction, 0.5～20 hour time, immerse then and contain in the aqueous solution of biologically active factors, the concentration of biologically active factors is 1～100mg/ml, 0～50 ℃ of temperature of reaction, 1～24 hour reaction times.
6. the method for preparing cell compatible biological material by described photo-oxidation graft of claim 1 and bioactive factor immobilizing, it is characterized in that said carbodiimide dehydrating condensation method comprises that the polymkeric substance that will introduce carboxyl earlier through the graft polymerization reaction rear surface is dipped in the phosphate buffered saline buffer (pH=7.4) of 1-ethyl-3-(the 3-dimethyl amine propyl group) carbodiimide (EDAC) that contains 1～50mg/ml, temperature of reaction is 0～40 ℃, reaction times is 1～24 hour, immerse then and contain in the aqueous solution of biologically active factors, the concentration of biologically active factors is 1～100mg/ml, 0～50 ℃ of temperature of reaction, 1～24 hour reaction times.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7323208B2 (en) * | 2004-11-30 | 2008-01-29 | The Regents Of The University Of Michigan | Modified porous materials and method of forming the same |
| CN101942105A (en) * | 2010-09-03 | 2011-01-12 | 苏州大学 | Polyurethane material capable of dissolving plasma clot in high efficiency and preparation thereof |
| US7993738B2 (en) | 2004-11-30 | 2011-08-09 | The Regents Of The University Of Michigan | Modified porous materials and method of forming the same |
| CN103958670A (en) * | 2011-12-01 | 2014-07-30 | 富士软件株式会社 | Method for long-term storage of porous body bearing chondrocytes |
| CN105861477A (en) * | 2016-06-13 | 2016-08-17 | 福建中微科创生物技术有限公司 | Method for immobilizing microorganisms with covalent binding of carboxylic resin |
| CN112432966A (en) * | 2020-12-14 | 2021-03-02 | 南京工程学院 | Microstructure characterization method of chitosan grafted modified polymer |
-
2002
- 2002-07-12 CN CNB021360324A patent/CN1164622C/en not_active Expired - Fee Related
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7323208B2 (en) * | 2004-11-30 | 2008-01-29 | The Regents Of The University Of Michigan | Modified porous materials and method of forming the same |
| US7993738B2 (en) | 2004-11-30 | 2011-08-09 | The Regents Of The University Of Michigan | Modified porous materials and method of forming the same |
| CN101942105A (en) * | 2010-09-03 | 2011-01-12 | 苏州大学 | Polyurethane material capable of dissolving plasma clot in high efficiency and preparation thereof |
| CN101942105B (en) * | 2010-09-03 | 2012-06-27 | 苏州大学 | Polyurethane material capable of dissolving plasma clot in high efficiency and preparation thereof |
| CN103958670A (en) * | 2011-12-01 | 2014-07-30 | 富士软件株式会社 | Method for long-term storage of porous body bearing chondrocytes |
| CN105861477A (en) * | 2016-06-13 | 2016-08-17 | 福建中微科创生物技术有限公司 | Method for immobilizing microorganisms with covalent binding of carboxylic resin |
| CN112432966A (en) * | 2020-12-14 | 2021-03-02 | 南京工程学院 | Microstructure characterization method of chitosan grafted modified polymer |
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