CN103071188A - Cell factor loaded nanofiber membrane and preparation method thereof - Google Patents
Cell factor loaded nanofiber membrane and preparation method thereof Download PDFInfo
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- CN103071188A CN103071188A CN2013100300247A CN201310030024A CN103071188A CN 103071188 A CN103071188 A CN 103071188A CN 2013100300247 A CN2013100300247 A CN 2013100300247A CN 201310030024 A CN201310030024 A CN 201310030024A CN 103071188 A CN103071188 A CN 103071188A
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Abstract
The invention provides a cell factor loaded nanofiber membrane which comprises loaded cell factors, glucan and a degradable high molecular material, wherein the cell factors are loaded in glucan vitreous body nano particles, and glucan vitreous body nano particles loaded with the cell factors are packaged in fibers of the degradable high molecular material. The cell factor loaded nanofiber membrane can effectively control slow release of the cell factors, and protect long-term activity of the cell factors during preparation and release, the biodegradable high molecular material can be degraded automatically, and the nanofiber membrane is nontoxic, has no immunogenicity, and good biocompatibility, improves a curative effect, reduces side effects, and has an important significance clinically.
Description
Technical field
The present invention relates to a kind of nano fibrous membrane, relate in particular to nano fibrous membrane of a kind of load cells factor and preparation method thereof.
Background technology
Adhesion of tendon is clinical common diseases, owing to lack effective adhesion prophylactico-therapeutic measures, usually makes and treats the vicious cycle that is absorbed in " adhesion-loosen-again adhesion ", has had a strong impact on patient's limb function.Between tendon and surrounding tissue, place the effect that Antiadhesive film has certain minimizing adhesion of tendon, but they do not have the function that promotes healing process of tendons and slip.In addition, because material or structure can only play the physical barrier effect behind the parcel tendon, the phenomenons such as the rejection that may occur and interference healing process of tendons have a strong impact on the recovery of tendon function.Therefore, seek suitable Antiadhesive film material and structure, load anti medicine, the continuous release promotion healing process of tendons by medicine reaches the purpose that prevents adhesion of tendon, and is significant.
The early stage Antiadhesive film of using adopts non-biological material (such as silicone rubber) to make more, but have that tissue reaction is large, rejection obviously, without permeability, affect tendon the endogenous healing with need the deficiency such as secondary operation taking-up, can make because of the nutrition that has intercepted tendon its generation degeneration when serious.Therefore, the Antiadhesive film of present this material formation substantially need not.In recent years, the Antiadhesive film of being made by degradable high polymer material comes out, in this class material, existing natural macromolecular material, such as cellulose derivative, hyaluronic acid, chitin and derivant thereof etc., synthetic high molecular polymer is also arranged, such as polylactic acid (polylactic acid, PLA), polycaprolactone (polycaprolactone, PCL), polyglycolic acid and their copolymer etc.
The healing of tendon and adhesions more complicated, the cytokines such as basic fibroblast growth factor (basic fibroblast growth factor, bFGF), insulin-like growth factor-i, epidermal growth factor, TGF-β1 3, platelet-derived growth factor have all participated in this process.Chan etc. have confirmed that normal Tenocyte cell and stndon sheath cell all can produce the cytokines such as bFGF, studies confirm that further the cytokine such as bFGF is to promote healing process of tendons by cell proliferative response, and find that in Mus kneecap tendon model the cytokine such as bFGF can promote synthesizing of Tenocyte cell propagation and III Collagen Type VI.Sha Defeng etc. place bFGF composite slow release degradative membrane at the rat tendon damage place of sewing up, experimental result shows that bFGF composite slow release degradative membrane has the effect that increases the inner healing ability of tendon, and can make the inner healing of tendon faster than tendon week connective tissue proliferation, not only accelerate agglutination, and reached the effect that alleviates or prevent Adhesion formation.Although cytokine has high bioactivity, promote healing process of tendons and reduce the advantage of Adhesion formation, also there is short, the easy deficiency such as inactivation in acid and alkali-resistance and the aqueous solution not of half-life.Therefore, desirable treatment pattern provides a carrier, makes it can be in the stable release of local slow, and guarantees cytokine activity.
Summary of the invention
The object of the invention is to overcome above-mentioned deficiency, a kind of nano fibrous membrane of the load cells factor is provided, can be the slowly stable release cells factor has guaranteed continuous release and the long period of activity of cytokine.
The invention provides a kind of nano fibrous membrane of the load cells factor, composition material comprises cytokine, glucosan and degradable high polymer material, wherein cytokine loads in the Vitrea nano-particle of described glucosan, and the glucosan vitreous body nano-particle of the load cells factor is encapsulated in the fiber of described degradable high polymer material.
Preferably, the mass ratio of cytokine and glucosan is (0.5-0.8) in the glucosan vitreous body nano-particle of the described load cells factor: (10-10000).
Preferably, the quality of described degradable high polymer material be cytokine and glucosan gross mass 1-200 doubly.
Preferably, the particle diameter of the glucosan vitreous body nano-particle of the described load cells factor is 0.05-10um.
Preferably, described cytokine is selected from one or more in basic fibroblast growth factor, insulin-like growth factor-i, epidermal growth factor, TGF-β1 3, the platelet-derived growth factor etc.
Preferably, described cytokine is basic fibroblast growth factor.
Preferably, described degradable high polymer material is elected one or more in copolymer, hydroxy carboxylic acid and polyol copolymer, poly phosphate, Merlon or the poly-anhydride of polyhydroxycarboxyliacid acid, several hydroxy carboxylic acid monomers as.
Preferably, described degradable high polymer material is polyhydroxycarboxyliacid acid.Wherein, hydroxy carboxylic acid is preferably alpha-hydroxy carboxylic acid compounds, and described alpha-hydroxy carboxylic acid compounds refers in the described carboxylic acid, has at least a hydroxyl to be positioned on the carbon atom adjacent with carboxyl, and molecular structure is R
1-C (R
2) (OH)-COOH, wherein R
1Be selected from the alkyl of H or C-C10, the alkyl of H or C1-C5 more preferably, the alkyl of H or C1-C3 more preferably is such as methyl, ethyl, propyl group, isopropyl etc., R
1Most preferably be methyl (being that alpha-hydroxy carboxylic acid compounds is lactic acid).Those skilled in the art can be understood that hydroxy carboxylic acid of the present invention also can substitute with lactone, substitutes hydroxycaproic acid such as caprolactone, because among the present invention, lactone is identical with the hydroxy carboxylic acid role, and therefore, lactone is also included within the described scope of hydroxyl of the present invention.
Preferably, described polyhydric alcohol is preferably dihydroxylic alcohols, most preferably is α-dihydroxylic alcohols, such as propylene glycol, ethylene glycol, most preferably is ethylene glycol.
Degradable high polymer material of the present invention most preferably is lactic acid homopolymer or lactic acid and other alpha-hydroxy carboxylic acid compounds copolymer or lactic acid and α-divalent alcohol copolymers or its mixture; More preferably lactic acid and α-divalent alcohol copolymers, more preferably lactic acid and glycol copolymer, lactic acid and α-propylene glycol copolymers or its mixture most preferably are lactic acid and glycol copolymer.Those skilled in the art can be understood that, dihydroxylic alcohols of the present invention also can substitute with epoxide, substitute ethylene glycol, the alternative propylene glycol of epoxy prapanol such as oxirane, because among the present invention, the alkylene oxide chemical compound is identical with the polyhydric alcohol role, therefore, the alkylene oxide chemical compound is also included within the described scope of hydroxyl of the present invention.
Preferably, described degradable high polymer material selects one or more in polyhydroxycarboxyliacid acid, polylactic-co-glycolic acid, PLA-PEG copolymer, polylactic acid-polycaprolactone copolymer, polycaprolactone, poly phosphate, Merlon or poly-anhydride or the medical class degradable high polymer material of other biological etc..
Preferably, described degradable high polymer material molecular weight is 20KDa-200KDa.
Preferably, described degradable high polymer material is polylactic acid, and molecular weight is 30-70KDa.
Preferably, the fibre diameter of the nano fibrous membrane of the described load cells factor is 0.1-30 μ m.
The present invention also provides a kind of preparation method of nano fibrous membrane of the above-mentioned load cells factor, may further comprise the steps:
Preferably, the concentration of dextran solution is 0.2-20wt% in the step 1, and the concentration of polyvalent alcohol is 0.2-20wt%.
Wherein, described polyvalent alcohol is preferably poly-dihydric alcohol, more preferably poly-α-dihydroxylic alcohols; α-dihydroxylic alcohols refers to have at least and is connected with respectively a hydroxyl on two adjacent carbon atoms, and molecular structure is R
3-C (R
4) (OH)-C (R
5) (OH)-R
6, wherein, R
3, R
4, R
5, R
6Be independently selected from respectively the alkyl of H or C1-C10, the alkyl of H or C1-C5 more preferably, the alkyl of H or C1-C3 more preferably is such as methyl, ethyl, propyl group, isopropyl; R
3, R
4, R
5, R
6Most preferably being independently respectively H(is that polyhydric alcohol or α-dihydroxylic alcohols are ethylene glycol).
Should be noted in the discussion above that above-mentioned dihydroxylic alcohols also can substitute with epoxide, substitute ethylene glycol, the alternative α-propylene glycol of expoxy propane such as oxirane, prepared polymer has identical structure.
Preferably, described polyvalent alcohol is Polyethylene Glycol.
Preferably, described Polyethylene Glycol is PEG6000 or PEG4000 etc.
Described organic solvent is preferably aliphatic hydrocarbon, aromatic hydrocarbon, chlorohydrocarbon, alcohol, ketone, aldehyde, ester, nitrile, carboxylic acid, sulfoxide, amide solvent.
The example of described aliphatic hydrocarbon comprises: pentane, hexane, octane, cyclohexane extraction etc.
The example of described aromatic hydrocarbon comprises: styrene, benzene,toluene,xylene etc.
The example of described chlorohydrocarbon comprises: dichloromethane, chloroform, carbon tetrachloride, bromofom, chlorobenzene, dichloro-benzenes (paracide, o-dichlorohenzene), sym-tetrachloroethane etc.
The example of described alcohol comprises: methanol, ethanol, ethylene glycol, propanol, isopropyl alcohol, propylene glycol, the tert-butyl alcohol, glycerol, butanediol, pentanediol, glycol monoethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether etc.
The example of described ketone comprises: acetone, butanone, methyl butyl ketone, Ketohexamethylene etc.
The example of described aldehyde comprises: acetaldehyde, propionic aldehyde, glutaraldehyde, Biformyl etc.
The example of described ester comprises: methyl acetate, ethyl acetate, propyl acetate, butyl acetate, pentyl acetate, methyl formate, Ethyl formate, butyl formate, amyl formate etc.
The example of described nitrile is such as acetonitrile etc.
The example of described carboxylic acid comprises: formic acid, acetic acid etc.
The example of described sulfoxide comprises: dimethyl sulfoxide, thionyl chloride, diphenyl sulfoxide etc.
The example of described amide comprises: DMF, N, N-diethylformamide etc.
Preferably, organic solvent described in the step 1 is one or more in normal hexane, dichloromethane, chloroform, acetone, oxolane, ethyl acetate, the dimethyl formamide etc.
Preferably, organic solvent described in the step 2 is for dissolving the solvent of degradable high polymer material.
Preferably, organic solvent described in the step 2 is for dissolving one or more in the degradable high polymer material etc. for methanol, ethanol, n-butyl alcohol, normal hexane, dichloromethane, chloroform, acetone, oxolane, ethyl acetate, DMF (DMF), isopropyl alcohol, trifluoroethanol or hexafluoroisopropanol or other.
Preferably, degradable high polymer material is dissolved in the organic solvent in the step 2, obtains degradable high polymer material solution, then with the glucosan vitreous body nanoparticulate dispersed of the load cells factor or be dissolved in the solution of Biodegradable high molecular.
Preferably, degradable high polymer material described in the step 2 is polylactic acid, and molecular weight is 30-70KDa.
Preferably, make the nano fibrous membrane of the load cells factor in the step 2 by the blend electrostatic spinning technique.
Preferably, the Electrospinning parameters condition is in the step 2: voltage 8-25kV, flow velocity 0.01-0.1mL/min, accept platform from spinning head apart from 10-20cm.
After the nano fibrous membrane of the load cells factor provided by the invention was wrapped in cytokine in the glucosan vitreous body nano-particle, the glucosan vitreous body nano-particle of the load cells factor further was encapsulated in the degradable high polymer material fiber again.Cytokine is wrapped in effectively overcomes the not easy defective such as inactivation in acid and alkali-resistance and the aqueous solution of cytokine in the glucosan vitreous body nano-particle, guaranteed the long period of activity of cytokine, and in succession spread by two coverings during release of cytokines, can make cytokine long effective release time.The nano fibrous membrane that experiment showed, the load cells factor provided by the invention does not have prominent releasing, and effectively can reach 30 days release time, and only is 10 days effective release time of the PLLA fiber of the existing load cells factor.
The nano fibrous membrane of the load cells factor provided by the invention is controlled the slow release of cytokine effectively, guaranteed the long period of activity of cytokine, Biodegradable polymer material is voluntarily degraded then, nontoxic, the non-immunogenicity of this preparation, good biocompatibility, improve curative effect, reduce side effect, significant clinically.
Description of drawings
Fig. 1 is the scanning electron microscope (SEM) photograph of the glucosan vitreous body nano-particle of embodiment 1 gained load bFGF;
Fig. 2 is the scanning electron microscope (SEM) photograph of the nano fibrous membrane of embodiment 1 gained load bFGF;
Fig. 3 is the vitro drug release experimental result picture of the nano fibrous membrane of embodiment 1 gained load bFGF;
Fig. 4 is the In vitro cell experiment hypertrophy figure as a result of the nano fibrous membrane of embodiment 1 gained load bFGF;
Fig. 5 is the In vitro cell experiment cytoactive figure of the nano fibrous membrane of embodiment 1 gained load bFGF;
Fig. 6 is the zoopery whole observation figure as a result of the nano fibrous membrane of embodiment 1 gained load bFGF;
Fig. 7 is the zooperal tissue slice figure of the nano fibrous membrane of embodiment 1 gained load bFGF.
Fig. 8 is the zooperal I collagen protein staining examine figure of the nano fibrous membrane of embodiment 1 gained load bFGF;
Fig. 9 is the zooperal protein expression detection figure of the nano fibrous membrane of embodiment 1 gained load bFGF.
The specific embodiment
The present invention is described in detail below in conjunction with the drawings and specific embodiments, to understand better the present invention.
0.1gbFGF is added in the 100mL5% glucan aqueous solution dissolving evenly, then use eddy mixer to mix-80 ℃ of pre-freeze 24h postlyophilizations with 1000mL5%PEG solution.Lyophilized powder is dispersed in the dichloromethane, eddy current, and the suspension of acquisition homogeneous, the centrifugal supernatant of removing adds dichloromethane (DCM) again, repeats aforesaid operations 3 times.Remove the glucosan vitreous body nano-particle (bFGF/DGNs) that obtains load bFGF after the residual dichloromethane.
Getting 100mg gained bFGF/DGNs is dispersed among the 2gDCM by the processing of ice-bath ultrasonic ripple, 0.5g poly-left lactic acid (PLLA) and 1g DMF stir by ice bath and join bFGF/DGNs, make the nano fibrous membrane (bFGF/DGNs-PLLA) of load bFGF by electrostatic spinning technique.Wherein, the Electrospinning parameters condition is: voltage 20kV, flow velocity 0.04mL/min, accept platform from spinning head apart from 15cm.
Adopt same preparation technology to prepare bFGF-PLLA fibrous membrane and PLLA fibrous membrane.
Scanning electron microscope (SEM) is observed the glucosan vitreous body nano-particle (bFGF/DGNs) of present embodiment gained load bFGF, the result as shown in Figure 1, the nano-particle mean diameter is about 200～500nm.Scanning electron microscope (SEM) is observed the nano fibrous membrane of present embodiment gained load bFGF, the result as shown in Figure 2, bFGF/DGNs successfully is encapsulated among the PLLA, bFGF/DGNs-PLLA fibre diameter homogeneous is about 0.77 ± 0.21 μ m.
The bFGF envelop rate reaches 48.71 ± 13.53% in the use bFGF enzyme-linked immunologic detecting kit measurement calculating present embodiment gained bFGF/DGNs-PLLA fibrous membrane; and only be 24.64 ± 16.43% in the bFGF-PLLA fibrous membrane; the bFGF envelop rate of bFGF/DGNs-PLLA fibrous membrane is higher than the bFGF-PLLA fibrous membrane far away; show that DGNs in the bFGF/DGNs-PLLA fibrous membrane can protect the activity of bFGF well, has guaranteed the long period of activity of bFGFs.
Set up the vitro drug release model; observe the drug release situation of present embodiment gained bFGF/DGNs-PLLA fibrous membrane; the result as shown in Figure 3; the bFGF/DGNs-PLLA fibrous membrane of glucosan protection bFGF does not have prominent releasing of initial stage; control discharges nearly 30 days of bFGF, and the Cumulative release amount of bFGF is 6100pg.Yet the control of bFGF-PLLA fibrous membrane discharges nearly 20 days of bFGF, and the Cumulative release amount of bFGF is 2900pg.The bFGF that discharges accumulative total in the bFGF/DGNs-PLLA fibrous membrane is that the twice in the bFGF-PLLA fibrous membrane is many.
Carry out cell in vitro hypertrophy experiment, the result as shown in Figure 4, compared with PLLA fibrous membrane and bFGF-PLLA fibrous membrane, Growth of Cells is better on the bFGF/DGNs-PLLA fibrous membrane.Test cell is active, and the result as shown in Figure 5, and is compared with PLLA fibrous membrane and bFGF-PLLA fibrous membrane, dead on the bFGF/DGNs-PLLA fibrous membrane/living cell rate is lower, shows that the bFGF/DGNs-PLLA fibrous membrane is more conducive to cytoadherence and hypertrophy.
Carry out zoopery, present embodiment gained bFGF/DGNs-PLLA fibrous membrane as physical barriers, is used for tendon injury, the adhesion of control tendon surrounding tissue, experimental result is shown in Fig. 6～8.Among Fig. 6, serious tendon week adhesion appears in blank group (control), needs sharp instrument to peel off to separate; PLLA group, bFGF-PLLA group and bFGF/DGNs-PLLA group are only observed a small amount of adhesion zone, and can peel off to separate by blunt, tendon thickness significantly increases in bFGF-PLLA group and the bFGF/DGNs-PLLA group, and especially the bFGF/DGNs-PLLA group shows that bFGF promotes healing process of tendons.Among Fig. 7, be covered with the fibrous tissue bundle between blank group (control) paratenon and the tendon; Reference examples group (PCL) is observed loose fiber tissue bundle in paratenon and tendon boundary; Almost do not have loose fibrous tissue bundle in PLLA group, bFGF-PLLA group and the bFGF/DGNs-PLLA group, observe collagen bundle in the obvious tendon in the bFGF/DGNs-PLLA group, show that bFGF/DGNs-PLLA group healing process of tendons is better, vessel density is higher.Among Fig. 8, I collagen protein positive expression is maximum in the bFGF/DGNs-PLLA group, arranges the most intensively, and it is better to have shown that also bFGF/DGNs-PLLA organizes healing process of tendons.Fig. 9 shows that also the I collagen protein is expressed the highest in the bFGF/DGNs-PLLA group.
0.1gbFGF is added in the 100mL5% glucan aqueous solution dissolving evenly, then use eddy mixer to mix-80 ℃ of pre-freeze 24h postlyophilizations with 1000mL5%PEG solution.Lyophilized powder is dispersed in the dichloromethane, eddy current, and the suspension of acquisition homogeneous, the centrifugal supernatant of removing adds dichloromethane (DCM) again, repeats aforesaid operations 3 times.Remove the glucosan vitreous body nano-particle (bFGF/DGNs) that obtains load bFGF after the residual dichloromethane.
Getting 120mg gained bFGF/DGNs is dispersed among the 2gDCM by the processing of ice-bath ultrasonic ripple, 0.5g poly-left lactic acid (PLLA) and 1g DMF stir by ice bath and join bFGF/DGNs, make the nano fibrous membrane (bFGF/DGNs-PLLA) of load bFGF by the blend electrostatic spinning technique.Wherein, the Electrospinning parameters condition is: voltage 20kV, flow velocity 0.04m L/min, accept platform from spinning head apart from 15cm.Embodiment 3
0.1gbFGF is added in the 100mL5% glucan aqueous solution dissolving evenly, then use eddy mixer to mix-80 ℃ of pre-freeze 24h postlyophilizations with 1000mL5%PEG solution.Lyophilized powder is dispersed in the dichloromethane, eddy current, and the suspension of acquisition homogeneous, the centrifugal supernatant of removing adds dichloromethane (DCM) again, repeats aforesaid operations 3 times.Remove the glucosan vitreous body nano-particle (bFGF/DGNs) that obtains load bFGF after the residual dichloromethane.
Getting 110mg gained bFGF/DGNs is dispersed among the 2gDCM by the processing of ice-bath ultrasonic ripple, 0.5g poly-left lactic acid (PLLA) and 1g DMF stir by ice bath and join bFGF/DGNs, make the nano fibrous membrane (bFGF/DGNs-PLLA) of load bFGF by the blend electrostatic spinning technique.Wherein, the Electrospinning parameters condition is: voltage 20kV, flow velocity 0.04mL/min, accept platform from spinning head apart from 15cm.
0.1gbFGF is added in the 100mL5% glucan aqueous solution dissolving evenly, then use eddy mixer to mix-80 ℃ of pre-freeze 24h postlyophilizations with 1000mL5%PEG solution.Lyophilized powder is dispersed in the dichloromethane, eddy current, and the suspension of acquisition homogeneous, the centrifugal supernatant of removing adds dichloromethane (DCM) again, repeats aforesaid operations 3 times.Remove the glucosan vitreous body nano-particle (bFGF/DGNs) that obtains load bFGF after the residual dichloromethane.
Getting 100mg gained bFGF/DGNs is dispersed among the 2gDCM by the processing of ice-bath ultrasonic ripple, 0.6g poly-left lactic acid (PLLA) and 1g DMF stir by ice bath and join bFGF/DGNs, make the nano fibrous membrane (bFGF/DGNs-PLLA) of load bFGF by the blend electrostatic spinning technique.Wherein, the Electrospinning parameters condition is: voltage 20kV, flow velocity 0.04m L/min, accept platform from spinning head apart from 15cm.
0.1gbFGF is added in the 100mL5% glucan aqueous solution dissolving evenly, then use eddy mixer to mix-80 ℃ of pre-freeze 24h postlyophilizations with 1000mL5%PEG solution.Lyophilized powder is dispersed in the dichloromethane, eddy current, and the suspension of acquisition homogeneous, the centrifugal supernatant of removing adds dichloromethane (DCM) again, repeats aforesaid operations 3 times.Remove the glucosan vitreous body nano-particle (bFGF/DGNs) that obtains load bFGF after the residual dichloromethane.
Getting 100mg gained bFGF/DGNs is dispersed among the 2gDCM by the processing of ice-bath ultrasonic ripple, 0.7g poly-left lactic acid (PLLA) and 1g DMF stir by ice bath and join bFGF/DGNs, make the nano fibrous membrane (bFGF/DGNs-PLLA) of load bFGF by the blend electrostatic spinning technique.Wherein, the Electrospinning parameters condition is: voltage 20kV, flow velocity 0.04m L/min, accept platform from spinning head apart from 15cm.
Vitro drug release experiment, the experiment of cell in vitro hypertrophy and zoopery show, the nano fibrous membrane of embodiment 2-5 gained load bFGF is with the nano fibrous membrane of embodiment 1 gained load bFGF, there be not prominent releasing of initial stage, medicine is about 30 days effective release time, can effectively improve the tissue adhesion, promote healing process of tendons.
In sum, after the nano fibrous membrane of load bFGF provided by the invention was wrapped in bFGF in the glucosan vitreous body nano-particle, the glucosan vitreous body nano-particle of load bFGF further was encapsulated in the degradable high polymer material fiber again.BFGF is wrapped in effectively overcomes the not easy defective such as inactivation in acid and alkali-resistance and the aqueous solution of bFGF in the glucosan vitreous body nano-particle, guaranteed the long period of activity of bFGFs, do not have prominent releasing of initial stage, and bFGF spreads in succession when discharging by two coverings, can make bFGF long effective release time.
More than specific embodiments of the invention are described in detail, but it is just as example, the present invention is not restricted to specific embodiment described above.To those skilled in the art, any equivalent modifications that the present invention is carried out and substituting also all among category of the present invention.Therefore, not breaking away from impartial conversion and the modification of doing under the spirit and scope of the present invention, all should contain within the scope of the invention.
Claims (10)
1. the nano fibrous membrane of a load cells factor, it is characterized in that, composition material comprises cytokine, glucosan and degradable high polymer material, wherein cytokine loads in the Vitrea nano-particle of described glucosan, and the glucosan vitreous body nano-particle of the load cells factor is encapsulated in the fiber of described degradable high polymer material.
2. the nano fibrous membrane of the described load cells factor according to claim 1 is characterized in that the mass ratio of cytokine and glucosan is (0.5-0.8) in the glucosan vitreous body nano-particle of the described load cells factor: (10-10000).
3. the nano fibrous membrane of the described load cells factor according to claim 1 is characterized in that, the quality of described degradable high polymer material be cytokine and glucosan gross mass 1-200 doubly.
4. the nano fibrous membrane of the described load cells factor according to claim 1, it is characterized in that described cytokine is selected from one or more in basic fibroblast growth factor, insulin-like growth factor-i, epidermal growth factor, TGF-β1 3, the platelet-derived growth factor.
5. the nano fibrous membrane of the described load cells factor according to claim 1, it is characterized in that described degradable high polymer material is selected from one or more in polyhydroxycarboxyliacid acid, polylactic-co-glycolic acid, PLA-PEG copolymer, polylactic acid-polycaprolactone copolymer, polycaprolactone, poly phosphate, Merlon or the poly-anhydride.
6. according to claim 1 or the nano fibrous membrane of the 5 described load cells factors, it is characterized in that described degradable high polymer material molecular weight is 20KDa-200KDa.
7. the nano fibrous membrane of the described load cells factor according to claim 1 is characterized in that the fibre diameter of the nano fibrous membrane of the described load cells factor is 0.1-30 μ m.
8. the preparation method of the nano fibrous membrane of the load cells factor as claimed in claim 1 is characterized in that, may further comprise the steps:
Step 1, cytokine, dextran solution and polyvalent alcohol solution are mixed, the mass ratio of control cytokine, glucosan and polyvalent alcohol is 1: (10-1000): (100-10000), then drying obtains solid, solid is removed polyvalent alcohol with organic solvent washing, obtain the glucosan vitreous body nano-particle of the load cells factor; Step 2, glucosan vitreous body nano-particle and the degradable high polymer material of the load cells factor that step 1 is obtained are dispersed or dissolved in the organic solvent, make the nano fibrous membrane of the load cells factor by electrostatic spinning technique, the quality of control degradable high polymer material be the load cells factor that obtains in the step 1 glucosan vitreous body nano-particle gross mass 1-200 doubly.
9. described preparation method according to claim 8 is characterized in that the concentration of dextran solution is 0.2-20wt% in the step 1, and the concentration of polyvalent alcohol is 0.2-20wt%.
10. according to claim 8 or 9 described preparation methoies, it is characterized in that polyvalent alcohol is Polyethylene Glycol in the step 1.
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| CN109328249A (en) * | 2016-04-05 | 2019-02-12 | 纳米医药有限公司 | Nanofiber mat containing the ceramic particle with releasable dopant therein |
| CN114870063A (en) * | 2022-05-30 | 2022-08-09 | 北京恒峰铭成生物科技有限公司 | Modified glucan nano-microsphere composite dressing and preparation method thereof |
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