CN104804195B - Mussel adhesion and the double bionical multi-arm PEG of cell membrane anti-soil and preparation method thereof - Google Patents
Mussel adhesion and the double bionical multi-arm PEG of cell membrane anti-soil and preparation method thereof Download PDFInfo
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Abstract
Double biomimetic modification multi-arm PEG of mussel adhesion and amphion imitating cell outer-layer membrane structure and preparation method thereof are imitated the invention discloses the catechol shown in a kind of general structure (I), and by it by the simple direct coating method such as drop coating, spraying, dip-coating or spin coating, the various substrate surfaces after poly-dopamine mediation construct the dual stable against biological contamination surface of multi-arm polyethylene glycol flexible chain and amphion imitating cell outer-layer membrane structure.Biomimetic modification multi-arm PEG provided by the invention provides possibility to prepare because of its branched structure and multiple modifiable ends containing a variety of functional groups and the regulatable functional polymer of ratio;Using the poly-dopamine with Ultrastrength adhesive performance as mediation layer, in multi-functional multi-arm PEG in the case of catechol restricted levels system, fine and close, stable dual stable against biological contamination coating can be still formed in substantially any substrate surface.
Description
Technical field
The present invention relates to a kind of adhesion of mussel and the double bionical multi-arm PEG of cell membrane anti-soil preparation method and use it for each
The application of kind substrate surface structure stable against biological contamination coating, belong to the process for modifying surface field of biological medical polymer material.
Background technology
In the last few years, thrombus, inflammation, infection etc. were a series of caused by the biological pollutants such as protein, cell, bacterium
Problem seriously limits the clinical practice of various biomaterials, and therefore, the effective biological pollution for solving biomaterial surface is asked
Topic is vital.At present, the structure on conventional simple and easy stable against biological contamination surface is mainly cured to existing biology
Surface modification is carried out with material, i.e., basad material surface is coated with the coating of antifouling effect, realized by control interface anti-
Biological pollution (Y. Arima,et al.Adv. Polym. Sci. 2012, 247, 167; R. Yang, et al.Soft Matter2012, 8, 31; S. R. Meyers, et al. Chem. Rev. 2012, 112, 1615.)。
In the molecule of numerous structure anti-pollution layers, polyethylene glycol (PEG) receives much concern.Because it has big volume row
Inhibition effect, flexible PEG chains can free movement, effectively prevent the biological pollutant such as protein from directly contacting surface;Simultaneously can shape
Into superpower hydration layer, suppress the generation of protein adsorption and denaturation in simplified reaction, and then suppress thus to trigger a series of asks
Topic (M. Heuberger,et al. Biophys. J. 2005, 88, 495.).But PEG stable against biological contamination effect
In the coverage density of substrate surface it is closely related with it, traditional single-stranded PEG is directly fixed to material surface
It is difficult to reach higher surface coverage.The research that this allows for carrying out surface modification using multi-arm PEG is more and more.Multi-arm
PEG has many advantages, such as that its branched structure can realize high superficial density first, effectively improves the stable against biological contamination energy of coating
Power;Secondly, multiple end groups provide more reaction sites and carry out modification to it, make its multifunction.
Phosphorylcholine is the terminal hydrophyllic group for forming cell membrane elementary cell, and critical role is accounted in outer cell membrane.Phosphinylidyne
For choline simultaneous with positive and negative two kinds of electric charges, this amphion group can form very firm hydration layer with hydrone;
In water environment can Spontaneous migration be enriched to surface, form the surface of imitating cell outer-layer membrane structure.Gathered with Phosphorylcholine amphion
Compound realizes that the mechanism of stable against biological contamination is analogized similar to the structure of extracellular tunic, sulphonic acid betaine and carboxylic acid beet
Alkali amphion group can also realize the antifouling effect of imitating cell outer-layer membrane structure.Separately there are some researches show Phosphorylcholine and PEG exist
Anti-protein adsorb and platelet adhesion reaction in terms of have cooperative effect (M. Tanaka,et al. Tetrahedron Lett.2009, 50, 4092; Y. Iwasaki, et al. Biomaterials2003, 24, 3599.), therefore in multi-arm
PEG ends introduce the amphion groups such as Phosphorylcholine, sulphonic acid betaine and carboxylic acid glycine betaine and are expected to obtain a kind of antibiosis pollution
The remarkable surface of effect.
The content of the invention
The main object of the present invention be to provide it is a kind of can spontaneous adhesion in various material surfaces mussel adhesion and cell membrane
The double bionical multi-arm PEG of anti-soil, structure branched multi-arm PEG can effectively solve the problems, such as that coating density is low;Peg moiety end
Catechol group can by the modes such as hydrophobic effect, coordination, oxidation polymerization and the almost spontaneous combination of various substrate surfaces,
The polymer coating of highly-hydrophilic is set to be fixed up in material surface;The amphion group of part arm terminal graft, due to it
Itself superpower hydrability, under water environment can Spontaneous migration be enriched to coating surface, formation is similar to cell outer-layer membrane structure
Surface, formed on the basis of polyethylene glycol and barrier resisted to the second layer of biological pollutant, form amphion and poly- second
The surface of the dual stable against biological contamination of glycol;Part arm end can also be grafted folic acid functional group, make its more multifunction.
It is a further object of the present invention to provide above-mentioned double bionical multi-arm PEG preparation method.
The implementation process of the present invention is as follows:
Polymer shown in general structure (I),
Wherein, m 1,1.5 or 2, n are 20 ~ 100 positive integer;
R1~R4Independently selected from structural formula(II)Shown catechol base, structural formula(III)Shown Phosphorylcholine base,
Sulphonic acid betaine base, carboxylic acid beet base, general structure(Ⅳ)Shown folic acid derives small molecule group,
, a is 1 ~ 5 positive integer;
X is 5 ~ 30 positive integer, and y is 1 ~ 10 positive integer, and z is 1 ~ 6 positive integer, and the molar content of wherein x monomers is
The molar content of 80% ~ 90%, y monomer is 10% ~ 20%;
。
Above-mentioned R1~R4In functional group, group molar content 20 ~ 90% is catechol base, and 10 ~ 80% be Phosphorylcholine, sulphur
Sour glycine betaine or carboxylic acid beet base, 0 ~ 15% is that folic acid derives small molecule group.
The preparation method of polymer shown in general structure (I):By the amino or hydroxyl of multi-arm PEG ends, with acid amides
The mode of key or ester bond is by R1~R4Functional group small molecule or oligomer be grafted to its arm end.
Application of the polymer in stable against biological contamination coating is prepared shown in general structure (I).Specifically, it is to polymerize
Thing is dissolved in the aqueous solution of pH 7 ~ 8.5 or aqueous organic solvent, polymer is existed with drop coating, spraying, dip-coating or the mode of spin coating
It is modified material or tool face forms the coating uniformly coated.
The substrate surface that need to be modified first coats poly-dopamine mediation coating with drop coating, spraying, dip-coating or the mode of spin coating, so
Polymer shown in coated structure formula (I) afterwards, the base material be glass, stainless steel, polyvinyl chloride, makrolon, polypropylene,
Polytetrafluoroethylene (PTFE), titanium dioxide, metal.In order to improve stability of the polymer in substrate surface, to the piece after coated polymer
Base heats 1 ~ 24 h in air phase in 90 ~ 150 °C of temperature ranges, aoxidize the catechol group in polymer molecule
Crosslinking, form stable polymer coating.Coating soaks 0.5 ~ 24 h into the water of 90 °C of temperature ranges in room temperature so that polymerization
Hydrophilic radical migration orientation in thing structure arrives coating surface, forms imitating cell outer-layer membrane structure hydrophilic coating, connects Static Water
Feeler is in the range of 30 ~ 52 °, and protein absorption reduces 70 ~ 98%, and bacterial adhesion reduces 90 ~ 99%.
Advantages of the present invention:1)From the multi-arm PEG with branched structure as research object, imitated in its arm terminal graft
The amphion of cell membrane anti-soil, the catechol of imitative mussel adhesion, the multiple functions group such as folic acid of targeting, are prepared a series of
The regulatable multi-arm PEG of function, ratio;2)Catechol and the double biomimetic modification multi-arm PEG coatings of amphion form poly- second two
Alcohol flexible chain and amphion imitating cell outer-layer membrane structure double barrier, significant inhibition is produced to biological pollutant;3)
Using the poly-dopamine with Ultrastrength adhesive performance as mediation layer, the catechol restricted levels in multi-functional multi-arm PEG
In the case of, fine and close polymer coating can be still formed in substantially any substrate surface.
Brief description of the drawings
Fig. 1 is the synthesis path that eight arm PEG are grafted Phosphorylcholine oligomer, catechol and folic acid small molecule;
Fig. 2 is double biomimetic modification multi-arm PEG 1H-NMR spectrograms(Specially:(catechol)6.5-g-PEG-g-
(PMN)1.5, solvent:D2O);
Fig. 3 be double biomimetic modification multi-arm PEG before modified after gold plaque surface static contact angle figure;
Fig. 4 be double biomimetic modification multi-arm PEG before modified after gold plaque surface AFM 2D shape appearance figures;
Fig. 5 be double biomimetic modification multi-arm PEG before modified after gold plaque surface XPS spectrograms entirely;
Fig. 6 is that rear gold plaque surface protein adsorbs SPR figures to double biomimetic modification multi-arm PEG before modified;
Fig. 7 is double biomimetic modification multi-arm PEG rear gold plaque surface platelet adhesion reaction scanning electron microscope (SEM) photographs before modified;
Fig. 8 is double biomimetic modification multi-arm PEG rear gold plaque surfaces before modifiedE.coliBacterial adhesion shows fluorescent microscopy images.
Embodiment
The imitative mussel attachment proteins of synthesis and the double bionical multi-arm PEG of membrane structure include 4 steps:
1)The preparation of the amphion oligomer such as Phosphorylcholine, sulphonic acid betaine or the carboxylic acid glycine betaine of reactivity;
2)Oligomer containing amphion is introduced in a manner of amido link or ester bond in multi-arm peg moiety arm end;
3)By amide condensed or ester condensation reaction, the neighbour with adhesion function is introduced in multi-arm peg moiety arm end
Resorcinol groups;
4)Also folic acid functional molecular can be introduced in a manner of amido link or ester bond in multi-arm peg moiety arm end.Pass through 1H
NMR, GPC and UV-Vis carry out structural characterization to obtained double biomimetic modification multi-arm PEG, determine that the grafting of each several part group contains
Amount.
Build poly-dopamine mediation layer:Dopamine hydrochloride is dissolved in the aqueous solution of pH 7 ~ 8.5 or water and ethanol, methanol, different
In the mixed solution of the organic solvent such as propyl alcohol or tetrahydrofuran, the mixed proportion of water and organic solvent is 1/0 ~ 1/1, and concentration is
0.1~5 mg/mL.Glass, stainless steel, polyvinyl chloride, poly- carbon are coated to by way of drop coating, spraying, dip-coating or spin coating
The common used material such as acid esters, polypropylene, polytetrafluoroethylene (PTFE), titanium dioxide, metal surface, pass through the polymerisation shape of dopamine itself
Layer is mediated into stable poly-dopamine.
Build mussel attachment proteins and the double biomimetic modification multi-arm PEG anti-pollution layers of cell membrane:Double biomimetic modifications of preparation
Multi-arm PEG be dissolved in the aqueous solution of pH 7 ~ 8.5 or water and ethanol, methanol, isopropanol, tetrahydrofuran, acetonitrile, dimethyl sulfoxide (DMSO) or
The in the mixed solvent of DMF etc., concentration are 0.5 ~ 5 mg/mL.Pass through the side of dip-coating, drop coating, spin coating or spraying
Substrate surface of the formula after poly-dopamine mediation uniformly coats double biomimetic modification multi-arm PEG.Coating is in 90 ~ 150 °C of temperature ranges
1 ~ 24 h of interior heating, makes the catechol group in polymer molecule oxidation cross-linked, forms stable polymer coating.It is extensive
After multiple room temperature, elute and adhere to unstable polymer molecule to remove.Method in reference literature(S. Yang,et al.J. Biomed. Mater. Res., Part A2008, 84, 837; N. Hao, et al. J. Biomed. Mater. Res., Part A, 2014, 102, 2972.)It is immersed in from room temperature to 0.5 ~ 24 h in the water of 90 °C of temperature ranges,
Hydrophilic regulation and control are carried out to coating so that amphion group in polymer architecture is spontaneous to be migrated, and is formed imitative extracellular
Film structure hydrophilic coating.
Embodiment 1
The oligomer preparation method of the formyl active ester group of oxygen containing p-nitrophenyl and Phosphorylcholine group is as follows:Reference literature
It is prepared by method(K. Ishihara,et al. Polym. J.1990, 22, 355; T. Konno, et al.Biomacromolecules2004, 5, 342.)2- methylacryoyloxyethyl Phosphorylcholines(MPC)With p-nitrophenyl oxygen first
Acyl(It is poly-)Glycolmethacrylate(NPEM).Pass through " starvation method " of document report(A .L. Lewis, et al.Biomaterials2000, 21, 1847.)Free radical randomcopolymer p (MPC-co-NPEM are synthesized), abbreviation PMN.Specifically
Process is as follows:In 250 mL three-necked bottles, 15 mL ethanol and 0.006 g ABVNs (ABVN) are added, condenser pipe is filled, adds
Heat is to 65 °C and logical N2Oxygen in 30 min removing systems.Weigh 5.113 g MPC, 1.271 g NPEM and 0.058 g triggers
Agent ABVN(ABVN)In 500 mL round-bottomed flasks, 200 mL drying ethanols and 6 mL tetrahydrofurans are added, make it
Fully it is transferred to after dissolving in constant pressure funnel.Electromagnetic agitation, N2Under protection, the mixed solution of monomer and initiator is added drop-wise to
In three-necked bottle, drip, be changed to enclosed system.React 24 h stoppings.React and reaction solution is loaded into molecular cut off for 3500
Bag filter in, with pH 3-4 cushioning liquid carry out dialysis 2 days.White solid is obtained after freeze-drying.1H NMR test results
The molar content for showing MPC and NPEM is respectively 75% and 25%, and GPC measures the molecular weight (M of polymerw) it is about 5000 g/
mol。
Embodiment 2
The oligomer preparation method of the formyl active ester group of oxygen containing p-nitrophenyl and sulphonic acid betaine group is as follows:Pass through
" starvation method " has synthesized 2- methylacryoyloxyethyl sulphonic acid betaines(SBMA)With p-nitrophenyl oxygen formyl(It is poly-)Ethylene glycol first
Base acrylate(NPEM)Free radical randomcopolymer p (SBMA-co-NPEM), abbreviation PSN.Detailed process is as follows:250 mL
In three-necked bottle, 10 mL ethanol and 0.003 g ABVNs (ABVN) are added, fills condenser pipe, is heated to 65 °C and logical N2
Oxygen in 30 min removing systems.2.295 g SBMA, 0.636 g NPEM and 0.029 g initiator As BVN are weighed in 500 mL
In round-bottomed flask, 100 mL drying ethanols and 6 mL tetrahydrofurans are added, it is transferred to constant pressure funnel after fully dissolving
In.Electromagnetic agitation, N2Under protection, the mixed solution of monomer and initiator is added drop-wise in three-necked bottle, dripped, is changed to obturator
System.React 24 h stoppings.React and be fitted into reaction solution in the bag filter that molecular cut off is 3500, with pH 3-4 cushioning liquid
Carry out dialysis 2 days.White solid is obtained after freeze-drying.1H NMR test results show SBMA and NPEM molar content difference
For 81% and 19%, GPC measures the molecular weight (M of polymerw) it is about 4500 g/mol.
Embodiment 3
The preparation method of eight arm peg moiety arm terminal graft Phosphorylcholine oligomer:Weigh 0.500 g PEG- (NH2)8With
40 mL ethanol/TEA and 3 mL distillation water mixed solutions(pH 6.5-7.0)It is dissolved in 50 mL round-bottomed flasks, immerses pre-
Under heat to 60 °C of oil bath magnetic agitation, after 0.376 g PMN polymer is dissolved with 20 mL ethanol, it is added drop-wise in three-necked bottle,
Drip, react 22 h.Stop removing small molecule caused by dereaction and not with the bag filter that molecular cut off is 12000 after reaction
The low molecule amount of grafting(Mw~5000 g/mol)The NaOH aqueous solution that polymer P MN is about 9 with pH is extracellular fluid dialysis to yellow
Take off(Hydrolyze unreacted active ester group), then distilled water is transitioned into, to the electrical conductivity and distilled water of extracellular fluid dialysis
Electrical conductivity it is basically identical.It is freeze-dried the eight arm PEG for producing part arm terminal graft PMN phosphoryl choline polymers.Fig. 2 1H
NMR confirms that PMN is successfully grafted to eight arm PEG part arm end, the change of molecular weight measured by being grafted GPC before and after PMN, meter
Calculation show that about 1.5 mol PMN are grafted to the arm PEG arms ends of 1 mol eight, then this polymer is represented by PEG-g- (PMN)1.5-
(NH2)6.5。
Embodiment 4
The preparation side of the arm peg moiety arm terminal graft catechol groups (catechol) of Fig. 1 eight and folic acid (FA) molecule
Method:In 50 mL three-necked bottles, 3,4- dihydroxy benzenes propionic acid (DHPA) is weighed(0. 039 g), FA(0.022 g), HOBt
(0.057 g)And triethylamine(0.054 g), it is 1 with 3.5 mL volume ratios:1 dichloromethane and N,N-dimethylformamide mixes
Close and disperseed under solution magnetic agitation, lead to N2, the h of ice-water bath priming reaction 1;Weigh HBTU(0.080 g)With 3 mL dichloromethanes
After alkane is disperseed, it is transferred in three-necked bottle, continues logical N2Ice-water bath activates 2 h;Weigh the preparation of 0.4125 g embodiments 3
PEG-g-(PMN)1.5-(NH2)6.5, 20 mL volume ratios are dissolved in as 1:1 dichloromethane and N,N-dimethylformamide mixing
In solution, it is added dropwise to by dropping funel in three-necked bottle, about 1 h is added.Continue logical N2, ice-water bath react about 3 h.Afterwards
Recover 24 h of room temperature reaction, before stopping reaction, add glacial acetic acid(2.0 mL)It is in acid state to make system(Dripped below immersed in liquid level
Add), in order to avoid cause the oxidation of catechol group in last handling process.Filter and remove solid impurity, filtrate is instilled in ether
Precipitation, -20 DEG C stand overnight.Incline supernatant, is fitted into after precipitation is dissolved with 30 mL dichloromethane in 3500 bag filters, according to
It is secondary that impurity is removed as dialysis medium using ethanol, ethanol/pH=2-3 mixed solutions, pH=2-3 cushioning liquid, it is freeze-dried and produces neighbour
8 arm PEG of the double biomimetic modifications of benzenediol, Phosphorylcholine and folic acid.1H NMR test results confirm catechol and folic acid success
It is grafted to eight arm PEG ends;GPC results show that this couple of arm PEG of biomimetic modification eight molecular weight is 22000 g/mol;Pass through UV-
The working curve of DHPA and folic acid under ultraviolet light absorption angle value and the same terms at Vis measure 280 nm and 360 nm, is calculated
Go out 1 mol PEG-g- (PMN)1.5-(NH2)6.5On be grafted 5.91 mol catechol and 0.47 mol FA, then this polymerize
Thing is represented by (catechol)6.0-g-PEG-g-(PMN)1.5-(FA)0.5。
Embodiment 5
Poly-dopamine mediates the structure of layer:Dopamine hydrochloride is dissolved in Tris-HCl (pH 8.5) cushioning liquid, matched somebody with somebody
Concentration processed is 2 mg/mL solution.In room temperature, air phase, by 2 × 2 cm2Gold plaque is immersed in 24 h in above-mentioned solution, makes DOPA
Amine spontaneous adhesion is aggregated to piece primary surface.Distillation water wash is used after taking out chip base 5 times, and poly-dopamine painting is obtained after naturally dry
Layer.Static contact angle changes to 68.2 ± 2.0 ° by 101.1 ± 0.5 ° of naked gold plaque(As shown in Figure 3);After poly-dopamine modified lithium
Obvious change occurs for chip base AFM 2D shape appearance figures(As shown in Figure 4);There are obvious N peaks in composing entirely in XPS(As shown in Figure 5), this
A little data all prove that gold plaque surface forms poly-dopamine coating.
Embodiment 6
The structure of catechol and the double bionical multi-arm PEG anti-pollution layers of Phosphorylcholine:The pollution resistance that will be prepared in embodiment 4
Can preferably double bionical multi-arm PEG((catechol)6.5-g-PEG-g-(PMN)1.5)Volume ratio is dissolved in for 1:1 ethanol is water-soluble
In liquid, the polymer solution that concentration is 5 mg/mL is configured to;After it fully dissolves 40 μ L polymerizations are pipetted with micropipettor
The poly-dopamine mediation gold plaque primary surface that the uniform drop coating of thing solution is prepared in embodiment 5, cold wind drying;In air phase,
12 h are heated in 100 °C of baking ovens, the catechol group in polymer architecture occur sufficiently oxidation cross-linked;Recover room temperature,
After elution piece primary surface 5 times, modified chip base is immersed in 30 min in 80 °C of water, makes polymer coating that regulation and control occur and is formed
The surface of surface enrichment hydrophilic radical.As Fig. 3 shows, catechol and the double bionical multi-arm PEG of Phosphorylcholine((catechol)6.5-
g-PEG-g-(PMN)1.5)Gold plaque static contact angle after coating is further decreased to 47.0 ± 1.0 °;Go out in AFM 2D height maps
Existing larger-sized shape characteristic(Fig. 4);There are Phosphorylcholine P peaks in composing entirely in corresponding XPS in Fig. 5, all fully proves double imitative
Raw modified multi-arm PEG is successfully fixed to the gold plaque primary surface of poly-dopamine mediation.
Embodiment 7
The anti-protein absorption property evaluation of double biomimetic modification multi-arm PEG surfaces:By what is prepared in embodiment 6
(catechol)6.5-g-PEG-g-(PMN)1.5Modified gold plaque base is installed to Reichert SR7500DC surface plasmas and is total to
On Vibration Meter.Using PBS7.4 as mobile phase, surface plasma resonance instrument is flowed through under 50 μ L/min flow velocity(SPR)Chip surface,
Stable baseline is obtained under 25 °C.Under identical flow velocity, the 1 mg/mL BSA or Fg min of PBS7.4 solution 10 is injected, is cut afterwards
Gain PBS7.4 cushioning liquid, surface is rinsed under identical flow velocity will adsorb unstable protein and wash off, by comparing injection egg
The protein quality of adsorption is calculated in the change of PBS7.4 baselines before and after white matter solution.Double bionical multi-arm PEG
(catechol)6.5-g-PEG- g-(PMN)1.5BSA and Fg SPR adsorption curves such as Fig. 6 shows before and after modified gold plaque, with naked golden watch
Face is compared, and modified surface is reduced to 98.7% to BSA adsorbance, and 75.1% is reduced to Fg adsorbance, is shown significantly
Anti- protein adsorption effect.
Embodiment 8
The antiplatelet adhesion property evaluation of double biomimetic modification multi-arm PEG surfaces:Prepared with embodiment 6
(catechol)6.5-g-PEG-g-(PMN)1.5Gold plaque base after modification, mediated to blank, coated with poly-dopamine and poly-dopamine
Double biomimetic modification multi-arm PEG gold plaque carry out platelet attachment experiment, as a result as shown in Figure 7.The blank gold plaque table of SEM shootings
Face is stained with substantial amounts of blood platelet, and blood platelet occurs aggregation and obvious deformation occurs;Gold plaque adheres to after poly-dopamine modified lithium
Obvious reduction, and pattern rule occur for blood platelet amount;Gold surface after double biomimetic modification multi-arm PEG modifications is almost without adhesion
Blood platelet.This result illustrates that the surface after catechol and the double biomimetic modifications of Phosphorylcholine has significant suppression effect to blood platelet
Fruit.
Embodiment 9
Double biomimetic modification multi-arm PEG surfaces anti-bacterial attachment performance evaluation:With the double biomimetic modification multi-arms of preparation in embodiment 6
PEG(catechol)6.5-g-PEG-g-(PMN)1.5Gold plaque base after modification, it is situated between by blank, coated with poly-dopamine and poly-dopamine
The double biomimetic modification multi-arm PEG led gold plaque is immersed in concentration as 5 × 107Cells/mL Gram-E. colis
(E.coli) PBS solution in, 37 °C, cultivate 24 h under saturated humidity.After taking out chip base, eluted 5 times with PBS, wash away adhesion
Unstable bacterium.The μ L/mL Syto 9 of 30 μ L 2 PBS solution is added dropwise in piece primary surface, and dark at room temperature dyes 20 min, falls
It is as shown in Figure 8 to put fluorescence microscope result.Blank gold plaque surface is almost completely covered by bacterium;It is golden after poly-dopamine modified lithium
Obvious reduce occurs for the amount of bacteria of piece adhesion;Gold surface after double biomimetic modification multi-arm PEG modification almost without the bacterium adhered to,
Suppression adhesion rate to bacterium reaches 99%.
Claims (8)
1. the polymer shown in general structure (I),
Wherein, m 1,1.5 or 2, n are 20 ~ 100 positive integer;
R1~R4Independently selected from structural formula(II)Shown catechol base, structural formula(III)Shown Phosphorylcholine base, structure
Formula(Ⅳ)Shown folic acid derives small molecule group,
, a is 1 ~ 5 positive integer;
X be 5 ~ 30 positive integer, y be 1 ~ 10 positive integer, z be 1 ~ 6 positive integer, wherein the molar content of x monomers be 80% ~
The molar content of 90%, y monomer is 10% ~ 20%;
,
In R1~R4In functional group, group molar content 20 ~ 90% is catechol base, and 10 ~ 80% be Phosphorylcholine base, 0 ~ 15%
Derive small molecule group for folic acid.
2. the preparation method of polymer described in claim 1, it is characterised in that:By the amino or hydroxyl of multi-arm PEG ends, with
The mode of amido link or ester bond will contain R1~R4The small molecule or oligomer of functional group are grafted to its arm end.
3. application of the polymer described in claim 1 in stable against biological contamination coating is prepared.
4. apply according to claim 3, it is characterised in that:Dissolve a polymer in the aqueous solution of pH 7 ~ 8.5 or aqueous organic
In solvent, polymer is set to be modified material or tool face forms uniform painting with drop coating, spraying, dip-coating or the mode of spin coating
The coating covered.
5. apply according to claim 3, it is characterised in that:The substrate surface that need to be modified first uses drop coating, spraying, dip-coating or rotation
The mode of painting coats poly-dopamine mediation coating, is then coated with the polymer shown in general structure (I).
6. apply according to claim 5, it is characterised in that:The base material is glass, stainless steel, polyvinyl chloride, poly- carbonic acid
Ester, polypropylene, polytetrafluoroethylene (PTFE), titanium dioxide, metal.
7. apply according to claim 3, it is characterised in that:In order to improve stability of the polymer in substrate surface, to applying
Cover the chip base after polymer and heat 1 ~ 24 h in 90 ~ 150 °C of temperature ranges in air phase, make the neighbour in polymer molecule
Resorcinol groups are oxidation cross-linked, form stable polymer coating.
8. apply according to claim 3, it is characterised in that:Coating soaks 0.5 into the water of 90 °C of temperature ranges in room temperature ~
24 h so that the hydrophilic radical migration orientation in polymer architecture arrives coating surface, forms the hydrophilic painting of imitating cell outer-layer membrane structure
Layer, makes Static water contact angles in the range of 30 ~ 52 °, and protein absorption reduces 70 ~ 98%, and bacterial adhesion reduces 90 ~ 99%.
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