CN102643448B - Preparation method and application of temperature-sensitive patterned polymer surface with orientation structure - Google Patents
Preparation method and application of temperature-sensitive patterned polymer surface with orientation structure Download PDFInfo
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- CN102643448B CN102643448B CN201210088698.8A CN201210088698A CN102643448B CN 102643448 B CN102643448 B CN 102643448B CN 201210088698 A CN201210088698 A CN 201210088698A CN 102643448 B CN102643448 B CN 102643448B
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Abstract
The invention discloses a preparation method and application of a temperature-sensitive patterned polymer surface with an orientation structure. The preparation method comprises the following steps: adopting monomers which can form a needle-like crystal intelligent polymer, and firstly forming a saturated solution of the monomers; adding a nucleating agent into the saturated solution, then enabling the monomers to form needle-like crystals by taking a nucleating point (center) as the center, rapidly diffusing to the periphery and forming the patterned surface with the orientation structure; and finally obtaining the various required orientation patterned temperature-sensitive surfaces by light-initiated polymerization. The temperature-sensitive surface prepared by the method has very high application value. According to the method, the defect of trivial steps of the traditional method can be overcome, and expensive equipment is not required; and simultaneously, the obtained patterned surface has excellent performances, and a broad space is further provided for more extensive application of temperature-sensitive type materials.
Description
Technical field
The invention belongs to technical field of function materials, specifically a kind of preparation method of the temperature sensitive patterned polymer surface with oriented structure, and in the application of technical field of biological material.
Background context
Intelligent material is owing to responding with external stimulus, and its research has been subject to people's great attention recently.A typical example is PNIPAM (Poly (N-isopropylacrylamid), PNIPAAm), under water surrounding this polymkeric substance near its lower critical solution temperature (lower critical solution temperature (LCST)) (～32 DEG C) due to molecule in/can there is reversible hydrophilic/hydrophobic and change in the competition of intermolecular hydrogen bond
[1]thereby be widely used in intelligent surface preparation.
[2]in addition, because its transition temperature approaches body temperature and velocity of transformation is very fast, reversibility is better, this polymkeric substance also in biological association area as pharmaceutical carrier, biosensor and biomaterial etc. is used widely.
[3]such as Okano etc. cultivates cell behind PNIPAAm surface under body temperature, reduces system temperature, and PNIPAAm wetting ability strengthens, thereby cell just obtains monolayer cell lamella from falling out gradually.
[4]in addition, the manipulation that utilizes PNIPAAm to carry out individual cells also has report with separating.
[5，6]
The topology of extracellular microenvironment
[7], mechanical property
[8]and chemical constitution
[9]cell is had to material impact.There is micron and the netted extracellular matrix of complexity (extracellular matrix (ECM)) of nanoscale and can be cell adhesion sites is provided, and differentiation, growth and migration to cell produces great effect.Along with the development of organizational project and regenerative medicine, the attention degree of people's extracellular matrix and extracellular microenvironment improves day by day.People imitate structure and the performance of extracellular matrix and have prepared bionical patterned surface, and result shows that the pattern on cell, propagation, migration, differentiation and genetic expression have impact equally on this surface.
[10]for example, cell cultures can be obtained having the cell sheets of complex construction on alignment patterned PNIPAAm surface and be applied to intravascular tissue engineering etc.
[11]in tumor model research, it is found that high invasive cancer cells is significantly higher than normal cell and the less cancer cells of aggressive in the travelling speed on oriented material surface in vitro, and significantly reduce in its travelling speed of random orientation material surface.
[12]therefore the preparation on alignment patterned surface is all significant to the foundation of regenerative medicine and external tumor model.
The preparation of common patterning intelligent surface comprises photoetch method, chemical etching method, contact printing method, stamped method etc., and these methods need to comprise multiple steps such as matrix modification, patterning preparation and polymerization conventionally,
[13]waste time and energy and price more expensive.Although EFI legal system is standby comparatively easy, but still needs Special Equipment, and the poor mechanical property of intelligent material itself is also to hinder serious problems of its application.
[14]
Reference:
[1]Z.B.Hu，Y.Y.Chen，C.J.Wang，Y.D.Zheng，Y.Li，Nature?1998，393，149-152.
[2]T.L.Sun，G.J.Wang，L.Feng，B.Q.Liu，Y.M.Ma，L.Jiang，D.B.Zhu，Angewandte?Chemie-International?Edition?2004，43，357-360.
[3]A.Chilkoti，M.R.Dreher，D.E.Meyer，D.Raucher，Advanced?Drug?Delivery?Reviews?2002，54，613-630.
[4]K.Nishida，M.Yamato，Y.Hayashida，K.Watanabe，K.Yamamoto，E.Adachi，S.Nagai，A.Kikuchi，N.Maeda，H.Watanabe，T.Okano，Y.Tano，New?England?Journal?of?Medicine?2004，351，1187-1196.
[5]A.Ichikawa，F.Arai，K.Yoshikawa，T.Uchida，T.Fukuda，Applied?Physics?Letters?2005，87.
[6]H.Takamatsu，S.Uchida，T.Matsuda，Journal?of?Biotechnology?2008，134，297-304.
[7]C.S.Chen，M.Mrksich，S.Huang，G.M.Whitesides，D.E.Ingber，Science?1997，276，1425-1428.
[8]A.J.Engler，S.Sen，H.L.Sweeney，D.E.Discher，Cell2006，126，677-689.
[9]M.M.Stevens，J.H.George，Science?2005，310，1135-1138..
[10]N.Idota，T.Tsukahara，K.Sato，T.Okano，T.Kitamori，Biomaterials?2009，30，2095-2101.
[11]C.Williams，A.W.Xie，M.Yamato，T.Okano，J.Y.Wong，Biomaterials2011，32，5625-5632；K.Itoga，T.Okano，Journal?of?Materials?Chemistry2010，20，8768-8775.
[12]J.Johnson，M.O.Nowicki，C.H.Lee，E.A.Chiocca，M.S.Viapiano，S.E.Lawler，J.J.Lannutti，Tissue?Engineering?Part?C-Methods2009，15，531-540
[13]C.Williams，Y.Tsuda，B.C.Isenberg，M.Yamato，T.Shimizu，T.Okano，J.Y.Wong，Advanced?Materials?2009，21，2161-+；B.C.Isenberg，Y.Tsuda，C.Williams，T.Shimizu，M.Yamato，T.Okano，J.Y.?Wong，Biomaterials?2008，29，2565-2572；
[14]J.W.J.Wang，A.Sutti，X.G.Wang，T.Lin，Soft?Matter?2011，7，4364-4369.
Summary of the invention
Object of the present invention is to set up a kind of method of conveniently preparing temperature sensitive patterned polymer surface, and has studied the application of this patterned polymer surface at cellular segregation and induced orientation reverse side.
Object of the present invention can be achieved through the following technical solutions:
The preparation method on the intelligent patterned polymer surface with oriented structure of the present invention, concrete steps comprise:
1) can form the monomer 80-98% of the intelligent polymer of needle crystal, light trigger 1-10%, linking agent 1-10% is dissolved in wiring solution-forming in the solvent that is easy to volatilization; It is more than mass percent;
2) by step 1) in solution spread in matrix, evaporating solvent makes joined monomer solution reach hypersaturated state, forms supersaturated solution film;
3) in step 2) add nucleator to make monomer crystallization form the patterned surface with oriented structure in the supersaturated solution film of gained;
4) by step 3) gained patterned surface carries out light initiation polymerization, can obtain needed alignment patterned polymer surfaces.
Described monomer is selected from the one in N-isopropylacrylamide, isopropyl methyl acrylamide and carboxyl N-isopropylacrylamide.
Described light trigger is free radical type, comprise bitter almond oil camphor and derivatives class (st-yrax, benzoin dimethylether, Benzoin ethyl ether, benzoin isopropyl ether, benzoin isobutyl ether), benzil class (phenylbenzene ethyl ketone, α, alpha, alpha-dimethyl oxygen base-α-phenyl methyl phenyl ketone), alkylbenzene ketone (α, α-diethoxy acetophenone, alpha-hydroxyalkyl benzophenone, α-amine alkyl phenones), acyl group phosphorous oxides (aroyl phosphine oxide, two benzoylphenyl phosphine oxides), benzophenone (benzophenone, 2, 4-dihydroxy benaophenonel, Michler's keton), thioxanthones (sulfo-propoxy-thioxanthone, isopropyl thioxanthone) and cationic (diaryl group iodized salt, triaryl salt compounded of iodine, alkyl salt compounded of iodine, the luxuriant iron hexafluorophosphate of isopropyl benzene etc.) in one or more.
Described linking agent is the free radical type linking agent containing many pairs of keys.
Described nucleator can be various organic or inorganic thing crystal, needle point, blade, plastics or metallic film etc., and they play nucleation site (center), and therefore some nucleator can be removed, as needle point.Therefore consumption is optionally determined with the nucleator kind adding.After Added Nucleating Agents, monomer will crystallization centered by nucleation site (center), and rapidly to surrounding diffusion, forms the patterned surface with oriented structure.
Described solvent is the volatile substances such as aromatic hydrocarbons, halon, alkane, naphthenic hydrocarbon, ketone, alcohols, ethers, acetone and ester class.
Described matrix can be the mechanically resistant materials such as glass, quartz, silicon chip and metal, can be also the bendable material such as paper, plastics, rubber, metallic film and Pressure sensitive adhesive tape.
Described patterned surface can be used for obtaining lamellar structure cell, various patterning and there is the cell of oriented structure and various dissimilar cells separate discriminating etc.
The present invention is the production technique on a kind of novelty and the temperature sensitive surface of fabricating patterned that operation is simple.Be the monomer that adopts the intelligent polymer that can form needle crystal, first form its supersaturated solution.In in supersaturated solution, add after nucleator, monomer will form needle crystal centered by nucleation site (center), and rapidly to surrounding diffusion, form the patterned surface with oriented structure.Finally can obtain the temperature sensitive surface of various required alignment patterned by light initiation polymerization again, temperature sensitive surface prepared by the method has very high using value.The method has overcome the defect of traditional method complex steps, does not also need expensive equipment, the patterned surface excellent performance of gained simultaneously, thus make the application more widely of temperature sensitive class material that wide space is provided.
Brief description of the drawings
Fig. 1 is the light microscopic figure with the radiate pattern surface (before polymerization) of oriented structure;
Fig. 2 is the scanning electron microscope (SEM) photograph with the radiate pattern surface (after polymerization) of oriented structure;
Fig. 3 is the light microscopic figure with two nucleation site patterned surfaces (after polymerization) of oriented structure;
Fig. 4 is the light microscopic figure with three nucleation site patterned surfaces (after polymerization) of oriented structure;
Fig. 5 is the light microscopic figure with four nucleation site patterned surfaces (after polymerization) of oriented structure;
Fig. 6 is the light microscopic figure with the patterned surface (after polymerization) of " fish bony spur " structure of the linear nucleation site formation of oriented structure;
Fig. 7 is the surface profile map of Fig. 6 institute presentation surface of surface profiler mensuration;
Fig. 8 is the microscope picture that human marrow mesenchymal stem cell (MSC) is planted in PNIPAAm patterned surface.Wherein, (a-c) light microscopic pattern (a), fluorescence mode (b) and the stack (c) of plantation after two days schemed.
Fig. 9 is the application of intelligent patterned surface aspect cell cultures.
Embodiment
Further set forth technical characterstic of the present invention below in conjunction with accompanying drawing and specific embodiment.
Monomer N-isopropylacrylamide (NIPAm) and linking agent (N, N '-bis-third rare acyl cystamines) and light trigger Irgacure651 are mixed to be dissolved in etc. in quality methyl alcohol with mass ratio at 25: 1: 1 and be made into uniform solution.Solution is added drop-wise to glass surface, is uniformly dispersed.Along with the evaporation of solvent, monomer reaches hypersaturated state gradually.Add minute quantity N-isopropylacrylamide crystal at supersaturated solution center, the solute in supersaturated solution is rapidly along being formed centrally needle crystal in this and to the radial patterned surface with oriented structure that diffuses to form of surrounding, seeing Fig. 1.Finally use uv-light polymerization, can make the stable patterning PNIPAM surface with oriented structure, after washing, this surperficial SEM as shown in Figure 2.This pattern its picture on surface after repeatedly washing, being dried is still very clear, proves that present method is the effective ways of the stable patterned surface of preparation.Contact angle experiments shows that the contact angle of this surface and water is 51 ° at 20 DEG C, and at 37 DEG C, is 92 °, proves that this surface has temperature-sensitive.
Embodiment 2
By changing over epipole, can make different microscopic pattern PNIPAM surfaces.If Fig. 1～6 are the pattern that multiple spot nucleation post polymerization forms; Fig. 3 is the pattern forming after uniform two nucleation site polymerizations; Fig. 4 is the pattern forming after uniform three nucleation site polymerizations; Fig. 5 is the pattern forming after four nucleation site polymerizations; Fig. 6 is the pattern forming after linear nucleation site polymerization.Shown by regulating nucleator to add implantation site and can regulate and control easily macroscopic pattern by Fig. 1-6, illustrate described in this patent that method is a kind of effective ways of conveniently preparing the intelligent patterned surface that has both macro and micro patterning concurrently.Polymer surfaces shown in Fig. 6 apart from linear nucleation site 1cm place, the position surface profiler mensuration surface profile that is parallel to linear nucleation site as shown in Figure 7.This surface has more regular crest-trough structure, and between crest-trough, average vertical height is several microns.
Human marrow mesenchymal stem cell (MSC) is planted in to PNIPAAm patterned surface, as Fig. 8, ((a) is light microscopic pattern, (b) be fluorescence mode, (c) be stacking diagram) shown in, the arrow in Fig. 8 (a) represents the differently-oriented directivity of patterned surface.MSC can be in the adhesion of PNIPAAm patterned surface and growth as seen from Figure 8 to see Fig. 8 (b, c) with the MSC that Calcium AM lives after dying.Moreover MSC can be in this surface orientation growth, and its differently-oriented directivity is consistent with the differently-oriented directivity of patterned surface, shows that this surface has " contact guidance " effect to cell.
Embodiment 4
By breast cancer cell MDA-MB-231 cell seeding on alignment patterned surface, at 37 DEG C, cultivate after two days, with observing after PBS washing, if Fig. 9 (a-c) is microscope light microscopic mode chart 9 (a), fluorescence mode Fig. 9 (b) and stacking diagram 9 (c) figure, cell can be along alignment surfaces oriented growth as seen from the figure, shows that this surface can provide cell adhesion site inducing cell orientation.By cell at room temperature cultivate one little after, wash with PBS.Fig. 9 (d-f) for washing rear surface light microscopic mode chart 9 (d), fluorescence mode Fig. 9 (e) and stacking diagram 9 (f).The cell of PNIPAAm patterned surface comes off completely as seen from the figure, show that this intelligence patterned surface not only can be orientated by inducing cell, and can make adherent cell desorption at low temperatures, this has proved that intelligent patterned surface prepared by the present invention is the good matrix of carrying out cell cultures.Fig. 9 (g-i) is the microscope picture at patterned surface edge-glass interface place in incubated at room temperature, the rear glass matrix of PBS washing.The orientation cell of PNIPAAm patterned surface comes off completely as seen from the figure, and visible a lot of cells on glass surface, and being random orientation, this has further proved the effect of alignment patterned surface to cell induction orientation and desorption.
Claims (8)
1. the preparation method with the intelligent patterned polymer surface of oriented structure, is characterized in that: concrete steps comprise:
1) can form the monomer 80-98% of the intelligent polymer of needle crystal, light trigger 1-10%, linking agent 1-10% is dissolved in wiring solution-forming in the solvent that is easy to volatilization; It is more than mass percent;
2) solution in step 1) is spread in matrix, evaporating solvent makes joined monomer solution reach hypersaturated state, forms supersaturated solution film;
3) in step 2) add nucleator to make monomer crystallization form the patterned surface with oriented structure in the supersaturated solution film of gained;
4) step 3) gained patterned surface is carried out to light initiation polymerization, can obtain needed alignment patterned polymer surfaces;
Described monomer is selected from one or more in N-isopropylacrylamide, isopropyl methyl acrylamide and carboxyl N-isopropylacrylamide.
2. the preparation method on the intelligent patterned polymer surface with oriented structure according to claim 1, is characterized in that: described light trigger is one or more in bitter almond oil camphor and derivatives class light trigger, benzil photoinitiator, alkyl phenones photoinitiator, acyl group phosphorous oxides light trigger, benzophenone photoinitiator, thioxanthone photoinitiator and cationic photoinitiator.
3. the preparation method on the intelligent patterned polymer surface with oriented structure according to claim 2, is characterized in that: described bitter almond oil camphor and derivatives class light trigger are selected from st-yrax, benzoin dimethylether, Benzoin ethyl ether, benzoin isopropyl ether or benzoin isobutyl ether; Benzil photoinitiator is selected from phenylbenzene ethyl ketone or α, alpha, alpha-dimethyl oxygen base-α-phenyl methyl phenyl ketone; Described alkyl phenones photoinitiator is selected from α, α-diethoxy acetophenone, alpha-hydroxyalkyl benzophenone or α-amine alkyl phenones; Acyl group phosphorous oxides light trigger is selected from aroyl phosphine oxide or two benzoylphenyl phosphine oxide; Benzophenone photoinitiator is selected from benzophenone, 2,4 dihydroxyl benzophenone or Michler's keton; Thioxanthone photoinitiator is selected from sulfo-propoxy-thioxanthone or isopropyl thioxanthone; Cationic photoinitiator is selected from the luxuriant iron hexafluorophosphate of diaryl group iodized salt, triaryl salt compounded of iodine, alkyl salt compounded of iodine or isopropyl benzene.
4. the preparation method on the intelligent patterned polymer surface with oriented structure according to claim 1, is characterized in that: described linking agent is the free radical type linking agent containing many pairs of keys.
5. the preparation method on the intelligent patterned polymer surface with oriented structure according to claim 1, is characterized in that: described nucleator is various organic or inorganic thing crystal, needle point, blade, plastics or metallic film.
6. the preparation method on the intelligent patterned polymer surface with oriented structure according to claim 1, is characterized in that: described solvent is the one in aromatic hydrocarbons, halon, alkane, naphthenic hydrocarbon, ketone, alcohols, ethers and ester class.
7. the preparation method on the intelligent patterned polymer surface with oriented structure according to claim 1, it is characterized in that: described matrix is selected from the one in glass, quartz, silicon chip and metal, also can be selected from the one in paper, plastics, rubber, metallic film and Pressure sensitive adhesive tape.
8. the intelligent patterned polymer surface applications with oriented structure that described in claim 1, preparation method obtains in obtain lamellar structure cell, various patterning and there is the cell of oriented structure and various dissimilar cells separate discriminating.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1241732A (en) * | 1998-07-15 | 2000-01-19 | 东进化成工业株式会社 | Photosensitive siloxane resin composition and patterning method using it |
| CN101177079A (en) * | 2007-12-07 | 2008-05-14 | 东南大学 | Method for printing micro contact pattern with hydrogel as template and colloid crystal as writing ink |
| CN101793996A (en) * | 2009-12-25 | 2010-08-04 | 北京理工大学 | Molecular imprinting photonic crystal for detecting glucose |
| CN102201535A (en) * | 2011-03-30 | 2011-09-28 | 合肥工业大学 | UV-lithographic micro-patterned organic thin film transistor semiconductor material and application |
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| US7347988B2 (en) * | 2001-11-15 | 2008-03-25 | University Of North Texas | Synthesis, uses and compositions of crystal hydrogels |
| WO2007038219A2 (en) * | 2005-09-23 | 2007-04-05 | University Of North Texas | Synthesis of columnar hydrogel colloidal crystals in water-organic solvent mixture |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1241732A (en) * | 1998-07-15 | 2000-01-19 | 东进化成工业株式会社 | Photosensitive siloxane resin composition and patterning method using it |
| CN101177079A (en) * | 2007-12-07 | 2008-05-14 | 东南大学 | Method for printing micro contact pattern with hydrogel as template and colloid crystal as writing ink |
| CN101793996A (en) * | 2009-12-25 | 2010-08-04 | 北京理工大学 | Molecular imprinting photonic crystal for detecting glucose |
| CN102201535A (en) * | 2011-03-30 | 2011-09-28 | 合肥工业大学 | UV-lithographic micro-patterned organic thin film transistor semiconductor material and application |
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