CN101507841A - Preparation method of inorganic calcium phosphate salt/biodegradable polymer fiber film composite material - Google Patents
Preparation method of inorganic calcium phosphate salt/biodegradable polymer fiber film composite material Download PDFInfo
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Abstract
The invention discloses a method for preparing composite material from inorganic calcium phosphate salt/biodegradable polymer fiber membrane. The method comprises the steps of superposing more than two inorganic calcium phosphate salt/biodegradable polymer fiber membranes to form a multilayer composite fiber membrane and hot press molding on the multilayer composite fiber membrane, wherein the orientation degree of fibers in the inorganic calcium phosphate salt/biodegradable polymer fiber membranes is more than 80 percent, and the included angle of the fiber orientation of adjacent layers of the multilayer composite fiber membrane is between 0 and 90 degrees. The method has the advantages of high adaptability, simple process, low cost and good repeatability. The prepared composite material has biological activity and remineralization performance, high mechanical properties and direction controllability.
Description
Technical field
The present invention relates to a kind of preparation method of biodegradable composite.
Background technology
Biodegradable composite is widely used in biomedical engineering fields such as medical implant, tissue repair and regeneration.Because homogenous material is difficult to the requirement of satisfied mechanical property clinically and biology performance, adopt different materials to carry out the compound composite that has property with acquisition, become the research focus of current bio-medical material.Inorganic phosphate calcium salt/biodegradable polymers composite has favorable biological degradability and biocompatibility, obtains broad research and application in the bone tissue engineer field.When using, advanced composite material (ACM) requires inorganic particulate uniform distribution in the compound system, adhesion is preferably arranged between inorganic particulate and polymeric substrate, the composite materials property height, biological degradation polyalcohol degradation process and bone tissue restoration regenerative process coupling, have good biology performance and remineralization performance, can play the effect of the fixing and tissue recovery support of good bone.
The preparation method of existing inorganic phosphate calcium salt/biodegradable polymers composite is: in advance synthetic inorganic phosphate calcium salt again with polyblend, directly hot pressing or injection mo(u)lding.As " adsorbable internal fixing material for bone fracture and the preparation method " of No. 02113025 public announcement of a patent application, promptly be that polylactic acid, tricalcium phosphate, hydroxyapatite are mixed, then through hot moulding or hot-extrudable making.Inorganic phosphate calcium salt/biodegradable polymers the composite of this class methods preparation still can not satisfy the requirement of medical implant, tissue repair and regrown material at aspects such as the combination at reinforcing material interface, the degradation rate of regulating material, the biological activity that improves the strength of materials, raising material and remineralization performances; Be in particular in: 1, the inorganic calcium phosphate salt particle is dispersed in the polymer by mechanical mixture, and between synthos and polymer a little less than the adhesion, the compound interface instability makes Compound Material Engineering strength-enhanced DeGrain; 2, the synthos particle generally is to exist with micron order or nano-scale particle, very easily reunites between particle, and above-mentioned physics dispersion method is difficult to agglomerated particles is disperseed, and is difficult for homodisperse in polymeric system; 3, be randomly distributed in the composite owing to the inorganic phosphate calcium salt presents usually, and polydispersion is unfavorable for bringing into play advantages such as synthos biotic induce and biocompatibility in composite inner.
Having occurred with the biodegradable polymers superfine fibre in recent years is base material, with the inorganic phosphate calcium salt/salt/biodegradable polymer fiber film composite material of the compound preparation of synthos particle.Because human body hard tissue mainly is made up of collagen fiber and inorganic phosphate calcium salt.Therefore inorganic phosphate calcium salt/biodegradable polymers superfine fibre composite can be realized microstructure and form upward anthropomorphic dummy's body sclerous tissues as bone tissue restoration, the alternative and fixed tissue engineering bracket of bone.The superfine fibre of method of electrostatic spinning preparation has the porosity height, advantages such as the aperture is adjustable, directivity unanimity, it not only has certain mechanical property, and has a good bionic structure, the combination of polymer and nanoparticle is in molecular dimension, the biological activity, remineralization performance and the mechanical property that help composite improve, thereby become the focus of tissue renovation material research; Nano inorganic synthos distribution of particles has stable combination interface in fiber surface simultaneously, and good mechanical stability and controllability, biological activity and remineralization performance are arranged.Therefore, the preparation method of superfine fibre composite normally: be distributed in the biodegradable polymer solution with inorganic calcium phosphate salt, carry out the electrospinning silk again and prepare composite fibre, be called the blended electro spinning method." macromolecular material/material with carbon element/hydroxyapatite hybridized fiber and preparation method thereof " as No. 200510053426 publics announcement of a patent application, it promptly is at first synthetic material with carbon element/hydroxyapatite nano-complex particle, the suspension for preparing degradable high polymer material and this nano-complex particle then, the electricity consumption spinning technique is prepared macromolecular material/material with carbon element/hydroxyapatite hybridized fiber, wherein material with carbon element and hydroxyapatite exist with the form of nano-complex particle, and it is three-dimensional porous that hybridized fiber is.But this preparation method has weak point: 1, because the adding of synthos has changed the electrospinning performance of polymer solution system, thereby influence the pattern, the degree of orientation, mechanical property etc. of composite fibre; 2, synthos distribute and to have not regulation and controllability, and the mechanical property instability can not be given full play to the biological activity and the remineralization of synthos; 3, the composite cellulosic membrane tensile property of preparing is uncontrollable on direction, can not control the space mechanics performance profile of composite; And the compound system of interior collagen fiber of body and hydroxyapatite nano particle is staggered at three dimensions, the osseous tissue material have satisfy the human body requirement on the mechanical property each to characteristic, require to have isotropic mechanics (stretching) performance as: knee joint place bone material, and the femur material requirements has and has mechanical property preferably in the vertical; Therefore, composite cellulosic membrane mechanics auxiliary type bone repair tissue engineering rack or product that existing method makes are difficult to possess the mechanical property of coincideing with the both injured bones tissue in three dimensions and each is to characteristic.
Summary of the invention
Purpose of the present invention just provides a kind of preparation method of inorganic phosphate calcium salt/salt/biodegradable polymer fiber film composite material, this method applicability is strong, technology is simple, with low cost, good reproducibility, composite biologically active that makes and remineralization performance, controlled on mechanical property height and the direction, can in three dimensions, possess the mechanical property of coincideing and each is to characteristic with the both injured bones tissue.
The present invention realizes its goal of the invention, the technical scheme that is adopted is: a kind of preparation method of inorganic phosphate calcium salt/salt/biodegradable polymer fiber film composite material, its practice is: with the two-layer above compound directional fiber film of inorganic phosphate calcium salt/biodegradable polymers, superimposed back forms multilayer composite fiber film, hot-forming; Wherein the fibre orientation degree in the compound directional fiber film of inorganic phosphate calcium salt/biodegradable polymers is more than 80%, and the angle of multilayer composite fiber film adjacent layer directional fiber film orientation is 0-90 °.
Compared with prior art, the invention has the beneficial effects as follows:
One, pass through the two-layer above compound directional fiber film of inorganic phosphate calcium salt/biodegradable polymers, superimposed back forms multilayer composite fiber film, hot-forming; And the fibre orientation degree in the compound directional fiber film of wherein every strata compound is more than 80%.Because the fibre orientation degree of compound directional fiber film is more than 80%, the compound directional fiber film of monolayer has excellent mechanical property, have excellent tensile properties on its fiber orientation directions, but tensile property is poor on non-differently-oriented directivity.Method of the present invention can analogue body when superimposed in the collagen fiber arrangement mode, and the differently-oriented directivity of the compound directional fiber film of each layer is carried out cross lamination by required angle, each that realizes tensile property on the required direction is to distribution.As: the number of plies of the directional fiber of multilayer composite fiber film can be made as more than 4 layers at the bone renovating material at knee joint place, the angle of adjacent layer directional fiber film orientation equates, between each fibrous layer all angles and equal 360 degree.Thereby make the isotropic composite of tensile property, to satisfy the isotropic requirement of bone renovating material tensile property at knee joint place.Then when superimposed, making the angle of adjacent layer directional fiber film orientation is zero to the femur repair materials, and the orientation of each layer directional fiber film is machine-direction oriented, has the bone renovating material of tensile mechanical properties preferably in the vertical thereby make; To other bone renovating materials, also can prepare as required and in three dimensions, possess the tensile mechanical properties that coincide with the both injured bones tissue and each is to characteristic.
And the present invention can be by the total amount of fiber number of plies decision mechanical property intensity and the variation of distribution; For the composite cellulosic membrane of same thickness, angle is more little, and the number of plies is many more, and the composite cellulosic membrane tensile property presents the trend of being evenly distributed along the fibrous membrane plane, and the ultimate tensile strength direction is many more, and the difference between maximum and the minima is more little.
The thing that makes of the present invention not only makes tensile property controlled on spatial distribution, and its tensile property also is improved on the whole.Experiment test proves, is equipped with inorganic phosphate calcium salt/biodegradable polymers composite than the blended electro spinning legal system, and the hot strength of the fibre reinforced composites that the present invention makes can improve more than 2 times.
Two, the present invention only need need not special process and equipment with superimposed hot-forming the getting final product of two-layer above composite cellulosic membrane, and its adaptability is strong, and technology is simple, with low cost, good reproducibility.
Three,, make composite biologically active and remineralization performance among the present invention because the nano inorganic synthos particle in the composite cellulosic membrane has good biological activity and remineralization performance.
Above-mentioned hot-forming concrete operations are: multilayer composite fiber film after superimposed in the following 0-50 of glass transition temperature of polymer ℃ scope pre-hot pressing 5-10 minute earlier, in the above 0-50 of glass transition temperature ℃ scope hot pressing 10-30 minute again.
The mechanical properties decrease that the following 0-50 of glass transition temperature of polymer ℃ low temperature precompressed can stop filament contraction to cause, 5-10 minute temperature retention time can reduce the contraction of fiber and keep interfibrous closely knit, and then, in the above 0-50 of glass transition temperature ℃ scope hot pressing 10-30 minute, can guarantee interfibrous fully good adhesion, can prevent that also fiber from overbating and cause fibre structure to disappear and the overaging of fibre structure and the mechanical properties decrease that causes.The density of the composite fibre after hot-forming, the adhesion degree between the fiber are enhanced, and have realized that the secondary of the mechanical property of composite cellulosic membrane strengthens.And can regulate the density of composite fibre by to hot pressing temperature, temperature retention time, the isoparametric control of hot pressing pressure, the physical parameters such as adhesion degree between the fiber realize the control as required to mechanical property.
The above-mentioned compound directional fiber film of inorganic phosphate calcium salt/biodegradable polymers of stating adopts following method to make: biodegradable polymer is prepared fibrous membrane by electrostatic spinning, and adopt the high speed rotary-drum collection to obtain the fibre orientation degree at the directional fiber film more than 80%; The directional fiber film forms nano inorganic synthos particle again through external mineralising on the surface.
Above-mentioned directional fiber film behind the surface grafting biomacromolecule, carries out external mineralising earlier again; Grafted biomacromolecule is one or more the mixture in chitosan, gelatin, collagen, sodium alginate, the serum albumin, and the grafting amount is 0.01-10nmol/cm
2
Behind the first grafting active group of above-mentioned biodegradable polymer, prepare fibrous membrane by electrostatic spinning again; Grafted active group is the active group of one or more in grafting hydroxyl, amino, the phosphate radical again behind carboxyl or the carboxyl grafting, and the grafting amount is 1-10nmol/cm
2
The present invention is by fiber surface grafting biomacromolecule or active group, induced nano inorganic calcium phosphate salt particle is in the fiber surface mineralising in simulated body fluid, obtain compound directional fiber film, synthetic in advance than the existing slightly solubility nano inorganic synthos particle that adopts, join again in the organic solution of polymer macromolecular material, carry out carrying out the electrospinning method for processing again behind the mechanical blending, have the following advantages: (1) nano inorganic synthos particle mainly is distributed in the directional fiber surface, nano surface inorganic calcium phosphate salt particle produces " pinning " effect (hindering the stretching vibration of strand) to polymer molecular chain, thereby the mechanical property of reinforced composite, simultaneously, do not destroy fibrous inner structure, the mechanical property that generates composite fibre is good, and physical and chemical performance is reliable and stable; (2) the nano inorganic synthos particle by the surface grafting induction and deposition is to mutually combine at molecular level and macromolecular material generation, combination interface is better, be uniformly dispersed, strengthened combining of mineralising particle and polymeric substrate, can effectively overcome the agglomeration traits of inorganic particulate, improve mechanical property greatly; (3) the nano inorganic synthos particle set by the surface grafting induction and deposition is distributed in fiber surface, help to simulate the biotic environment of collagen fiber extracellular matrix, strengthen the remineralization performance of embedded material and tissue engineering bracket, help the performance of adhesion, growth and the bone conduction effect of cell; (4) mechanical property of composite fibre can be regulated by regulating fibre diameter and nano inorganic synthos particle content easily.
Grafted biomacromolecule has excellent biological compatibility, biodegradability and biological activity; And grafted above active group has biotic induce and specific bond.These biomacromolecules and active group all can easier be grafted to the biodegradable polymers fiber surface, and do not change the ins and outs of biomacromolecule and group.Grafting biomacromolecule content is at 0.01-10nmol/cm
2Variation, activity group content are at 1-10nmol/cm in the scope
2Change generating rate and the induction and deposition amount that effectively to regulate the inorganic phosphate calcium salt in the scope.
Above-mentioned biodegradable polymer is one or more a mixture of polylactic acid, polylactic acid-polyglycolic acid copolymer, polylactic acid-polyglycol copolymer, polylactic acid-poly-epsilon-caprolactone copolymer, Merlon, poly-anhydride.
Above biodegradable polymers is existing sophisticated biodegradable polymers, with simple, with low cost, the good reproducibility, safe of its preparation biodegradable polymers fibre technology.
Below in conjunction with concrete embodiment, the present invention is further detailed explanation.
The specific embodiment
Embodiment one:
A kind of specific embodiment of the present invention is, a kind of preparation method of inorganic phosphate calcium salt/salt/biodegradable polymer fiber film composite material, and its method is:
Polylactic acid is prepared the acid fiber by polylactic film that thickness is 100 μ m by method of electrostatic spinning, and adopt the high speed rotary-drum collection of linear velocity 16.7m/s to obtain the polylactic acid directional fiber film of fibre orientation degree more than 80%; This directional fiber film is soaked in gelatin/phosphate buffer of 2mg/mL, and 2-4 ℃ was reacted 24 hours down, and after the cleaning, obtaining gelatin grafting amount is 0.02nmol/cm
2Polylactic acid directional fiber film; Carry out external mineralising then, be about to it and be soaked in the human body simulation body fluid of 1.5 times of concentration, soaked 7 days down, after taking-up is cleaned at 37 ℃, obtain the compound directional fiber film of nano inorganic synthos/biodegradable polylactic acid, wherein low-crystalline synthos content is 15.1%.
Is 30 ° of superimposed arrangements with the compound directional fiber film of 6 layers of inorganic phosphate calcium salt/biodegradable polylactic acid by the orientation angle of directional fiber film between adjacent layer, again through the hot-forming composite that obtains.Concrete hot press forming technology is: polylactic acid glass transition temperature below 55 ℃ 15 ℃ promptly under 40 ℃ the temperature, 1MPa pressure, precompressed 8 minutes, be warming up to 60 ℃ (polylactic acid glass transition temperatures more than 55 ℃ 5 ℃) again, hot pressing is 10 minutes under 2MPa pressure, be cooled to room temperature and remove load again, promptly obtaining tensile property isotropic is the inorganic phosphate calcium salt/salt/biodegradable polymer fiber film composite material of base material with the acid fiber by polylactic.Kept complete fibre structure in the composite, realized adhesion between fiber simultaneously, the tensile property of this composite on all directions is almost consistent.
Embodiment two:
Polylactic acid is prepared the acid fiber by polylactic film that thickness is 75 μ m by method of electrostatic spinning, and adopt the high speed rotary-drum of linear velocity 16.7m/s to collect the polylactic acid directional fiber film of fibre orientation degree more than 80%; This directional fiber film is soaked in gelatin/phosphate buffer of 2mg/mL, and 2-4 ℃ was reacted 24 hours down, and after the cleaning, obtaining gelatin grafting amount is 0.02nmol/cm
2Polylactic acid directional fiber film; Carry out external mineralising then, being about to it is soaked in the human body simulation body fluid of 1.5 times of concentration, soaked 7 days down at 37 ℃, after taking out cleaning, obtain the compound directional fiber film of nano inorganic synthos/biodegradable polylactic acid, wherein low-crystalline synthos content is 15.1% (the compound directional fiber membrane preparation method of this routine polylactic acid is identical with embodiment one).
Is 0 ° of superimposed arrangement with 8 layer of 75 thick composite cellulosic membrane of μ m by fibre orientation angle between adjacent layer, obtains composite through hot-pressing processing again.Concrete heat pressing process is: precompressed is after 8 minutes under 40 ℃ (glass transition temperatures of polylactic acid electrospinning fibre below 55 ℃ 15 ℃), 1MPa pressure, be warming up to 60 ℃ (glass transition temperatures of polylactic acid electrospinning fibre more than 55 ℃ 5 ℃), hot pressing is 20 minutes under 2MPa pressure, be cooled to room temperature and remove load again, obtain composite.
Embodiment three:
Present embodiment and embodiment two are basic identical, different only be:
Polylactic acid is prepared the thick acid fiber by polylactic film of 150 μ m by method of electrostatic spinning.
Is 45 ° of superimposed arrangements with 4 layer of 150 thick composite cellulosic membrane of μ m by fibre orientation angle between adjacent layer, obtains composite through hot-pressing processing again.
Embodiment four:
Present embodiment and embodiment two are basic identical, different only be:
Polylactic acid is prepared the thick acid fiber by polylactic film of 300 μ m by method of electrostatic spinning.
Is 90 ° of superimposed arrangements with 2 layer of 300 thick composite cellulosic membrane of μ m by fibre orientation angle between adjacent layer, obtains composite through hot-pressing processing again.
Embodiment five:
Merlon is prepared the polycarbonate film that thickness is 300 μ m by method of electrostatic spinning, and adopt the high speed rotary-drum collection of linear velocity 16.7m/s to obtain the Merlon directional fiber film of fibre orientation degree more than 80%; This directional fiber film is soaked in collagen/phosphate buffer of 2mg/mL, and 2-4 ℃ was reacted 24 hours down, and after the cleaning, obtaining collagen grafting amount is 10nmol/cm
2The directional fiber film; Carry out external mineralising then, be about to it and be soaked in the human body simulation body fluid of 1.5 times of concentration, soaked 7 days down at 37 ℃, taking-up obtains containing nano inorganic synthos particle composite cellulosic membrane after cleaning.
Is 0 ° of superimposed arrangement with 2 layers of composite cellulosic membrane by fibre orientation angle between adjacent layer, obtains composite through hot-pressing processing again; Concrete heat pressing process is: precompressed is after 8 minutes under 92 ℃ (glass transition temperatures of Merlon electrospinning fibre below 142 ℃ 50 ℃), 1MPa pressure, be warming up to 192 ℃ (its glass transition temperatures more than 142 ℃ 50 ℃), hot pressing is 30 minutes under 2MPa pressure, be cooled to room temperature and remove load again, obtain composite.
Embodiment six:
Present embodiment and embodiment five are basic identical, different only be: biodegradable polymer is the mixture of polylactic acid and poly-anhydride, the thickness of the blend fibers film of polylactic acid and poly-anhydride is 200 μ m, grafted macromole is a serum albumin, and serum albumin grafting amount is 0.5nmol/cm
2
Is 60 ° of superimposed arrangements with 3 layers of composite cellulosic membrane by fibre orientation angle between adjacent layer, obtains composite through hot-pressing processing again; Concrete heat pressing process is: precompressed is after 10 minutes under 56 ℃ (glass transition temperatures of polylactic acid and poly-anhydride blend electrospinning fibre below 56 ℃ 0 ℃), 1MPa pressure, be incubated in 56 ℃ (glass transition temperatures more than 56 ℃ 0 ℃), hot pressing is 20 minutes under 2MPa pressure, be cooled to room temperature and remove load again, obtain composite.
Embodiment seven:
Present embodiment and embodiment five are basic identical, different only be: biodegradable polymer is poly-anhydride, and the thickness of poly-anhydride fibrous membrane is 60 μ m, and grafted macromole is a sodium alginate, and sodium alginate grafting amount is 0.01nmol/cm
2, obtaining thickness is that 60 μ m contain nano inorganic synthos particle composite cellulosic membrane; Is 18 ° of superimposed arrangements with 10 layers of composite cellulosic membrane by fibre orientation angle between adjacent layer, obtains composite through hot-pressing processing again.Concrete heat pressing process is: precompressed is after 5 minutes under 42 ℃ (glass transition temperatures of poly-anhydride electrospinning fibre below 72 ℃ 30 ℃), 1MPa pressure, be warming up to 72 ℃ (its glass transition temperatures more than 72 ℃ 0 ℃), hot pressing is 30 minutes under 2MPa pressure, be cooled to room temperature and remove load again, obtain composite.
Embodiment eight:
Present embodiment and embodiment five are basic identical, different only be: biodegradable polymer is polylactic acid-poly-epsilon-caprolactone copolymer, the thickness of polylactic acid-poly-epsilon-caprolactone copolymer fibre film is 100 μ m, grafted macromole is sodium alginate and collagen, and the grafting amount of sodium alginate and collagen is 0.04nmol/cm
2Is 30 ° of superimposed arrangements with 6 layers of composite cellulosic membrane by fibre orientation angle between adjacent layer, obtains composite through hot-pressing processing again.Concrete heat pressing process is: precompressed is after 10 minutes under 45 ℃ (glass transition temperatures of polylactic acid-poly-epsilon-caprolactone copolymer electrospinning fibre below 45 ℃ 0 ℃), 1MPa pressure, be incubated in 95 ℃ (its glass transition temperatures more than 45 ℃ 50 ℃), hot pressing is 30 minutes under 2MPa pressure, be cooled to room temperature and remove load again, obtain composite.
Embodiment nine:
Present embodiment and embodiment five are basic identical, different only be: biodegradable polymer is the polylactic acid-polyglycolic acid copolymer, the thickness of polylactic acid-polyglycolic acid copolymer fibre film is 300 μ m, and grafted macromole is a chitosan, and the chitosan graft amount is 3nmol/cm
2Is 90 ° of superimposed arrangements with 2 layers of composite cellulosic membrane by fibre orientation angle between adjacent layer, obtains composite through hot-pressing processing again; Concrete heat pressing process is: precompressed is after 10 minutes under 59 ℃ (glass transition temperatures of polylactic acid-polyglycolic acid copolymer electrospinning fibre be below 59 ℃ 0 ℃), 1MPa pressure, be warming up to 109 ℃ (glass transition temperatures be more than 59 ℃ 50 ℃), hot pressing is 10 minutes under 2MPa pressure, be cooled to room temperature and remove load again, obtain composite.
Embodiment ten:
Polylactic acid is dissolved in dichloromethane, adds maleic anhydride and dibenzoyl peroxide, at N
2Under the protection, 100 ℃ were reacted 8 hours, and obtained maleic anhydride modified polylactic acid (MPLA).Maleic anhydride modified polylactic acid is dissolved in the oxolane, splashes in the distilled water, obtain the polydactyl acid (CPLA) of grafting active group-carboxyl; CPLA is carried out electrostatic spinning processing, thickness is the CPLA fibrous membrane of the carboxyl grafting of 300 μ m, and the cylinder by linear velocity 16.7m/s collect obtain, the fibre orientation degree is the CPLA directional fiber film of the carboxyl grafting more than 80%, wherein grafted carboxyl amount is 0.94 ± 0.11nmol/cm
2Carry out external mineralising then, be about to it and be soaked in the human body simulation body fluid of 1.5 times of concentration, soaked 7 days down, after taking-up is cleaned at 37 ℃, obtain the compound directional fiber film of inorganic phosphate calcium salt/biodegradable polylactic acid after the external mineralising, wherein low-crystalline synthos content is 16.2%.
Is 90 ° of superimposed arrangements with the compound directional fiber film of 2 layers of inorganic phosphate calcium salt/biodegradable polylactic acid by two interlayer fibre orientation angles, obtains composite through hot-pressing processing again.Concrete heat pressing process is: in the precompressed after 8 minutes under 15 ℃ (promptly 40 ℃), the 1MPa pressure below 55 ℃ of the glass transition temperature of electrospinning acid fiber by polylactic, be warming up to its glass transition temperature more than 55 ℃ 5 ℃ (promptly 60 ℃), hot pressing is 10 minutes under 2MPa pressure, be cooled to room temperature and remove load again, obtain two-layer inorganic phosphate calcium salt/biodegradable acid fiber by polylactic film composite material.Kept complete fibre structure in the composite, realized adhesion between fiber simultaneously, and composite has good tensile property on 90 ° two orthogonal directions of interlacing.
Embodiment 11:
Take by weighing the 4g polylactic acid and be dissolved in dichloromethane, add 0.8g maleic anhydride and 0.024g dibenzoyl peroxide, at N
2Under the protection, 100 ℃ were reacted 8 hours, and obtained maleic anhydride modified polylactic acid (MPLA).MPLA and the reaction of 3-amido propanol are obtained hydroxyl and carboxy-modified polylactic acid (HCPLA).HCPLA is mixed with 10% acetone soln, carry out electrostatic spinning and process the fibrous membrane that thickness is 200 μ m, cylinder by linear velocity 16.7m/s is collected and obtained the fibre orientation degree is directional fiber film more than 80%, and fiber surface carboxyl and hydroxy radical content are respectively 0.47 and 0.44nmol/cm
2Carry out external mineralising then, be about to it and be soaked in the human body simulation body fluid of 1.5 times of concentration, soaked 7 days down, after taking-up is cleaned at 37 ℃, obtain containing nano inorganic synthos particle/polylactic acid composite cellulosic membrane, wherein low-crystalline synthos content is 16.8%.
With 3 layers of composite cellulosic membrane that above method makes, be 60 ° of superimposed arrangements by fibre orientation angle between adjacent layer, obtain composite through hot-pressing processing again.Concrete heat pressing process is: precompressed is after 8 minutes under 40 ℃ (glass transition temperatures of polylactic acid electrospinning fibre below 55 ℃ 15 ℃), 1MPa pressure, be warming up to 60 ℃ (its glass transition temperatures more than 55 ℃ 15 ℃), hot pressing is 10 minutes under 2MPa pressure, be cooled to room temperature and remove load again, obtain composite.Keep complete fibre structure in the composite, realized adhesion between fiber simultaneously.
Embodiment 12:
Take by weighing 4g polylactic acid-polyglycol copolymer and be dissolved in dichloromethane, add 0.8g maleic anhydride and 0.024g dibenzoyl peroxide, at N
2Under the protection, 100 ℃ were reacted 8 hours, and obtained maleic anhydride modified polylactic acid-polyglycol copolymer (MPELA).Successively with 3-aminopropanol, 1,6-hexamethylene diamine modification MPELA obtains carboxyl, amino and hydroxyl modification polylactic acid-polyglycol copolymer (AHCPELA); AHCPELA is mixed with 10% acetone soln, carry out electrostatic spinning processing, obtain the fibrous membrane that thickness is 200 μ m, the cylinder by linear velocity 16.7m/s is collected and obtained the fibre orientation degree is directional fiber film 80% or more, and the surperficial carboxyl-content of fibrous membrane is 10.0nmol/cm
2, amino content is 5.14nmol/cm
2, hydroxy radical content is 4.82nmol/cm
2Carry out external mineralising then, be about to it and be soaked in the human body simulation body fluid of 1.5 times of concentration, soaked 7 days down, after taking-up is cleaned at 37 ℃, obtain containing nano inorganic synthos particle/polylactic acid composite cellulosic membrane, wherein low-crystalline synthos content is 16.8%.
Is 60 ° of superimposed arrangements with 3 layers of composite cellulosic membrane by fibre orientation angle between adjacent layer, obtains composite through hot-pressing processing again.Concrete heat pressing process is: precompressed is after 5 minutes under 50 ℃ (glass transition temperatures of polylactic acid-polyglycol copolymer electrospinning fibre below 50 ℃ 0 ℃), 1MPa pressure, be warming up to 80 ℃ (glass transition temperatures of polylactic acid electrospinning fibre more than 50 ℃ 30 ℃), hot pressing is 10 minutes under 2MPa pressure, be cooled to room temperature and remove load again, obtain composite.
Embodiment 13:
Present embodiment and embodiment dodecyl are originally identical, different only be: with carbamyl phosphate maleic anhydride modified polylactic acid-polyglycol copolymer (MPELA) is carried out modification, obtain containing the polymer (PCPELA) of carboxyl and phosphate radical, again (PCPELA) carried out electrostatic spinning to fibrous membrane, electrospun fiber membrane surface carboxyl-content is 1.0nmol/cm
2, phosphate content is 1.0nmol/cm
2Is 60 ° of superimposed arrangements with 3 layers of composite cellulosic membrane by fibre orientation angle between adjacent layer, obtains composite through hot-pressing processing again.Concrete heat pressing process is: precompressed is after 5 minutes under 35 ℃ (glass transition temperatures of polylactic acid-polyglycol copolymer electrospinning fibre below 50 ℃ 15 ℃), 1MPa pressure, be warming up to 55 ℃ (glass transition temperatures of polylactic acid-polyglycol copolymer electrospinning fibre more than 50 ℃ 5 ℃), hot pressing is 20 minutes under 2MPa pressure, be cooled to room temperature and remove load again, obtain composite.
The electrospinning time when thickness of fibrous membrane can be by electrostatic spinning among the present invention is controlled and regulates; The fibre orientation degree of directional fiber film is determined by the linear velocity of high speed rotary-drum that then the high speed rotary-drum of employing linear velocity 16.7m/s can be collected and obtain the directional fiber film of fibre orientation degree more than 80%.As adopt the more cylinder of high linear speed, then can collect the directional fiber film that obtains higher fibre orientation degree.
Experiment showed, that below the composite that the inventive method makes has the mechanical property of certain controlled, good biological activity and remineralization performance.
Experiment one: the Mechanics Performance Testing of monolayer composite cellulosic membrane
Monolayer composite cellulosic membrane with embodiment one, ten, 11 preparations carries out tension test on the omnipotent stretching testing machine of American I nstron5567, specimen is of a size of 80 * 4 * 0.5mm
3, sample size is n 〉=4, rate of extension is 5mm/min.The extension test result is as shown in table 1.
The mechanical property of table 1 composite cellulosic membrane
| Sample | Ultimate tensile strength (MPa) | Stretch modulus (MPa) | Elongation at break (%) |
| Composite cellulosic membrane among the embodiment one | 9.6±1.4 | 113.4±16.5 | 25.2±8.7 |
| Composite cellulosic membrane among the embodiment ten | 7.2±1.1 | 64.1±9.7 | 25.6±5.4 |
| Composite cellulosic membrane among the embodiment 11 | 7.2±0.7 | 53.1±5.1 | 30.4±6.2 |
| The blended electro spinning composite cellulosic membrane | 3.0±0.6 | 45.4±9.1 | 18.7±5.6 |
Table 1 result adopts the mechanical property of the monolayer composite cellulosic membrane that grafting induced deposition method of the present invention forms apparently higher than adopting the blended electro spinning fibrous membrane.
Experiment two: the Mechanics Performance Testing of composite
Inorganic phosphate calcium salt/salt/biodegradable polymer fiber film composite material with embodiment one, ten, 11 preparations carries out tension test on the omnipotent stretching testing machine of American I nstron5567, specimen is of a size of 80 * 4 * 0.5mm
3, sample size is n 〉=4, rate of extension is 5mm/min.The extension test result is as shown in table 2.
The mechanical property of table 2 composite
| Sample | Hot strength (MPa) | Stretch modulus (MPa) | Elongation at break (%) |
| The composite of embodiment one | 20.4±2.4 | 242.9±28.2 | 15.2±2.7 |
| The composite of embodiment ten | 10.8±1.3 | 96.2±11.6 | 12.6±3.4 |
| The composite of embodiment 11 | 13.2±0.6 | 97.4±4.4 | 13.2±4.2 |
| The blended electro spinning composite | 5.4±0.7 | 81.8±10.6 | 10.7±1.6 |
The composite that table 2 result adopts the mechanical property of the composite of grafting induced deposition method formation of the present invention to prepare apparently higher than the employing blended electro spinning.
Experiment three: each of the mechanical property of composite is to characteristic
Composite with embodiment one to four preparation, at the omnipotent stretching testing machine of American I nstron5567 upper edge X, Y (directions X be in the composite along arbitrary fibrous membrane differently-oriented directivity, the Y direction is for perpendicular to this fiber orientation directions) direction carries out tension test, specimen is of a size of 80 * 4 * 0.5mm
3, sample size is n 〉=4, rate of extension is 5mm/min.The extension test result is as shown in table 3.
Table 3 composite is along the hot strength difference of different directions
Table 3 result adopts the mechanical property of the composite of grafting induced deposition method formation of the present invention to have specificity in different directions.The mechanical strength size that the composite that also promptly adopts grafting induced deposition method of the present invention to form is gone up in any direction all can realize controlling as required by fibrous membrane interlayer angle.
Experiment four: the biocompatibility of composite
Composite with embodiment one, ten and 11 preparations adopts myeloma cell strain MC3T3-E1, cultivates after 7 days in 48 orifice plates, detects the proliferative amount and the activity of cell respectively.The propagation of cell adopts CCk-8 test kit (Japanese colleague chemical company) test, and the differentiation capability of cell adopts the test of alkali phosphatase (ALP) method.Cell experiment and test result are as shown in table 4.
The biocompatibility test result of table 4 superfine fibre reinforced composite
| Sample | The cell proliferation test absorbance | Alkali phosphatase test absorbance |
| The composite of embodiment one | 0.384±0.039 | 0.471±0.051 |
| The composite of embodiment ten | 0.314±0.027 | 0.381±0.047 |
| The composite of embodiment 11 | 0.351±0.043 | 0.443±0.051 |
| The blended electro spinning composite | 0.264±0.022 | 0.331±0.025 |
Table 4 result shows that three kinds of composites of the present invention all can impel the differentiation and the propagation of cell, and cell and composite show excellent biological compatibility in conjunction with closely.Adopt the composite of the present invention's preparation can improve osteoblastic differentiation capability, impel cell differentiation and mineralized tissue to form.
Experiment five: the remineralization performance of composite
The superfine fibre reinforced composite of embodiment one, ten and 11 preparations is soaked in the human body simulation body fluid, soaked 7 days down at 37 ℃, after the cleaning, vacuum drying gets the remineralization composite under the room temperature.Adopt thermogravimetric analyzer (TG) to characterize the growing amount of inorganic phosphate calcium salt in the compound system; Adopt X-ray diffractometer (XRD) to investigate the crystallization situation that generates the inorganic phosphate calcium salt.The TG analysis result shows that the inorganic phosphate calcium salt content all increases 18-24% (not considering the degraded of polymer) in the remineralization composite, and behind the composite remineralization of blended electro spinning preparation inorganic phosphate calcium salt recruitment less than 5%; XRD result show the remineralization composite in 2 θ=25.8 ° and 31.8 ° of strong broad peaks of locating and 2 θ=28,40 and 47 a ° weak broad peak of locating be representative HA feature peak crystallization, and behind the composite remineralization of blended electro spinning preparation inorganic phosphate calcium salt peak intensity a little less than.The result shows that composite shows good remineralization performance, can realize bone conductibility and osteoinductive preferably.
In sum, the present invention in conjunction with electrostatic spinning, graft modification, induce mineralising, spatial configuration and hot press forming technology, realize the uniform distribution of nano inorganic synthos particle at fiber surface, the mechanical property of structure composite each to characteristic.Composite fibre itself has specific mechanical property, biological activity and remineralization performance, can induce osteanagenesis directly as tissue engineering bracket.Fibrous membrane can be used as mechanical property auxiliary type bone and repairs multi-functional product through spatial configuration and hot-forming composite, realizes the spatial distribution of mechanical property from structure.In the process from the composite cellulosic membrane to the Composite Preparation, the integrity that keeps fibre structure, provide the superior mechanical property of composite, remineralization performance and biology performance, for the preparation of bone-repairing composite material of new generation provides new structure thinking and method.
Claims (6)
1, a kind of preparation method of inorganic phosphate calcium salt/salt/biodegradable polymer fiber film composite material, its practice is: with the two-layer above compound directional fiber film of inorganic phosphate calcium salt/biodegradable polymers, superimposed back forms multilayer composite fiber film, hot-forming; Wherein the fibre orientation degree in the compound directional fiber film of inorganic phosphate calcium salt/biodegradable polymers is more than 80%, and the angle of multilayer composite fiber film adjacent layer directional fiber film orientation is 0-90 °.
2, the preparation method of a kind of inorganic phosphate calcium salt/salt/biodegradable polymer fiber film composite material as claimed in claim 1, it is characterized in that, described hot-forming concrete operations are: multilayer composite fiber film after superimposed in the following 0-50 of glass transition temperature of polymer ℃ scope pre-hot pressing 5-10 minute earlier, in the above 0-50 of glass transition temperature ℃ scope hot pressing 10-30 minute again.
3, the preparation method of a kind of inorganic phosphate calcium salt/salt/biodegradable polymer fiber film composite material as claimed in claim 1, it is characterized in that, the compound directional fiber film of described inorganic phosphate calcium salt/biodegradable polymers adopts following method to make: biodegradable polymer is prepared fibrous membrane by electrostatic spinning, and adopt the high speed rotary-drum collection to obtain the fibre orientation degree at the directional fiber film more than 80%; The directional fiber film forms nano inorganic synthos particle again through external mineralising on the surface.
4, the preparation method of a kind of inorganic phosphate calcium salt/salt/biodegradable polymer fiber film composite material as claimed in claim 3 is characterized in that, described directional fiber film behind the surface grafting biomacromolecule, carries out external mineralising earlier again; Grafted biomacromolecule is one or more the mixture in chitosan, gelatin, collagen, sodium alginate, the serum albumin, and the grafting amount is 0.01-10nmol/cm
2
5, the preparation method of a kind of inorganic phosphate calcium salt/salt/biodegradable polymer fiber film composite material as claimed in claim 3 is characterized in that, behind the first grafting active group of described biodegradable polymer, prepares fibrous membrane by electrostatic spinning again; Grafted active group is the active group of one or more in grafting hydroxyl, amino, the phosphate radical again behind carboxyl or the carboxyl grafting, and the grafting amount is 1-10nmol/cm
2
6, the preparation method of a kind of inorganic phosphate calcium salt/salt/biodegradable polymer fiber film composite material as claimed in claim 3 is characterized in that: described biodegradable polymer is one or more a mixture of polylactic acid, polylactic acid-polyglycolic acid copolymer, polylactic acid-polyglycol copolymer, polylactic acid-poly-epsilon-caprolactone copolymer, Merlon, poly-anhydride.
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