CN107137773A - Three-dimensional porous composite of fiber base for Bone Defect Repari and preparation method thereof and products formed - Google Patents
Three-dimensional porous composite of fiber base for Bone Defect Repari and preparation method thereof and products formed Download PDFInfo
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- CN107137773A CN107137773A CN201710357431.7A CN201710357431A CN107137773A CN 107137773 A CN107137773 A CN 107137773A CN 201710357431 A CN201710357431 A CN 201710357431A CN 107137773 A CN107137773 A CN 107137773A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/42—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
- A61L27/425—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix of phosphorus containing material, e.g. apatite
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/42—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
- A61L27/427—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix of other specific inorganic materials not covered by A61L27/422 or A61L27/425
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
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Abstract
The present invention provides a kind of three-dimensional porous composite of fiber base for Bone Defect Repari, its preparation method and products formed.The three-dimensional porous composite composition of fiber base includes micro nanometer fiber powder and adhesive, the micro nanometer fiber powder footpath is 10 500 μm, the fibre diameter for constituting the micro nanometer fiber powder is 0.1 100 μm, and the micro nanometer fiber powder is dispersed in adhesive；The adhesive include it is biodegradable and can self-curing inorganic matter component；In terms of the composite porous gross mass, the micro nanometer fiber powder content is 5 50 mass %, and the composite porous porosity is 30 85%, and compression strength is 1 15MPa.The three-dimensional connected porous support of fiber base that the present invention is built, preparation method is simple, possesses micro/nano fiber structure so that support has notable induced osteogenesis effect；The filling demand at Cranial defect position can be better met, and better mechanical property can be provided.
Description
Technical field
The present invention relates to it is a kind of for fiber-based porous composite of Bone Defect Repari and preparation method thereof and use the fiber
Products formed prepared by base porous compound material, more particularly to a kind of three-dimensional porous rack and preparation method thereof, belong to organizational project
Recovery technique field.
Background technology
At present, because the fracture case that industrial injury, traffic accident etc. are caused gradually increases, aging population is also brought more
Vertebra retrogression pathological changes, osteoporosis diseases, bone tumour, osteomyelitis, constitutional bone disease etc. are also clinical more typical orthopaedics
Disease.Bone tissue self-healing capability is limited, and the Cranial defect cavity of most disease of bone formation is difficult to heal, it usually needs operation
Bone grafting fills up defect, to provide mechanics support and lifting defect it is biological prosthetic.
It is considered as the golden standard that bone filling is repaired, ilium, rib, shin calf that autologous bone transplanting, which is filled in current medical field,
Bone is clinically main at present to take bony site.But autologous bone transplanting unavoidably has its limitation：Take bone amount limited, it is extra to increase
Plus operation wound and operating time, easily there are the complication such as bleeding, hemotoncus, infection, chronic ache and sensory disturbance in Qu Gu areas.
Allograph bone or bone- xenograft source relative abundance, but there is immunological rejection and virus or bacterium infection after the filling of allograph bone, bone- xenograft
Risk, and there is ethics problem.Conventional manual's bone has good biocompatibility and osteoconductive, but due to its shortage
Osteoinductive, causes New born formation speed slower；And the artificial bone containing bone-inducing factor (such as BMP) facilitates bone excellent effect,
But its is expensive, heavier financial burden is caused to patient, and there is the risk of ectopic osteogenesis.With living standard
With the raising of medical level, there is higher requirement to bone collection, bone renovating material, thus with preferable osteogenic induction effect and
The relatively low bone repairing support of price, can preferably meet the demand of clinical and patient.
The main collagen by a diameter of 50-500nm of natural extracellular matrix (Extracellular Matrix, ECM)
Azelon constitutes (citation [1]), and the fibre structure has regulating and controlling effect (citation [2]) to cell behavior.Naturally
The ECM of bone tissue main component is the ordered arrangement structure of the type i collagen of mineralising, type i collagen fiber and hydroxyapatite crystal
Into ripe bone matrix.The bionic model of bone repairing support is the ECM of natural bone tissue, and research shows, class ECM fiber
Reparation of the structure to Various Tissues all there is the relevant cell in preferable facilitation, bone tissue (to be filled between Gegenbaur's cell, marrow
Matter stem cell (MSCs) etc.) also there is certain identification function for fiber topological structure, therefore bone repairing support can be thin
Born of the same parents' tactophily and bone tissue reparation provide suitable three-dimensional environment.K.M.Woo et al. is confirmed first, with flat surface structure phase
Than MC3T3-E1 Gegenbaur's cells have more preferable Adhesion property on fibre structure surface, and research finds that the phenomenon is due to fibre
Dimension structure stand has selective absorption function (citation [3]) to such as fibronectin, vitronectin, laminin.
H.Yoshimoto et al. confirm MSCs also can preferably stick in fiber surface, breed, migrating, Osteoblast Differentiation and outer base
Matter mineralising (citation [4]).
It is capable of the mechanism of induced osteogenesis differentiation based on fibre structure, researcher mutually divides frequently with electrostatic spinning technique with thermic
From the structure that technology carries out the bone repairing support with fibre structure.S.-H.Jegal et al. is prepared for using electrostatic spinning technique
The PLCL tunica fibrosas of lactic acid-polycaprolactone co-polymer (PLCL) tunica fibrosa, addition gelatin and apatite, Rat calvarial is implanted into 6 weeks
As a result show, fibre structure can be effectively facilitated the growth of new bone, and the addition of gelatin and apatite enhances this and facilitated
Bone is acted on.However, fiber base bone repairing support prepared by this method is membrane-like, it is difficult to meet different shape Cranial defect to implantation
The requirement of thing, be difficult carry out dense packing effect, and the support do not possess any mechanical strength, implantation after can not be carried at Cranial defect position
For any mechanical support (citation [5]).K.M.Woo et al. is prepared for fibre structure using Thermal inactive technology
PLLA (PLLA) support, Rat calvarial implantation experiment shows, compared with compact structure, the new bone in fibre structure support
Growing amount significantly increases.But the technology requires higher to experiment condition, and operating process is numerous and diverse, unsuitable largely to be produced
(citation [6]).Citation [7] discloses a kind of system of the three-dimensional large aperture tissue engineering scaffold based on fibre structure
Standby, for the defect repair of the tissues such as bone, tendon, cartilage, skin, this method is cut by the tunica fibrosa for preparing electrostatic spinning
A diameter of 10 μm of -1mm fibre bundle is made, the fibre bundle is stacked and is assembled into three-dimensional structure, and uses suitable macromolecule material
It is adhesively fixed material.But the internal stent does not possess equally distributed fibre structure, to the guiding function of tissue repair
It can be short of.
As can be seen here, the fibre structure of mineralising can carry out bone tissue ECM bionic structure to the full extent, and this is imitative
Growth of the raw structure to new bone has preferable inducing function.But for current research, for existing biomimetic features
Major part is still limited on one-dimensional or two-dimensional structure, so that, for mechanical property or because fiber disperses what inequality was brought
The improvement of performance is still not sufficient enough.Therefore, a kind of bone filling bracket with three-dimensional fiber based structures, solution are built
The problems of certainly current fibre structure bone filler, can preferably meet operation and the demand repaired.
In addition, there is also the bone renovating material for being combined and being prepared with bone cement using fiber, its fiber chi in the prior art
Very little longer, the role of fiber is to increase the intensity and toughness of bone cement, such as citation [8], citation [9].
But in such technical scheme, fiber can not play the inducing function of the growth to new bone, and be merely possible to common
Enhancing component and use.
Citation：
[1]K.E.Kadler,D.F.Holmes,J.A.Trotter,J.A.Chapman.Collagen fibril
formation.Biochem J.1996；316:1-11.
[2]E.Cukierman,R.Pankov,D.R.Stevens,K.M.Yamada.Taking cell-matrix
adhesions to the third dimension.Science.2001；294(5547):1708-1712.
[3]K.M.Woo,V.J.Chen,P.Ma.Nano-fibrous scaffolding architecture
selectively enhances protein adsorption contributing to cell attachment.J
Biomed Mater Res Part A.2003；67(2):531-537.
[4]H.Yoshimoto,Y.M.Shin,H.Terai,J.P.Vacanti.A biodegradable nanofiber
scaffold by electrospinning and its potential for bone tissue
engineering.Biomaterials.2003；24:2077-2082.
[5]S.-H.Jegal,J.-H.Park,J.-H.Kim,T.-H.Kim,U.S.Shin,T.-I.Kim and H.-
W.Kim.Functional composite nanofibers of poly(lactide-co-caprolactone)
containing gelatin-apatite bone mimetic precipitate for bone
regeneration.Acta Biomaterialia.2011；7:1609-1617.
[6]K.M.Woo,V.J.Chen,H.-M.Jung,T.-I.Kim,H.-I.Shin,J.-H.Baek,H.-M.Ryoo,
and P.X.Ma.Comparative evaluation of nanofibrous scaffolding for bone
regeneration in critical-size calvarial defects.Tissue Eng Part A.2009；15(8):
2155-2162.
[7] Chinese patent CN200810163691.1
[8] Chinese patent CN103877621B
[9] Chinese patent CN103668940B
The content of the invention
Problems to be solved by the invention
The problem of lacking osteoinductive for current artificial filling material of bone, and fibre structure filling material of bone do not possess
Macroscopic three dimensional structure, do not possess mechanical support, or internal fiber skewness, it is impossible to meet Cranial defect position to material property
Demand the problem of, present invention firstly provides a kind of three-dimensional porous composite of the fiber base for Bone Defect Repari, it has grand
Three-dimensional fibrous structure is seen, material microstructure in itself there is good osteoinductive and fiber to be evenly distributed in the structure, possess
The characteristic of cancellous bone mechanical property can be reached, the effect of osteoacusis, mechanical support is provided simultaneously with.And then, the present invention is also provided
A kind of method for preparing the three-dimensional porous composite of above-mentioned fiber base.In addition, being based on above-mentioned fibre present invention provides one kind
The products formed of the three-dimensional porous composite of Wiki, especially artificial bone fill product, such as three-dimensional porous rack.
The solution used to solve the problem
Present invention firstly provides a kind of three-dimensional porous composite of the fiber base for Bone Defect Repari, the fiber base is three-dimensional more
Hole composite material composition includes micro nanometer fiber powder and adhesive,
The particle diameter of the micro nanometer fiber powder is 10-500 μm, constitute the micro nanometer fiber powder fiber it is a diameter of
0.1-100μm；
The adhesive include it is biodegradable and can self-curing inorganic matter component；
The three-dimensional porous composite of fiber base by the way that micro nanometer fiber powder is dispersed in the adhesive, and
Obtained by hole creating technology；
In terms of the gross mass of the three-dimensional porous composite of the fiber base, the content of the micro nanometer fiber powder is 5-50 matter
Measure %, preferably 20-50 mass %.
The three-dimensional porous composite of fiber base in accordance with the above, its porosity is 30-85%, preferably 60-85%；It is anti-
Compressive Strength is 1-15MPa, preferably 2-10MPa.
The three-dimensional porous composite of fiber base in accordance with the above, it is fine that the micro nanometer fiber powder is derived from synthesis macromolecule
One or more in dimension, natural polymer subbundle, inorfil.
The three-dimensional porous composite of fiber base in accordance with the above, the micro nanometer fiber powder is handled by mineralising, excellent
Selection of land, the mineralising is processed as carrying out fiber surface the processing of calcium phosphorus precipitation.
The three-dimensional porous composite of fiber base in accordance with the above, in the mineralising before processing, first to described micro-nano
Fiber powder is pre-processed, and the pretreatment is plasma pretreatment, alkali process pretreatment, chemical oxidation pre-treatment, chemistry
One or both of grafting pretreatment combination of the above.
Inorganic matter component in the three-dimensional porous composite of fiber base in accordance with the above, the adhesive is selected from：Can
Self-curable calcium phosphate system, can self-curing calcium silicates system, can self-curing calcium sulfate system, can be in self-curing magnesium phosphate system
It is one or more.
Also include additive component, institute in the three-dimensional porous composite of fiber base in accordance with the above, the adhesive
State additive component be selected from gelatin, collagen, hyaluronate, alginate, citrate, starch, natural plant gum, chitosan and its
One or more in derivative, cellulose and its derivates, polyvinylpyrrolidone, it is preferable that the additive component
Mass fraction is the 0.1-10 mass % of solid-phase component in adhesive.
In addition, present invention also offers a kind of preparation method of the three-dimensional porous composite of the fiber base for Bone Defect Repari,
Methods described comprises the following steps：
Step 1：A diameter of 0.1-100 μm of fiber is prepared by electrostatic spinning, then using crushing technology by the fibre
Dimension is crushed, and obtains the micro nanometer fiber powder that particle diameter is 10-500 μm；
Step 2：The step of micro nanometer fiber powder and adhesive are uniformly mixed to get mixed system；
Step 3：The mixed system is handled through pore-forming technique to obtain the three-dimensional porous composite of the fiber base
Step；
The adhesive include it is biodegradable and can self-curing inorganic matter component；It is three-dimensional porous multiple with the fiber base
The gross mass meter of condensation material, the content of the micro nanometer fiber powder is 5-50 mass %.
Preparation method more than, the porosity of the three-dimensional porous composite of fiber base is 30-85%, pressure resistance
Spend for 1-15MPa.
According to more than preparation method, described in step 1 crush include manually or electrically cutting type crushing technology, manually or
Technical battery more than one or both of electric grinding crushing technology, electronic ball mill grinding technology uses, and all crushing technologies are excellent
Choosing is carried out under freezing conditions.
Micro nanometer fiber powder in preparation method in accordance with the above, the step 1 is derived from synthesis macromolecular fibre, day
One or more in right macromolecular fibre, inorfil.
Preparation method in accordance with the above, the micro nanometer fiber powder is first passed through before being mixed with the adhesive
Mineralising processing.
Preparation method in accordance with the above, the mineralising processing comprises the following steps：By micro nanometer fiber powder leaching
Steep in mineralized liquid, carry out calcium phosphorus precipitation in fiber surface, the mineralized liquid is preferably simulated body fluid.
Inorganic matter component in preparation method in accordance with the above, step 2 adhesive is selected from：Can self-curing phosphoric acid
Calcium system, can self-curing calcium silicates system, can self-curing calcium sulfate system, can be in self-curing magnesium phosphate system one kind or many
Kind.
Also include additive component, the additive group in preparation method in accordance with the above, step 2 adhesive
It is selected from gelatin, collagen, hyaluronate, alginate, citrate, starch, natural plant gum, Chitosan-phospholipid complex, fibre
One or more in dimension element and its derivative, polyvinylpyrrolidone, it is preferable that the mass fraction of the additive component is
The 0.1-10 mass % of solid-phase component in adhesive.
Also include liquid phase ingredient, the liquid phase ingredient choosing in preparation method in accordance with the above, step 2 adhesive
One or more from deionized water, physiological saline, blood, phosphate solution, it is preferable that the liquid phase ingredient and adhesive
The mixed proportion of middle solid-phase component is 0.3-1.5mL/g.
Pore-forming technique in preparation method in accordance with the above, the step 3 is selected from：3D printing pore-forming technique, orientation
One kind in ice crystal-freeze-drying pore-forming technique, particle leaching pore-forming technique, foaming pore-forming technique.
Further, the present invention also provides a kind of products formed, and the products formed is to be used for bone according to any of the above
The three-dimensional porous composite of fiber base of reparation or the fiber base for Bone Defect Repari in accordance with the above are three-dimensional porous compound
The three-dimensional porous composite of fiber base that the preparation method of material is obtained is obtained through shaping.
Products formed in accordance with the above, the products formed is artificial bone filled articles, preferably three-dimensional connected porous branch
Frame.
The effect of invention
The present invention constructs a kind of three-dimensional porous composite of fiber base for human body Bone Defect Repari, especially a kind of three-dimensional
Porous support, compared with existing artificial bone, possesses following advantage：
(1) presence of fiber topological structure causes support to have the effect of significant induced osteogenesis；
(2) compared with existing membrane-like fibrous framework, three-dimensional fiber based structures support can better meet Cranial defect portion
The filling demand of position, and better mechanical property can be provided；
(3) the osteogenic induction performance that material microstructure has in itself, the material phase with addition growth factor (such as BMP)
Than with higher security and lower cost；
(4) technical scheme, preparation method is simple, shaping is easy, is adapted to the production of industrial-scale.
Brief description of the drawings
Histotomy HE colored graphs after bone repairing support animals of the Fig. 1 prepared by embodiment 1 is implanted into 4 weeks；
Histotomy HE colored graphs after bone repairing support animals of the Fig. 2 prepared by comparative example 1 is implanted into 4 weeks；
Histotomy HE colored graphs after bone repairing support animals of the Fig. 3 prepared by embodiment 2 is implanted into 4 weeks；
Histotomy HE colored graphs after bone repairing support animals of the Fig. 4 prepared by comparative example 2 is implanted into 4 weeks.
Embodiment
Hereinafter, the various embodiments to the present invention are described in detail.
First embodiment
There is provided a kind of three-dimensional porous composite of the fiber base for Bone Defect Repari in the first embodiment of the present invention.
The three-dimensional porous composite composition of fiber base includes micro nanometer fiber powder and adhesive, by micro nanometer fiber powder
Uniformly mix, and prepared by pore-forming technique with adhesive.Specifically：
<Fiber>
Micro nanometer fiber powder in the present invention, refer to crush fibrous raw material and with or without surface mineralising at
Obtained from reason.
Fibrous raw material in the present invention can be various conventional fibrous raw materials in this area.Such as can be selected from synthesis macromolecule
A kind of fiber or two or more composite fibre in fiber, natural polymer subbundle, inorfil.
The synthesis macromolecular fibre of the present invention can be selected from the good fiber of artificial synthesized degradable and biocompatibility,
PLA, polyglycolic acid, polycaprolactone, polymeric polyglycolide-polylactide, makrolon, polyaminoacid, poly- hydroxyl can be such as derived from
Fiber in base fatty acid ester obtained by one or more, or the copolymer from plurality of raw materials monomer in these polymer
Resulting fiber.
Natural polymer subbundle in the present invention can be selected from gelatin, collagen, hyaluronic acid, alginic acid, fibroin albumen, fibre
The fiber prepared by one or more raw materials in fibrillarin, Chitosan-phospholipid complex, cellulose and its derivates.
In addition, the inorfil can be selected from biological glass fiber, carborundum (SiC) fiber, silica (SiO2)
Mixture more than one or both of fiber, zinc oxide (ZnO) fiber, carbon nano-fiber.
Fiber more than of the invention has good degradability or biocompatibility, as human body tissue repair material
When material, especially bone renovating material, it can preferably promote the healing or reparation of tissue, while it is bad to there will not be generation
The worry of effect.
By the way that the raw material of above-mentioned fiber is obtained into continuous fiber through electrostatic spinning in the present invention.The principle of electrostatic spinning is
During electrostatic spinning, high voltage is applied to polymeric liquid, electric charge is introduced liquid.When the accumulation in liquid to one
When quantitative, liquid can overcome surface tension formation liquid to penetrate in shower nozzle formation taylor cone in the presence of extra electric field power
Stream, then jet is under the collective effect of electrostatic repulsion, Coulomb force (Coulomb) and surface tension, and polymer jet edge is not advised
Then spiral trajectory is moved.Jet is drafted in very short time, and as solvent volatilization or heat scatter and disappear, polymer jet is consolidated
Change forms micrometer/nanometer fiber.During electrostatic spinning, many parameters can produce influence to final electrospun fibers, pass through
Control process parameter, can prepare the micrometer/nanometer fiber of different sizes, form and different structure.
In the present invention, as long as disclosure satisfy that the requirement that fibre diameter is made, the mode just for electrostatic spinning is not special
Requirement, can be electrostatic spinning mode commonly used in the art, specifically, by reaction raw materials or macromolecule material in the present invention
Material is dissolved in suitable solvent, is prepared into certain density solution.Material solution spinning is turned into straight using electrostatic spinning technique
The fiber in 0.1-100 μm of footpath, the form of fiber can be thread, cotton-shaped or membrane-like fiber aggregate.
<Micro nanometer fiber powder>
In the present invention, the particle diameter of described micro nanometer fiber powder is 10-500 μm, constitutes the fibre of the micro nanometer fiber powder
A diameter of 0.1-100 μm of dimension.Therefore, the micro-nano fiber powder that can be understood as here is on particle diameter (length or granularity) direction
Size with micron level, diametrically has nanometer to the size of micron in (section) of fiber.
After the aggregation of fiber or fiber is obtained by electrostatic spinning process, these are passed through drying process by the present invention
Fiber or the aggregation of fiber proceed pulverization process to obtain fiber powder.In the present invention, as long as disclosure satisfy that acquisition originally
The particle diameter of the micro nanometer fiber powder of invention, to the pulverization process available for the present invention, just there is no particular limitation, i.e. as long as can
Satisfactory length or grain are arrived into thread, the cotton-shaped or membrane-like fiber aggregate processing of long fibre, long-fiber bundle or more
Degree.In the present invention, available crushing technology is included：Manually or electrically cutting type crushing technology, manually or electrically grounds travel
Technology combination more than one or both of broken technology, electronic ball mill grinding technology, all crushing technologies are preferably in freezing bar
Crushed under part.
It can be 10-500 μm by the particle diameter (length or granularity) of micro nanometer fiber powder obtained from pulverization process.Typically
For, in above-mentioned illustrated use electrostatic spinning process, obtained fiber aggregate can be the situation of tunica fibrosa etc..Cause
This, can also have bonding situation (such as fiber of multiple fibers more than single in the fiber powder obtained after being crushed
Piece or nodular fibrous group), described as the particle diameter of fiber powder after crushing, therefore be not limited to tiny single fiber particle
Length.It is self-evident, the particle diameter of above-mentioned micro nanometer fiber powder in the present invention, it should be understood that independent fiber grain (can
If thinking single fiber or the aggregation of dry fibers) full-size.For example, when the fiber powder is single
During fiber, the particle diameter refers to the length of single fiber；When the fiber powder is fiber sheet, the particle diameter refers to fibre plate most
Large scale；When the fiber powder is that nodular fibrous is rolled into a ball, the particle diameter is the diameter of coma.
Although in addition, fiber aggregate or fibre bundle that prior art is also related to obtain electrostatic spinning sheared with
Obtain the record of chopped strand, but the general scope at several millimeters or more than ten millimeters of length of the chopped strand obtained by it with
It is interior.And according to the viewpoint of the present invention, it is size-reduced in the present invention to handle the obtained length of micro nanometer fiber powder or granularity is smaller, because
This, it is follow-up by surface it is modified mix with adhesive cohere when, be more easily dispersed in adhesive,
Aggregation or distribution gradient problem without fiber.And the fiber topological structure formed by the fiber powder of such size
In the presence of so that support has the effect of significant induced osteogenesis.
<The surface treatment of micro nanometer fiber powder>
In a preferred embodiment of the present invention, above-mentioned resulting micro nanometer fiber powder can be carried out at the mineralising of surface
Reason.
For the surface mineralising processing of fiber, surface mineralising processing directly can be carried out to fiber, it is preferred that the present invention is micro-
Nanofiber powder, which carries out surface mineralising before processing, first to be pre-processed to these fiber powders, and such as using plasma is located in advance
The preprocess methods such as reason, alkali process pretreatment, chemical oxidation pre-treatment and chemical graft pretreatment.According to the sight of the present invention
Point, such pretreatment can assign that fiber surface is preferably reactive, be conducive to follow-up surface mineralising processing.
After advance surface preparation, and then surface mineralising processing can be carried out to micro nanometer fiber powder.For fiber
The mineralising processing on surface refers to the deposition that calcium and phosphorus are carried out in fiber surface.In general, deposition side used in the art
Formula exists a variety of, e.g., the inorganic matter containing calcium and phosphorus can be directly added into the electrostatic spinning stage in electrostatic spinning liquid, so
The fiber that electrostatic spinning is surface-treated is carried out afterwards.Further, it is also possible to pass through electrojet method, alternating mineralising method, electrodeposition process
With the method such as simulated body fluid mineralising method, by the inorganic deposition containing calcium and phosphorus in fiber surface.The fiber used in the present invention
Mineralization process in the method that surface is modified refers to after the micro nanometer fiber powder that crushing is obtained is soaked in mineralized liquid, in fiber
Surface carries out the process of calcium phosphorus precipitation.The mineralized liquid can realize the solution of calcium phosphorus precipitation comprising conventional in material surface, preferably
Simulated body fluid.
The simulated body fluid, ion concentration contained therein is close with ion concentration contained in serum.At present according to institute
How much divisions containing ion concentration, conventional simulated body fluid has three kinds, one times of simulated body fluid (SBF), five times of simulated body fluids
(5SBF) and ten times of simulated body fluids (10SBF) etc..If contained ion concentration is relatively low in SBF, it is possible to which it is effectively heavy to cause
Time required for product is longer, therefore, and five times of simulated body fluids (5SBF) and ten times of simulated body fluids are preferably used in the present invention
(10SBF) etc..Temperature during for mineralising, there is no particular limitation, can use mineralising temperature conventional in the art, such as protects
Hold under conditions of 37 DEG C of constant temperature.
In addition, for the mineralising time, it is different depending on the composition of different mineralized liquids, for example can be a few minutes to several days.
In the present invention, in the case of using simulated body fluid, the mineralising time is -5 days 2 hours, preferably 1-3 days.
For the micro nanometer fiber powder after surface-modified, before being continuing with, generally go through and the mode such as dry and received
Collection is standby, typically can be by way of freeze-drying, and such drying means is conducive to eliminating micro nanometer fiber powder again
The worry of aggregation, is conducive to being uniformly dispersed in the adhesive.
In above the preferred embodiment of the present invention, handled through mineralising and carry out calcium phosphorus precipitation in material surface, so that
Must be used for the material of skeletonization have more preferable cellular affinity or with the more preferable connectivity of surrounding inorganic class material.The present invention
Mineralising step progress so that fiber powder can with surrounding inorganic class adhesive formation be connected chemically so that beneficial to improve
The overall mechanical property of fibrous framework.In addition, although in some existing researchs, for example, fibre has been prepared by electro-spinning process
Film is tieed up, then mineralising is carried out on tunica fibrosa surface, to reach the purpose of bionic extracellular matrix.It should be noted, however, that adopting
Such method is used, mineralising synthos can only be unable to reach completely in membrane surface formation crystal cluster, membrane-like material
The calcium microcosmic salt of deposition is not present in (each section or tangent plane) on even mineralising, internal fiber.The present invention is obtained using crushing technology
The fiber powder of yardstick very little, is carried out after mineralising, can uniformly be formed one layer of apatite layer on each surface of fiber, is more nearly bionical
The purpose of mineralising epimatrix.
For above-mentioned surface treated or not surface treated micro nanometer fiber powder consumption be 5-50 mass %, with institute
State the gross mass meter of the three-dimensional porous composite of fiber base.
<Adhesive>
In the present invention, adhesive is uniformly scattered in by above-mentioned process or without the micro nanometer fiber powder of surface treatment
In.In the preferred embodiment of the present invention, adhesive includes solid-phase component and liquid phase ingredient.
The solid-phase component can be with it is biodegradable and can self-curing performance inorganic matter, such as can self-curing
Calcium Phosphate System, can self-curing calcium silicates system, can self-curing calcium sulfate system, can be in self-curing magnesium phosphate system one kind or
Two or more mixed systems.
Specifically can the main solid-phase component of self-curable calcium phosphate system include：Hydroxyapatite, type alpha tricalcium phosphate, β-phosphorus
Mixture more than one or both of sour DFP, tetracalcium phosphate, calcium dihydrogen phosphate, calcium phosphate dibasic dihydrate.
Can self-curing calcium silicate bodies owner want solid-phase component to include：One kind in monocalcium silicate, dicalcium silicate, tricalcium silicate
Or two or more mixtures.
Can the main solid-phase component of self-curing calcium sulfate system include：Dead plaster, half-H 2 O calcium sulphate, calcium sulphate dihydrate
One or both of more than mixture.
Can the main solid-phase component of self-curing magnesium phosphate system include：Material containing magnesium and superphosphate.Material containing magnesium is oxygen
Change mixture more than one or both of magnesium, magnesium phosphate, superphosphate is ammonium dihydrogen phosphate, potassium dihydrogen phosphate, phosphoric acid
Mixture more than one or both of sodium dihydrogen.
According to the present invention viewpoint, in the adhesive using the solid-phase component of composition described above, it is possible to use its own from
Curing performance is solidified, so as to avoid the use of additional curing agent, particular avoid some has toxicity to organism
Additional curing agent or crosslinker component use.
Liquid phase ingredient is used in adhesive of the present invention, it can be by the solid-phase component of adhesive and the modified fibre of addition
Carry out sufficiently uniform mixing.Such liquid phase ingredient can select the liquid parts blindly dated with organism, can such as be selected from and go
Mixed solution more than one or both of ionized water, physiological saline, blood, phosphoric acid salt solution.
For the consumption of liquid phase ingredient, as long as solid-phase component and micro nanometer fiber powder can be made to be sufficiently mixed uniformly i.e.
Can.Typically, the ratio of the consumption of liquid phase ingredient and solid-phase component is 0.3-1.5mL/g.
In adhesive, in addition to above-mentioned mentioned liquid phase ingredient and solid-phase component, it is preferable that also containing gelatin, glue
Original, hyaluronate, alginate, citrate, starch, natural plant gum, Chitosan-phospholipid complex, cellulose and its derivative
One or both of thing, polyvinylpyrrolidone thing mixed above are used as outer doping.It is above-mentioned according to the viewpoint of the present invention
The use of additive can further improve final composite porous bioaffinity.Specifically, gelatin etc. is added
Agent composition is water-soluble substances, and solution has certain viscosity, in addition that can be in self-curing inorganic binder, can be improved glutinous
The overall cohesive of agent is tied, makes adhesive and the mixed slurry of micro nanometer fiber powder that there is more preferable processability, carries simultaneously
High interface bond strength between micro nanometer fiber powder and adhesive, and further improve the biological affine of bone renovating material
Property.
<Cohere and pore-forming>
In the present invention, the process of cohering refers to the process of micro nanometer fiber powder is uniformly mixed and solidified with adhesive.Typical case
, the solid-phase component of micro nanometer fiber powder and adhesive is first mixed into uniform mixed powder in the present invention, added afterwards glutinous
The liquid phase ingredient of knot agent reconciles into uniform slurry, can subsequently be cohered by self-curing course of reaction.
The base for the slurry that the pore-forming technique of the present invention can be formed in above-described adhesive and micro nanometer fiber powder
Follow-up pore processing is carried out on plinth, it is preferred that carry out in the case where not being additionally added foaming agent or pore-foaming agent.
The pore-forming technique that the present invention can be used includes：3D printing hole creating technology, orientation ice crystal-freeze-drying pore-forming skill
One kind in art, particle leaching hole creating technology, foaming hole creating technology.
<The three-dimensional porous composite of fiber base>
Above-mentioned pore-forming technique can be carried out in suitable container, for example, it is preferable to can be selected according to required shape
Select appropriate pore-forming container, i.e. moulding process is carried out while pore-forming technique.In particular, can in using 3D printing technique
With the more convenient three-dimensional porous composite of fiber base for directly printing required shape.
The technique of subsequent treatment is not fully identical for different technique, in principle, article shaped derived above
Can occur self-curing in the presence of self-curing inorganic matter in the adhesive, the temperature of solidification can be normal temperature or in heating
Under the conditions of carry out.The time of solidification, there is no particular limitation, can be a few houres or several days.In addition it is also possible to enter to article shaped
Row solidify afterwards handle further to improve the mechanical property of article shaped.
The porosity of the three-dimensional porous composite of final fiber base obtained by the present invention is 30-85%, preferably 60-
85%.When porosity is too small, then cause the composite after shaping when as Bone Defect Repari product, specific surface area is reduced, i.e. subtracted
Lack the contact area with tissue, cause desired bone growth inducing effect insufficient；When porosity is excessive, then having can
The intensity deficiency of composite in itself can be caused, the uniformity of structure is also insufficient.
In addition, the three-dimensional porous composite compression strength of fiber base is 1-15MPa, preferably 2-10MPa.The three of the present invention
The application mode for tieing up porous bone repairing support is the filling reparation of Cranial defect, i.e. applied to cancellous bone defect position, above-mentioned hair
The compression strength scope of the bright three-dimensional porous composite of middle fiber base matches with human body cancellous bone compression strength.
After the fiber base three-dimensional porous composite shaping of the present invention can for cylindrical, spherical, square, wedge-shaped, bar shaped or
Personalized irregular shape.
The detection method of the porosity of the present invention can be specifically as follows according to the method generally used in the prior art：
The porosity of testing sample is calculated according to the following equation,
In formula：M is sample mass (g)；
V is volume of sample (cm3)；
ρ s are the skeletal density (g/cm of sample material3) or be real density.
Described compression strength is measured by the following method.
Described compression strength is completed by the mechanics machine generally used in the prior art.I.e. by sample preparation
Into cylindric (such as diameter 6mm, high 10mm) of certain size, it is positioned between two platens up and down of mechanics machine, platen
At the uniform velocity pressurization is carried out to sample until sample fragmentation, the process can obtain the numerical value for the maximum compression strength that sample can be born.
Second embodiment
Second embodiment of the present invention provides a kind of prepare for the three-dimensional porous composite of the fiber base of Bone Defect Repari
Preparation method.Methods described comprises the following steps：
Step 1：A diameter of 0.1-100 μm of fiber is prepared by electrostatic spinning, then using crushing technology by the fibre
Dimension is crushed, and obtains the micro nanometer fiber powder that particle diameter is 10-500 μm；
Step 2：The step of micro nanometer fiber powder and adhesive are uniformly mixed to get mixed system；
Step 3：The mixed system is handled through pore-forming technique to obtain the three-dimensional porous composite of the fiber base
Step；
The adhesive include it is biodegradable and can self-curing inorganic matter component；With described composite porous total
Quality meter, the content of the micro nanometer fiber powder is 5-50 mass %.
Typically, preparation method of the invention can be carried out in accordance with the following steps：
Prepare the raw material for forming fiber in advance, such as reaction raw materials or high polymer material be dissolved in suitable solvent,
It is prepared into certain density solution.The solution is preferred to be formed in the presence of shearing force, can such as use conventional stirring
Equipment, more typically such as uses magnetic stirring equipment.
The temperature for forming above-mentioned solution is preferably 20-40 DEG C, is not had for forming the specific concentration of solvent species of solution
It is special to limit, as long as it disclosure satisfy that the requirement of follow-up electrostatic spinning process.Typically, solvent can use water, hydrocarbon
Series solvent, halogenated hydrocarbon solvent, amide solvent, ether solvent, esters solvent or containing fluorous solvent etc..Preferably use water, chloroform, two
NMF or containing fluorous solvent.
Material solution is spinned by thread, the cotton-shaped or diaphragm as 0.1-100 μm of fibre diameter using electrostatic spinning technique
Shape fiber aggregate.Can be by adjusting spinning parameter (such as feed rate, application voltage and reception distance during electrostatic spinning
Deng), solution parameter (viscosity and surface tension etc.), receive instrument and spinning environment etc. prepare needed for fiber or fibril aggregation
Body.
Further, use crushing technology that the dried fiber aggregate is ground into particle diameter length micro- for 10-500 μm
Nanofiber powder.In the present invention, available crushing technology is included：Manually or electrically cutting type crushing technology, manually or electrically grind
Technical battery more than one or both of crushing technology, electronic ball mill grinding technology is ground to use.In addition, for these grinding modes
Specific equipment there is no particular limitation, as long as the fiber powder of desired size can be obtained.Further, it is all to crush
Preferably crushed under freezing conditions in technology, on the one hand, this is in order at the consideration of production efficiency, on the other hand, in the bar of freezing
Carry out crushing under part and can avoid the undesirable shadow produced when shearing to corpus fibrosum due to caused by the toughness of polymer
Ring.
In the preferred embodiment of the present invention, surface modification treatment can be carried out to the micro nanometer fiber powder after crushing,
Become the fiber powder with surface mineralized layer of class ECM structures.
For the surface mineralising processing of fiber powder, surface mineralising processing directly can be carried out to fiber, it is preferred that the present invention
Surface mineralising before processing is carried out to micro nanometer fiber powder first to pre-process these fibers, such as using plasma pretreatment,
The preprocess methods such as alkali process pretreatment, chemical oxidation pre-treatment and chemical graft pretreatment.According to the present invention viewpoint, this
The pretreatment of sample can assign that fiber surface is preferably reactive, be conducive to follow-up surface mineralising processing.
Mineralization process in the method for the fiber surface modification used in the present invention refers to fiber being soaked in mineralized liquid
Surface carries out the process of calcium phosphorus precipitation afterwards.The mineralized liquid can realize all molten of calcium phosphorus precipitation comprising conventional in material surface
Liquid, preferably simulated body fluid.Further, preferably 5 times or more than 10 times of simulated body fluid.
In the present invention, the process that micro nanometer fiber powder is uniformly mixed and solidified with adhesive during cohering.Typically,
The solid-phase component of micro nanometer fiber powder and adhesive is first mixed into uniform mixed powder in the present invention, adhesive is added afterwards
Liquid phase ingredient reconcile into uniform slurry, can subsequently be cohered by self-curing course of reaction.The group of the adhesive
Into may be referred to the composition of the adhesive disclosed in first embodiment.
The base for the slurry that the pore-forming technique of the present invention can be formed in above-described adhesive and micro nanometer fiber powder
Follow-up pore processing is carried out on plinth, it is preferred that carry out in the case where not being additionally added foaming agent or pore-foaming agent.
The pore-forming technique that the present invention can be used includes：3D printing hole creating technology, orientation ice crystal-freeze-drying pore-forming skill
One kind in art, particle leaching hole creating technology, foaming hole creating technology.
The place that the techniques such as mixing, pore-forming for above-described micro nanometer fiber powder and adhesive are carried out, according to not
With preparation technology can be different, for example, in 3D printing hole creating technology, the step of the mixing of micro nanometer fiber powder and adhesive
It can be carried out in the raw material storage device of printing device, or the storage that advance progress mixing is then injected into printer apparatus is set
In standby.And then, according to different design needs, required shape is printed, meanwhile, pore-forming work can also be completed in the process
Skill.
In orientation ice crystal-freeze-drying hole creating technology, the mixed system of micro nanometer fiber powder and adhesive is injected and closed
In suitable grinding tool, the shape of grinding tool is selected according to needed for, is not limited specifically in principle.When system mixed above is full of
After grinding tool, it is dried under cold conditions, and pore-forming process is completed in this process.
In above procedure, use it is biodegradable can self-curing inorganic matter for adhesive, by a certain amount of (ore deposit
Change) micro nanometer fiber powder is glued together, and mass ratio shared by (mineralising) micro nanometer fiber powder is 5-50 mass %, with reference to pore-forming work
Skill, is more conducive to become the dispersed product of internal fiber.
3rd embodiment
There is provided a kind of products formed in third embodiment of the present invention, the formed products is according to first embodiment institutes
The three-dimensional porous composite of the fiber base for Bone Defect Repari stated is used for Bone Defect Repari according to second embodiment
The three-dimensional porous composite of fiber base that the preparation method of the three-dimensional porous composite of fiber base is obtained, is obtained through shaping.
The products formed of the present invention, can be typically medical bio repair materials, can be human body Bone Defect Repari more specifically
Material.
By different moulding process, any required product, further, the 3rd embodiment party of the invention can be obtained
A kind of three-dimensional porous rack for human body Bone Defect Repari is provided in formula.
In such products formed, the presence of nanofibrous structures causes support to have the effect of significant induced osteogenesis；Especially
It is that three-dimensional fibrous structure porous support can better meet filling out for Cranial defect position compared with existing membrane-like fibrous framework
Demand is filled, and better mechanical property can be provided.In addition, the osteogenic induction performance that material microstructure has in itself,
Compared with the material of addition growth factor (such as BMP), with higher security and lower cost.
According to the constructed support with macroscopic fibres base three-dimensional porous structure of the present invention, its porosity is 30-85%, excellent
Elect 60-85% as, compression strength is 1-15MPa, preferably 2-10MPa.Such characteristic is further enhanced obtained by the present invention
The technique effect arrived, i.e. possess the characteristic that can reach cancellous bone mechanical property, be provided simultaneously with excellent osteoacusis, self-bone grafting,
The effect of mechanical support.
Embodiment
Hereinafter, the present invention will be explained in detail and will be enumerated by specific embodiment, it should be noted that the present invention
It is not limited in following embodiment, meanwhile, following embodiment is also not construed as that the present invention can be made that
Extra limitation.
Embodiment 1
The present embodiment is prepared for modified polymeric polyglycolide-polylactide fiber first, then uses and contains carboxymethyl cellulose
Can self-curing type alpha tricalcium phosphate and calcium carbonate system as inorganic binder, prepare three-dimensional porous rack, wherein carboxylic first
The mass fraction of base cellulose is 0.5% of solid-phase component in adhesive.Specific implementation step is as follows：
(1) 1g polymeric polyglycolide-polylactides (5 are weighed:5), in the presence of 37 DEG C of magnetic agitations, it is dissolved in 10mL chloroforms.
The solution is added in the syringe of electrostatic spinning apparatus, the speed of regulation micro-injection pump, high pressure generator voltage, roller
Distance is received, the tunica fibrosa that fibre diameter is 50-100 μm is prepared.
(2) above-mentioned tunica fibrosa is removed, the tunica fibrosa is ground into granularity using mortar formula beveller under freezing conditions is
300-500 μm of micron order fiber powder.The fiber powder is collected, alkali process surface treatment (use quality is carried out to it successively
Fraction is 5% NaOH solution) 10min, deionized water wash 3 times, surface mineralising 3 days in 1 × simulated body fluid (SBF), then
Modified fiber powder is freeze-dried, collected standby.
(3) the lyophilized modified polymeric polyglycolide-polylactide fiber powders of 0.3g, 0.6g type alpha tricalcium phosphates, 0.1g are weighed
Calcium carbonate, 0.0035g carboxymethyl celluloses, are well mixed, obtain solid phase mixing powder.Using deionized water as liquid phase into
Point, the ratio of liquid phase ingredient and solid phase mixing powder for addition 1mL in 1mL/g, i.e. 1g solid phase mixing powder liquid phase ingredient.
Two-phase is reconciled into after uniform slurry, and slurry is poured into cylindrical die, using orientation ice crystal-freeze-drying hole creating technology
Prepare the bone repairing support of cylinder.
Comparative example 1
Using with step (3) identical pore-forming technique in embodiment 1, it is fine using the carboxymethyl containing mass fraction as 0.5%
Dimension element can self-curable calcium phosphate system be matrix, prepare porous support.
1 two kinds of supports of embodiment 1 and comparative example are implanted into new zealand white rabbit lateral side of femur anklebone defect respectively, planted
Enter to carry out histotomy HE dyeing observation after 4 weeks (as shown in drawings), as a result show, there is more new in the support of embodiment 1
It is fiberfaced in ostosis (figure one), and the new bone of generation to exist.And New Bone Quantity is obviously reduced in the support of comparative example 1
(figure two) illustrates that the fibre structure in support plays the role of preferably to induce new bone formation.
Embodiment 2
The present embodiment is prepared for modified carbon nano-fiber first, then using containing sodium alginate can self-curing silicon
Sour DFP system prepares three-dimensional porous rack as inorganic binder, during the mass fraction of wherein sodium alginate is adhesive
The 2% of solid-phase component.Specific implementation step is as follows：
(1) 2g polyacrylonitrile is weighed, is dissolved in 10mL dimethylformamides.The solution is added to electrostatic spinning apparatus
In syringe, speed, high pressure generator voltage, the roller reception distance of micro-injection pump are adjusted, preparing fibre diameter is
200-500nm nanofiber precursor.The nanofiber precursor is collected, under nitrogen protection atmosphere, by it at 800-900 DEG C
Pyrolysis is performed, its carbonization is obtained carbon nano-fiber silk.
(2) hand-ground method is used, carbon nano-fiber silk is ground to form into the fiber powder that granularity is 10-100 μm.Receive
Collect the fiber powder, by the fiber powder in 5 × simulated body fluid (SBF) surface mineralising 3 days, then to modified fiber powder
Body is freeze-dried, and is collected standby.
(3) the lyophilized modified carbon nano-fiber powders of 0.5g, 0.5g tricalcium silicates powder, 0.01g alginic acids are weighed
Sodium powder body, is well mixed, obtains solid phase mixing powder.Liquid phase ingredient, liquid phase ingredient and solid phase mixing are used as using physiological saline
The ratio of powder for 0.8mL/g, i.e. 1g solid phase mixing powder in add 0.8mL liquid phase ingredient.Two-phase is reconciled into uniformly
After slurry, square bone repairing support is prepared using 3D printing technique.
Comparative example 2
Using with step (3) identical pore-forming technique in embodiment 2, using containing mass fraction as 2% sodium alginate
Can self-curing calcium silicates system be matrix, prepare porous support.
2 two kinds of supports of embodiment 2 and comparative example are implanted into new zealand white rabbit lateral side of femur anklebone defect respectively, planted
Enter to carry out histotomy HE dyeing observation after 4 weeks (as shown in drawings), as a result show, there are more new bones in the support of embodiment 2
Generate (figure three), and fiberfaced presence in the new bone of generation.And (figure is obviously reduced in New Bone Quantity in the support of comparative example 2
Four), illustrate that the fibre structure in support plays the role of preferably to induce new bone formation.
Embodiment 3：
The present embodiment is prepared for modified nano grade biological glass fibre first, using can consolidate certainly containing Sodium Hyaluronate
The dead plaster and half-H 2 O calcium sulphate system of change prepare three-dimensional porous rack, wherein hyaluronic acid as inorganic binder
The mass fraction of sodium is 1% of solid-phase component in adhesive.Specific implementation step is as follows：
(1) 0.1mL concentrated hydrochloric acids (12mol/L), 10mL tetraethyl orthosilicates, 1mL triethyl phosphates are measured respectively, are sequentially added
Into 5mL deionized waters, it is hydrolyzed in the presence of magnetic agitation.After the completion of hydrolysis, 6g calcium nitrate is added into solution, after
Continuous stirring is until being completely dissolved.Above-mentioned solution is aged 24h formation bio-vitric colloidal sols at room temperature.Configuration quality fraction is
The ethanol solution of 10% polyvinyl butyral resin, the solution is mixed in equal volume with bio-vitric colloidal sol, and is stirred to solution
It is transparent.
The solution is added in the syringe of electrostatic spinning apparatus, speed, the high pressure generator of micro-injection pump is adjusted
Voltage, roller receive distance, prepare the biological glass fiber precursor that fibre diameter is 100-200nm.Collect the biological glass
Glass fiber precursor, it is heat-treated at 600-650 DEG C, obtains biological glass fiber silk.
(2) hand-ground method is used, above-mentioned biological glass fiber silk is ground to form into the fiber powder that granularity is 10-200 μm
Body.
(3) the present embodiment prepares bone repairing support using the method for particle leaching.The lyophilized biological glass of 0.4g is weighed respectively
Glass fiber powder, 0.3g dead plasters powder, 0.3g half-H 2 O calcium sulphates powder, 0.006g Sodium Hyaluronate powders, 0.2g
Grain size is 100-300 μm of sucrose granules, is well mixed, obtains solid phase mixing powder.Using deionized water as liquid phase into
Point, the ratio of liquid phase ingredient and solid phase mixing powder for added in 0.6mL/g, i.e. 1g solid phase mixing powder 0.6mL liquid phases into
Point.Two-phase is reconciled into after uniform slurry, and slurry is filled into strip mould and voluntarily solidifies 2h.By the bar shaped sample after solidification
It is dipped into deionized water, deionized water is changed daily, is completely dissolved until sucrose granules, untill sample quality no longer mitigates.
It is final it is freeze-dried after obtain the bone repairing support of bar shaped.
Comparative example 3
Using with step (3) identical pore-forming technique in embodiment 3, using the Sodium Hyaluronate containing mass fraction as 1%
Dead plaster and half-H 2 O calcium sulphate system be matrix, prepare porous support.
3 two kinds of supports of embodiment 3 and comparative example are implanted into new zealand white rabbit lateral side of femur anklebone defect respectively, planted
Enter to carry out histotomy HE dyeing observations after 4 weeks.As a result show there are more New born formations in the support of embodiment 3, and generation
It is fiberfaced in new bone to exist.And New Bone Quantity is obviously reduced in the support of comparative example 3, illustrate support fibre structure have compared with
The effect of good induction new bone formation.
Embodiment 4：
The present embodiment is prepared for the composite fibre of modified PLA and gelatin first, using containing sodium citrate can from
The magnesia and sodium dihydrogen phosphate system of solidification prepares three-dimensional porous rack as inorganic binder, wherein sodium citrate
Mass fraction is 1% of solid-phase component in adhesive.Specific implementation step is as follows：
(1) 0.5g PLAs and 0.5g gelatin are weighed respectively, in the presence of 37 DEG C of magnetic agitations, are dissolved in 10mL hexafluoros different
In propyl alcohol.The solution is added in the syringe of electrostatic spinning apparatus, speed, the high pressure generator electricity of micro-injection pump is adjusted
Pressure, roller receive distance, prepare the tunica fibrosa that fibre diameter is 50-100 μm.
(2) above-mentioned tunica fibrosa is removed, the tunica fibrosa is ground into granularity using vibrations ball mill under freezing conditions is
300-500 μm of micron order fiber powder.The fiber powder is collected, corona treatment, 10 × analogue body are carried out to it successively
Surface mineralising 1 day, is then freeze-dried to modified fiber powder in liquid (SBF), collects standby.
(3) the present embodiment prepares bone repairing support using the method for gas foaming.Lyophilized modified of 0.2g is weighed respectively
Fiber powder, 0.4g magnesium oxide powders, 0.4g sodium dihydrogen phosphates powder, 0.008g sodium citrate powders, 0.5g sodium acid carbonates
Powder, is well mixed, obtains solid phase mixing powder.Liquid phase ingredient, liquid phase ingredient and solid phase mixing powder are used as using physiological saline
The ratio of body for 0.9mL/g, i.e. 1g solid phase mixing powder in add 0.9mL liquid phase ingredient.Two-phase reconciles into uniform slurry
After body, slurry is filled into cylindrical type mould and voluntarily solidifies 2h.Sodium dihydrogen phosphate and sodium acid carbonate in solidification process
Learn reaction generation CO2Gas, so as to form hole in support after hardening.The final bone that cylinder is obtained after 60 DEG C of drying
Recovery support.
Comparative example 4
Using with step (3) identical pore-forming technique in embodiment 4, using containing mass fraction as 1% sodium citrate
Can self-curing magnesia and sodium dihydrogen phosphate system be matrix, prepare porous support.
4 two kinds of supports of embodiment 4 and comparative example are implanted into new zealand white rabbit lateral side of femur anklebone defect respectively, planted
Enter to carry out histotomy HE dyeing observation after 4 weeks, as a result show, there are more New born formations in the support of embodiment 4, and generation
It is fiberfaced in new bone to exist.And New Bone Quantity is obviously reduced in the support of comparative example 4, illustrate support fibre structure have compared with
The effect of good induction new bone formation.
In addition, the compression strength and porosity test data of above example are as shown in table 1.
The performance parameter for the three-dimensional porous rack that the embodiment 1-4 of table 1. is prepared
| Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | |
| Compression strength (MPa) | 12±0.2 | 1.5±0.12 | 8±0.3 | 15±0.5 |
| Porosity (%) | 65-70 | 70-75 | 65-70 | 60-65 |
Industrial applicibility
Three-dimensional porous composite of the fiber base for Bone Defect Repari of the present invention and preparation method thereof can industrially enter
Row production, also, the three-dimensional porous composite of the fiber base for Bone Defect Repari of the present invention can be as three-dimensional porous rack
Use.
Claims (16)
1. the three-dimensional porous composite of a kind of fiber base for Bone Defect Repari, it is characterised in that the fiber base is three-dimensional porous multiple
Condensation material composition includes：Micro nanometer fiber powder and adhesive,
The particle diameter of the micro nanometer fiber powder is 10-500 μm, constitutes a diameter of 0.1- of the fiber of the micro nanometer fiber powder
100μm；
The adhesive include it is biodegradable and can self-curing inorganic matter component；
The three-dimensional porous composite of fiber base is passed through by the way that micro nanometer fiber powder is dispersed in the adhesive
Hole creating technology is obtained；
In terms of the gross mass of the three-dimensional porous composite of the fiber base, the content of the micro nanometer fiber powder is 5-50 matter
Measure %, preferably 20-50 mass %.
2. the three-dimensional porous composite of fiber base according to claim 1, it is characterised in that its porosity is 30-85%,
It is preferred that 60-85%；Compression strength is 1-15MPa, preferably 2-10MPa.
3. the three-dimensional porous composite of fiber base according to claim 1 or 2, it is characterised in that the micro nanometer fiber
Powder is derived from the one or more in synthesis macromolecular fibre, natural polymer subbundle, inorfil.
4. the three-dimensional porous composite of fiber base according to claim any one of 1-3, it is characterised in that described micro-nano
Fiber powder is handled by mineralising, it is preferable that the mineralising is processed as carrying out fiber surface the processing of calcium phosphorus precipitation.
5. the three-dimensional porous composite of fiber base according to claim 4, it is characterised in that in the mineralising before processing,
First the micro nanometer fiber powder is pre-processed, the pretreatment pre-processes for plasma pretreatment, alkali process, chemical oxygen
Change one or both of pretreatment, chemical graft pretreatment combination of the above.
6. the three-dimensional porous composite of fiber base according to claim any one of 1-5, it is characterised in that the adhesive
In inorganic matter component be selected from：Can self-curable calcium phosphate system, can self-curing calcium silicates system, can self-curing calcium sulfate system,
One or more that can be in self-curing magnesium phosphate system.
7. the three-dimensional porous composite of fiber base according to claim any one of 1-6, it is characterised in that the adhesive
In also include additive component, the additive component be selected from gelatin, collagen, hyaluronate, alginate, citrate,
One or more in starch, natural plant gum, Chitosan-phospholipid complex, cellulose and its derivates, polyvinylpyrrolidone, it is excellent
Selection of land, the mass fraction of the additive component is the 0.1-10 mass % of solid-phase component in adhesive.
8. a kind of preparation method of the three-dimensional porous composite of fiber base for Bone Defect Repari, it is characterised in that methods described bag
Include following steps：
Step 1：A diameter of 0.1-100 μm of fiber is prepared by electrostatic spinning, is then entered the fiber using crushing technology
Row is crushed, and obtains the micro nanometer fiber powder that particle diameter is 10-500 μm；
Step 2：Micro nanometer fiber powder and adhesive are uniformly mixed to get mixed system；
Step 3：The mixed system is handled through pore-forming technique to obtain the three-dimensional porous composite of the fiber base；
The adhesive include it is biodegradable and can self-curing inorganic matter component；With the composite porous gross mass
Meter, the content of the micro nanometer fiber powder is 5-50 mass %.
9. method according to claim 8, it is characterised in that the porosity of the three-dimensional porous composite of fiber base is 30-
85%, compression strength is 1-15MPa.
10. method according to claim 8 or claim 9, it is characterised in that being crushed described in step 1 includes manually or electrically cutting
Cut formula crushing technology, manually or electrically grind the technology of one or both of technology, electronic ball mill grinding technology above
Combination, the crushing is preferably carried out under freezing conditions.
11. the method according to claim any one of 8-10, it is characterised in that the micro nanometer fiber powder is sticked with described
Tie before agent mixing, first pass through mineralising processing.
12. method according to claim 11, it is characterised in that the mineralising processing comprises the following steps：Will be described micro-
Nanofiber powder is soaked in mineralized liquid, carries out calcium phosphorus precipitation in fiber surface, the mineralized liquid is preferably simulated body fluid.
13. the method according to claim any one of 8-12, it is characterised in that also include adding in step 2 adhesive
Plus agent component, the additive component is selected from gelatin, collagen, hyaluronate, alginate, citrate, starch, plant
One or more in glue, Chitosan-phospholipid complex, cellulose and its derivates, polyvinylpyrrolidone, it is preferable that described
The mass fraction of additive component is the 0.1-10 mass % of solid-phase component in adhesive.
14. the method according to claim any one of 8-13, it is characterised in that the pore-forming technique in the step 3 is selected from：
One in 3D printing pore-forming technique, orientation ice crystal-freeze-drying pore-forming technique, particle leaching pore-forming technique, foaming pore-forming technique
Kind.
15. a kind of products formed, it is characterised in that the products formed is being repaiied for bone according to claim any one of 1-7
The three-dimensional porous composite of multiple fiber base or the fiber base for Bone Defect Repari according to claim any one of 8-14
The three-dimensional porous composite of fiber base that the preparation method of three-dimensional porous composite is obtained is obtained through shaping.
16. products formed according to claim 15, it is characterised in that the products formed is artificial bone filled articles, preferably
For three-dimensional porous rack.
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| CN113750291A (en) * | 2021-10-18 | 2021-12-07 | 诺一迈尔(苏州)生命科技有限公司 | Articular cartilage scaffold and preparation method thereof |
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