CN109045364A - A kind of 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket and its preparation method and application - Google Patents
A kind of 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket and its preparation method and application Download PDFInfo
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- 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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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
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- 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
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- A61L27/58—Materials at least partially resorbable by the body
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- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y10/00—Processes of additive manufacturing
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- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
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- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
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- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
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Abstract
The present invention is a kind of 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket and preparation method and application, belongs to Bioengineered body implant.This method is using poly epsilon caprolactone lactone as substrate, and poly-dopamine is as surface modifying material, in combination with the Nano silver grain for having anti-infection bio performance, to realize biological function that is anti-infective, promoting Bone Ingrowth and bone defect healing.The present invention have it is simple and reliable for structure, shape is controllable with micro-structure, and mechanical property is reliable, and plasma diffusing W,Mo performance is controllable, implantation facilitate, the advantage that wound is small, at low cost.
Description
Technical field
The present invention relates to 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket and preparation method and application, belong to
Bioengineered body implant can be used for treating various pathogens, such as: staphylococcus aureus, streptococcus pyogenes, β-are molten
Acute and chronic osteomyelitis caused by hemorrhagic streptococcus, bacillus anthracis, corynebacterium diphtheriae etc., pyogenic arthritis osteoclasia treatment and
The repairing and treating of bone defect after infection.
Background technique
It infects the balance being defined as between host tissue and microorganism local concentration to be broken, it is considered that internal micro- life
Object is more than 105A per gram of tissue or the presence for having the pathogenic bacteria such as staphylococcus aureus, streptococcus pyogenes, beta hemolytic streptococcus
It is considered the presence of infection.In numerous infectious diseases, the infection of bone, joint is not only orthopaedics common frdquently encountered disease, Er Qieshou
The defects of being limited to poor, low to bacterial resistance local blood supply, antibiotic poor permeability, it tends to be difficult to it heals, much acute,
Subacute infection is finally delayed for chronic infection.The previous common anti-infective strategy of the orthopaedics is usually one-stage operation debridement, quiet
Arteries and veins gives antibiotic, the antibiotic spacer block of topical application or a bone cement beading.In general, this method obtains preferably
Effect.Then can secondary operation removal be locally filled with object, row revision procedure.But with the appearance of antibody-resistant bacterium, even if office
Portion and vein use in conjunction antibiotic, it is also possible to anti-infectious failure occur.
Bone, the infection of joint treatment in, since local microcirculation is poor, growth factor is few, activity is low, cell-membrane receptor knot
Structure variation causes to lose coupling between growth factor and receptor, and bacterium is also possible to be attached on implants position and is formed in biomembrane causes
There are biomaterials to be integrated into the competition etc. of surrounding tissue and bacterial adhesion to material surface for plant surface.Meanwhile venereal infection
Become the erosion to bone, destroy and often bring local sequestrum formation and bone defect, or even the sinus shape with skin, soft tissue
At debridement surgical failure rate, infection and recurrence rate are high, often lead to the serious limitation of activity of patient.Therefore, reason how is realized at present
The local antibacterial thought can effectively promote Bone Ingrowth after sequestrum and infectious lesions are dispelled in debridement, while be not necessarily to secondary hand
Art is always the emphasis of Orthopedic Clinical and scientific research concern.
The therapeutic strategy of current the classic and clinical is based on polymethyl methacrylate
The antibiotic pelletron implantation of (Polymethylmethacrylate, PMMA), but this method cannot degrade, and second operation is needed to take
Out, and suitable growing environment can be provided for the growth of pathogen, causes infection and recurrence, and without self-bone grafting and Bone Ingrowth
Can, therefore be badly in need of new method and substituted.
With the progress of organizational engineering, there are many new engineered biological material-antibiotic compound rests to make in recent years
It is studied in laboratory for anti-infection of bone repair materials, comprising: hydroxyapatite (Hydroapatite, HA)-antibiotic bracket,
Calcium-phosphate cement (Alcium phosphate cement, CPC)-antibiotic-chitosan compound rest, polylactic acid
The artificial class such as (Polylacticacid, PLA), polyglycolic acid (Polyglycolicacid, PGA), PGA-PLA copolymer
ECM material-antibiotic compound rest etc., part research are also attempted to combine recombinant human bone form raw on bracket using a variety of methods
At albumen 2 (Recombinant human bone morphogenetic protein-2, rhBMP-2), Peritoneal fibrosis
The bioactie agents such as β (transforming growth factor- β, TGF-β) are to promote Bone Ingrowth.But these materials are equal
Have the defects that certain, comprising: the brittleness of the materials such as 1.HA, CPC is high, processing performance is low, it is difficult to carry out specific three dimensional form
Processing and plasticity, tend to rely on the 3-d modelling of material itself；The bioactivity of the materials such as 2.PGA, PLA is low, elasticity modulus,
Exist in tensile strength, three-dimension finishing mode certain insufficient；3. still lacking the structure to engineered timbering material at present
The means of finely regulating are carried out with ingredient, therefore are difficult to the use for different infective stages (acute stage, subacute stage, chronic infection)
Medicine feature realizes effective and reasonable drug release；4. bioactie agent there are immunological rejection, pathogen propagation, allergic reaction,
Potential cause tumour, teratogenesis shape possibility, biological safety cannot be guaranteed, and the biologies such as the rhBMP-2 of clinical grade, TGF-β
The factor generally requires import, and expensive, and every milligram of purchasing price just reaches nearly thousand dollars.
In conclusion developing, one kind is simple and reliable for structure, and elasticity and support force are suitable, and operation is implanted into conveniently, to human body
Wound is small, low cost, the engineered anti-infection of bone bracket pair that can induce Bone Ingrowth and antibiotic control release may be implemented
Acute and chronic osteomyelitis, pyogenic arthritis osteoclasia treatment and infection after the repairing and treating of bone defect, the hygienic thing to China
Industry development has important realistic meaning to the innovative country of construction.
Summary of the invention
In order to overcome the above problem of existing anti-infection of bone material, the object of the present invention is to provide a kind of structures simply may be used
It leans on, shape is controllable with micro-structure, and mechanical property is reliable, and medicine-releasing performance is controllable, and implantation is convenient, the small 3D printing PCL- of wound
PDA-AgNPs Anti-infective bone tissue engineering bracket and preparation method and application are used for acute and chronic osteomyelitis, pyogenic arthritis
The repairing and treating of bone defect after the treatment and infection of osteoclasia.
The purpose of the present invention can be achieved through the following technical solutions:
A kind of 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket, which is to be prepared via a method which
It obtains:
Step 1: preparation 3D printing PCL bracket
PCL is warming up to liquid by the heating system of melted extrusion modeling formula 3D printing, shaping fiber beam is squeezed out, leads to
The different levels and angle splicing framework for crossing fibre bundle obtain 3D bracket PCL；
Step 2: preparation 3D printing PCL-PDA bracket
Tris is dissolved in water, HCL regulation system is added later is 8~9 to pH value, and it is molten that preparation obtains Tris-HCL
Liquid；Dopamine is dissolved in Tris-HCL solution, stirring and dissolving, is configured to DA-Tris-HCL solution；DA- is added in 3D bracket PCL
It in Tris-HCl solution, is stirred under conditions of being protected from light, takes out bracket after the auto polymerization of the surface PCL forms PDA after DA, obtain 3D and beat
Print PCL-PDA bracket；
Step 3: preparation 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket
Under the action of dispersing agent, the 3D printing PCL-PDA bracket of preparation is added in silver ammino solution, 25 DEG C are stirred to react
After fiber surface of the AgNPs adhering nanoparticles in 3D printing bracket, bracket is taken out, cleans and is dried in vacuo, obtain
Product be 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket.
A kind of preparation method of 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket, this method includes following
Step:
Step 1: preparation 3D printing PCL bracket
PCL is warming up to liquid by the heating system of melted extrusion modeling formula 3D printing, shaping fiber beam is squeezed out, leads to
The splicing framework of the different levels and angle of crossing fibre bundle obtains 3D bracket PCL；
Step 2: preparation 3D printing PCL-PDA bracket
Tris is dissolved in water, HCl regulation system is added later is 8~9 to pH value, and it is molten that preparation obtains Tris-HCL
Liquid；Dopamine is dissolved in Tris-HCL solution, stirring and dissolving, is configured to DA-Tris-HCL solution；DA- is added in 3D bracket PCL
It in Tris-HCl solution, is stirred under conditions of being protected from light, takes out bracket after the auto polymerization of the surface PCL forms PDA after DA, obtain 3D and beat
Print PCL-PDA bracket；
Step 3: preparation 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket
Under the action of dispersing agent, the 3D printing PCL-PDA bracket of preparation is added in silver ammino solution, 25 DEG C are stirred to react
After fiber surface of the AgNPs adhering nanoparticles in 3D printing bracket, bracket is taken out, cleans and is dried in vacuo, obtain
Product be 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket.
In technical solution of the present invention: the layer-by-layer accumulation and spelling that the fiber of 3D printing passes through different levels and angle in the first step
Multi-pore structure made of framework is connect, hole is that each layer fiber intersects in the range of 0-180 ° and accumulate and formed, and forms 0-
Regular porous including 90 ° of orthogonal row structures, 0-45-90-135-180 ° of diamond structure, 0-60-120-180 ° of triangular structure
Gap can also form special gradient distribution, stratification intersection according to actual needs.
In technical solution of the present invention: dissolved mass content is 0.05~0.2% to Tris in water in second step；Tris
Mass ratio with dopamine is 0.3~1:1.
In technical solution of the present invention: silver ammino solution described in third step is slow in the silver nitrate solution of 8~15g/L
Ammonium hydroxide is added dropwise, solution is become cloudy by transparent, is continued dropwise addition ammonium hydroxide and is just clarified to solution, and obtained clear solution is that silver-colored ammonia is molten
Liquid.
In technical solution of the present invention: dispersing agent described in third step is the polyvinyl pyrrole that concentration is 0.5~10wt%
Alkanone.
In technical solution of the present invention: the bracket is preparing the application in bone impairment renovation material field.
In technical solution of the present invention: 3D bracket PCL shape can carry out 3D according to the bone defect form in different areas to be repaired
Individual character manufacturing is printed, the timbering material for being fabricated to fixed profile can also be printed by FDM3D, and during surgery according to practical
The requirement of bone defect is filled.
3D printing micro-structure of the invention (hole size, hole shape, hole orientation, porosity and connectivity including bracket and
Rack surface characteristic etc.) it can regulate and control the release characteristics of the mechanical property of bracket, cell adherence performance and AgNPs particle.
Meanwhile the reaction time by changing the concentration of the solution containing Ag in manufacturing process, the solution containing Ag, controllable rack surface AgNPs
The load capacity of particle, and then regulate and control the release characteristics of AgNPs particle.It, can be with by the regulation of the release characteristics to AgNPs particle
For the intensity of the different state of an illness (acute stage, subacute stage, chronic infection) selection rational use of medicines.
Porous microstructure of the invention, PCL material has certain elasticity modulus and tensile strength, by the micro- knot of hole
The regulation of structure, PCL ratio can precisely match the mechanical environment in area to be repaired, according to the Wolf law of bone uptake, be beneficial to
New bone grow into and moulding；And PCL itself there is good biocompatibility can be provided with conducive to stem cell adherency, expansion
The local microenvironment of increasing, Osteoblast Differentiation and bone matrix accumulation.Meanwhile the modification of PDA can further improve the hydrophilic of rack surface
Property and biocompatibility, and its alkalescent can neutralize the acidulous material during scaffold degradation, give cell
Well-grown environment.Meanwhile porous structure is conducive to the exchange of nutritional ingredient, and then can promote growing into for new bone.Therefore, with
The continuous degradation of bracket substrate PCL, the formation of freshman bone tissue and filling pore, it will be able to it is good to be formed in host position
Osseointegration character, and then induce, new bone tissue is promoted to be formed.
PCL, PDA and AgNPs that the present invention uses are high-biocompatibility and biological safety material, wherein PCL material
Material is nontoxic to organism, and final catabolite is CO2And H2O, be approved by the fda in the United States for as can clinical use it is oral
Medicine substrate, Medical liquid-state packaging or even tissue engineering bracket substrate etc.；AgNPs is begun to extensively as a kind of antibacterial from ancient times
It is Bioabsorbable materials for anti-infective and anti-corrosion, and has good biological safety, since it is with excellent stabilization
Property, the antibacterial action of wide spectrum, lower drug resistance, stronger oligodynamic action (especially for those superbacterias), AgNPs is
It is widely used in the antimicrobial coating of implant.DA is one of hypothalamus and pituitary key neurotransmitter, and PDA is that DA is molten
Liquid polymerize under certain condition and is formed, and is complete biodegradable material.
The characteristics of 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket, is: 1. passing through FMD3D printing technique structure
It builds, the precise controlling of shape, internal pore structure may be implemented；2. by (the hole including bracket of porosity micro-structure in material
Size, hole shape, hole orientation, porosity and connectivity and rack surface characteristic etc.) precise controlling and for PDA,
The regulation of AgNPs release may be implemented in the regulation of AgNPs reaction condition；3. by the control to material proportion, pore structure,
It may make bracket that there is good mechanical property, while PCL-PDA bracket has hydrophily, biocompatibility, Bone Ingrowth characteristic
Equal physicochemical properties；4. PCL, PDA and AgNPs for using are high-biocompatibility and biological safety material, bracket can be in life
Degradable absorption in object.
The beneficial effects of the invention are as follows design a kind of novel 3D printing PCL-PDA-AgNPs Anti-infective bone organizational project branch
Frame has also given full play to the property of 3D printing technique, timbering material itself while overcoming existing anti-infection of bone material disadvantage
Can so that the present invention have it is simple and reliable for structure, shape is controllable with micro-structure, and mechanical property is reliable, and plasma diffusing W,Mo performance is controllable,
Implantation is convenient, the advantage that wound is small, at low cost, can be used for acute and chronic osteomyelitis, pyogenic arthritis osteoclasia treatment and
The repairing and treating of bone defect after infection.
Detailed description of the invention:
Fig. 1 is fibre lay-up arrangement of the invention, the schematic diagram for establishing three-dimensional porous structure.A: scaffold fibers stacked arrangement
Two dimension view, B: the structural schematic diagram of the square hole bracket of 0-90 ° of stacked arrangement of fiber, C: 0-60-120-180 ° of fiber
The structural schematic diagram of the triangle hole bracket of stacked arrangement, D: the diamond shape hole of 0-45-90-135-180 ° of stacked arrangement of fiber
The structural schematic diagram of bracket.
Fig. 2 is the schematic diagram that PDA, AgNPs of the present invention are adhered to bracket PCL fiber surface.
Fig. 3 is to play the signal that anti-infective, bone tissue grows into biological action after the present invention is implanted into bony metachromia defective region
Figure.
Fig. 4 is the pictorial diagram for the Universal support that the present invention carries out 3D printing preparation using different aperture micro-structure.
Fig. 5 is exemplary diagram of the present invention using CAD design and the personalized bracket of 3D printing preparation.A: it is obtained by CT scan
The infectious bone defect area three-dimensional image taken, B: personalized bracket CAD design figure, C: personalized bracket pictorial diagram
Fig. 6 is the result figure of physicochemical property test experience of the invention.A: bracket bacteriostasis property detection figure, B: scanning electron microscope
Fiber view, C: high power scanning electron microscope view.
Fig. 7 is the result figure of Acute toxicity and Bone Defect Repari experiment of the invention.A: bony metachromia defect view, B: bracket
It is implanted into rearview, C: stenter to implant view in January, D: 2 months views of stenter to implant, E: stenter to implant view in March.
Specific embodiment
Below with reference to embodiment, the present invention will be further described, and but the scope of the present invention is not limited thereto:
Embodiment 1
A kind of 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket, which is to be prepared via a method which
It obtains:
Step 1: preparation 3D printing PCL bracket
As shown in Fig. 1 (A), PCL is warming up to liquid by the heating system of melted extrusion modeling formula 3D printing, is squeezed out
Shaping fiber beam is arranged under the overlay acquisition 3D bracket PCL by the different levels of fibre bundle；
Step 2: preparation 3D printing PCL-PDA bracket
0.61gTris is dissolved in 500mL water, HCL regulation system is added later is 8~9 to pH value, and preparation obtains
Tris-HCL solution；1g dopamine is dissolved in Tris-HCL solution, stirring and dissolving, is configured to DA-Tris-HCL solution；By 3D branch
Frame PCL is added in DA-Tris-HCl solution, stirs under conditions of being protected from light, and takes out after the auto polymerization of the surface PCL forms PDA after DA
Bracket obtains 3D printing PCL-PDA bracket；
Step 3: preparation 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket
Using the polyvinylpyrrolidone of 3wt% as dispersing agent, silver ammino solution is added in the 3D printing PCL-PDA bracket of preparation
In, 25 DEG C are stirred to react after fiber surface of the AgNPs adhering nanoparticles in 3D printing bracket, and bracket is taken out, and clean
And be dried in vacuo, obtained product is 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket.Wherein: described
Silver ammino solution is that ammonium hydroxide is slowly added dropwise in the silver nitrate solution of 8g/L, and solution is become cloudy by transparent, continues to be added dropwise ammonium hydroxide to molten
Liquid is just clarified, and obtained clear solution is silver ammino solution.
Embodiment 2
A kind of 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket, which is to be prepared via a method which
It obtains:
Step 1: preparation 3D printing PCL bracket
As shown in Fig. 1 (B), PCL is warming up to liquid by the heating system of melted extrusion modeling formula 3D printing, is squeezed out
Shaping fiber beam, the square hole 3D bracket PCL of 0-90 ° of stacked arrangement of fiber；
Step 2: preparation 3D printing PCL-PDA bracket
0.4gTris is dissolved in 500mL water, HCL regulation system is added later is 8~9 to pH value, and preparation obtains
Tris-HCL solution；1g dopamine is dissolved in Tris-HCL solution, stirring and dissolving, is configured to DA-Tris-HCL solution；By 3D branch
Frame PCL is added in DA-Tris-HCl solution, stirs under conditions of being protected from light, and takes out after the auto polymerization of the surface PCL forms PDA after DA
Bracket obtains 3D printing PCL-PDA bracket；
Step 3: preparation 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket
Using the polyvinylpyrrolidone of 5wt% as dispersing agent, silver ammino solution is added in the 3D printing PCL-PDA bracket of preparation
In, 25 DEG C are stirred to react after fiber surface of the AgNPs adhering nanoparticles in 3D printing bracket, and bracket is taken out, and clean
And be dried in vacuo, obtained product is 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket.Wherein: described
Silver ammino solution is that ammonium hydroxide is slowly added dropwise in the silver nitrate solution of 10g/L, and solution is become cloudy by transparent, continues to be added dropwise ammonium hydroxide to molten
Liquid is just clarified, and obtained clear solution is silver ammino solution.
Embodiment 3
A kind of 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket, which is to be prepared via a method which
It obtains:
Step 1: preparation 3D printing PCL bracket
As shown in Fig. 1 (C), PCL is warming up to liquid by the heating system of melted extrusion modeling formula 3D printing, is squeezed out
0-60-120-180 ° of shaping fiber beam, fibre bundle stacked arrangement framework obtain 3D bracket PCL；
Step 2: preparation 3D printing PCL-PDA bracket
0.8gTris is dissolved in 500ml water, HCL regulation system is added later is 8~9 to pH value, and preparation obtains
Tris-HCL solution；1g dopamine is dissolved in Tris-HCL solution, stirring and dissolving, is configured to DA-Tris-HCL solution；By 3D branch
Frame PCL is added in DA-Tris-HCl solution, stirs under conditions of being protected from light, and takes out after the auto polymerization of the surface PCL forms PDA after DA
Bracket obtains 3D printing PCL-PDA bracket；
Step 3: preparation 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket
Using the polyvinylpyrrolidone of 10wt% as dispersing agent, it is molten that silver-colored ammonia is added in the 3D printing PCL-PDA bracket of preparation
In liquid, 25 DEG C are stirred to react after fiber surface of the AgNPs adhering nanoparticles in 3D printing bracket, bracket are taken out, clearly
It washes and is dried in vacuo, obtained product is 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket.Wherein: described
Silver ammino solution be that ammonium hydroxide is slowly added dropwise in the silver nitrate solution of 15g/L, solution is become cloudy by transparent, continue be added dropwise ammonium hydroxide extremely
Solution is just clarified, and obtained clear solution is silver ammino solution.
For infectious bone defect patient, if the interference that defective region does not have metallic foreign body etc. that may influence CT scan image
Factor can obtain anatomical data by CT scan, and combine the coincident with severity degree of condition of infection, bone defect, and design has individual character
The 3D printing bracket of outside the pale of civilization shape and physicochemical property is simultaneously implanted into infectious bone defect region.For precise anatomical data can not be obtained
Patient determines to plant using preprepared PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket according to actual defect situation
Enter the quantity of bracket.After stenter to implant, as the release of AgNPs controls infection, at the same time, with PCL, PDA,
The degradation of AgNPs, freshman bone tissue then constantly grow into, the final target for realizing control infection, bone defect healing.
As shown in Figure 1, the PCL fibre bundle that the porous structure of bracket is arranged by different levels is superimposed and is formed, Figure 1A is bracket
The two-dimensional representation that fiber is arranged under the overlay according to different levels, it can be seen that the pore morphology of bracket is laminated by the difference of scaffold fibers
Method determines, including hole size, hole shape, hole orientation, porosity and connectivity etc..Figure 1B, C, D points are to provide using 0-
90 °, 0-60-120-180 °, 0-45-90-135-180 ° of stacked arrangement form the 3D with square, triangle, diamond shape hole
Print the structural schematic diagram of PCL bracket.It in actual operation, can also be according to difference area's mechanical environment to be repaired, gradient of infection
Deng actual requirement, by the regulation that scaffold fibers are laminated, and then prepare personalized designs, have specific pore micro-structure
Bracket.
Fig. 2 is that PDA, AgNPs of the embodiment of the present invention 2 are adhered to the schematic diagram of bracket PCL fiber surface.1 is 3D printing
PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket schematic three dimensional views；2 be the signal of single scaffold fibers after partial enlargement
Figure；3 can see PDA adherency AgNPs nano particle of the PCL fiber by surface for the fiber surface schematic diagram of bracket.
The 1-6 of Fig. 3 is played anti-infective, bone tissue and grows into biological action behind present invention implantation bony metachromia defective region
Schematic diagram.1 is stenter to implant bone defect position；2 enlarged drawings local when being stenter to implant；3 display 3D printing PCL-PDA-
The fiber surface of AgNPs Anti-infective bone tissue engineering bracket adheres to AgNPs nano particle by the PDA on surface；Work as stenter to implant
4 (AgNPs nano particles) discharge afterwards, and kill in tissue to 5 (bacteriums), when bacterium contacts or is attached on bracket
It can directly be eliminated by AgNPs, meanwhile, AgNPs is discharged into tissue local environment also from bracket and can kill around tissue
Bacterium；6-7 is with the release of AgNPs and the degradation of PCL, PDA, and bracket is gradually absorbed by the body, while having bone tissue long
Enter, until 8 display brackets are degradable, infection of bone is cured, while bone defect region is substituted by freshman bone tissue.
Fig. 4 A, B, C are according to aforementioned techniques route, the universal 3D printing PCL-PDA- of the different structure of preparation respectively
The pictorial diagram of AgNPs Anti-infective bone tissue engineering bracket, wherein A is that fiber at 0-60-120-180 ° of stacked arrangement has three
The bracket of angular porosity micro-structure, B are that fiber at 0-45-90-135-180 ° of stacked arrangement has diamond shape porosity micro-structure
Bracket, C are the bracket that has square microstructure of the fiber at 0-90 ° of stacked arrangement.
Fig. 5 A, B, C are the exemplary diagram that personalized bracket preparation is carried out according to aforementioned techniques route respectively, and wherein A is to pass through
The infectious bone defect area three-dimensional image that CT scan obtains, B are the three-dimensional CAD figure of the personalized bracket of CAD
Picture, C are using the personalized 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket arranged at 0-90 ° of fibre lay-up.
Fig. 6 A, B, C are the 3D printing PCL-PDA-AgNPs Anti-infective bone group weaver constructed according to aforementioned techniques route respectively
The result figure of the physicochemical property test experience of engineering support, wherein A is the 3D printing PCL-PDA- for arranging 0-90 ° of fibre lay-up
The implantation of AgNPs Anti-infective bone tissue engineering bracket carries out bacteriostatic experiment in the culture dish containing S. aureus L-forms, it can be seen that in culture 2
Zhou Hou, branch frame peripheral have annular inhibition zone, it is seen that 3D printing bracket prepared by the present invention has reliable Antifungal activity, and B is low
Times scanning electron microscope detection figure, it can be seen that there are a large amount of AgNPs nano particles on scaffold fibers surface, and C is that high power scanning electron microscope detects
Figure, it can be seen that AgNPs nano particle adheres to extensively in PCL material surface, and forms the fiber surface with certain roughness.
Fig. 7 A-E is the result figure of Acute toxicity and Bone Defect Repari experiment of the invention, and wherein A is infectious bone defect area
Domain；B is that stenter to implant infectivity bone defect region is shown that 3D printing bracket is completely embedded into bone defect region；C is stenter to implant
January afterwards, local infection are effectively controlled, and osteochondral tissue is grown into；D, E be respectively stenter to implant 2 months, the photo in March,
Show that local infection disappears, newborn osteochondral tissue grows into and substitutes timbering material.
Claims (10)
1. a kind of 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket, it is characterised in that: the bracket is by as follows
Method is prepared:
Step 1: preparation 3D printing PCL bracket
PCL is warming up to liquid by the heating system of melted extrusion modeling formula 3D printing, shaping fiber beam is squeezed out, passes through fibre
The different levels and angle splicing framework for tieing up beam obtain 3D bracket PCL；
Step 2: preparation 3D printing PCL-PDA bracket
Tris is dissolved in water, HCL regulation system is added later is 8~9 to pH value, and preparation obtains Tris-HCL solution；
Dopamine is dissolved in Tris-HCL solution, stirring and dissolving, is configured to DA-Tris-HCL solution；DA- is added in 3D bracket PCL
It in Tris-HCl solution, is stirred under conditions of being protected from light, takes out bracket after the auto polymerization of the surface PCL forms PDA after DA, obtain 3D and beat
Print PCL-PDA bracket；
Step 3: preparation 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket
Under the action of dispersing agent, the 3D printing PCL-PDA bracket of preparation is added in silver ammino solution, 25 DEG C be stirred to react until
AgNPs adhering nanoparticles take out bracket after the fiber surface of 3D printing bracket, clean and are dried in vacuo, obtained production
Product are 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket.
2. 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket according to claim 1, it is characterised in that:
Dissolved mass content is 0.05~0.2% to Tris in water in second step；The mass ratio of Tris and dopamine is 0.3~1:
1。
3. 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket according to claim 1, it is characterised in that:
Silver ammino solution described in third step is that ammonium hydroxide is slowly added dropwise in the silver nitrate solution of 8~15g/L, and solution becomes muddy by transparent
It is turbid, continue dropwise addition ammonium hydroxide and just clarified to solution, obtained clear solution is silver ammino solution.
4. 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket according to claim 1, it is characterised in that:
Dispersing agent described in third step is the polyvinylpyrrolidone that concentration is 0.5~10w%t.
5. a kind of preparation method of 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket, it is characterised in that: this method
The following steps are included:
Step 1: preparation 3D printing PCL bracket
PCL is warming up to liquid by the heating system of melted extrusion modeling formula 3D printing, shaping fiber beam is squeezed out, passes through fibre
The splicing framework of the different levels and angle of tieing up beam obtains 3D bracket PCL；
Step 2: preparation 3D printing PCL-PDA bracket
Tris is dissolved in water, HCl regulation system is added later is 8~9 to pH value, and preparation obtains Tris-HCL solution；
Dopamine is dissolved in Tris-HCL solution, stirring and dissolving, is configured to DA-Tris-HCL solution；DA- is added in 3D bracket PCL
It in Tris-HCl solution, is stirred under conditions of being protected from light, takes out bracket after the auto polymerization of the surface PCL forms PDA after DA, obtain 3D and beat
Print PCL-PDA bracket；
Step 3: preparation 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket
Under the action of dispersing agent, the 3D printing PCL-PDA bracket of preparation is added in silver ammino solution, 25 DEG C be stirred to react until
AgNPs adhering nanoparticles take out bracket after the fiber surface of 3D printing bracket, clean and are dried in vacuo, obtained production
Product are 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket.
6. the preparation method of 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket according to claim 5,
Be characterized in that: dissolved mass content is 0.05~0.2% to Tris in water in second step.
7. the preparation method of 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket according to claim 5,
Be characterized in that: the mass ratio of Tris and dopamine is 0.3~1:1 in second step.
8. the preparation method of 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket according to claim 5,
Be characterized in that: silver ammino solution described in third step is that ammonium hydroxide is slowly added dropwise in the silver nitrate solution of 8~15g/L, solution by
It is transparent to become cloudy, continue dropwise addition ammonium hydroxide and just clarified to solution, obtained clear solution is silver ammino solution.
9. the preparation method of 3D printing PCL-PDA-AgNPs Anti-infective bone tissue engineering bracket according to claim 5,
Be characterized in that: dispersing agent described in third step is the polyvinylpyrrolidone that concentration is 0.5~10wt%.
10. bracket described in claim 1 is preparing the application in bone impairment renovation material field.
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| CN111643725A (en) * | 2020-06-01 | 2020-09-11 | 四川大学 | Artificial bone material for repairing bone defect and preparation method of artificial bone particles |
| WO2023051093A1 (en) * | 2021-09-30 | 2023-04-06 | 上海市浦东新区人民医院 | Bone tissue engineering composite scaffold |
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