CN110302419A - A kind of 3D printing compound bio ink material and the preparation method and application thereof - Google Patents

A kind of 3D printing compound bio ink material and the preparation method and application thereof Download PDF

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CN110302419A
CN110302419A CN201910533244.9A CN201910533244A CN110302419A CN 110302419 A CN110302419 A CN 110302419A CN 201910533244 A CN201910533244 A CN 201910533244A CN 110302419 A CN110302419 A CN 110302419A
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compound bio
ink material
bio ink
printing
bracket
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CN110302419B (en
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罗丙红
朱凌
刘文军
文伟
周长忍
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Jinan University
University of Jinan
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Jinan University
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/12—Phosphorus-containing materials, e.g. apatite
    • 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
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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
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • 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
    • B33Y70/00—Materials specially adapted for additive manufacturing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • 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
    • B33Y80/00—Products made by additive manufacturing
    • 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
    • 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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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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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
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    • A—HUMAN NECESSITIES
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    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • 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
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A—HUMAN NECESSITIES
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Abstract

The invention discloses a kind of 3D printing compound bio ink materials and the preparation method and application thereof.The constituent of the compound bio ink material includes Biodegradable polyester, activeness and quietness agent and ternary solvent system.Wherein, ternary solvent system contains organic solvent 40~90%, surfactant 5~45%, plasticizer 5~45% by mass percentage.Compared to single low boiling point organic solvent system, ternary solvent system not only increases the printability of compound bio ink, also improve the interface cohesion between Biodegradable polyester matrix and activeness and quietness agent, and, the interfacial bonding of fiber between layers in print procedure is enhanced, the good three-dimensional structure of 3D printing complex stephanoporate bracket and mechanical property can be assigned.In addition, activeness and quietness agent used can further improve the mechanical property and osteogenic activity of Biodegradable polyester, assign complex stephanoporate bracket excellent rush bone tissue reparation ability.

Description

A kind of 3D printing compound bio ink material and the preparation method and application thereof
Technical field
The invention belongs to 3D biometric print technical field, in particular to a kind of 3D printing compound bio ink material and its system Preparation Method and application.
Background technique
Bone defect caused by congenital disorders, wound, tumour and operation etc. is clinical most commonly seen and multiple illness, Bone defect healing is also the main bugbear that Reconstructive surgery faces always.Document report is for constructing osseous tissue engineering stephanoporate branch There are many technologies of frame, but the 3D printing shown one's talent in recent years is concerned because of its advantage outstanding.3D printing is with computer Three Dimensional Design Model is source, using technologies such as laser aiming, inkjet printings, biomaterial is bonded by successively accumulation, is folded Add plastotype, ultimately forms the tissue or organ of emulation.3D printing have can flexibly construct specific shape and be interconnected Porous structure, can the porous support of " individual customization " with personal feature, realize the individuation and precision of bone surgery, with And can have many advantages, such as ease for use, flexibility and operability with the celliferous tissue of direct construction or organ.
So far, the biomedical and widely used Biodegradable polyester of field of tissue engineering technology include poly- (L- lactide), Poly(D,L-lactide), poly- (6-caprolactone), poly- (lactide-co-glycolide), this kind of material have good bio-compatible The excellent properties such as property, degradable absorbability, the nontoxic, easy processing of catabolite and obtained answering extensively in bone tissue reparation field With.However, the mechanical performance of single creature degradation polyester is poor such as poly- (L- lactide), it is unable to satisfy bone injury site Fixed and treatment requires；In addition, Biodegradable polyester does not have osteoconductive, the speed of repairing bone defect as bone renovating material It spends very slow.By adding nanofiller, the mechanical strength and modulus of Biodegradable polyester matrix can be effectively improved, but often adjoint The decline of toughness of material.
Cause 3D printing porous support mechanical strength difference a main cause be printing adjacent fiber between layers Seamless binding is not formed, the binding force between fibrous layer is poor.If 3D melts printing building polylactic acid porous scaffold, due to fiber The rapid cooling on surface solidifies, and binding force is poor between layers for adjacent fiber, cause the compression performance of bracket, tensile property compared with It is weak.
3D solution printing technique can print the solution state ink of composite Nano filler, cell or biomolecule at room temperature Three dimensional biological composite material is formed, and is able to maintain high-performance, high fidelity and precision.However, reporting more solution at present 3D printing polylactic acid ink generallys use volatile single solvent system, due to the quick volatilization of solvent, is easy in fiber Internal and surface generates stomata, these stomatas become stress concentration point in material stress, cause material fragility big；In addition, by Solidify in polymer substrate fast deposition, it is poor not only result in binding force between adjacent fibrous layers and layer, nor is conducive to polymerization Object matrix is in the abundant cladding of filler surface, so that filler is reunited seriously, interface cohesion is poor between matrix and filler, thus into one Step leads to the decline of material mechanical performance.
Summary of the invention
In order to overcome the shortcomings and deficiencies of the prior art described above, the primary purpose of the present invention is that provide a kind of 3D printing multiple Symphysis object ink material.
Another object of the present invention is to provide a kind of preparation method of above-mentioned 3D printing compound bio ink material.
Still a further object of the present invention is to provide a kind of by the three-dimensional compound of above-mentioned 3D printing compound bio ink material preparation Porous support.
Still a further object of the present invention is to provide a kind of preparation method of above-mentioned three-dimensional complex stephanoporate bracket.
Still a further object of the present invention is to provide application of the above-mentioned three-dimensional complex stephanoporate bracket of one kind in bone tissue reparation.
The purpose of the present invention is realized by following proposal:
A kind of 3D printing compound bio ink material comprising the constituent of following mass fraction:
Biodegradable polyester 2~25%
Activeness and quietness agent 0.2~25%
Ternary solvent system 50~97.8%.
The surface-active that the ternary solvent system is specifically volatilized by the volatile organic solvent of low boiling point, higher boiling difficulty Agent and plasticizer are formed；
Preferably, the organic solvent is methylene chloride, chloroform, tetrahydrofuran, acetone, hexafluoroisopropanol and toluene At least one of.
Preferably, the surfactant be butoxy ethanol, stearic acid and neopelex at least It is a kind of.
Preferably, the plasticizer is dibutyl phthalate, citrate and (the 2- ethyl hexyl of phthalic acid two At least one of base) ester.
The mass percentage of the ternary solvent system forms are as follows: organic solvent 40~90%, surfactant 5~ 45%, plasticizer 5~45%.
The Biodegradable polyester be poly- (L- lactide), poly- (D, L- lactide), poly- (6-caprolactone), polyglycolide and At least one of poly- (lactide-co-glycolide)；The activeness and quietness agent is chitin whisker, hydroxyapatite crystal whisker, mixes At least one of the hydroxyapatite crystal whisker of miscellaneous strontium and magnesium-doped hydroxyapatite crystal whisker.
In the present invention, the chitin whisker is prepared by the acid hydrolyzation of this field routine；A diameter of 5 ~70nm, length are 80nm~1 μm, and draw ratio is 10~200；
The hydroxyapatite crystal whisker is prepared by the hydrothermal synthesis method of this field routine；A diameter of 5~ 100nm, length are 400nm~2 μm, and draw ratio is 5~400；
The hydroxyapatite crystal whisker of the doping strontium is prepared by the hydrothermal synthesis method of this field routine；It is straight Diameter is 10~500nm, and length is 50nm~2 μm, and draw ratio is 5~200；The molar ratio of strontium and calcium is 0.5:99.5~15:85.
The magnesium-doped hydroxyapatite crystal whisker is prepared by the hydrothermal synthesis method of this field routine；It is straight Diameter is 20~500nm, and length is 200nm~2 μm, and draw ratio is 2~100；The molar ratio of magnesium and calcium is 0.5:99.5~20: 80。
A kind of preparation method of above-mentioned 3D printing compound bio ink material, specific steps are as follows:
After activeness and quietness agent is mixed with organic solvent, carries out ultrasonic disperse and form homogeneous suspension liquid；Then biology is added Degradation polyester stirs evenly, and forms homogeneous single solvent compound system, then sequentially adds surfactant and plasticizer is uniform It is mixed to form tri compound dicyandiamide solution, is again stirring for, 3D printing compound bio ink material is prepared.
The time of the ultrasonic disperse is 20~60min.
The time of the first time stirring is 3~10 hours, and the time being again stirring for is 2~12 hours.
A kind of three-dimensional complex stephanoporate bracket, is prepared by above-mentioned 3D printing compound bio ink material.
A kind of preparation method of the three-dimensional complex stephanoporate bracket, specific steps are as follows:
Above-mentioned 3D printing compound bio ink material is excluded into bubble, and controlling print speed is 5~40mm/s, is filled close Degree 30~95%, is printed on receiving platform through syringe needle by syringe at a temperature of 20~35 DEG C, along Z axis layer upon layer, is obtained It to the complex stephanoporate bracket with three-dimensional structure, will be purified after the drying of gained complex stephanoporate bracket, then be dried in vacuo to obtain Three-dimensional complex stephanoporate bracket after purification.
The purifying is to impregnate the complex stephanoporate bracket after drying 1~24 hour through ethyl alcohol.
Application of the three-dimensional complex stephanoporate bracket in bone tissue reparation.
The present invention compared with the existing technology, have the following advantages and the utility model has the advantages that
1. the present invention is used for the compound bio ink material of 3D printing using ternary solvent system preparation, low compared to single Boiling point organic solvent system, ternary solvent system not only increase the printability of compound bio ink, meanwhile, be conducive to biology Degradation polyester matrix is coated on the surface of activeness and quietness agent, improves the interface cohesion between matrix and filler.Moreover, can avoid institute The rapid curing for printing fiber surface, significantly improves the interfacial bonding of fiber between layers, overcomes single solvent ink material Many deficiencies existing for 3D printing can finally assign the good three-dimensional structure of 3D printing complex stephanoporate bracket and mechanical property.
2. the surfactant in the ternary solvent system that the present invention uses can also significantly improve Biodegradable polyester base Interface cohesion between body and activeness and quietness agent, and the use of plasticizer then can effectively improve the printable of compound bio ink Property.
3. can further improve 3D by adding the activeness and quietness agent of whisker this kind in 3D printing compound bio ink and beat Print the mechanical property of composite porous support material；Moreover, assign the excellent hydrophily of complex stephanoporate bracket, cellular affinity and at Bone active is expected to have a good application prospect in bone tissue reparation field.
4. the compound bio ink that the present invention designs can be directly used for 3D printing, print conditions are mild, material therefor price Cheaply, it is easy preparation, it is easy to industrialized production.
Detailed description of the invention
Fig. 1 be in embodiment 1 using 3D printing preparation containing different quality percentage composition chitin whisker (0%, 5%, 10%, 20%, 40%) the mechanical property figure of the base composite porous bracket of PLLA；Wherein figure (A) is that the ess-strain under dry state is bent Line, figure (B) are the stress-strain diagram under hygrometric state, and figure (C) is compressive strength figure, and figure (D) is compression modulus figure.
Fig. 2 contains different quality percentage composition hydroxyapatite prepared by 2 gained 3D printing of embodiment for osteoblast 1,4 and 7 day proliferation results figure is cultivated on the PDLLA compound rest of whisker (0%, 15%, 30%, 45%, 60%).
Fig. 3 be in embodiment 5 containing different quality percentage composition strontium-doped hydroxyapatite whisker (0%, 3%, 6%, 12%, 24%) the base composite porous bracket material object photo of PLLA.
Fig. 4 be osteoblast 6 gained of embodiment containing different quality percentage composition hydroxyapatite crystal whisker (0%, 4%, 8%, 16%, 32%) 21 days calcium tubercle quantitative result figures are cultivated on PCL compound rest.
Fig. 5 is the whisker for the chitin containing 10wt% that in comparative example 1 prepared by single solvent system compound bio ink material The top view (a) and side view (c) of complex stephanoporate bracket；What in embodiment 8 prepared by ternary solvent compound bio ink material contains The top view (b) and side view (d) of the complex stephanoporate bracket of 10wt% chitin.
Specific embodiment
Below with reference to embodiment and attached drawing, the present invention is described in further detail, but embodiments of the present invention are unlimited In this.
Agents useful for same can routinely be bought unless otherwise specified from market in embodiment.
Embodiment 1 adds the preparation and its 3D printing of the ternary solvent compound bio ink material of chitin whisker
The chitin whisker of different quality (CHW) is mixed with 4mL methylene chloride respectively, ultrasonic 60min forms homogeneous outstanding Supernatant liquid takes 1g poly- (L- lactide) (PLLA, Mn=100000) that above-mentioned suspension is added, magnetic agitation 6 hours, adds The butoxy ethanol and 0.5mL dibutyl phthalate of 1.3mL, ultrasound discharge bubble, is contained after stirring 4 hours The ternary solvent compound bio ink material of CHW.Then, syringe bubble side by side is moved it into, according to the mathematical model built up, That is print speed 10mm/s, packed density 90%, through needle at 28 DEG C is arranged in the cylindric 3D model of thickness 10mm, diameter 5mm Head prints on receiving platform, finally prepares complex stephanoporate bracket by layer upon layer, then by the complex stephanoporate bracket after drying It is impregnated 2 hours with ethyl alcohol, removes surfactant and plasticizer, vacuum drying obtains final percentage composition containing different quality The three-dimensional composite porous support material of (0%, 5%, 10%, 20%, 40%) CHW.
The ternary solvent compound bio ink material of the addition CHW prepared in the present embodiment has good printing, PLLA matrix can be coated on the surface of CHW well, form stable interface cohesion, and PLLA in print procedure between the two Scaffold fibers have good bonding between layers, advantageously form three-dimensional structure.Final PLLA scaffold fibers size obtained Uniformly indeformable, moreover, bracket uniform pore diameter, shape is regular, highly controllable, more meets the demand of clinical bone tissue reparation.
To different quality percentage composition chitin whisker prepared by above-described embodiment 1 (0%, 5%, 10%, 20%, 40%) mechanical property of PLLA base compound rest is studied, the result is shown in Figure 1.As seen from the figure, relative to pure PLLA branch Frame, a certain amount of CHW, which is added, can significantly improve the compressive strength and compression modulus of PLLA basis material.With the increasing of Whisker Content Add, the compressive strength and compression modulus of bracket are in rising trend.Moreover, the mechanical property measured under dry state obviously compares in hygrometric state It is more preferable under (compound rest is soaked in PBS solution and takes out after 6 hours), especially when Whisker Content is 20wt%, relative to Pure PLLA group, compressive strength and compression modulus are promoted respectively to 4.29MPa and 74.43MPa, this shows that CHW, which is added, to be reached The effect of activeness and quietness PLLA bracket.But when Whisker Content is 40wt%, mechanical properties decrease is obvious, this may be nanometer Chitin whisker content is easy to reunite and the mechanical property of complex stephanoporate bracket is caused to be declined when more.
Embodiment 2 adds the preparation and its 3D printing of the ternary solvent compound bio ink material of hydroxyapatite crystal whisker
The hydroxyapatite crystal whisker of different quality (HAP) is mixed with 3mL chloroform respectively, ultrasonic 35min is formed Phase suspension takes 1.2g poly(D,L-lactide) (PDLLA, Mn=200000) to be added above-mentioned suspension, and magnetic agitation 5 hours, 1.5mL neopelex and 0.5mL citric acid rouge are added, bubble is discharged in room temperature ultrasound after stirring 10 hours, obtains Add the ternary solvent compound bio ink material of HAP.Then, syringe bubble side by side is moved it into, according to the digital mould built up The cylindric 3D model of type, i.e. thickness 5mm, diameter 5mm, is arranged print speed 5mm/s, and packed density 70% passes through at 20 DEG C Syringe needle prints on receiving platform, finally prepares three-dimensional complex stephanoporate bracket by layer upon layer, then will be compound more after drying Hole bracket is impregnated 7 hours with ethyl alcohol, removes surfactant and plasticizer, and vacuum drying obtains final percentage containing different quality and contains Measure the three-dimensional composite porous support material of HAP (0%, 15%, 30%, 45%, 60%).
The ternary solvent compound bio ink material of the addition HAP prepared in the present embodiment has good printing, PDLLA matrix can be coated on the surface of HAP well, form stable interface cohesion between the two, and in print procedure PDLLA scaffold fibers have good bonding between layers, conducive to three-dimensional structure is formed.Final PDLLA scaffold fibers obtained Of uniform size indeformable, moreover, bracket uniform pore diameter, shape is regular, highly controllable, more meets the need of clinical bone tissue reparation It asks.
The mechanical property of the PDLLA compound rest of different quality percentage composition HAP prepared by above-described embodiment 2 is carried out Research, the results are shown in Table 1.
The mechanical property of the PDLLA compound rest of 1 different quality percentage composition HAP of table
For data in contrast table it is found that relative to pure PDLLA bracket, a certain amount of HAP, which is added, can significantly improve PDLLA matrix material The compressive strength and compression modulus of material.Moreover, the mechanical property measured under dry state obviously compares, in hygrometric state, (compound rest is soaked in Taken out after 6 hours in PBS solution) under it is good, especially Whisker Content be 30wt% when, relative to pure PDLLA group, compressive strength Improve nearly 2.3 times and 2 times respectively with compression modulus, this shows that HAP, which is added, can reach the effect of activeness and quietness PDLLA bracket Fruit.
Osteoblastic proliferation experiment:
The PDLLA of different quality percentage composition HAP (0%, 15%, 30%, 45%, 60%) will be contained obtained by embodiment 2 Composite porous support material is placed in 24 orifice plates, is embathed 2 times after ultraviolet sterilization 2 hours with PBS buffer solution, with every hole 1 × 104It is close 1mL culture solution (the mould of fetal calf serum (FBS), 1wt% containing 10wt% is added in degree inoculation osteoblast (MC3T3-E1) afterwards The basal medium of element/streptomysin and 89wt%), 37 DEG C of incubators are interior to cultivate Isosorbide-5-Nitrae, uses CCK-8 kit after 7 days respectively Cell proliferation level is detected, concrete outcome is shown in Fig. 2.
It can be seen from the figure that as time increases, absorbance value of the cell on each group material gradually increases, especially It is the 7th day, compared to pure PDLLA group (0%HAP), the PDLLA compound rest absorbance value of HAP whisker group has been added to be obviously improved, The especially PDLLA compound rest containing 45wt%HAP, than about 1.6 times of pure PDLLA support lift, the results showed that the addition of HAP Be conducive to the proliferation and growth of osteoblast.
Embodiment 3 adds the preparation and its 3D printing of the ternary solvent compound bio ink material of hydroxyapatite crystal whisker
The hydroxyapatite crystal whisker of different quality (HAP) is mixed with 10mL hexafluoroisopropanol respectively, ultrasonic 45min is formed Homogeneous suspension liquid takes 1.0g poly- (lactide-co-glycolide) (PLGA, Mn=300000) that above-mentioned suspension, magnetic agitation is added 10 hours, 1.2mL neopelex and 0.4mL dibutyl phthalate are added, room temperature is super after stirring 6 hours Bubble is discharged in sound, obtains the ternary solvent compound bio ink material for adding HAP.Then, syringe bubble side by side is moved it into, is pressed According to the mathematical model built up, i.e. print speed 25mm/ is arranged in the strip 3D model of length 5cm, width 1cm, thickness 1.5mm S, packed density 45% print on receiving platform at 25 DEG C through syringe needle, finally three-dimensional compound more by layer upon layer preparation Hole bracket, then the ethyl alcohol of the complex stephanoporate bracket after drying is impregnated 2 hours, surfactant and plasticizer are removed, vacuum is dry The dry three-dimensional complex stephanoporate bracket material for obtaining final percentage composition containing different quality (0%, 10%, 20%, 40%, 60%) HAP Material.
The ternary solvent compound bio ink material of the addition HAP prepared in the present embodiment has good printing, PLGA matrix can be coated on the surface of HAP well, form stable interface cohesion, and PLGA in print procedure between the two Scaffold fibers have good bonding between layers, conducive to three-dimensional structure is formed.Final PLGA scaffold fibers size obtained is equal Even indeformable, moreover, bracket uniform pore diameter, shape is regular, highly controllable, more meets the demand of clinical bone tissue reparation.
The mechanical property of the PLGA compound rest of different quality percentage composition HAP prepared by above-described embodiment 3 is carried out Research, the results are shown in Table 2.
The mechanical property of the PLGA compound rest of 2 different quality percentage composition HAP of table
For data in contrast table it is found that relative to pure PLGA bracket, a certain amount of HAP, which is added, can significantly improve PLGA basis material Tensile strength and stretch modulus.Moreover, the mechanical property measured under dry state obviously compares, in hygrometric state, (compound rest is soaked in Taken out after 6 hours in PBS solution) under it is good, especially Whisker Content be 20wt% when, relative to pure PLGA group, tensile strength Improve nearly 2 times and 1.6 times respectively with stretch modulus.Especially it is noted that after the HAP whisker of 20wt% is added, material Energy to failure improved by about one time relative to pure PLGA sample, this shows that HAP, which is added, can not only improve the intensity of PLGA, and And the toughness of material is largely improved, show that HAP can achieve the effect that activeness and quietness PLGA bracket.
Embodiment 4 adds the preparation and its 3D printing of the ternary solvent compound bio ink material of chitin whisker
The chitin whisker of different quality (CHW) is mixed with 7mL acetone respectively, ultrasonic 45min forms homogeneous suspension liquid, It takes 2.5g PDLLA (Mn=250000) that above-mentioned suspension is added, magnetic agitation 5 hours, adds 1.3mL stearic acid and 0.6mL Citrate, bubble is discharged in room temperature ultrasound after stirring 8 hours, obtains the ternary solvent compound bio ink material for adding CHW.With Afterwards, syringe bubble side by side is moved it into, according to the mathematical model built up, i.e. the cylindric 3D model of thickness 8mm, diameter 4mm, Print speed 12mm/s is set, and packed density 75% prints on receiving platform at 30 DEG C through syringe needle, finally by heap layer by layer Product prepares three-dimensional complex stephanoporate bracket, then the ethyl alcohol of the complex stephanoporate bracket after drying is impregnated 6 hours, removes surfactant And plasticizer, vacuum drying obtain the three-dimensional of final percentage composition containing different quality (0%, 6%, 12%, 24%, 48%) CHW Composite porous support material.
The ternary solvent compound bio ink material of the addition CHW prepared in the present embodiment has good printing, PDLLA matrix can be coated on the surface of CHW well, form stable interface cohesion between the two, and in print procedure PDLLA scaffold fibers have good bonding between layers, conducive to three-dimensional structure is formed.Final PDLLA scaffold fibers obtained Of uniform size indeformable, moreover, bracket uniform pore diameter, shape is regular, highly controllable, more meets the need of clinical bone tissue reparation It asks.
The mechanical property of the PDLLA compound rest of different quality percentage composition CHW prepared by above-described embodiment 4 is carried out Research, the results are shown in Table 3.
The mechanical property of the PDLLA compound rest of 3 different quality percentage composition CHW of table
For data in contrast table it is found that relative to pure PDLLA bracket, a certain amount of CHW, which is added, can significantly improve PDLLA matrix material The compressive strength and compression modulus of material.With the increase of Whisker Content, the compressive strength and compression modulus of bracket are in rising trend. Moreover, the mechanical property measured under dry state is obviously than more preferable under hygrometric state, especially when Whisker Content is 24wt%, relatively In pure PDLLA group, compressive strength and compression modulus improve nearly 2.6 times and 1.7 times respectively, this shows that CHW, which is added, to be reached The effect of activeness and quietness PDLLA bracket.
The preparation of the hydroxyapatite crystal whisker ternary solvent compound bio ink material of the addition doping strontium of embodiment 5 and its 3D Printing
Respectively by different quality mix strontium hydroxyapatite crystal whisker (SrHAP, wherein the molar ratio of strontium and calcium be 2.5: 97.5) it is mixed with 4mL toluene, ultrasonic 20min forms homogeneous suspension liquid, takes 2g PLLA (Mn=250000) that above-mentioned suspension is added Liquid magnetic agitation 8 hours, adds 1mL stearic acid and 0.2mL phthalic acid two (2-ethylhexyl) ester, stirs 4 hours Bubble is discharged in room temperature ultrasound afterwards, obtains the ternary solvent compound bio ink material for adding SrHAP.Then, syringe is moved it into Bubble side by side, according to the mathematical model built up, i.e. print speed is arranged in the cylindric 3D model of thickness 2mm, diameter 10mm 15mm/s, packed density 50% print on receiving platform at 25 DEG C through syringe needle, finally three-dimensional multiple by layer upon layer preparation Porous support is closed, then the ethyl alcohol of the complex stephanoporate bracket after drying is impregnated 24 hours, removes surfactant and plasticizer, very Sky is dried to obtain the compound porous branch of three-dimensional of final percentage composition containing different quality (0%, 3%, 6%, 12%, 24%) SrHAP Frame material is specifically shown in Fig. 3.
As seen from the figure, the ternary solvent compound bio ink material of the addition SrHAP prepared in the present embodiment has good Printing, PLLA matrix can be coated on the surface of SrHAP well, form stable interface cohesion between the two, and beat PLLA scaffold fibers have good bonding between layers during print, conducive to three-dimensional structure is formed.Final PLLA branch obtained Frame fiber size is uniformly indeformable, moreover, bracket uniform pore diameter, shape is regular, highly controllable, more meets clinical bone tissue reparation Demand.
To the mechanical property of the PLLA compound rest of different quality percentage composition SrHAP prepared by above-described embodiment 5 into It has gone research, the results are shown in Table 4.
The mechanical property of the PLLA compound rest of 4 different quality percentage composition SrHAP of table
For data in contrast table it is found that relative to pure PLLA bracket, a certain amount of SrHAP, which is added, can significantly improve PLLA matrix material The compressive strength and compression modulus of material.With the increase of Whisker Content, the mechanical property of compound rest is gradually increasing.Moreover, The mechanical property measured under dry state is obviously than good under hygrometric state, when Whisker Content is 12wt%, relative to pure PLLA group, pressure Contracting intensity and compression modulus improve nearly 2.3 times and 2.0 times respectively, this shows that SrHAP, which is added, can reach activeness and quietness PLLA The effect of bracket.
Embodiment 6 adds the preparation and its 3D printing of the ternary solvent compound bio ink material of hydroxyapatite crystal whisker
The hydroxyapatite crystal whisker of different quality (HAP) is mixed with 15mL toluene respectively, ultrasonic 40min forms homogeneous outstanding Supernatant liquid takes 2g poly- (6-caprolactone) (PCL, Mn=150000) that above-mentioned suspension is added, magnetic agitation 8 hours, adds 1mL ten Dialkyl benzene sulfonic acids sodium and 0.1mL phthalic acid two (2-ethylhexyl) ester, bubble is discharged in room temperature ultrasound after stirring 8 hours, Obtain the ternary solvent compound bio ink material for adding HAP.Then, syringe bubble side by side is moved it into, according to the number built up Print speed 22mm/s, packed density 75%, 25 is arranged in the cylindric 3D model of word model, i.e. thickness 5mm, diameter 10mm It is printed on receiving platform at DEG C through syringe needle, finally prepares three-dimensional complex stephanoporate bracket by layer upon layer, then will be after drying Complex stephanoporate bracket is impregnated 6 hours with ethyl alcohol, removes surfactant and plasticizer, and vacuum drying obtains finally containing different quality The three-dimensional composite porous support material of the HAP of percentage composition (0%, 4%, 8%, 16%, 32%).
The ternary solvent compound bio ink material of the addition HAP prepared in the present embodiment has good printing, PCL Matrix can be coated on the surface of HAP well, form stable interface cohesion, and PCL bracket in print procedure between the two Fiber has good bonding between layers, conducive to three-dimensional structure is formed.Final PCL scaffold fibers obtained are of uniform size constant Shape, moreover, bracket uniform pore diameter, shape is regular, highly controllable, more meets the demand of clinical bone tissue reparation.
The mechanical property of the PCL compound rest of different quality percentage composition HAP prepared by above-described embodiment 6 is carried out Research, the results are shown in Table 5.
The mechanical property of the PCL compound rest of 5 different quality percentage composition HAP of table
For data in contrast table it is found that relative to pure PCL bracket, a certain amount of HAP, which is added, can significantly improve PCL basis material Compressive strength and compression modulus.With the increase of Whisker Content, the compressive strength and compression modulus of bracket are in rising trend.And And the mechanical property measured under dry state is obviously than more preferable under hygrometric state, especially when Whisker Content is 16wt%, relative to Pure PCL group, compressive strength and compression modulus improve about 1.7 and 2.0 times, this shows that HAP, which is added, can reach activeness and quietness The effect of PCL bracket.But when Whisker Content is 32wt%, mechanical property slightly declines, this may be nano-chitosan crystalline substance Palpus content is easy to reunite and influence the mechanical property of complex stephanoporate bracket when more.
The experiment of osteoblast calcium tubercle:
The PCL for containing different quality percentage composition HAP (0%, 4%, 8%, 16%, 32%) obtained by embodiment 6 is compound Porous support materials are placed in 24 orifice plates, are embathed 2 times after ultraviolet sterilization 2 hours with PBS buffer solution, with every hole 1 × 104Density connect Simultaneously 1mL culture solution is added in kind osteoblast (MC3T3-E1), cultivates 21 days in 37 DEG C of incubators.Start within the 3rd day in culture, Osteoinductive differentiation complete medium is used within every 3 days instead (containing 10%FBS, 1% penicillin/streptomycin and 86.8% base Basal culture medium, 1% glutamine, 0.2% ascorbic acid, 1% sodium β-glycerophosphate, 0.01% dexamethasone) to MC3T3-E1 Cell carries out Osteoinductive differentiation.By Alizarin red staining calcium scoring sample after 21 days, cetylpyridinium chloride(CPC) is then used It is dissolved, collect lysate and OD value is measured at 540nm using spectrophotometer, on each component compound rest MC3T3-E1 cell carries out calcium tubercle quantitative detection, and concrete outcome is shown in Fig. 4.
It can be seen from the figure that, in pure PCL rack surface, calcium tubercle quantity was few by 21 days Fiber differentiations.Work as addition When 4wt%HAP, the calcium tubercle quantity on PCL compound rest is slightly increased；With further increasing for Whisker Content, hence it is evident that see Calcium tubercle increases on to bracket, especially the calcium tubercle on the PCL compound rest of 8wt%HAP and 16wt%HAP, induces mine Change effect highly significant.The result shows that adding a certain amount of HAP in compound bio ink material, it is remarkably improved 3D printing The osteogenic ability of complex stephanoporate bracket assigns the good osteogenic activity of complex stephanoporate bracket.
Embodiment 7 adds preparation and its 3D of magnesium-doped hydroxyapatite crystal whisker ternary solvent compound bio ink material Printing
Respectively by the hydroxyapatite crystal whisker for mixing magnesium of different quality (MgHAP, wherein the molar ratio of magnesium and calcium is 5:95) It is mixed with 7mL hexafluoroisopropanol, ultrasonic 50min forms homogeneous suspension liquid, and 1g polyglycolide (PGA, Mn=300000) is taken to be added Above-mentioned suspension magnetic agitation 4 hours, adds 1.6mL2- butyl cellosolve and 0.3mL citrate, after stirring 7 hours often Warm ultrasound discharge bubble, obtains the ternary solvent compound bio ink material for adding MgHAP.Then, syringe is moved it into side by side Bubble, according to the mathematical model built up, i.e. the cylindric 3D model of thickness 2mm, diameter 8mm print at 28 DEG C through syringe needle On receiving platform, print speed 18mm/s, the three-dimensional complex stephanoporate bracket finally formed by layer upon layer, then will be after drying Complex stephanoporate bracket is impregnated 20 hours with ethyl alcohol, removes surfactant and plasticizer, and vacuum drying obtains finally containing not homogeneity Measure the three-dimensional composite porous support material of the MgHAP of percentage composition (0%, 10%, 20%, 30%, 40%).
The ternary solvent compound bio ink material of the addition MgHAP prepared in the present embodiment has good printing, PGA matrix can be coated on the surface of MgHAP well, form stable interface cohesion, and PGA in print procedure between the two Scaffold fibers have good bonding between layers, conducive to three-dimensional structure is formed.Final PGA scaffold fibers obtained are of uniform size Indeformable, moreover, bracket uniform pore diameter, shape is regular, highly controllable, more meets the demand of clinical bone tissue reparation.
The mechanical property of the PGA compound rest of different quality percentage composition MgHAP prepared by above-described embodiment 7 is carried out Research, the results are shown in Table 6.
The mechanical property of the PGA compound rest of 6 different quality percentage composition MgHAP of table
For data in contrast table it is found that relative to pure PGA bracket, a certain amount of MgHAP, which is added, can significantly improve PGA basis material Compressive strength and compression modulus.Moreover, the mechanical property measured under dry state is obviously than good under hygrometric state, especially in whisker When content is 30wt%, relative to pure PGA group, compressive strength and compression modulus improve nearly 2.2 times and 2.4 times, this shows MgHAP, which is added, can achieve the effect that activeness and quietness PGA bracket.
Embodiment 8 adds the preparation and its 3D printing of the ternary solvent compound bio ink material of chitin whisker
It takes chitin whisker to mix with 3mL methylene chloride, forms homogeneous suspension liquid after ultrasonic 30min, then 1g PLLA is added Enter above-mentioned suspension, magnetic agitation 6 hours, 1.3mL butoxy ethanol and 0.5mL dibutyl is added after forming equal phase emulsion Phthalic acid ester, ultrasound discharge bubble, obtains the ternary solvent compound bio ink of addition chitin whisker after stirring 6 hours Material.Then, syringe bubble side by side is moved it into, according to the mathematical model built up, the i.e. cylinder of thickness 10mm, diameter 5mm Shape 3D model, is arranged print speed 10mm/s, and packed density 90% prints on receiving platform at 28 DEG C through syringe needle, finally Prepare complex stephanoporate bracket by layer upon layer, then the ethyl alcohol of the bracket after drying impregnated 8 hours, remove surfactant and Plasticizer, vacuum drying obtain the composite porous support material of the chitin whisker containing 10wt%.
Embodiment 9 adds the preparation and its 3D printing of the ternary solvent compound bio ink material of hydroxyapatite crystal whisker
It takes hydroxyapatite crystal whisker to mix with 4mL toluene, forms homogeneous suspension liquid after ultrasonic 50min, then 2g PLLA is added Enter above-mentioned suspension, magnetic agitation 10 hours, 1mL stearic acid and 0.2mL phthalic acid two (2 is added after forming equal phase emulsion - ethylhexyl) ester, ultrasound discharge bubble, obtains the compound life of ternary solvent of addition hydroxyapatite crystal whisker after stirring 10 hours Object ink material.Then, syringe bubble side by side is moved it into, according to the mathematical model built up, i.e. thickness 2mm, diameter 10mm Cylindric 3D model, print speed 15mm/s is set, and packed density 50% prints to receiving platform through syringe needle at 35 DEG C On, PLLA complex stephanoporate bracket finally is prepared by layer upon layer, then the ethyl alcohol of the complex stephanoporate bracket after drying is impregnated 12 Hour, vacuum drying obtains the composite porous support material of the hydroxyapatite crystal whisker containing 5wt%.
Embodiment 10 adds the preparation and its 3D printing of the ternary solvent bio-ink material of strontium-doped hydroxyapatite whisker
Take strontium-doped hydroxyapatite whisker (SrHAP, wherein the molar ratio of strontium and calcium is 10:90) mixed with 3mL chloroform It closes, forms homogeneous suspension liquid after ultrasonic 35min, then above-mentioned suspension is added in 1.2g PDLLA, magnetic agitation 5 hours, formed 1.5mL neopelex and 0.5mL citric acid rouge are added after equal phase emulsion, gas is discharged in room temperature ultrasound after stirring 4 hours Bubble obtains the ternary solvent compound bio ink material of addition strontium-doped hydroxyapatite whisker.Then, syringe is moved it into simultaneously Drive bubble away, according to the mathematical model built up, i.e. print speed 5mm/ is arranged in the cylindric 3D model of thickness 5mm, diameter 5mm S, packed density 70% print on receiving platform at 20 DEG C through syringe needle, finally compound more by layer upon layer preparation PDLLA Hole bracket, then the ethyl alcohol of the complex stephanoporate bracket after drying is impregnated 8 hours, surfactant and plasticizer are removed, vacuum is dry The dry composite porous support material for obtaining the whisker of strontium-doped hydroxyapatite containing 20wt%.
Embodiment 11 adds the preparation for mixing the ternary solvent compound bio ink material of magnesium hydroxyapatite crystal whisker and its 3D Printing
It takes and mixes magnesium hydroxyapatite crystal whisker (MgHAP, wherein magnesium and the molar ratio of calcium are 15:85) and mixed with 5mL acetone, it is super Homogeneous suspension liquid is formed after sound 40min, then above-mentioned suspension is added in 1.5g PCL, magnetic agitation 8 hours, forms equal phase emulsion 1.7mL stearic acid and 0.1mL dibutyl phthalate are added afterwards, bubble is discharged in room temperature ultrasound after stirring 2 hours, is mixed The ternary solvent compound bio ink material of magnesium hydroxyapatite crystal whisker.Then, it moves it into syringe and drives bubble away, according to The mathematical model built up, the cylindric 3D model of thickness 8mm, diameter 5mm, setting print speed 20mm/s, packed density 30%, It is printed on receiving platform at 30 DEG C through syringe needle, finally prepares three-dimensional complex stephanoporate bracket by layer upon layer, then will dry Complex stephanoporate bracket afterwards is impregnated 6 hours with ethyl alcohol, removes surfactant and plasticizer, and vacuum drying obtains mixing containing 40wt% The three-dimensional composite porous support material of magnesium hydroxyapatite crystal whisker.
Comparative example 1 adds the preparation and its 3D printing of the single solvent compound bio ink material of chitin whisker
It takes chitin whisker to mix with 3mL methylene chloride, forms homogeneous suspension liquid after ultrasonic 30min, then by 1g PLLA (Mn=100000) above-mentioned suspension is added, forms within magnetic agitation 6 hours equal phase emulsion, then ultrasound discharge bubble, obtains crust The single solvent compound bio ink material of plain whisker.Then, it moves it into syringe and bubble is discharged, according to the number built up Print speed 10mm/s, packed density 90%, at 28 DEG C is arranged in the cylindric 3D model of model, i.e. thickness 10mm, diameter 5mm It is printed on receiving platform through syringe needle, finally prepares complex stephanoporate bracket by layer upon layer, then by the bracket second after drying Alcohol impregnates 8 hours, removes surfactant and plasticizer, and vacuum drying obtains the compound porous branch of the chitin whisker containing 10wt% Frame material.
Fig. 5 is that the chitin whisker containing 10wt% that in comparative example 1 prepared by single solvent compound bio ink material is compound more The top view (a) and side view (c) of hole bracket；What in embodiment 8 prepared by ternary solvent compound bio ink material contains 10wt% The top view (b) and side view (d) of the complex stephanoporate bracket of chitin whisker.From figure (a) and (b) as can be seen that single solvent For porous support prepared by compound bio ink material since solvent quickly volatilizees, the caking property of fiber is poor, cannot the company of being formed Continuous tow.In addition, being difficult to form three-dimensional knot by the porous support for scheming single solvent compound bio ink material preparation known to (c) Structure, and syringe needle is easily blocked in print procedure, it influences subsequent ink and squeezes out.And from figure (d) it is found that ternary solvent compound bio ink Water material has good printability, and extrusion fiber has good bonding between layers in print procedure, is conducive to shape At three-dimensional structure.Not only even thickness is indeformable for the compound rest fiber finally prepared, moreover, the uniform pore diameter of bracket, shape It is regular, it is highly controllable, more meet the demand of clinical bone tissue reparation.
Comparative example 2 adds the preparation and its 3D printing of the single solvent compound bio ink material of hydroxyapatite crystal whisker
It takes hydroxyapatite crystal whisker to mix with 4mL toluene, forms homogeneous suspension liquid after ultrasonic 50min, then by 2g PLLA (Mn=50000) above-mentioned suspension is added, magnetic agitation 10 hours, is formed after equal phase emulsion and bubble is discharged in ultrasound, added Add the single solvent compound bio ink material of hydroxyapatite crystal whisker.Then, it moves it into syringe and drives bubble out of, according to Print speed 15mm/s, packed density is arranged in the cylindric 3D model of the mathematical model built up, i.e. thickness 2mm, diameter 10mm 50%, printed on receiving platform through syringe needle at 35 DEG C, finally prepare complex stephanoporate bracket by layer upon layer, then will it is dry after Bracket impregnated 24 hours with ethyl alcohol, remove surfactant and plasticizer, vacuum drying obtains hydroxyapatite whisker containing 5wt% The composite porous support material of palpus.
It can be observed in print procedure, the compound life of single solvent of the addition hydroxyapatite crystal whisker prepared in this comparative example Object ink material evaporation rate is fast, and the PLLA fibers adhesion of extrusion is poor, and prepared bracket is difficult to be formed three-dimensional structure, and Syringe needle is easily blocked in print procedure, shadow is unfavorable for subsequent ink and squeezes out.And addition hydroxyapatite crystal whisker obtained in embodiment 9 The preparation of ternary solvent compound bio ink material scaffold fibers even thickness it is indeformable, and fiber is squeezed out in print procedure There is good bonding between layers, conducive to three-dimensional structure is formed, moreover, complex stephanoporate bracket uniform pore diameter, shape is regular, high Degree is controllable, more meets the demand of clinical bone tissue reparation.
Comparative example 3 adds the preparation of the single solvent compound bio ink material of strontium-doped hydroxyapatite whisker and its 3D is beaten Print
It takes strontium-doped hydroxyapatite whisker to mix with 3mL chloroform, forms homogeneous suspension liquid after ultrasonic 45min, then will Above-mentioned suspension is added in 1.2g PDLLA (Mn=200000), magnetic agitation 5 hours, forms ultrasound discharge gas after equal phase emulsion Bubble obtains the single solvent compound bio ink material of addition strontium-doped hydroxyapatite whisker.Then, syringe is moved it into simultaneously Drive bubble out of, according to the mathematical model built up, i.e. print speed 5mm/ is arranged in the cylindric 3D model of thickness 5mm, diameter 5mm S, packed density 70% are printed on receiving platform through syringe needle at 20 DEG C, finally prepare complex stephanoporate bracket by layer upon layer, The ethyl alcohol of the bracket after drying is impregnated 14 hours again, removes surfactant and plasticizer, vacuum drying is obtained containing 20wt% The composite porous support material of strontium-doped hydroxyapatite whisker.
The single solvent ink material of the addition strontium-doped hydroxyapatite whisker prepared in this comparative example is in print procedure Since solvent quickly volatilizees, quickly, the caking property of fiber is poor for PDLLA matrix curing rate, cannot form continuous tow, institute The bracket of preparation is difficult to form three-dimensional structure.And the ternary solvent of addition strontium-doped hydroxyapatite whisker prepared by embodiment 10 is raw Object ink material has good printability, and fiber is squeezed out in print procedure good bonding between layers, is conducive to Three-dimensional structure is formed, not only even thickness is indeformable for the scaffold fibers of preparation, moreover, the uniform pore diameter of bracket, shape is regular, high Degree is controllable, more meets the demand of clinical bone tissue reparation.
Comparative example 4 adds the preparation for mixing the single solvent compound bio ink material of magnesium hydroxyapatite crystal whisker and its 3D is beaten Print
It takes and mixes magnesium hydroxyapatite crystal whisker and mixed with 5mL acetone, form homogeneous suspension liquid after ultrasonic 40min, then by 1.5g Above-mentioned suspension is added in PCL (Mn=150000), magnetic agitation 8 hours, forms ultrasound discharge bubble after equal phase emulsion, is added Add the single solvent compound bio ink material for mixing magnesium hydroxyapatite crystal whisker.Then, it is injected into syringe and bubble is discharged, According to the mathematical model built up, print speed 20mm/s, packed density is arranged in the cylindric 3D model of thickness 8mm, diameter 5mm 30%, it is printed on receiving platform through syringe needle at 30 DEG C, finally prepares porous support by layer upon layer, then will be more after drying Hole bracket is impregnated 6 hours with ethyl alcohol, removes surfactant and plasticizer, and vacuum drying obtains mixing magnesium hydroxy-apatite containing 40wt% Stone crystal whisker porous support materials.
Addition 40wt% in this comparative example mixes prepared by the compound ink material of single solvent of magnesium hydroxyapatite crystal whisker Bracket be difficult to form three-dimensional structure, since solvent quickly volatilizees, the caking property of fiber is poor, cannot form continuous tow. And syringe needle is easily blocked in print procedure, it influences subsequent ink and squeezes out.And addition 40wt% obtained by embodiment 11 mixes magnesium hydroxyl phosphorus The ternary solvent compound bio ink material of grey stone crystal whisker has printing property well, in print procedure PCL scaffold fibers layer with There is good bonding between layer, conducive to three-dimensional structure is formed.Final PCL scaffold fibers obtained are of uniform size indeformable, moreover, Bracket uniform pore diameter, shape is regular, highly controllable, more meets the demand of clinical bone tissue reparation.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention, It should be equivalent substitute mode, be included within the scope of the present invention.

Claims (10)

1. a kind of 3D printing compound bio ink material, which is characterized in that it includes the constituent of following mass fraction:
Biodegradable polyester 2~25%
Activeness and quietness agent 0.2~25%
Ternary solvent system 50~97.8%；
Wherein the ternary solvent system is specifically made of organic solvent, surfactant and plasticizer.
2. 3D printing compound bio ink material according to claim 1, it is characterised in that:
The mass percentage of the ternary solvent system forms are as follows: organic solvent 40~90%, surfactant 5~45%, Plasticizer 5~45%.
3. 3D printing compound bio ink material according to claim 1 or 2, it is characterised in that:
The organic solvent is at least one in methylene chloride, chloroform, tetrahydrofuran, acetone, hexafluoroisopropanol and toluene Kind；
The surfactant is at least one of butoxy ethanol, stearic acid and neopelex；
The plasticizer be dibutyl phthalate, citrate and phthalic acid two (2- ethylhexyl) ester in extremely Few one kind.
4. 3D printing compound bio ink material according to claim 1, it is characterised in that:
The Biodegradable polyester is poly- (L- lactide), poly- (D, L- lactide), poly- (6-caprolactone), polyglycolide and poly- At least one of (lactide-co-glycolide)；
The activeness and quietness agent is chitin whisker, hydroxyapatite crystal whisker, adulterates the hydroxyapatite crystal whisker of strontium and magnesium-doped At least one of hydroxyapatite crystal whisker.
5. 3D printing compound bio ink material according to claim 4, it is characterised in that:
The diameter of the chitin whisker is 5~70nm, and length is 80nm~1 μm, and draw ratio is 10~200；
The diameter of the hydroxyapatite crystal whisker is 5~100nm, and length is 400nm~2 μm, and draw ratio is 5~400；
It is described doping strontium hydroxyapatite crystal whisker diameter be 10~500nm, length be 50nm~2 μm, draw ratio be 5~ 200；The molar ratio of strontium and calcium is 0.5:99.5~15:85；
The diameter of the magnesium-doped hydroxyapatite crystal whisker be 20~500nm, length be 200nm~2 μm, draw ratio be 2~ 100；The molar ratio of magnesium and calcium is 0.5:99.5~20:80.
6. a kind of method for preparing any one of Claims 1 to 5 3D printing compound bio ink material, which is characterized in that Specific steps are as follows:
After activeness and quietness agent is mixed with organic solvent, carries out ultrasonic disperse and form homogeneous suspension liquid；Then biodegrade is added Polyester stirs evenly, and forms homogeneous single solvent compound system, then sequentially adds surfactant and plasticizer uniformly mixes Tri compound dicyandiamide solution is formed, is again stirring for, 3D printing compound bio ink material is prepared.
7. the preparation method of 3D printing compound bio ink material according to claim 6, it is characterised in that:
The time of the ultrasonic disperse is 20~60min；
The time of the first time stirring is 3~10 hours, and the time being again stirring for is 2~12 hours.
8. a kind of three-dimensional complex stephanoporate bracket, any one of according to claim 1~5 3D printing compound bio ink material system It is standby to obtain.
9. a kind of method for preparing three-dimensional complex stephanoporate bracket described in claim 8, which is characterized in that specific steps are as follows:
Above-mentioned 3D printing compound bio ink material is excluded into bubble, and controlling print speed is 5~40mm/s, packed density 30 ~95%, it is printed on receiving platform by syringe through syringe needle at a temperature of 20~35 DEG C, along Z axis layer upon layer, is had There is the complex stephanoporate bracket of three-dimensional structure, will be purified after the drying of gained complex stephanoporate bracket, then be dried in vacuo and purified Three-dimensional complex stephanoporate bracket afterwards.
10. application of the three-dimensional complex stephanoporate bracket in bone tissue reparation according to claim 8.
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CN112843337A (en) * 2021-01-27 2021-05-28 暨南大学 Silk bionic bio-ink and preparation method and application thereof
CN113858610A (en) * 2021-09-06 2021-12-31 江苏卓见医疗用品有限公司 Medical fibrous surface dressing and preparation method and application thereof
CN113858610B (en) * 2021-09-06 2024-04-19 江苏卓见医疗用品有限公司 Medical fibrous surface dressing and preparation method and application thereof
CN113845700A (en) * 2021-09-28 2021-12-28 四川大学 Barium titanate matrix composite material and DIW printing forming method and application thereof
CN113845700B (en) * 2021-09-28 2022-10-14 四川大学 Barium titanate matrix composite material and DIW printing forming method and application thereof
CN117511494A (en) * 2024-01-08 2024-02-06 山东德亿佳胶业有限公司 High-transparency shadowless adhesive and preparation method thereof
CN117511494B (en) * 2024-01-08 2024-03-22 山东德亿佳胶业有限公司 High-transparency shadowless adhesive and preparation method thereof

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