CN115282344A

CN115282344A - Ionic polymer 3D printing ink and preparation method and application thereof

Info

Publication number: CN115282344A
Application number: CN202210963487.8A
Authority: CN
Inventors: 王祖勇; 刘鹏; 马超; 丁元力
Original assignee: Hunan University
Current assignee: Hunan University
Priority date: 2022-08-11
Filing date: 2022-08-11
Publication date: 2022-11-04

Abstract

The invention discloses ionic polymer 3D printing ink and a preparation method and application thereof. The ionic polymer 3D printing ink comprises a polymer solute which is biocompatible and contains negative electricity groups and/or neutral polar groups, salts containing metal ions with bioactivity and D-layer hollow orbitals and a solvent capable of dissolving the polymer solute and the salts; the 3D printing ink is biocompatible in formula design, stable in component chemistry, high in compatibility with target materials, high in solute concentration, controllable in positioning and fluidity, particularly suitable for 3D printing of rapid manufacturing materials, capable of being applied to novel tissue engineering supports, capable of providing appropriate biomedical materials for clinical application of in-situ tissue engineering technology, and expected to improve the regeneration treatment effect of damaged tissues and organs clinically.

Description

Ionic polymer 3D printing ink and preparation method and application thereof

Technical Field

The invention relates to 3D printing ink, in particular to ionic polymer ink for 3D printing, a preparation method of the ionic polymer ink, and a material processing and forming method for regulating ink viscosity and increasing fluidity by adopting metal ions, and belongs to the technical field of material manufacturing.

Background

The polymer material is widely applied to the fields of traffic, construction, energy, medical treatment and the like, and plays an important role in promoting the development of economy and science and technology. Compared with metal and ceramic materials, the high polymer material is formed by the actions of intra-chain covalent bonds, intra-chain and inter-chain hydrogen bonds and the like, and has the advantages of unique high elasticity, toughness, fatigue resistance, corrosion resistance, light weight and the like. In recent years, with the great development and wide use of plastics, polymer materials cause serious "white pollution" to the environment, and even tiny plastic particles appear in living bodies such as humans and animals. This makes the new polymer materials such as Polycaprolactone (PCL), polylactic acid (PLA) and the like have unique degradability and good biocompatibility, and thus are widely regarded as important materials, for example, for food and medical and health products.

The function of the high molecular material depends on chemical composition and structure, and the characteristics and the use performance of the high molecular material are closely related to the processing and forming process of the high molecular material. Conventional polymer processing methods such as injection molding, extrusion molding, blow molding, electrospinning, etc. have been widely used industrially. In recent years, mechanical equipment is rapidly developed, and a novel polymer material manufacturing technology is developed in large quantities. Among them, 3D printing technology (also called additive manufacturing technology) has gained rapid development and market favor. The technology is based on computer-aided digital model design and accurate layer-by-layer manufacturing process, and realizes rapid material manufacturing through 3D printing of ink. In general, 3D printing requires the use of ink in solution or molten state to impart fluid characteristics to the material. Among these, viscosity is an important characteristic of ink and a key factor affecting 3D printing speed and quality. Too high ink viscosity results in significantly reduced material flow, severe tailing, increased energy consumption, and reduced printing speed. Currently, approaches to reduce the viscosity of polymeric fluids include increasing the temperature, reducing the solute concentration, and using adjuvants. Recent studies have shown that increasing Temperature can reduce The Viscosity of Polydimethylsiloxane (PDMS) by increasing The distance between polymer chains by increasing kinetic energy, resulting in lower attraction between polymer chains and reduced friction, resulting in lower Viscosity and faster material flow (Yuri et al, in flow of The Temperature on The Viscosity of Different Types of silicones, the Journal of plastics 30 (2018): 4-9). However, the increase in temperature affects the physicochemical properties of the material, and easily results in the loss of the biological activity of the material. Meanwhile, the reduction of the solute concentration is also one of the effective methods for controlling the viscosity of the ink. For example, concentration has a large effect on the viscosity of a Polystyrene (PS) solution, and the higher the concentration of PS at the same shear rate, the higher the viscosity, the higher the probability of entanglement between Polymer chains, and the significantly reduced flow ability (Mumbach et al, A closed-loop process design for recycling expanded polystyrene by dispersion and polymerization, polymer 209 (2020): 122940). In addition, the viscosity of the ink can be changed by regulating and controlling the concentration of the solute, and the 3D printing quality is further influenced. For example, during electro-hydrodynamic 3D printing, the decrease in the concentration of the solute Polycaprolactone (PCL) (5%g/mL) can control the viscoelasticity of the ink, transition the jet from a trailing state to a non-trailing jet state, and significantly improve the positioning accuracy of 3D printing (Guo et al, electro-hydrodynamic jet printing via low-solvent communication inputs for enhanced positioning access, materials Technology, 2022). However, the significantly reduced solute concentration significantly degrades the 3D printing rate and quality. At present, the solute concentration of the electrohydrodynamic 3D printing PCL ink is mostly between 20% and 40% (g/mL), and the maximum concentration is not more than 70% (g/mL).

In the aspect of using the auxiliary agent, the intermolecular interaction force between chains is reduced mainly by weakening the secondary valence bond between the polymer chains, so that the viscosity of the system is reduced. The latest research finds that the cellulose is used for chlorinating 1-butyl-3-methyl imidazole chloride ([ Bmim) in the ionic liquid]Cl) and the viscosity of the system is in copper chloride (CuCl) ₂ ) Is significantly reduced when it occurs by the mechanism of copper ion and [ Bmim ]]Cl action weakens the hydrogen bonding between ionic liquids (family al, A novel strand to reduce the sensitivity of cellulose-ionic liquid adsorbed by transition metals, carbohydrate Polymers256 (2021): 117535). In addition, it has also been reported that poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) formulations can be supplemented withTriethyl citrate (TEC) can significantly reduce its melt viscosity and simultaneously lower the melting point and glass transition temperature, so that the prepared sample obtains ductility: (

al, green compositions of poly (3-hydroxybutylate-co-3-hydroxyvalete) and succinane basic fibers plated with tertiary circuits: thermal, mechanical and morphological properties, journal of Applied Polymer Science (2022): e 52782). The adjuvant method has the advantages of simple process and low cost. However, the use of more auxiliary agents such as o-benzene organic plasticizers has the risk of carcinogenesis, serious safety problems of health hazard and environmental pollution, and production and use of the o-benzene organic plasticizers are prohibited in many countries. Therefore, reducing the viscosity of an ink system to improve the fluidity and the printing quality thereof while increasing the solute concentration of the ink to increase the manufacturing speed is an urgent problem to be solved in the field of 3D printing technology.

Disclosure of Invention

In order to solve the above technical problems, an object of the present invention is to provide an ionic polymer 3D printing ink, which is biocompatible in formulation design, chemically stable in composition, high in compatibility with target materials, and has high solute concentration and controllable viscosity and fluidity, and is particularly suitable for 3D printing of rapid manufacturing materials, can be applied to a novel tissue engineering scaffold, provides a suitable biomedical material for clinical application of in-situ tissue engineering technology, and is expected to improve the regeneration treatment effect of damaged tissues and organs clinically.

The second purpose of the invention is to provide a method for preparing ionic polymer 3D printing ink with simple operation and good repeatability, the method combines metal ions and a composite solvent to prepare ionic polymer 3D printing ink with high solute concentration, adjustable and controllable viscosity and fluidity, and solves the problem that the existing 3D printing ink cannot meet the requirements of high solute concentration, adjustable viscosity and adjustable fluidity due to coupling of solute concentration and material viscosity/fluidity, and the manufacturing speed and quality of 3D printing materials cannot be broken through.

The third purpose of the invention is to provide a method for stably manufacturing a functional tissue engineering scaffold with large size, which combines the common 3D printing technology and the ionic polymer ink to realize the 3D printing of the ink with high solute concentration and manufacture the tissue engineering scaffold with the loading of bioactive metal ions and specific geometric clues, and solves the problems that the current polymer scaffold has single function, is not easy to degrade and regulate, has complex manufacturing process, cannot meet the reconstruction requirement of the key microenvironment for tissue and organ regeneration, and causes poor clinical treatment effect.

In order to achieve the technical purpose, the invention provides ionic polymer 3D printing ink which comprises a component I, a component II and a component III; the component I is a high molecular solute which is biocompatible and comprises electronegative groups and/or neutral polar groups; the component II is salts containing metal ions with bioactivity and d-layer empty orbits; the component III is a solvent A, or a solvent A and a solvent B, or a solvent A, a solvent B and a solvent C: the solvent A is a non-ionic liquid solvent capable of dissolving the component I; the solvent B is a solvent capable of dissolving the component II; the C solvent is an amphiphilic solvent.

The invention provides ionic polymer 3D printing ink which comprises three hierarchical systems: the component I has biocompatibility and contains a high molecular material with electronegative groups and/or neutral polar groups as a macroscopically uniform solute system; taking the salt with bioactivity of the component II and d-layer empty orbit metal ions as a macroscopically uniform additive system; and a solvent with good solubility to high polymer materials and salts in the component III is used for forming a macroscopically uniform solvent system. The polymer solute can participate in coordination and complexation of metal ions by utilizing negative electricity groups or polar groups of the polymer solute, the ink can be ensured to have low viscosity and high fluidity under the condition of improving the concentration of the polymer solute, and the solvent is a benign solvent capable of dissolving polymers and metal salts simultaneously, so that the formation of a homogeneous system is facilitated.

As a preferable mode, the component I (polymeric solute) is a degradable and/or non-degradable polymeric material formed by participating in at least one of the element C and the element N, O, S, P. Preferably at least one of polycaprolactone and derivatives thereof, polylactic acid and derivatives thereof, polyglycolic acid and derivatives thereof, polyvinyl alcohol and derivatives thereof, cellulose and derivatives thereof, polyethylene oxide and derivatives thereof, polyaryletherketone and derivatives thereof, polyamide and derivatives thereof, and polyimide and derivatives thereof. The polymer materials are common polymer materials with good biocompatibility, and the polymer materials contain polar groups or negative electricity groups which can participate in coordination and complexation of metal ions.

As a preferable embodiment, the component II contains at least one metal ion of titanium ion, vanadium ion, manganese ion, iron ion, copper ion, zinc ion, zirconium ion, niobium ion, silver ion, and tantalum ion. Also contains anions for balancing metal ions, such as F-, cl-, and CO ₃ ^2- 、SO ₄ ^2- 、NO ^3- 、PO ₄ ^3- At least one of them. The preferable metal ions contain d layers of empty orbits, have certain biological activity, and have the regulation effect on the structures and functions of cells, tissues and organs, including metabolism, immunity and differentiation, by slowly releasing the metal ions.

In a more preferred embodiment, the solvent a is at least one selected from the group consisting of water, alcohol solvents (more preferably small molecule alcohol solvents such as methanol, ethanol, isopropanol, n-butanol, etc.), tetrahydrofuran, ethyl acetate, dichloromethane, and carbon tetrachloride. In a preferred embodiment, the solvent B is at least one selected from water and alcohol solvents. As a preferable embodiment, the solvent C is selected from alcohol solvents (more preferably, small molecule alcohol solvents such as methanol, ethanol, isopropanol, n-butanol, etc.). When the solvent A is selected from water and alcohol solvents, the solvent A and the solvent B are the same because the water and alcohol solvents can dissolve salts at the same time, and thus the solvent C does not need to be added. Alternatively, when the solvent A is selected from, for example, oily organic solvents other than water and alcohol solvents, if the solvent A is well compatible with the solvent B (selected from, for example, alcohol solvents), the solvent C need not be added. Or, when the solvent A needs to be selected from oily organic solvents except water and alcohol solvents, if the compatibility of the solvent A and the solvent B is poor, the solvent C needs to be added, and the amphiphilic solvent is utilized to enhance the intersolubility and stability between the solvent A and the solvent B, so that a homogeneous ink system is obtained. The volume percentage composition of the solvent A and the solvent B is 100 percent, 0 percent to 50 percent and 50 percent (mL/mL). The choice of solvent C is determined by the compatibility degree and volume ratio between solvent A and solvent B, and the choice of solvent C is easily determined by those skilled in the art based on the solvent A and solvent B disclosed in the present invention.

As a preferred embodiment, the mass/volume fraction of component I to component III does not exceed 1000% (g/mL); the mass/volume fraction of the component I and the component III is further preferably 100 to 600% (g/mL).

As a preferred embodiment, the mass/mole ratio of component I to component II is 10 ² ～2×10 ⁷ g/mol; the mass/mole ratio of the component I to the component II is further preferably 1X 10 ³ ～1×10 ⁵ g/mol。

The adjustable and controllable viscosity and fluidity of the ionic polymer 3D printing ink provided by the invention are mainly determined by the metal element type of the metal salt, the metal ion concentration and the action time of the metal salt with the polymer, and are reduced along with the increase of the electrophilic capacity of the metal element, the metal ion concentration and the action time of the polymer.

The invention also provides a formula and a preparation method of the ionic polymer 3D printing ink, wherein the method comprises the following steps of uniformly mixing the component I and the component II, and adding the component III in the following modes of a, b or c: a: adding the solvent B in the component III, and stirring for dissolving; b: adding the solvent B in the component III, stirring for dissolving, adding the solvent A in the component III, and stirring for dissolving; c: adding the solvent B in the component III, stirring for dissolving, then adding the solvent A in the component III, stirring for dissolving, then adding the solvent C in the component III, and stirring for dissolving.

The preparation method of the ionic polymer 3D printing ink comprises the following steps:

1) Uniformly mixing a component I (high molecular solute) and a component II (metal salt) to obtain a solid mixture;

2) Adding the solvent B in the component III into the mixture, and uniformly mixing to obtain a mixed system (or solution);

3) Adding the solvent A in the component III into the mixture and uniformly mixing to form a solution (or layering phenomenon exists);

4) Adding the solvent C in the component III to form a solution;

of course, it will be appreciated that when solvent B is added a homogeneous solution is formed, no further addition of solvent A and solvent C is required, and when solvent A is added a homogeneous solution is formed, no further addition of solvent C is required.

As a preferable scheme, in the step 1), the blending process parameters of the component I and the component II are as follows: the temperature is 15-30 ℃, the rotating speed is 40-80 rpm, and the time is 3-8 min.

As a preferable scheme, in the step 1), the mass/mol ratio of the component I to the component II is determined by the solubility of the component I and the component II in the composite solvent system, wherein the mass/mol ratio of the component I to the component II can be 1-100g ^-8 ～1×10 ^-2 mol。

As a preferable mode, in the step 1), the mass/volume fraction of the component I (high molecular material) as a solute to the component III (solvent) is not more than 1000% (g/ml).

As a preferable mode, in the step 2) and the step 3), when the solvent B in the component III is amphiphilic and the solvent a is hydrophilic or lipophilic, the volume percentage of the solvent B to the total volume of the component III is 5 to 50% v/v; when the solvent B and the solvent A are respectively hydrophilic and lipophilic, the solvent C is required to establish a composite solvent system, the latter is amphiphilic, and the total volume of the solvent B and the solvent B accounts for 5 to 50 percent of the total volume of the component III; the solvent A and the solvent B are the same solvent or homologous compounds, and when the solvents are both hydrophilic or lipophilic, the volume ratio of the solvents is not limited.

As a preferable scheme, in the step 2), when the solvent B and the solvent A in the component III are different solvents or non-homologous compounds, the component II solution and the component I form a solid-liquid mixture; when the solvent B and the solvent A are the same solvent or homologous compounds, the component II solution and the component I form a solution.

As a preferable scheme, in the step 2), the component II solution and the component I are fully stirred and uniformly mixed, and the process parameters are as follows: the temperature is 15-30 ℃, the rotating speed is 40-80 rpm, and the time is 0.5-1.5 min.

As a preferred variant, in step 3), the percentage of the volume of solvent A in component III based on the total volume of component III is from 50 to 95% v/v.

As a preferable scheme, in the step 3), the solvent a in the component III is fully and uniformly mixed in the adding process, and the process parameters are as follows: the temperature is 15-30 ℃, the rotating speed is 40-80 rpm, and the time is 3-8 min. Then, the container is slowly rotated to completely dissolve the component I, and the process parameters are as follows: the temperature is 15-30 ℃, the rotating speed is 5-20 rpm, and the time is not less than 24h.

As a preferable scheme, in the step 3), when the mass volume fraction of the component I exceeds the solubility, the component I is heated to be dissolved and fully reacts with metal ions, and the process parameters are as follows: the temperature is 10-20 ℃ higher than the melting point of the polymer, the rotating speed is 1-3 rpm, and the time is 20-40 min. Then, cooling at room temperature, wherein the process parameters are as follows: the temperature is 15-30 ℃, the rotating speed is 5-20 rpm, and the time is not less than 1h.

The invention also provides a method for preparing a device by 3D printing of the ionic polymer ink, which comprises the following steps:

1) Loading the ionic polymer 3D printing ink into an injector;

2) Importing a pre-designed device structure into a3D printing system, setting printing parameters, and printing;

3) And peeling the printed device from the substrate to obtain the printed device.

As a preferred aspect, the viscosity of the ionic polymer 3D printing ink is not more than 1000pa · s.

As a preferable scheme, the printing parameters are set as: the feeding speed is 5-100 mu L/min, the diameter of the nozzle is 19-31G, and the relative speed of the platform is more than 1mm/s.

Preferably, the ionic polymer 3D printing ink has a mass/volume percentage concentration of greater than 100% g/ml.

The printing device prepared from the ionic polymer 3D printing ink has adjustable geometric structure and degradation rate, and has the functions of structural support and cell regulation.

The ionic polymer 3D printing ink provided by the invention is used for 3D printing to realize the processing and forming of high-concentration and ultrahigh-concentration fluid and the rapid and high-precision material manufacturing, and specifically comprises the following steps:

1) Loading the ionic polymer 3D printing ink into an injector;

2) Importing a pre-designed device structure into a3D printing system, setting printing parameters and printing;

3) And peeling the printed material structure from the substrate to form the self-supporting bracket.

As a preferable scheme, in the step 1), the ionic polymer 3D printing ink is required to have proper fluidity, and the viscosity thereof is not more than 1000pa × s.

As a preferred solution, in step 1), the ink injection process needs to avoid air bubbles entering the conduit.

As a preferable scheme, in the step 2), the pre-designed device structure is composed of fibers, a sheet structure is formed by single fibers, and a3D structure is formed by stacking sheets. The single fibers form a specific geometric pattern, so that the lamellar structure has bionic human tissue structure characteristics including at least one of linear shape, circular shape, elliptical shape, spiral shape, diamond shape and square shape. The single fibers are fused into a geometric pattern structure through materials, and then the lamination of the lamellar structure and the interlayer is realized.

As a preferable scheme, in the step 2), the 3D printing parameter setting includes a feeding speed, a nozzle diameter, a voltage, a nozzle-substrate spacing and a platform relative speed, wherein the feeding speed is 5 to 100 μ L/min, the nozzle diameter is 19 to 31G, and the platform relative speed is greater than 1mm/s.

As a preferable scheme, in step 2), the 3D printing can be performed in at least one of three modes. Wherein the nozzle-substrate spacing of the first mode is 5-200 μm, the nozzle-substrate spacing of the second mode is 0.200-5 mm, and the nozzle-substrate spacing of the third mode (i.e., the electrospinning mode) is 5-20 cm.

As a preferable scheme, in the step 3), the length, the width and the height of the bracket respectively do not exceed 20cm, 20cm and 15cm.

As a preferable scheme, in the step 3), the width of the fiber forming the bracket is 1-1000 μm, wherein the positioning precision of the fiber is better than 10 μm.

As a preferable scheme, in the step 3), the degradation rate and the mechanical property of the fiber forming the scaffold are adjustable and controllable. Wherein the degradation rate increases with increasing content of component II; the mechanical strength, elasticity and plasticity are reduced along with the increase of the content of the component II.

As a preferred solution, in step 3), component I of the 3D printing ink provides structural support, mechanical properties and geometric clues to the scaffold during tissue engineering regeneration treatment, and component II provides bioactive ions to the scaffold.

The present invention provides an ionic polymer 3D printing ink built with high concentration of solute (mass/volume fraction greater than 100%) and bioactive metal salt, comprising a three component system (as shown in FIG. 1):

macroscopically homogeneous solute system (component i): the ink is composed of high polymer materials, is derived from synthetic or natural materials, is used as a solute component of the ink, and provides structural support, mechanical properties and geometric clues for regulating and controlling cells and tissues of a3D printing support;

macroscopically homogeneous active agent system (component ii): the ink consists of metal salt, is derived from the metal salt (metal ions contain D layers of empty orbitals), is used as an active agent component of the ink, reduces the fluid viscosity of the ink, and provides degradation regulation of a3D printing bracket and bioactive ions for regulating and controlling cells and tissues;

macroscopically homogeneous solvent system (component iii): the ink consists of a solvent A (a benign solvent for dissolving macromolecules), a solvent B (a benign solvent for dissolving metal salts) and a solvent C (an amphiphilic auxiliary solvent), is derived from hydrophilic, lipophilic and amphiphilic organic or inorganic liquid, is used as a solvent component of the ink, dissolves macromolecules and metal salts, stabilizes a solvent system, provides the fluidity of the ink in the 3D printing process, and provides the possibility of the interaction of the macromolecules and metal ions.

The formula and the preparation method of the ionic polymer ink provided by the invention comprise the following specific steps:

(1) Adding component I to a glass container so that the mass/volume fraction of component I to the solvent is 50-1000% g/ml; weighing component II metal salt into a glass container, wherein the mass/mol ratio of the component II metal salt to the polymer is 1-100g ^-8 ～1×10 ^- ² Between mol; stirring and uniformly mixing the polymer and the metal salt; the technological parameters of solid mixing are as follows: the temperature was 21 ℃, the rotation speed was 60rpm, and the time was 5min.

(2) Adding solvent B to the glass container of step (1), the volume of solvent B as a percentage of the volume of component III being 5-50% v/v; if the solvent B is incompatible with the solvent A, the solvent C is required to be measured, wherein the volume of the solvent B and the solvent C and the volume percentage of the solvent B to the volume of the component III are 5 to 50 percent; if the physical properties of the solvent B are the same as those of the solvent A, the solvent B is not limited by the volume fraction; stirring to dissolve metal salt, and mixing with polymer; the technological parameters of solid-liquid stirring are as follows: the temperature was 21 ℃, the rotation speed was 60rpm, and the time was 1min.

(3) Adding solvent A to the glass container of step (2) in a volume percent of 50-95% based on the volume of component III; if the physical properties of the solvent A and the solvent B are the same, the solvent A is not limited by the volume fraction; rapidly stirring to uniformly mix the component I with the component II and the solvents A and B, wherein the process parameters are as follows: the temperature is 21 ℃, the rotating speed is 60rpm, and the time is 5min; slowly mixing the component I, the component II and the component III uniformly when the component I begins to dissolve, wherein the process parameters are as follows: the temperature is 21 ℃, the rotating speed is 10rpm, and the time is not less than 1h; if the solubility of the component I exceeds the solubility, sequentially heating to melt the component I, fully reacting with metal ions, and cooling at room temperature, wherein the heating process parameters are as follows: the melting point of the component I at a temperature higher than the melting point of the component I is 10-20 ℃, the rotating speed is 2rpm, the time is 30min, and the cooling process parameters are as follows: the temperature is 21 ℃, the rotating speed is 10rpm, and the time is not less than 1h.

The application method of the ionic polymer 3D printing ink provided by the invention comprises the following specific steps:

(1) And loading the selected ionic polymer 3D printing ink into a3D printing device, so that bubbles are prevented from entering a conduit, and the printing viscosity of the ink is not more than 1000Pa-s.

(2) Introducing the selected pre-designed device structure into a3D printing system, wherein the device structure consists of single fibers, the repeated bionic pattern units of the device structure comprise linear, circular, oval, spiral, rhombic and square shapes, and the single fibers form a laminated layer and are superposed to form a bracket; printing single fibers on the surface of a substrate, wherein the process parameters are as follows: (a) The distance between the nozzle and the substrate is 50-200 mu m, the feeding speed is 5-100 mu L/min, the diameter of the nozzle is 19-31G, and the relative speed of the platform is less than 200mm/s, or (b) the distance between the nozzle and the substrate is 0.200-5.000 mm; electrospinning fibers on the surface of a substrate, wherein the process parameters are as follows: the distance between the nozzle and the substrate is 5-20 cm, the feeding speed is 5-100 mu L/min, the diameter of the nozzle is 19-31G, and the relative speed of the platform is less than 200mm/s.

(3) Stripping the selected printed or prepared material structure from the substrate surface to obtain a specific fiber micropattern, a supported metal salt and a simply prepared self-supporting scaffold; the fiber micropattern endows the scaffold with geometric clues for biological regulation, and the metal salt endows the scaffold with degradation regulation capability and bioactive metal ions.

The invention provides ionic polymer 3D printing ink with high solute concentration and bioactivity and a manufacturing method thereof, wherein the printing ink comprises the following components in parts by weight: firstly, physically blending to obtain a uniform polymer/metal salt solid mixture; then adding a good solvent of metal salt to completely dissolve the metal salt in the mixture; and finally, adding a high-molecular good solvent to completely dissolve the high molecules in the mixture to obtain the ionic high-molecular ink. The polymer function of the ionic polymer ink is designed to provide viscoelasticity necessary for the ink to be suitable for 3D printing and processing molding, provide structural support, mechanical property and biological control geometric clues for manufactured fibers and scaffolds, and guide the structural reconstruction of cells and tissues; the metal salt function of the ionic polymer ink is designed to improve the fluidity of the ink, so that the ink can obtain a high-concentration solute, provide degradation regulation and active metal ions for manufactured fibers and scaffolds, regulate and control the phenotype and differentiation of cells, and help the functional reconstruction of tissues; the solvent function of the ionic polymer ink is designed to provide the ink with the ability to dissolve both the polymer and the metal salt, allow the polymer and metal salt to interact to form a suitable viscosity and allow for high solute concentrations, and evaporate during the manufacturing process to facilitate fiber and scaffold formation.

The invention provides a method for realizing the characteristic functions of ionic polymer 3D printing ink with high solute concentration and bioactivity, which comprises the following steps: firstly, the high solute concentration of the ink weakens the winding and hydrogen bond actions among polymer chains through the interaction of cations of metal salts and negative electricity and strong polar groups such as carbonyl, hydroxyl, amino, sulfydryl and the like of the polymer in a dissolved state, further reduces the system viscosity of the ink, and allows the solute polymer in the ink to still have the fluidity suitable for 3D printing and processing molding when the concentration is increased; second, the biological activity of the ink is achieved by the interaction of the metal ions with the cells, wherein the metal salts are dissolved in the microenvironment of the cells and released from the scaffold, resulting in metal ions such as Fe ³⁺ 、Cu ²⁺ 、Zn ²⁺ 、Zr ²⁺ The like has the functions of regulating and controlling immunity, histiocyte phenotype and angiogenesis; thirdly, the biological activity of the ink provides a specific fiber pattern through a scaffold formed by 3D printing, and geometric clues are delivered based on a contact guiding mechanism to guide the arrangement of cells and extracellular matrix so as to regulate and control the organization structure; fourthly, the biological activity of the ink respectively regulates and controls the functional differentiation and the structure of the cells through the execution of metal ions and geometric patterns, which is beneficial to realizing the functional reconstruction of damaged tissues; fifthly, the degradation rate of the fiber is regulated and increased by the dissolution of the metal salt and the interaction of the cations in the metal salt and the negative electricity and strong polar groups of the polymer, so that the ingrowth of cells, tissues and blood vessels is facilitated.

Compared with the existing 3D printing ink, the technical scheme of the invention has the following advantages:

1. in the design of the ink, the invention adopts the interaction between metal ions and macromolecules, so that the ink has adjustable and controllable viscosity, and the necessary fluidity of the 3D printing ink is realized. The method for adjusting and reducing the viscosity of the polymer ink by the metal ions can improve the fluidity of the ink in the aspect of ink design, and further allows more solute polymers to be dissolved in an ink system, so that a3D printing technology of the ink with high solute concentration is realized; according to the method for reducing the viscosity of the polymer ink by the metal ions, the fluidity of the ink can be improved in the ink design, so that the trailing effect can be weakened, the positioning precision can be improved, and the 3D printing quality can be improved; the metal ions for regulating and controlling the viscosity and the fluidity of the polymer ink have biological activity, can be released from the bracket in a cell microenvironment, and further regulate the phenotype and the function of tissue cells and immune cells; the polymer which interacts with the metal ions can be degraded biologically and environmentally, and the degradation rate of the polymer can be regulated and controlled by metal salt, so that 3D printing of the scaffold matched with the tissue growth rate becomes possible; the ionic polymer ink provided by the invention can be used for realizing single fiber manufacturing by a3D printing technology and can also be used for realizing the manufacturing of a 2D fiber sheet layer and a3D fiber bracket; the ionic polymer 3D printing ink provided by the invention has excellent process compatibility, and can also be applied to other material processing and forming methods, such as electrostatic spinning, casting and forming, and freeze drying.

2. In the construction method of the ink, the metal salt and the polymer are dissolved in sequence, so that the metal salt and the polymer are dissolved and interacted sufficiently, the phenomena of overhigh local concentration of the metal salt, formation of precipitate and difficulty in diffusion are avoided, the obtained ink is uniform in property, adjustable and controllable in viscosity, and greatly shortened in preparation time; the invention adopts a heating-assisted dissolving process, so that the complete dissolving time of the high polymer is further reduced, simultaneously the ultrahigh-concentration high polymer is allowed to be dissolved and the viscosity is proper, and a3D printing method and technology of high solute concentration (defined as exceeding the solubility of the specific component I at a given temperature) and ultrahigh solute concentration (defined as exceeding the solubility of the combination of the specific components I and II at the given temperature) is established; the process is environment-friendly; high concentration, ultra high concentration solutes; the invention adopts the green process with simple steps, clear mechanism and biocompatible material to realize the ink configuration, and the established method and technology have high repeatability and high material compatibility, are suitable for large scale and accord with the development concept of 'double carbon'.

3. The physicochemical characteristics and the mechanical behavior of the ink obtained by the invention can be regulated and controlled. The method has the advantages that the viscosity, the conductivity and the fluidity of the obtained ink are adjustable and controllable by controlling key process parameters such as the type and the molar concentration of metal salt, the type and the concentration of high polymers, the complexing time and the ambient temperature, so that personalized design can be carried out according to different processing methods and field application requirements; the mechanical property, the degradation property and the biological response of the fiber and the scaffold printed by the obtained ink in a3D mode are adjustable and controllable, wherein the mechanical property and the degradation property of the fiber and the scaffold are adjustable through metal salt and polymer types and concentrations, and the biological response of the fiber and the scaffold is adjustable through metal salt, polymers and fiber micropatterns, so that damaged tissue function regeneration is achieved.

In conclusion, the invention provides the construction method of the ionic polymer 3D printing ink based on the high-concentration solute and the bioactive metal salt, and the obtained ink has adjustable viscosity, flowability and positioning precision and is suitable for the application of the 3D printing technology. The preparation method of the ionic polymer ink has the advantages of high material compatibility, adjustable physicochemical properties, simple process flow and high repeatability, and the preparation method of the obtained ink is suitable for large scale. The ionic polymer ink is suitable for 3D printing of tissue engineering scaffolds, has controllable components, structures, degradation properties and mechanical properties, and has the functions of simulating a key microenvironment of a natural tissue and guiding cell structures and functional differentiation.

Drawings

FIG. 1 is a schematic diagram of an ionic polymer 3D printing ink of the present invention, wherein I is a solute system; II is a metal salt system; and III is a composite solvent system.

FIG. 2 is a macro-optical photograph and a Taylor cone-optical photograph of the conventional polymer ink in comparative example 1, in which (a) the solute mass% concentration is 40%.

FIG. 3 is a macro photo of the flow of the conventional polymer ink in comparative example 2 according to the present invention.

FIG. 4 is a macro-optic photograph of the flow of the ionic polymer 3D printing ink of comparative example 3 of the present invention, wherein the metal salt is derived from the free D-layer empty orbital metal ions.

FIG. 5 is a macro photo showing the flow of ionic polymer 3D printing ink in example 1 of the present invention, wherein (a), (b), and (c) are metal salts of Zn, cu, and Fe ions respectively derived from D-layer empty orbitals.

FIG. 6 is a macro photo, taylor cone photo, and 3D photo of ionic polymer 3D printing ink in example 2, wherein the mass/mole ratios of PCL and different amounts of metal copper salt are 1.706 × 10 ⁴ (g/mol)、4.266×10 ³ (g/mol)、2.133×10 ³ (g/mol)。

FIG. 7 is a3D printing holder macro-optical photograph, taylor cone optical photograph, and holder photomicrograph of the ionic polymer 3D printing ink in example 3 of the present invention, wherein the concentrations (a), (b), (c), and (D) are 100%, 150%, 200%, and 300% respectively for the different polymer mass-volume percentage concentrations.

FIG. 8 is a macro optical photograph showing the flow of the ultrahigh concentration ionic polymer 3D printing ink in example 4 of the present invention, wherein the polymer mass volume percentage concentration is 600 g/mL.

Detailed Description

The following specific examples are intended to further illustrate the present disclosure, but not to limit the scope of the claims.

The chemical reagents referred to in the following examples are conventional commercially available reagents unless otherwise specified. The molecular weights of all polycaprolactone in the following comparative examples and examples are Mn =80000.

Comparative example 1

This comparative example illustrates the metal ion-free Polycaprolactone (PCL) maximum print density.

According to the design, 2g and 2.5g of Polycaprolactone (PCL) are respectively weighed in two glass reagent bottles and poured into the reagent bottles, a magnetic rotor is added, then 1mL of ethanol and 3.5mL of dichloromethane are added into each reagent bottle to serve as solvents, the reagent bottles are placed at room temperature, after PCL particles are dissolved, stirring of the magnetic rotor is carried out, and 3D printing is carried out at room temperature after the solution is prepared for 3 days.

The polymer solution prepared by the comparative example is 40% (g/mL) printable and 50% (g/mL) non-printable, which shows that the maximum printing concentration of Polycaprolactone (PCL) at room temperature does not exceed 50% (g/mL) under the action of no metal ions.

Comparative example 2

This comparative example illustrates the flow of a metal ion-free high-concentration solution.

Weighing 5g of Polycaprolactone (PCL) in a glass reagent bottle according to the design, pouring the Polycaprolactone (PCL) into the glass reagent bottle, weighing 1mL of ethanol and 2.3mL of dichloromethane, adding the ethanol and the dichloromethane into the glass reagent bottle, placing the glass reagent bottle at room temperature, and repeatedly inverting the glass reagent bottle to uniformly mix the solution after PCL particles are dissolved. The solution was inverted on day 5 at room temperature to observe flow and recorded by taking pictures at 1min.

This comparative example prepared a metal ion-free high-concentration solution and its fluidity at room temperature was recorded.

Comparative example 3

This comparative example illustrates the flow of a metal ion high concentration solution containing no d-layer empty orbital.

Weighing 5g of Polycaprolactone (PCL) in a glass reagent bottle according to the design, pouring the PCL into the glass reagent bottle, adding a magnetic rotor, and adding 0.05g of magnesium chloride powder (Mg) ²⁺ Is 0.526 × 10 ^-3 mol) are mixed with the mixture and stirred evenly; measuring 1mL of ethanol, adding the ethanol into the glass reagent bottle, and rotating a magnetic rotor after magnesium chloride is dissolved in the ethanol to enable salt solution to uniformly wrap and cover PCL particles; and finally, measuring 2.3mL of dichloromethane, adding the dichloromethane into the solution respectively, placing the solution at room temperature, and repeatedly inverting the solution after the PCL particles are dissolved so as to achieve the purpose of uniformly mixing the solution. The solution was inverted on day 5 at room temperature to observe flow and recorded by taking pictures at 1min.

This comparative example prepared a highly concentrated solution containing no d-layer empty orbital metal ions and recorded its fluidity at room temperature.

Example 1

The preparation method of the high-concentration 3D printing ink containing different metal ions of the D-layer empty orbit comprises the following steps:

weighing 5 in three glass reagent bottles according to designg Polycaprolactone (PCL) is poured into the magnetic rotor, and 0.05g of copper chloride, zinc chloride and ferric chloride (Cu) are sequentially added ²⁺ Is 0.293X 10 ^-3 mol、Zn ²⁺ Is 0.366X 10 ^-3 mol、Fe ³⁺ Is 0.308 × 10 ^-3 mol) are mixed with the mixture and stirred evenly; measuring 1mL of ethanol, respectively adding the ethanol into the three glass reagent bottles, and rotating the magnetic rotor after the ethanol dissolves the metal ion salt so that the salt solution uniformly wraps and covers the PCL particles; and finally, measuring 2.3mL of dichloromethane, respectively adding the dichloromethane into the glass reagent bottles, placing the glass reagent bottles at room temperature until PCL particles are dissolved, and then, when the system viscosity is too high, stirring by a magnetic rotor cannot be carried out, and repeatedly inverting the glass reagent bottles to promote uniform contact between copper ions and PCL. And (5) stirring by a magnetic rotor after the viscosity of the system is reduced. The solution was inverted on day 5 at room temperature to observe flow and recorded by taking pictures at 1min.

Comparing comparative example 2 and comparative example 3, it can be seen that the different metal ions containing d layers of empty orbitals prepared in this example all have the effect of increasing the fluidity.

Example 2

The first step is as follows: the preparation method of the high-concentration 3D printing ink for different concentrations of metal ions comprises the following steps:

weighing 5g of Polycaprolactone (PCL) in three glass reagent bottles according to design, pouring the PCL into the reagent bottles, adding a magnetic rotor, and sequentially adding 0.05g, 0.2g and 0.4g of copper chloride (Cu) ²⁺ Is 0.293X 10 ^-3 mol、0.117×10 ^-2 mol、0.235×10 ^-2 mol) are mixed with the mixture and stirred evenly; measuring 1.5mL of ethanol, adding the ethanol into the three glass reagent bottles respectively, and rotating a magnetic rotor after the copper chloride is dissolved in the ethanol to enable the salt solution to uniformly wrap and cover the PCL particles; and finally, 3.5mL of dichloromethane is measured and added into the solution respectively, the solution is placed at room temperature, after PCL particles are dissolved, the viscosity of the system is too high, magnetic rotor stirring cannot be carried out, and the uniform contact between copper ions and PCL is promoted by repeatedly inverting the glass reagent bottle. And (3) stirring by a magnetic rotor after the viscosity of the system is reduced, and preparing the solution for 3 days and carrying out 3D printing at room temperature.

The second step is that: the high-concentration 3D printing method for different metal ion concentrations is as follows:

the 3D printing technology adopts an Electrohydrodynamic (EHD) printing technology, the silicon wafer of the collecting substrate is arranged on an XY platform and grounded according to design, a3D printing solution with high concentration is filled into a 5mL injector and air is discharged, the injector is connected with a stainless steel flat-head needle with the model number of 21G through a conduit, and the stainless steel flat-head needle is connected with the anode of a high-voltage power supply. The syringe containing the solution was loaded into a push pump and the solution flow rate was set at 20. Mu.L/min. And (3) introducing a pattern printing program into a computer, setting the moving speed of an XY platform to be 30mm/s, setting the distance between a stainless steel flat-head needle head and a collection substrate silicon wafer to be 2mm, and adjusting a high-voltage power supply to 2.3kV to provide electric field force for a printing system. And starting a program, and printing a preset pattern on the collecting substrate under the action of an electric field force according to different finely-adjustable process parameters of the viscosity of the system.

The mass/mole ratio of PCL to copper ion prepared in this example was 1.706 × 10 ⁴ (g/mol)、4.266×10 ³ (g/mol)、2.133×10 ³ (g/mol) of high concentration inks can be printed.

Example 3

The first step is as follows: the high-concentration 3D printing solutions for different polymer concentrations were prepared as follows:

0.05g of copper chloride (Cu) is weighed in three glass reagent bottles according to the design ²⁺ Is 0.293X 10 ^-3 mol) is poured into the mixture, a magnetic rotor is added, and 5g, 7.5g, 10g and 15g of polycaprolactone are sequentially added and mixed uniformly; measuring 1.5mL of ethanol, adding the ethanol into the three glass reagent bottles respectively, and rotating a magnetic rotor after the copper chloride is dissolved in the ethanol to enable the salt solution to uniformly wrap and cover the PCL particles; and finally, 3.5mL of dichloromethane is measured and added into the solution respectively, the solution is placed at room temperature, after PCL particles are dissolved, the part of PCL which cannot be dissolved is heated to 65 ℃ to promote the dissolution of the system, the viscosity of the system is too high to carry out magnetic rotor stirring, and the uniform contact of copper ions and PCL is promoted by repeatedly inverting the glass reagent bottle. And (3) stirring by a magnetic rotor after the viscosity of the system is reduced, and preparing the solution for 3 days for 3D printing at room temperature.

The second step: the high-concentration 3D printing method for different polymer concentrations is as follows:

The high-concentration ink with the polycaprolactone concentration of 100%, 150%, 200% and 300% (g/mL) and different concentrations prepared in the embodiment can be printed.

Example 4

The preparation method of the 3D printing ink for ultrahigh solute concentration comprises the following steps:

weighing 20g of Polycaprolactone (PCL) in a glass reagent bottle according to the design, pouring the PCL into the glass reagent bottle, adding a magnetic rotor, and adding 0.1g of zirconium (IV) chloride powder (Zr) ⁴⁺ Is 0.429X 10 ^-3 mol) mixing and stirring evenly; measuring 1mL of ethanol, adding the ethanol into the glass reagent bottle, and rotating a magnetic rotor after the zirconium chloride (IV) is dissolved in the ethanol to enable salt solution to uniformly wrap and cover the PCL particles; and finally, measuring 2.3mL of dichloromethane, respectively adding the dichloromethane into the solution, and rotating the magnetic rotor after the PCL particles are dissolved so as to achieve the purpose of uniformly mixing the solution. The solution was inverted at room temperature for flow and recorded by taking a photograph at 1min.

This example successfully prepared ultra-high solute concentration ink (600% g/mL) and recorded its flow.

Example 5

The 3D printing solutions for the different polymers were prepared as follows:

weighing 3g of polylactic acid (PLA) and 3g of polyvinyl alcohol (PVA) in two glass reagent bottles according to the designPouring into the reaction vessel, adding a magnetic rotor, and adding 0.06g of copper chloride (Cu) into each glass reagent bottle in turn ²⁺ Is 0.352X 10 ^-3 mol) are mixed and stirred evenly. Adding 3mL of ethanol into a glass reagent bottle containing polylactic acid (PLA), and then adding PLA particles; finally, 7mL of dichloromethane was added thereto to obtain ionic PLA3D printing ink. 15mL of distilled water is taken from a glass reagent bottle containing polyvinyl alcohol (PVA), the temperature is heated to 80 ℃ and maintained for 30min, so that the PVA is dissolved and interacts with metal ions, and the ionic PVA3D printing ink is obtained after the temperature is cooled to the room temperature.

Compared with a blank group of polylactic acid (PLA) and polyvinyl alcohol (PVA) which are not added with metal ions containing D-layer empty tracks, the ionic polymer 3D printing ink prepared by the embodiment has remarkably increased fluidity.

Claims

1. The utility model provides an ionic polymer 3D prints ink which characterized in that: comprises a component I, a component II and a component III; the component I is a high molecular solute which is biocompatible and comprises electronegative groups and/or neutral polar groups; the component II is salts containing metal ions with bioactivity and d-layer empty orbits;

the component III is a solvent A, or a solvent A and a solvent B, or a solvent A, a solvent B and a solvent C:

the solvent A is a nonionic liquid solvent capable of dissolving the component I;

the solvent B is a solvent capable of dissolving the component II;

the C solvent is an amphiphilic solvent.

2. The ionic polymer 3D printing ink according to claim 1, wherein: the component I is at least one selected from polycaprolactone and derivatives thereof, polylactic acid and derivatives thereof, polyglycolic acid and derivatives thereof, polyvinyl alcohol and derivatives thereof, cellulose and derivatives thereof, polyethylene oxide and derivatives thereof, polyaryletherketone and derivatives thereof, polyamide and derivatives thereof, and polyimide and derivatives thereof.

3. The ionic polymer 3D printing ink according to claim 1, wherein: the component II contains at least one metal ion of titanium ion, vanadium ion, manganese ion, iron ion, copper ion, zinc ion, zirconium ion, niobium ion, silver ion and tantalum ion.

4. The ionic polymer 3D printing ink according to claim 1, wherein:

the solvent A is at least one selected from water, alcohol solvents, tetrahydrofuran and derivatives thereof, ethyl acetate and derivatives thereof, dichloromethane and derivatives thereof, and carbon tetrachloride and derivatives thereof;

the solvent B is at least one selected from water and alcohol solvents;

the C solvent is selected from alcohol solvents.

5. The ionic polymer 3D printing ink according to any one of claims 1 to 4, wherein: the mass/volume fraction of component I to component III does not exceed 1000% g/ml;

the mass/mole ratio of the component I to the component II is 10 ² ～2×10 ⁷ g/mol。

6. The ionic polymer 3D printing ink according to claim 5, wherein: the component III contains 100 percent of solvent A and 50 percent of solvent B by volume percentage.

7. The method for preparing ionic polymer 3D printing ink according to any one of claims 1 to 6, wherein the method comprises the following steps: after the component I and the component II are mixed evenly, the component III is added by selecting the following a, b or c modes:

a: adding the solvent B in the component III, and stirring for dissolving;

b: adding the solvent B in the component III, stirring for dissolving, adding the solvent A in the component III, and stirring for dissolving;

c: adding the solvent B in the component III, stirring for dissolving, then adding the solvent A in the component III, stirring for dissolving, then adding the solvent C in the component III, and stirring for dissolving.

8. The method for preparing a device by 3D printing by using the ionic polymer 3D printing ink according to any one of claims 1 to 6, wherein the method comprises the following steps: the method comprises the following steps:

1) Loading the ionic polymer 3D printing ink into an injector;

9. The method for preparing a device through 3D printing by using the ionic polymer 3D printing ink according to claim 8, wherein the method comprises the following steps: the ionic polymer 3D printing ink has a mass volume percent concentration of greater than 100% g/ml.

10. The method for preparing the device through 3D printing by using the ionic polymer 3D printing ink according to claim 8, wherein the method comprises the following steps: the printing parameters are set as: the feeding speed is 5-100 mu L/min, the diameter of the nozzle is 19-31G, the platform relative speed is more than 1mm/s, and the distance between the nozzle and the substrate is 5-200 mu m, or 0.200-5 mm, or 5-20 cm.