TWI695864B - 3d printable and photocurable composite and producing method thereof - Google Patents

Abstract

Present invention is related to a 3D printable and photocurable composite having a photocurable resin 50-99wt% and an acidized calcium silicate 1-50 wt%. The acidized calcium silicate is uniformly dispersed in the photocurabe resin and its pH value is closed to the photocurabe resin or neutral. The acidized calcium silicate of the present invention can increase the dispersibility of the composite and solve the problem of precipitate occurred during 3D printing. Scaffolds made by the present invention have great bone regeneration ability and bioavailability.

Description

Photo-curable resin capable of three-dimensional printing and preparation method thereof

A photo-curable resin, especially a photo-curable resin that can be applied to three-dimensional printing and does not cause precipitation for a long time.

Three-dimensional printing (Three Dimension, 3D printing) is a popular technology that is rapidly developing at present, mainly using metal, ceramic or polymer (plastic) materials to print layer by layer, stack forming new product processing technology. Photopolymers in plastic materials will harden quickly after being irradiated with specific light, and have the advantages of excellent printing fineness, good surface characteristics and smooth surface of finished products, and become the mainstream of rapid prototyping (RP) In the field of biomedicine or tissue engineering, biological scaffolds or fillers can be quickly produced to solve the shortcomings of existing technologies that require mold opening and cannot be customized in a small amount, and have relatively more advantages.

However, in general, the photo-curable resin used for three-dimensional printing needs to add an organic solvent during the manufacturing process, thus causing biological toxicity, environmental pollution or a pungent odor. The photo-curable waterborne polyurethane in the photocurable resin does not require the use of organic solvents, but due to the excessive water content, it is necessary to additionally use infrared (IR) or oven baking to remove the water in order to fully cure the molding, increasing the manufacturing cost and environmental burden , Can not be directly applied to 3D printing.

On the other hand, calcium silicate ceramic materials that can increase bone hyperplasia characteristics are currently used by extrusion molding three-dimensional printing methods, but because calcium silicate ceramic materials are printed due to poor mixing uniformity with the resin and material precipitation and other problems As a result, the shortcomings of the three-dimensional printing accuracy are reduced, and it is more difficult for the technical threshold of customized medical materials with high accuracy to meet their demands.

In order to solve the biotoxicity, environmental pollution or pungent odor caused by the addition of organic solvents in the manufacturing process of the current photocurable resins used in 3D printing, and the cumbersome steps of extra water removal during the curing of the photocurable water-based polyurethane, it is not applicable In three-dimensional printing, the calcium silicate ceramic material cannot be applied to high-precision three-dimensional printing molding technology and other problems. The present invention provides a photocurable resin that does not require the addition of organic solvents and does not require additional water removal steps in the process. Contains calcium silicate ceramic material with high uniformity and not easy to precipitate.

The invention provides a photocurable resin capable of three-dimensional printing, which comprises: a photocurable resin material 50-99 wt%; and an acidified calcium silicate 1-50 wt%, the acidified calcium silicate dispersed in the photocurable resin In the material, and the pH value of the acidified calcium silicate tends to be close to the photocurable resin material or to neutral.

Wherein, the photo-curable resin material contains the following mass percentages: photo-curable waterborne polyurethane with a water content of 0-50 mass percent 10-90%; acrylate copolymer 9-86 wt%; and photo-initiator 1- 4 wt%.

Wherein, the photocurable resin material further includes thermoplastic waterborne polyurethane 30-70 wt%; at this time, the photocurable waterborne polyurethane 20-30 wt%; the acrylic copolymer 9-40 wt%; and the light start Agent at least 1wt%.

Among them, the aforementioned so-called pH value tends to be neutral as the pH value is between 6.5 and 7.5.

Further, the present invention provides a method for preparing a three-dimensionally printable photocurable resin. The steps include: taking a photocurable resin material; acidifying a calcium silicate to a pH value close to the photocurable resin material or approaching Neutral; and mixing and dispersing the calcium silicate in the photocurable resin.

Wherein, the photocurable resin material first removes the water content of a photocurable waterborne polyurethane to less than 15% by mass, and then adds an acrylate copolymer and a photoinitiator to the photocurable waterborne polyurethane. Heat and stir until fully mixed to obtain the photocurable resin material.

Wherein, before mixing the photo-curable water-based polyurethane with the acrylate and photo-initiator, it is uniformly mixed with a thermoplastic water-based polyurethane, and heated and continuously stirred until the mass percentage of the water content is below 15%.

Among them, the process of acidifying the calcium silicate is to add 1N hydrochloric acid in the ratio of 1:10 for the first acidification, and then add 1N hydrochloric acid in the ratio of 1:12.5 for the second acidification. Washed twice with 95% alcohol and dried once.

As can be seen from the above description, the advantages of the present invention are as follows:

1. The feature of the present invention is that the calcium silicate after acidification treatment can increase its dispersion in the photocurable resin material and increase the printability of three-dimensional printing. In addition, the use of calcium silicate as the base material of the photocurable resin material mixed preparation using three-dimensional printing out the stent can effectively improve the benefits of bone regeneration, improve the calcium silicate pH value to improve bioavailability and its photocurable resin The degree of dispersion to increase the printability of three-dimensional printing and other issues.

2. The photocurable resin material of the present invention uses a photocurable waterborne polyurethane whose solvent is water, which has the advantages of non-toxicity, environmental protection and biocompatibility, and can be applied in the field of biomedicine or tissue engineering related fields. Because the material does not need to use any organic solvents, it will not produce biological toxicity, pollute the environment or irritating odor, and can be widely used in biological, medical or tissue engineering related fields. Then, by dewatering the waterborne polyurethane to less than 15% by mass in the manufacturing process, and then through the role of the photoinitiator and the light curing aid, the subsequent three-dimensional printing and curing of the present invention does not require additional use. The cumbersome steps of water or solvent removal can be directly cured, and the water-based polyurethane has been successfully applied to the rapid manufacturing of three-dimensional printing.

3. The present invention improves the shortcomings of the existing photocurable resin material and calcium silicate that are difficult to apply to photocurable three-dimensional printing, and successfully prepares a highly dispersed photocurable resin material containing calcium silicate, which is not only applicable to photocurable three-dimensional Printing is more precise and suitable for customized medical materials. It is an innovative and forward-looking invention.

The invention is a photo-curable resin capable of three-dimensional printing, which comprises: One photo-curable resin material 50-99 wt%; and Acidified calcium silicate 1-50 wt%, the calcium silicate is dispersed in the photocurable resin material, and the pH value of the calcium silicate tends to be close to the photocurable resin material or to neutrality, the so-called The pH is preferably between 6.5 and 7.5.

Wherein, for the aforementioned photocurable resin material, it includes the following mass percentage composition: Water-based polyurethanes (PU) with a water content of 0 to 50% by mass, more preferably 0 to 15% by mass; 10 to 90 wt%; 9-86 wt% of acrylate copolymer, preferably 9-40 wt%; and The photoinitiator is at least 1 wt%, preferably 1 to 4 wt%.

The materials selected in the present invention are all environmentally-friendly materials with biocompatibility. Among them, in addition to being biocompatible, the water-curable waterborne polyurethanes contain functional groups that can be photocured, and have relatively The excellent photo-curing characteristics can reduce the curing time during subsequent 3D printing, and further increase the printing resolution and hardness of the finished 3D printing, so as to improve product quality.

The internal components of the light-curable waterborne polyurethane are mainly water and polyurethane, and the polyurethane content is preferably 40 to 60% by mass. The light-curable waterborne polyurethane is a new polyurethane system that uses water instead of an organic solvent as a dispersion medium, also known as water dispersion. Polyurethane, water-based polyurethane or water-based polyurethane has the advantages of no pollution, safety, excellent mechanical properties, good biocompatibility and easy modification, but due to the relationship of excessive water content, light-curable waterborne polyurethane is generally in the curing molding stage Requires additional dewatering steps and cannot be used directly in rapid prototyping processes such as three-dimensional printing. In the present invention, the water-based polyurethane is heated and stirred to remove water to a moisture content of less than 15% by mass, and then acrylate copolymer and photoinitiator are added , And optionally thermoplastic water-based polyurethane, no organic solvent is added to the formulation, and it can be directly cured without complicated steps of water or solvent removal during molding, which is environmentally friendly and biocompatible. The acrylate copolymer in the foregoing formulation is mainly used as a diluent, which can adjust the viscosity of the material of the present invention during 3D printing, and improve the printing resolution of the digital light processing three-dimensional printing technology.

The natural photoinitiator used in the present invention is also preferably a biocompatible photoinitiator, which has the function of absorbing light and inducing polymerization, and may be vitamin B; and the present invention may be further Add light curing aids, such as graphene, nanotubes, nanodiamonds, graphene-like compounds such as boron nitride, macromolecules with phenolic functional groups, such as dopamine, tannic acid or caffeic acid, In addition to assisting the light curing effect and reducing the curing time of three-dimensional printing, the photo-curing auxiliary agent can also improve the resolution of three-dimensional printing, so that the invention can print a finer and more precise biological scaffold structure, and Graphene can further produce electrical conductivity and can help angiogenesis, and dopamine can be used as a nerve-conducting substance. The addition amount of the photocuring aid is less than 20% by mass, preferably 0.001 to 20%, for optimal printing The effect is also biocompatible.

The aforementioned formula may further be added with a thermoplastic water-based polyurethane that is also biocompatible and has a mass percentage of 50-99 wt%, preferably 30-70 wt%. Compared to the photocurable water-based polyurethane, the thermoplastic water-based polyurethane Conversely, it can delay curing time and reduce the hardness of the three-dimensional printed products, making the products more flexible and elastic, and can be applied to biological implants, etc., to reduce the time when the device is too hard and too rigid to cause the device to be on the user or the body Discomfort. In the process of mixing the thermoplastic water-based polyurethane and the light-curing water-based polyurethane, it is preferable to simultaneously remove the moisture contained in the water-based polyurethane to less than 15% by mass, together with a light initiator and/or light curing aid Agent, so that the subsequent three-dimensional printing molding can be directly cured and molded, without the need for extra tedious steps of water removal. The user can adjust the added range of the photocurable waterborne polyurethane and the thermoplastic waterborne polyurethane of the present invention to adjust the hardness, light curing time and resolution of the finished product to achieve the most ideal material characteristics. The excellent biocompatibility and three-dimensional printing characteristics of the present invention are very suitable for application in the biomedical industry or tissue engineering industry, such as the manufacture of biological scaffolds and fillers.

Next, the present invention provides a manufacturing method corresponding to the aforementioned photocurable resin material. The steps of the preferred embodiment are as follows:

Preparation of light-curing waterborne polyurethane: the raw material of waterborne polyurethane is LUX260 (Alberdingk Boley, Krefeld, Germany). The raw material LUX260 is stirred at high temperature to remove water for about 2 hours, reaching more than 50% of the water. After cooling down, add 1.5% photoinitiator TPO (2,4,6-trimethylbenzoyl-diphenyl-phosphineoxide, Ciba, Switzerland) dissolved in 30% HEMA (2-Hydroxylethyl methacrylate, Sigma-Aldrich, St. Louis, MO, USA), stir evenly in the dark to obtain the photocurable waterborne polyurethane. In order to increase the print resolution, 0.1% HMBS (2-Hydroxy-4-methoxybenzophenone-5-sulfonic Acid Hydrate, TCI America, Portland, OR, USA) and 0.01% TEMPO (4-Isothiocyanato-2 ,2,6,6-tetramethylpiperidine-1-oxide, Acros Organics, Geel, Belgium).

The photocurable waterborne polyurethane and the thermoplastic waterborne polyurethane are uniformly mixed in a homogenizer, wherein the mass ratio of the photocurable waterborne polyurethane and the thermoplastic waterborne polyurethane is 10 to 90: 90 to 10;

The mixed light-curable water-based polyurethane and thermoplastic water-based polyurethane are heated to above 100 ^o C, preferably 130 ^o C and continuously stirred until the moisture is removed, and the amount of moisture removed is preferably at least the aforementioned water-based polyurethane removed The mass percentage of the material is below 15%;

Add 10% to 40% acrylic copolymer, 0.1% to 4% photoinitiator and 0.001% to 0.20% photocuring aid to the aforementioned light-curable waterborne polyurethane and thermoplastic waterborne polyurethane, and heat To 60 ~ 80 ^o C, stir with a homogenizer until fully mixed, to obtain the biocompatible three-dimensional printing photocurable resin of the present invention, and subsequently save the biocompatible three-dimensional printing photocurable resin by The dark form is better.

Generally, when the light-curable water-based polyurethane is applied to the film coating technology, the curing of the light-curable water-based polyurethane requires additional infrared water removal or oven baking to be completely cured, so it is difficult to apply the light-curable water-based polyurethane to the DLP (projection type) 3D printing, Digital Light Processing) rapid prototyping manufacturing technology. The process of this case is to first remove the water of the light-curable water-based polyurethane to a moisture content of less than 15% by mass, and then add the acrylate copolymer and the photoinitiator to participate in the mixing, so that the subsequent application in the three-dimensional printing process, due to water It can be hardened quickly with a small amount of light initiator or light curing aid, no need to use additional infrared or oven heating and curing, in order to meet the needs of rapid prototyping technology.

On the other hand, the calcium silicate used in the present invention is also called bioceramic and has the function of stimulating bone growth. Calcium silicate is a strong alkaline material, and it is difficult to mix and disperse with the above-mentioned photocurable resin and other acidic materials uniformly. Therefore, in the present invention, through the process of acidifying the calcium silicate, the calcium silicate is cured with the light The same or similar pH value of the resin, or at least a neutral pH value, promotes the uniformity of subsequent mixing and dispersion and improves the precipitation problem.

The following examples of the invention illustrate the process of acidification preparation: calcium silicate is added with 1N hydrochloric acid (HCl) at a ratio of 1:10 for one-time acidification, and then 1N HCl is added at a ratio of 1:12.5 for a second acidification to complete After acidification, it is washed twice with pure water, and 95% alcohol is dried once.

Subsequently, calcium silicate containing different concentrations is added to the photocurable resin material, and the photocurable resin capable of three-dimensional printing according to the present invention is evenly mixed at high speed. The subsequent three-dimensional printing of the present invention is preferably printed with a DLP3D printer (Miicraft+ or Miicraft 100). The thickness of the cut layer is set to 5-100 µm, the curing time is about 15-20 seconds, and the printed sample is 95% alcohol Do cleaning. The present invention is applicable to any photo-curing three-dimensional printing method, which is not limited herein.

In order to confirm that the present invention can improve the degree of dispersion of the acidified calcium silicate in the photocurable resin material, please refer to FIG. 1 and Table 1 below. The present invention selects the photocurable resin material group to which the calcium silicate is not added. (Code CS0) and photocurable resin materials (codes CS5, CS10 and CS15) with 5, 10 and 15% of bioceramics dissolved in them respectively. Measure their contact angle (Contact Angel), and the contact angle test shows that this In the invention, the contact angle of the group added with the bio-calcium silicate decreased, showing good dispersibility.

Table 1. The mixing ratio Contact angle 0% (Code CS0) 66 ^o 5% (codename CS5) 57 ^o 10% (Code CS10) 51 ^o 15% (Code CS15) 49 ^o

Please refer to FIG. 2, which is an XRD chart of the aforementioned CS0 and CS5-CS15 of the present invention. Please refer to FIG. 3, which is a test chart of the degradation rates of the aforementioned groups CS0 and CS5 to CS15 of the present invention. As can be seen from FIG. 3, the increased calcium silicate content of the present invention can increase the degradation rate.

Calcium silicate materials will dissociate and release calcium ions and phosphate ions when immersed in Simulated body fluid (SBF), and spherical hydroxyapatite crystals accumulate on the surface of the material. This crystal has the characteristics of inducing the formation of new bone in the application of bone tissue engineering. Please refer to FIG. 4, which is the three-dimensionally printed scaffolds of the aforementioned CS0 and the photo-curable resin materials containing 0-15% calcium silicate of the CS5-CS15 of the present invention, respectively, soaked in simulated body fluids, and collected at different time points. The surface of the material was observed with an electron scanning microscope. From the observation results, it can be seen that as time increases and the concentration of calcium silicate increases, the accumulation of hydroxyapatite crystal spheres increases.

Please refer to FIG. 5, which is a leaf stem cell growth test between the present invention. As can be seen from FIG. 5, as the time increases and the calcium silicate concentration increases, the cell growth test has a positive result.

The activity of alkaline phosphatase is an indicator for evaluating the early differentiation of osteoblasts. Please refer to FIG. 6. The present invention cultivates human Wharton's jelly mesenchymal stem cells (WJMSC) to contain 0-15% On the three-dimensionally printed support made of calcium silicate photocurable resin material, samples were collected on the 3rd, 7th and 14th days to detect the alkaline phosphatase activity. As shown in Figure 6, with the increase of time and the increase of calcium silicate concentration on the 3rd, 7th and 14th days, the activity of alkaline phosphatase increased, showing time dependence and concentration dependence, showing silicate Calcium polyurethane scaffolds have a positive effect on bone differentiation.

Please refer to FIG. 7 and Table 2 below, which is the mixed light absorption test data of the present invention. From FIG. 7 and Table 2 below, it can be seen that the absorbance value of the group added with the acidified calcium silicate of the present invention is maintained until 28 days after mixing The absorbance value at the time of mixing is equivalent. Compared with the absorbance value of the unacidified calcium silicate group, the present invention can achieve uniformity of mixing for a long time without precipitation, and is particularly suitable for three-dimensional printing. Application category.

Table 2. Test group days and absorbance Pure PU PU and unacidified calcium silicate PU and acidified calcium silicate (present invention) After mixing 0.135 1.514 1.524 One day after mixing 0.142 0.803 1.511 Seven days after mixing 0.138 0.504 1.439 28 days after mixing 0.135 0.412 1.428

The above are only preferred examples of the present invention, and are not intended to limit the scope of the claims of the present invention. Any other equivalent changes or modifications made without mentioning the spirit disclosed by the present invention should be included in this Within the scope of patent applications for inventions.

FIG. 1 is a contact angle test chart of various embodiments of the present invention. FIG. 2 is an XRD test chart of various embodiments of the present invention. FIG. 3 is a test chart of degradation rates of various embodiments of the present invention. FIG. 4 is an observation result of an electron scanning microscope of each embodiment of the present invention. FIG. 5 is a cell growth test of various embodiments of the present invention. FIG. 6 is a performance test of stimulating human Wharton’s mesenchymal stem cells and alkaline phosphatase in various embodiments of the present invention. FIG. 7 is the mixed light absorption test data of various embodiments of the present invention.

Claims (10)

A photo-curable resin capable of three-dimensional printing, comprising: a photo-curable resin material 50-99wt%, the photo-curable resin material comprises the following mass percentage composition: photo-curable waterborne polyurethane 10 having a water content of 0-50 mass percent ~90%, acrylate copolymer 9~86wt% and photoinitiator at least 1wt%; and acidified calcium silicate 1-50wt%, one of the functions of stimulating bone growth, the acidified calcium silicate dispersed in the photocurable resin material The pH value of the acidified calcium silicate tends to be close to that of the photocurable resin material or neutral. For example, the three-dimensionally printable photo-curable resin of claim 1 of the patent scope, wherein the photo-curable resin material further contains thermoplastic water-based polyurethane 30~70wt%; at this time, the photo-curable water-based polyurethane 20~30wt%; The acrylic copolymer is 9-40 wt%; and the photoinitiator is at least 1 wt%. For example, for the three-dimensionally printable photo-curable resin of item 1 or 2 of the patent application, the water content of the photo-curable water-based polyurethane or the photo-curable water-based polyurethane and the thermoplastic water-based polyurethane is 15% by mass or less. For example, for the three-dimensionally printable photo-curable resin in the patent application scope 1 or 2, the pH value tends to be neutral, and the pH value is between 6.5 and 7.5. A preparation method of photo-curable resin capable of three-dimensional printing, the steps include: taking a photo-curable resin material 50-99wt%, the photo-curable resin material comprises the following mass percentage composition: light with a water content of 0-50 mass percent Cure waterborne polyurethane 10~90%, acrylate copolymer 9~86wt% and photoinitiator at least 1wt%; acidify calcium silicate, which has the function of stimulating bone growth, to a pH value close to the photocurable resin material or Approaching neutrality; and mixing and dispersing the calcium silicate 1-50wt% in the photocurable resin. For example, the preparation method of the photo-curing resin in item 5 of the patent application range, in which the photo-curing resin material first removes the water content of a photo-curable water-based polyurethane to less than 50% by mass, and then adds an acrylate copolymer And a photoinitiator in the photocurable water-based polyurethane, heating and stirring until fully mixed to obtain the photocurable resin material. For example, the preparation method of the photo-curing resin in item 6 of the patent application scope, in which the photo-curable water-based polyurethane is uniformly mixed with a thermoplastic water-based polyurethane before being mixed with the acrylate and photo initiator, and heated and continuously stirred The mass percentage of moisture in it is below 50%. For example, the preparation method of the photo-curable resin in item 5 of the patent application scope, wherein the process of acidifying the calcium silicate is to add 1N hydrochloric acid to the calcium silicate at a ratio of 1:10 for the first acidification, and then to 1:12.5 Proportionally add 1N hydrochloric acid for the second acidification. After the acidification, rinse with pure water twice and 95% alcohol and dry once. For example, the preparation method of the photo-curing resin in item 6 of the patent application range, wherein the moisture content of the photo-curing water-based polyurethane is removed to 15% by mass or less. For example, the preparation method of the photo-curable resin of item 7 of the patent application scope, wherein the moisture content of the photo-curable water-based polyurethane and the thermoplastic water-based polyurethane is removed to a mass percentage of 15% or less.

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