TWI631178B - Printable biocompatible photo-curing resin and producing method thereof - Google Patents

Abstract

A biocompatible three-dimensional printing photocurable resin comprising the following composition by mass percentage: photo-curable waterborne polyurethane having a water content of 0 to 15% by mass of 10 to 90%; acrylate copolymer 10 to 40 %; and photoinitiator 0.1~4%; the invention uses non-toxic, environmentally friendly and biocompatible photocurable water-based polyurethane as a three-dimensional printing material, which can be applied to the production of biomedical or tissue engineering products, The photocurable water-based polyurethane uses only water as a solvent, and does not use a harmful organic solvent in the process; and further, the aqueous polyurethane is dehydrated to a water content of 15% by mass or less with a photoinitiator in the process, and the invention is used for the present invention. When three-dimensional printing is cured, it can be directly cured without additional steps of removing water, which is quite fast and convenient.

Description

Biocompatible three-dimensional printing photocurable resin and manufacturing method thereof

A photocurable resin suitable for three-dimensional printing, in particular a photocurable resin which is biocompatible and suitable for three-dimensional printing.

Three Dimension (3D printing) is a hot technology that is rapidly developing. It mainly uses metal, ceramic or polymer (plastic) materials to print and stack products to obtain new processing technology.

Photopolymer, which is quickly cured by specific light, has the advantages of excellent print quality, good surface characteristics and smooth surface finish, and becomes the mainstream of Rapid Prototyping (RP). For biomedical or tissue engineering, bio-scaffolds or fillers can be quickly fabricated to solve the shortcomings of existing technologies that require mold opening and can not be customized in a small amount, and are relatively advantageous.

In general, three-dimensional printing uses a photocurable resin to add an organic solvent in the process, thereby causing biological toxicity, environmental pollution or pungent odor. The photocurable water-based polyurethane in the photocurable resin does not require the use of an organic solvent. However, due to excessive water content, it is necessary to additionally use infrared (IR) or oven to bake water to fully cure the molding, thereby increasing the manufacturing cost and environmental burden. Cannot be directly applied to 3D printing.

In order to solve the phototoxic resin currently used in three-dimensional printing, the biological toxicity, environmental pollution or pungent odor generated by adding an organic solvent in the process; or the cumbersome step of additionally removing water when curing the photocurable water-based polyurethane, However, it is not applicable to various disadvantages such as three-dimensional printing, and the present invention provides a biocompatible three-dimensional printing photocurable resin comprising the following composition by mass percentage: photocurable waterborne polyurethane having a water content of 0 to 15% by mass. 10 to 90%; acrylate copolymer 10 to 40%; and photoinitiator 0.1 to 4%.

Wherein, the three-dimensional printing photocurable resin further comprises a thermoplastic polyurethane resin in a mass percentage of 20 to 70%.

Wherein, the three-dimensional printing photocurable resin further comprises a photocuring auxiliary agent in a mass percentage of 0.001 to 20%.

Wherein the photoinitiator comprises vitamin B.

Wherein, the photocuring auxiliary agent comprises graphene, a carbon nanotube, a nanodiamond, a boron nitride or a macromolecule having a phenolic functional group.

Among them, the macromolecule having a phenolic functional group contains dopamine, tannic acid or caffeic acid.

The present invention further provides a method for producing the three-dimensional printing photocurable resin, comprising the steps of: removing a photocurable aqueous polyurethane and removing the moisture to 15% by mass or less; and adding an acrylate copolymer and a a photoinitiator to the photo-curable aqueous polyurethane, heated to 60 ~ 80 ^o C and stirred until thoroughly mixed to obtain a three-dimensional biocompatible print photo-curable resin.

Wherein, the photocurable aqueous polyurethane is uniformly mixed with a thermoplastic aqueous polyurethane before being mixed with the acrylate and the photoinitiator, and heated to 100 ^o C or more and continuously stirred until the mass percentage of moisture is 15% or less. .

Wherein, when the acrylate copolymer and the photoinitiator are added to the photocurable aqueous polyurethane, one or more photocuring auxiliary agents are further added.

As can be seen from the above description, the present invention has the following advantages:

1. The invention uses the solvent-based water-curable water-based polyurethane, which has the advantages of non-toxicity, environmental protection and biocompatibility, and can be applied to the fields of biomedical or tissue engineering, and the organic material of the invention does not need to use any organic materials. Solvents, which do not cause biotoxicity, environmental pollution or irritating odors, can be widely used in biological, medical or tissue engineering related fields.

2. The present invention removes the water-based polyurethane by water in the process until the water content is less than 15% by mass, and then passes through the action of the photoinitiator and the photocuring auxiliary agent, so that the subsequent three-dimensional printing and curing of the present invention does not need to be performed. It can be directly cured by the cumbersome steps of removing water or removing solvent, and successfully applied water-based polyurethane to the rapid manufacturing of three-dimensional printing.

3. The invention utilizes photocurable water-based polyurethane and thermoplastic water-based polyurethane, and the ratio of two different water-based polyurethane materials can adjust the photo-curing speed in three-dimensional printing, the mechanical strength of the printed product, and further added light curing. In addition to the effect of assisting photocuring, the additive can also increase the resolution of three-dimensional printing, making the invention suitable for the manufacture of related products having small size, complicated structure or high precision.

A biocompatible three-dimensional printing photocurable resin with a compositional mass percentage as follows:

20 to 90% of the photocurable water-based polyurethane having a water content of 0 to 15% by mass;

Acrylate copolymer 5 to 40%;

Photoinitiator 0.1~4%.

The materials selected for use in the present invention are all biocompatible organic materials. Among them, the photocurable waterborne polyurethane has biocompatible properties, and the polyurethane contained therein has functional groups which can be photocured. The excellent light curing property can reduce the curing time of the subsequent three-dimensional printing, and further increase the printing resolution and hardness of the three-dimensional printing finished product, thereby improving the product quality.

The photocurable water-based polyurethane contains mainly water and polyurethane, and the polyurethane content is preferably 40-60% by mass. The photocurable water-based polyurethane is a new polyurethane system in which water is used as a dispersion medium instead of an organic solvent, which is also called water dispersion. Polyurethane, water-based polyurethane or water-based polyurethane has the advantages of no pollution, safety, good mechanical properties, good biocompatibility and easy modification. However, due to the high water content, photocurable waterborne polyurethane is generally in the curing stage. , an additional water removal step is required, and the rapid prototyping process such as three-dimensional printing cannot be directly used, and the present invention heats and stirs the aqueous polyurethane to water to a water content of less than 15% by mass, and then adds the acrylate copolymer and the photoinitiator. It has no added organic solvent and can be directly solidified without any additional steps of removing water or removing solvent. It is environmentally friendly and biocompatible.

The acrylate copolymer in the above formula is mainly used as a diluent, and can adjust the viscosity of the material in the 3D printing of the present invention, and improve the printing resolution of the digital light processing three-dimensional printing technology.

The photoinitiator (Naturl Photoinitiator) used in the present invention is preferably a biocompatible photoinitiator having the function of absorbing light and inducing a polymerization reaction, which may be vitamin B; and the present invention may further be added. a photocuring auxiliary such as graphene, a carbon nanotube, a nanodiamond, a graphene-like compound such as boron nitride, a macromolecule having a phenolic functional group such as dopamine, tannic acid or caffeic acid. In addition to assisting the photocuring effect and reducing the curing time of three-dimensional printing, the photocuring auxiliary can also improve the resolution of three-dimensional printing, so that the invention can print a finer and more precise biological scaffold structure, and the graphite therein. The olefin further produces electrical conductivity and can help angiogenic properties, and dopamine can be used as a nerve conduction material. The photocuring auxiliary agent is added in an amount of 20 or less by mass, preferably 0.001 to 20%, and has the best printing effect. And at the same time biocompatible.

The above formula may further add a thermoplastic water-based polyurethane which is also biocompatible and has a mass percentage of 20 to 70%. Compared with the photocurable water-based polyurethane, the thermoplastic water-based polyurethane may inversely delay the curing time and reduce the three-dimensionality. Print the hardness of the finished product to make the finished product softer and more elastic. It can be applied to biological implants, etc., to reduce the discomfort of the device when it is too hard or too rigid to cause the device to be on the user or in the body. In the process of mixing the thermoplastic water-based polyurethane with the photocurable water-based polyurethane, it is preferred to simultaneously remove the moisture contained therein to 15% by mass or less with a photoinitiator and/or a photocuring aid. The agent can be directly solidified and formed in the subsequent three-dimensional printing, without the cumbersome steps of removing water.

The user can adjust the hardness, photocuring time and finished product resolution of the finished product by adjusting the ratio range of the photocurable water-based polyurethane and the thermoplastic water-based polyurethane of the present invention to achieve the most ideal material characteristics. The invention has excellent biocompatibility and three-dimensional printing characteristics, and is very suitable for application in the biomedical industry or tissue engineering industry, such as the manufacture of biological scaffolds, fillers and the like.

Referring to FIG. 1, a preferred embodiment of the manufacturing method of the present invention includes the following steps:

Step 1: The photocurable water-based polyurethane and the thermoplastic water-based polyurethane are uniformly mixed by a homogenizer, wherein the photo-curable water-based polyurethane and the thermoplastic water-based polyurethane are added in a mass ratio of 10 to 90:90 to 10.

Step 2: heating the mixed photocurable aqueous polyurethane and thermoplastic aqueous polyurethane to 100 ^o C or higher, preferably 130 ^o C and continuously stirring to remove moisture therein, and the moisture removal amount is preferably at least removed to Step 1 The mass percentage of the aqueous polyurethane material is 15% or less.

Step 3: adding 10 to 40% by mass of acrylate copolymer, 0.1 to 4% of photoinitiator and 0.001 to 0.20% of photocuring auxiliary agent in the aforementioned photocurable waterborne polyurethane and thermoplastic waterborne polyurethane And heating to 60-80 ^o C, stirring with a homogenizer until fully mixed, that is, the biocompatible three-dimensional printing photocurable resin of the invention is obtained, and the biocompatible three-dimensional printing photocuring is subsequently preserved. The resin is preferably in the form of a light shield.

When the photocurable waterborne polyurethane is applied to the film coating technology, the curing of the photocurable waterborne polyurethane requires additional infrared water removal or oven baking to fully cure, thus making the photocurable waterborne polyurethane difficult to apply to DLP (projection type). 3D Printing, Digital Light Processing). In the process of the present invention, the photocurable water-based polyurethane is first dehydrated to a water content of less than 15% by mass, and then the acrylate copolymer and the photoinitiator are added to participate in the mixing, so that the subsequent application to the three-dimensional printing process is due to Low water content and fast curing with the action of photoinitiator or photocuring auxiliary, no need to use additional infrared or oven heating to meet the needs of rapid prototyping technology.

Please refer to the following Table 1. The formulation of the various examples of the present invention and the characteristics and curing schedule of the present invention can be seen by adjusting the amount of the photocurable polyurethane and the thermoplastic polyurethane by adjusting the addition amount of the photocurable polyurethane and the thermoplastic polyurethane. Controls the cure time of the material formulation and the effect of hardness. The addition of thermoplastic waterborne polyurethanes does reduce the hardness of the material but accelerates the curing time. [Table 1] The unit of the added amount is the mass percentage.  <TABLE border="1" borderColor="#000000" width="85%"><TBODY><tr><td> Example code</td><td> A </td><td> B </ Td><td> C </td><td> D </td><td> E </td></tr><tr><td> Light-curable waterborne polyurethane</td><td> 39.5 < /td><td> 47.4 </td><td> 55.3 </td><td> 71.2 </td><td> 89 </td></tr><tr><td> Thermoplastic Waterborne Polyurethane< /td><td> 39.5 </td><td> 31.6 </td><td> 23.7 </td><td> 17.8 </td><td> 0 </td></tr><tr> <td> Acrylate Copolymer</td><td> 20 </td><td> 20 </td><td> 20 </td><td> 10 </td><td> 10 </td ></tr><tr><td> Light Initiator</td><td> 1 </td><td> 1 </td><td> 1 </td><td> 1 </td ><td> 1 </td></tr><tr><td> Shore Hardness (D) </td><td> 24.3 </td><td> 42.0 </td><td> 51.7 < /td><td> 59.3 </td><td> 67.0 </td></tr><tr><td> Film thickness 100 um curing seconds (s) </td><td> 20 </td ><td> 18 </td><td> 15 </td><td> 10 </td><td> 7 </td></tr></TBODY></TABLE>

Please refer to the following Table 2, which is a plurality of examples of the addition of the photocuring auxiliary agent and the physical property test data thereof according to the embodiment F~J of the present invention. As can be seen from Table 2, it is confirmed that the G-J of the present invention is added with a nano diamond. It reduces the time required for photocuring. [Table 2] The unit of the added amount is the mass percentage.  <TABLE border="1" borderColor="#000000" width="85%"><TBODY><tr><td> Example code</td><td> F </td><td> G </ Td><td> H </td><td> I </td><td> J </td></tr><tr><td> Light-curable waterborne polyurethane</td><td> 79 < /td><td> 78.995 </td><td> 78.99 </td><td> 78.95 </td><td> 78.9 </td></tr><tr><td> acrylate copolymer< /td><td> 20 </td><td> 20 </td><td> 20 </td><td> 20 </td><td> 20 </td></tr><tr> <td> Light Initiator</td><td> 1 </td><td> 1 </td><td> 1 </td><td> 1 </td><td> 1 </td ></tr><tr><td> Nano Diamond (Photo Curing Aid) </td><td> 0 </td><td> 0.005 </td><td> 0.01 </td><td > 0.05 </td><td> 0.1 </td></tr><tr><td> Shore Hardness (D) </td><td> 64 </td><td> 67.3 </td> <td> 78 </td><td> 76.7 </td><td> 55 </td></tr><tr><td> Film thickness 100 um curing seconds (s) </td><td > 10 </td><td> 7 </td><td> 6 </td><td> 8 </td><td> 8 </td></tr></TBODY></TABLE>

Please refer to FIG. 2 and FIG. 3 , which are the cell attachment experiments performed by using the MG63 and WJ-MSC cell lines in Example E of Table 2 of the present invention, and the two cells are prepared in the formula E. The growth of the membrane on the membrane for 1 day, as shown in Fig. 2 and Fig. 3, can confirm that the two cells can be attached to the product printed by the present invention and have biocompatibility.

Please refer to FIG. 4, which is a WJ-MSC cell cultured on the membrane of the method of Example F in Table 2 of the present invention. It can be seen from the fluorescence image of FIG. 4 that the WJ-MSC cells can sustainably grow in the column. The printed brackets last for more than 7 days.

Please refer to FIGS. 5-6, which are images before and after the addition of the dopamine component of the present invention, and (a) in FIG. 5 is a group in which no dopamine is added, and the result of (a) shows the resolution of the finished product after three-dimensional printing. Obviously poor; in contrast, group (b) with dopamine added, the resolution of the finished product in three-dimensional printing is greatly improved, and can be further applied to products with extremely small size, complicated structure or precise printing, such as the tubular shape in Fig. 6. The fine structure, the porous biological scaffold, and the like can be printed with high quality by the material formulation of the present invention, and the fineness can be at least about 200 micron.

The photocurable water-based polyurethane used in the present invention can be used as a solvent in the process, without adding other organic solvents, and the cell growth experiment performed by the present invention can confirm that the present invention is biocompatible, and is more advanced than the current technology. Environmentally friendly and environmentally friendly, it can be further applied to the biomedical industry or tissue engineering industry, such as the use of biological scaffolds, fillers and other related products.

1 is a schematic view showing a manufacturing process of a preferred embodiment of the present invention. Figure 2 is a photomicrograph of the cell attachment experiment of the MG63 cell line. Figure 3 is a SEM image of a cell attachment experiment of WJ-MSC cell line. Figure 4 is a fluorescence image of WJ-MSC cell growth. 5 to 6 are three-dimensional printed products of the present invention before and after adding a photocuring auxiliary to dopamine.

Claims (6)

A biocompatible three-dimensional printing photocurable resin comprising the following composition by mass percentage: photo-curable waterborne polyurethane having a water content of 0 to 15 mass%, 10 to 90%; acrylate copolymer 10 to 40%; The photocuring auxiliary agent is 0.001 to 20%, and the photocuring auxiliary agent comprises dopamine, tannic acid or caffeic acid; and the photoinitiator is 0.1 to 4%. The biocompatible three-dimensional printing photocurable resin according to claim 1, which further comprises a thermoplastic polyurethane resin in a mass percentage of 20 to 70%. A biocompatible three-dimensional printing photocurable resin according to claim 1, wherein the photoinitiator comprises vitamin B. A biocompatible three-dimensional printing photocurable resin according to claim 1, 2 or 3, which further comprises graphene, a carbon nanotube, a nanodiamond or a boron nitride. A method for producing a biocompatible three-dimensional printing photocurable resin, comprising the steps of: taking a photocurable aqueous polyurethane containing moisture, and removing the moisture to a mass percentage of 15% or less; and adding one An acrylate copolymer, a photoinitiator, and a photocuring auxiliary agent in the photocurable water-based polyurethane, heated and stirred until thoroughly mixed to obtain a biocompatible three-dimensional printing photocurable resin; wherein the photocuring aid The agent is dopamine, tannic acid or caffeic acid. The method for producing a biocompatible three-dimensional printing photocurable resin according to claim 5, wherein the photocurable aqueous polyurethane is mixed with the acrylate and the photoinitiator It is uniformly mixed with a thermoplastic aqueous polyurethane, and heated and continuously stirred until the mass percentage of water is 15% or less.