Degradable photocurable resin containing disulfide bonds and preparation method and application thereof

Abstract

The present invention relates to the field of 3D printing materials, and discloses a degradable photocurable resin containing a disulfide bond, a preparation method thereof, and an application thereof. The degradable photocurable resin contains polycaprolactone lipoate and a photoinitiator in a weight ratio of 98-99.5:1; wherein the polycaprolactone lipoate is a compound represented by formula (1), wherein R1, R2, and R3 are each independently selected from the group represented by formula (2). The degradable photocurable resin containing a disulfide bond provided by the present invention not only has biological activity, but also has degradability and recyclability, and can be printed at room temperature without the addition of a diluent, and the printed product can meet the corresponding mechanical properties and precision requirements. Formula (1) #imgabs0# Formula (2) #imgabs1#

Description

Technical Field

[0001] The present invention relates to the field of 3D printing materials, and in particular to a degradable photocurable resin containing a disulfide bond, and a preparation method and application thereof. Background Art

[0002] Tissue engineering combines life sciences, engineering and other disciplines to develop biological grafts that help repair / regenerate damaged tissues or improve morphology and function. The three elements of tissue engineering include seed cells, bioactive factors and scaffolds. Among them, bioactive factors have the function of efficiently promoting cell growth and proliferation and ultimately tissue regeneration; while three-dimensional porous scaffolds can provide space for cells to grow and proliferate, which helps to transport nutrients and discharge metabolic waste. Therefore, optimizing the bioactivity and porous structure of three-dimensional scaffolds can effectively promote tissue repair / regeneration.

[0003] 3D printing technology can form complex porous structures, so it is widely used in the preparation of tissue engineering scaffolds. Among them, 3D printing technologies based on photocuring include stereolithography (SLA) and digital light processing (DLP) printing technology, which can achieve personalized and rapid preparation of three-dimensional structures with high resolution, complex three-dimensional structure and high surface quality. However, due to the high requirements of photocuring 3D printing technology on material viscosity and curing performance, the types of materials available in the existing technology are relatively lacking, especially degradable materials.

[0004] Among them, polycaprolactone (PCL), polytrimethylene carbonate (PTMC), polypropylene fumarate (PPF), etc. are available printing materials, which are used directly or after functional group modification for photocuring printing of degradable scaffolds. In order to regulate the printing performance of the above materials, especially the viscosity, it is generally necessary to add additional diluents such as diethyl fumarate (DEF) to the photocurable resin to achieve the viscosity range required for printing, or it is necessary to print at a temperature of 40-80°C. However, the addition of the diluent DEF and the gradual increase in its content tend to reduce the mechanical properties of the printed product and increase its shrinkage rate, thereby reducing the printing accuracy and fidelity.

[0005] In addition, in order to promote tissue repair, it is essential to prepare a tissue engineering scaffold with biological activity. However, the currently prepared degradable scaffolds generally have no biological activity, or require the addition of additional biologically active substances (such as bioglass) to make them have appropriate biological activity.

[0006] Therefore, there is a need for a bioactive, degradable, and recyclable 3D printing material that can be printed at room temperature without the addition of a diluent, and the printed products can meet the corresponding mechanical properties and precision requirements. Summary of the invention

[0007] The purpose of the present invention is to overcome the problem that the 3D printing materials in the prior art cannot take into account the corresponding viscosity requirements and recyclability and degradability, and need to add additional biologically active substances to have biological activity.

[0008] In order to achieve the above-mentioned object, the first aspect of the present invention provides a disulfide bond-containing degradable photocurable resin, wherein the degradable photocurable resin contains polycaprolactone lipoic acid ester and a photoinitiator in a weight ratio of 98-99.5:1;

[0009] Wherein, the polycaprolactone lipoic acid ester is a compound represented by formula (1);

[0010] Formula (1)

[0011] Wherein, R1, R2, and R3 are each independently selected from the group represented by formula (2);

[0012] Formula (2)

[0013] Wherein, the value of n is an integer from 1 to 6;

[0014] The photoinitiator is selected from (2,4,6-trimethylbenzoyl)diphenylphosphine oxide and / or photoinitiator 784.

[0015] The second aspect of the present invention provides a method for preparing a degradable photocurable resin containing a disulfide bond, which method is carried out using the components of the photocurable resin described in the first aspect, comprising: mixing the polycaprolactone lipoic acid ester described in the first aspect and a photoinitiator for 60-180 minutes at a temperature of 15-25° C. and a stirring speed of 400-800 rpm to obtain the degradable photocurable resin containing a disulfide bond;

[0016] Wherein, the weight ratio of the polycaprolactone lipoic acid ester to the photoinitiator is 98-99.5:1;

[0017] The photoinitiator is selected from (2,4,6-trimethylbenzoyl)diphenylphosphine oxide and / or photoinitiator 784.

[0018] The third aspect of the present invention provides a disulfide bond-containing degradable photocurable resin prepared by the method described in the second aspect.

[0019] The fourth aspect of the present invention provides the use of the disulfide bond-containing degradable photocurable resin described in the first aspect or the third aspect in the field of 3D printing materials.

[0020] The disulfide bond-containing degradable photocurable resin provided by the present invention not only has biological activity, but is also degradable and recyclable, and can be printed at room temperature without adding a diluent, and the printed products can meet the corresponding mechanical properties and precision requirements. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 It is a characterization of the morphology of a product printed by a photocurable resin in a preferred embodiment provided by the present invention;

[0022] Figure 2 It is a curing depth of the photocurable resin and a printed model diagram in a preferred embodiment provided by the present invention;

[0023] Figure 3 It is a nuclear magnetic hydrogen spectrum of polycaprolactone and polycaprolactone lipoic acid ester in a preferred embodiment provided by the present invention;

[0024] Figure 4 It is a UV-visible spectrum of a cross-linking kinetics study of polycaprolactone lipoic acid ester in a preferred embodiment provided by the present invention;

[0025] Figure 5 It is an evaluation curve of the ability of PCL-LA sheet and PCL-TA sheet to eliminate active oxygen in a preferred embodiment provided by the present invention;

[0026] Figure 6 It is the degradation curve of PCL-LA sheet and PCL-TA sheet in the preferred embodiment provided by the present invention;

[0027] Figure 7 This is a self-healing performance evaluation of a PCL-LA sheet in a preferred embodiment provided by the present invention. DETAILED DESCRIPTION

[0028] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0029] As mentioned above, the first aspect of the present invention provides a disulfide bond-containing degradable photocurable resin, wherein the degradable photocurable resin contains polycaprolactone lipoic acid ester and a photoinitiator in a weight ratio of 98-99.5:1;

[0030] Wherein, the polycaprolactone lipoic acid ester is a compound represented by formula (1);

[0031] Formula (1)

[0032] Wherein, R1, R2, and R3 are each independently selected from the group represented by formula (2);

[0033] Formula (2)

[0034] Wherein, the value of n is an integer from 1 to 6;

[0035] The photoinitiator is selected from (2,4,6-trimethylbenzoyl)diphenylphosphine oxide and / or photoinitiator 784.

[0036] It should be noted that n is an integer of 1-6, which means that n is an integer of 1 to 6, such as 1, 2, 3, 4, 5 or 6.

[0037] Preferably, the polycaprolactone lipoic acid ester is a compound represented by formula (3);

[0038] Formula (3) The value of n is an integer from 1 to 6. The inventors have found that the degradable photocurable resin prepared in this preferred embodiment has better printing, recycling and degradation performance.

[0039] Preferably, the weight ratio of the polycaprolactone lipoic acid ester to the photoinitiator is 98.5-99:1.

[0040] Preferably, the polycaprolactone lipoic acid ester is a product obtained by contacting polycaprolactone with a solvent, lipoic acid, a condensing agent, and 4-dimethylaminopyridine, and the operation of the contact reaction includes:

[0041] (1) mixing the polycaprolactone and the solvent for a first time for 20-60 min at 15-25° C. and a rotation speed of 400-800 rpm to obtain a mixture I;

[0042] (2) mixing the mixture I with the thioctic acid, the 4-dimethylaminopyridine, and the condensing agent for a second time at 15-25° C. and a rotation speed of 400-800 rpm under light-proof conditions for 18-24 hours to obtain the polycaprolactone thioctic ester after purification;

[0043] Wherein, the number average molecular weight of the polycaprolactone is 400-2000;

[0044] The solvent is selected from at least one of dichloromethane, tetrahydrofuran, dimethylformamide and toluene. The inventors found that the degradable photocurable resin prepared under this preferred condition has better printing, recycling and degradation performance.

[0045] It should be noted that the present invention has no requirements on the source of the polycaprolactone, which can be obtained from the market or prepared by conventional methods in the art. The following is an exemplary embodiment of a preferred method for preparing polycaprolactone, including:

[0046] The caprolactone is subjected to reduced pressure distillation at a temperature of 90-120° C. and a vacuum degree of <1 bar; the caprolactone collected after the reduced pressure distillation is mixed with trimethylolpropane, stannous octoate and anhydrous toluene after vacuum drying in a polymerization bottle for reaction, and the mixture is sealed and vacuumized and allowed to stand for 2-3 days; toluene and water are then removed, and the polymerization bottle is then placed in an oil bath at 125-135° C. for reaction for 1-2 days, the polymerization bottle is quenched, dichloromethane is added to dissolve, and then the precipitate is precipitated in petroleum ether to obtain the precipitate, and the precipitation is repeated three times, and vacuum drying is performed to obtain the polycaprolactone;

[0047] The weight ratio of the caprolactone, the trimethylolpropane and the stannous octoate is 50:0.451-25.235:0.035-0.053; and for every 50 g of the caprolactone, the amount of the anhydrous toluene is 8-12 mL, the amount of the dichloromethane is 200-500 mL, and the amount of the petroleum ether is 1000-2000 mL.

[0048] It should be noted that the present invention has no special requirements for the vacuum drying method, and it can be carried out by commonly used technical means in the art, such as using a vacuum oven.

[0049] According to a preferred embodiment, the purification operation comprises: extracting the second mixed product with dilute hydrochloric acid 0.5-1 times the volume of the solvent, water 0.5-1 times the volume of the solvent, and saturated brine 0.5-1 times the volume of the solvent in sequence, removing water with anhydrous sodium sulfate, and then performing rotary evaporation to remove the solvent, followed by precipitation in petroleum ether 5-10 times the volume of the solvent, repeating the precipitation three times on the precipitate and then vacuum drying to obtain polycaprolactone lipoic acid ester, wherein the concentration of the dilute hydrochloric acid is 5-10wt%.

[0050] It should be noted that the present invention has no special requirements on the operation and instruments of the rotary evaporation, and the rotary evaporation can be carried out using the commonly used technical means and instruments in the art.

[0051] Preferably, the condensing agent is at least one of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, N,N-dicyclohexylcarbodiimide and 1,3-diisopropylcarbodiimide.

[0052] More preferably, the condensing agent is 1-(3-dimethylaminopropyl)-3-ethylcarbocyanine.

[0053] According to a preferred embodiment, the solvent is dichloromethane.

[0054] Preferably, the photoinitiator is phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide.

[0055] Preferably, the molar ratio of the polycaprolactone to the lipoic acid is 1:3-4.

[0056] Preferably, for every 1 mmol of the polycaprolactone, the volume of the solvent is 1-15 mL, the weight of the condensing agent is 3-4 mmol, and the weight of the 4-dimethylaminopyridine is 3-4 mmol.

[0057] As mentioned above, the second aspect of the present invention provides a method for preparing a disulfide bond-containing degradable photocurable resin, comprising: mixing the polycaprolactone lipoic acid ester and the photoinitiator described in the first aspect for 60-180 minutes at 15-25° C. and a stirring speed of 400-800 rpm under light-proof conditions to obtain the disulfide bond-containing degradable photocurable resin;

[0058] Wherein, the weight ratio of the polycaprolactone lipoic acid ester to the photoinitiator is 98-99.5:1;

[0059] The photoinitiator is selected from (2,4,6-trimethylbenzoyl)diphenylphosphine oxide and / or photoinitiator 784.

[0060] According to a preferred embodiment, the method of the present invention further comprises: after mixing the polycaprolactone lipoic acid ester with the photoinitiator, removing bubbles by ultrasound to obtain the disulfide bond-containing degradable photocurable resin, wherein the ultrasound conditions at least meet the following conditions: power of 100-200 W and time of 10-30 min.

[0061] As mentioned above, the third aspect of the present invention provides a degradable photocurable resin containing disulfide bonds prepared by the method described in the second aspect.

[0062] As mentioned above, the fourth aspect of the present invention provides the use of the disulfide bond-containing degradable photocurable resin described in the first aspect or the third aspect in the field of 3D printing materials.

[0063] In the following examples, unless otherwise specified, the mass ratios are all based on the total mass of the solution, powder or solid of the substance.

[0064] In the following examples, unless otherwise specified, the room temperature refers to a temperature of 25±5°C.

[0065] In the following examples, unless otherwise specified, all commodities used are commercially available.

[0066] Solvent: dichloromethane;

[0067] Condensation agent: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., brand number E106172-100g;

[0068] Photoinitiator I: phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide, purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., brand number P138333;

[0069] Photoinitiator II: Photoinitiator 784, purchased from Yuanye Biotechnology Co., Ltd., brand number Y46976-5g;

[0070] Petroleum ether: boiling range 60-90°C, purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., brand number P116176.

[0071] Ultrasonic equipment: The model is a medical ultrasonic cleaning machine purchased from Jiangsu Kangbang Medical Technology Co., Ltd.;

[0072] 3D printer: model is nanoArch P140, purchased from Mofang New Materials Technology Co., Ltd.

[0073] Preparation Example A-1

[0074] This preparation is used to illustrate a preferred method for preparing polycaprolactone provided by the present invention, comprising:

[0075] 50 g of caprolactone was subjected to reduced pressure distillation at a temperature of 100°C and a vacuum degree of 0.8 bar; the caprolactone collected after the reduced pressure distillation was mixed with trimethylolpropane, stannous octoate and anhydrous toluene that were vacuum dried in a vacuum oven in a polymerization bottle for reaction, and then the mixture was sealed and vacuumed and allowed to stand for 2 days; toluene and water were then removed, and the polymerization bottle was then placed in an oil bath at 130°C for reaction for 1 day, the polymerization bottle was quenched and dichloromethane was added to dissolve it, and then the precipitate was precipitated in petroleum ether to obtain the precipitate, and the precipitation was repeated three times, and vacuum-dried to obtain polycaprolactone with a number average molecular weight of 1000, which was named PCL1k;

[0076] The weight ratio of the caprolactone, the trimethylolpropane and the stannous octoate is 50:7.8:0.04; and for every 50 g of the caprolactone, the amount of anhydrous toluene is 5 mL, the amount of dichloromethane is 100 mL, and the amount of petroleum ether is 1 L.

[0077] Preparation Example A-2

[0078] This preparation example is carried out in the same manner as Preparation Example A-1, except that the weight ratio of the caprolactone, the trimethylolpropane, and the stannous octoate is 50:25.236:0.053; the polycaprolactone having a number average molecular weight of 400 is obtained and is named PCL0.4k.

[0079] Preparation Example A-3

[0080] This preparation example adopts the same method as that of preparation example A-1, except that the weight ratio of the caprolactone, the trimethylolpropane and the stannous octoate is 50:3.595:0.038;

[0081] The polycaprolactone with a number average molecular weight of 2000 was obtained and named PCL2k.

[0082] Preparation Example A-4

[0083] This preparation example adopts the same method as that of Preparation Example A-1, except that the weight ratio of the caprolactone, the trimethylolpropane and the stannous octoate is 50:1.379:0.036

[0084] The polycaprolactone with a number average molecular weight of 5000 was obtained and named PCL5k.

[0085] Preparation Example A-5

[0086] This preparation example is carried out in the same manner as in Preparation Example A-1, except that the weight ratio of the caprolactone, the trimethylolpropane, and the stannous octoate is 50:1.144:0.036;

[0087] The polycaprolactone with a number average molecular weight of 6000 was obtained and named PCL6k.

[0088] Preparation Example A-6

[0089] This preparation example is carried out in the same manner as in Preparation Example A-1, except that the weight ratio of the caprolactone, the trimethylolpropane and the stannous octoate is 50:0.977:0.036;

[0090] The polycaprolactone with a number average molecular weight of 7000 was obtained and named PCL7k.

[0091] Preparation Example A-7

[0092] This preparation example is carried out in the same manner as in Preparation Example A-1, except that the weight ratio of the caprolactone, the trimethylolpropane, and the stannous octoate is 50:0.451:0.035;

[0093] The polycaprolactone with a number average molecular weight of 15,000 was obtained and named PCL15k.

[0094] Preparation Example B-1

[0095] This preparation is used to illustrate a preferred method for preparing polycaprolactone lipoic acid ester provided by the present invention, comprising:

[0096] (1) dissolving 50 g of polycaprolactone (PCL1k) in 200 mL of solvent (dichloromethane) at 25° C. and 800 rpm for 30 min to obtain a mixture I;

[0097] (2) mixing the mixture I obtained in step (1) with 34 g of thioctic acid, 21.9 g of 4-dimethylaminopyridine, and 34.5 g of a condensing agent for a second time at 25° C. and 800 rpm in the dark for 24 h to obtain a second mixed product;

[0098] (3) extracting the second mixed product with dilute hydrochloric acid (1 times the volume of the solvent), water (1 times the volume of the solvent), and saturated brine (1 times the volume of the solvent), removing water with anhydrous sodium sulfate, and removing the solvent by rotary evaporation. Then, precipitating in petroleum ether (10 times the volume of the solvent), repeating the precipitation three times, and then vacuum drying to obtain the polycaprolactone lipoic acid ester, named PCL-LA1k.

[0099] Preparation Example B-2

[0100] This preparation example is carried out by a method similar to that of Preparation Example 1, except that PCL0.4k is used instead of PCL1k for the first mixing to obtain the polycaprolactone lipoic acid ester, which is named PCL-LA0.4k.

[0101] Preparation Example B-3

[0102] This preparation example is carried out by a method similar to that of Preparation Example 1, except that PCL2k is used instead of PCL1k for the first mixing to obtain the polycaprolactone lipoic acid ester, which is named PCL-LA2k.

[0103] Preparation Example B-4

[0104] This preparation example is carried out by a method similar to that of Preparation Example 1, except that PCL5k is used instead of PCL1k for the first mixing to obtain the polycaprolactone lipoic acid ester, which is named PCL-LA5k.

[0105] Preparation Example B-5

[0106] This preparation example is carried out by a method similar to that of Preparation Example 1, except that PCL6k is used instead of PCL1k for the first mixing to obtain the polycaprolactone lipoic acid ester, which is named PCL-LA6k.

[0107] Preparation Example B-6

[0108] This preparation example is carried out by a method similar to that of Preparation Example 1, except that PCL7k is used instead of PCL1k for the first mixing to obtain the polycaprolactone lipoic acid ester, which is named PCL-LA7k.

[0109] Preparation Example B-7

[0110] This preparation example is carried out by a method similar to that of Preparation Example 1, except that PCL15k is used instead of PCL1k for the first mixing to obtain the polycaprolactone lipoic acid ester, which is named PCL-LA15k.

[0111] Preparation Example B-8

[0112] This preparation example is carried out using a method similar to that of Preparation Example 1, except that PCL15k is used instead of PCL1k for the first mixing, and acryloyl chloride and potassium carbonate are used instead of lipoic acid, condensation agent and 4-dimethylaminopyridine for the second mixing, and finally the polycaprolactone triacrylate is obtained, which is named PCL-TA7k.

[0113] Example 1

[0114] This example is used to illustrate a preferred method for preparing a disulfide bond-containing degradable photocurable resin provided by the present invention, which specifically includes:

[0115] At 25° C. and a stirring speed of 600 rpm in a dark environment, polycaprolactone lipoate (PCL-LA1k) and photoinitiator I were mixed at a weight ratio of 99:1 for 120 min, and bubbles were removed by ultrasound at a power of 100 W for 15 min to obtain the disulfide bond-containing degradable photocurable resin, named P1.

[0116] Example 2

[0117] This example is used to illustrate a preferred method for preparing a disulfide bond-containing degradable photocurable resin provided by the present invention, which specifically includes:

[0118] At 20°C and a stirring speed of 500 rpm in a dark environment, polycaprolactone lipoate (PCL-LA0.4k) and photoinitiator II were mixed at a weight ratio of 98.5:1 for 150 minutes, and bubbles were removed by ultrasound at a power of 150 W for 10 minutes to obtain the disulfide bond-containing degradable photocurable resin, named P2.

[0119] Example 3

[0120] This example is used to illustrate a preferred method for preparing a disulfide bond-containing degradable photocurable resin provided by the present invention, which specifically includes:

[0121] Under light-proof conditions at 20° C. and a stirring speed of 400 rpm, polycaprolactone lipoate (PCL-LA2k) and photoinitiator I were mixed at a weight ratio of 99:1 for 120 min, and bubbles were removed by ultrasound at a power of 200 W for 10 min to obtain the disulfide bond-containing degradable photocurable resin, named P3.

[0122] Comparative Example 1

[0123] This comparative example was carried out in a similar manner to Example 1, except that PCL-LA5k was used instead of PCL-LA1k to mix with the photoinitiator I to obtain the disulfide bond-containing degradable photocurable resin, which was named DP1.

[0124] Comparative Example 2

[0125] This comparative example was carried out in a similar manner to Example 1, except that PCL-LA6k was used instead of PCL-LA1k to mix with the photoinitiator I to obtain the disulfide bond-containing degradable photocurable resin, which was named DP2.

[0126] Comparative Example 3

[0127] This comparative example was carried out in a similar manner to Example 1, except that PCL-LA7k was used instead of PCL-LA1k to mix with the photoinitiator I to obtain the disulfide bond-containing degradable photocurable resin, which was named DP3.

[0128] Comparative Example 4

[0129] This comparative example was carried out in a similar manner to Example 1, except that PCL-LA15k was used instead of PCL-LA1k to mix with the photoinitiator I to obtain the disulfide bond-containing degradable photocurable resin, which was named DP4.

[0130] Comparative Example 5

[0131] This comparative example was carried out in a similar manner to Example 1, except that polycaprolactone triacrylate (PCL-TA7k) was mixed with photoinitiator I to obtain the disulfide bond-containing degradable photocurable resin, named DP5.

[0132] Test Example 1

[0133] The degradable photocurable resin containing disulfide bonds prepared in the above examples 1-3 and comparative examples 1-5 was added into the material tank of the 3D printer, and the 3D model image was sliced ​​into a 2D projection image and then imported into the computer of the 3D printer. The ultraviolet wavelength was 405nm, each layer was printed with a thickness of 30μm, each layer was exposed for 3s, and the exposure capacity was 50mJ / cm 2 Printing was performed under the conditions of , and the obtained printed product was centrifuged to remove excess resin and then placed in a UV curing box for curing for 1 hour, with an ultraviolet wavelength of 405nm to obtain the final product;

[0134] The printing results are shown in Table 1, where: Figure 1 The figure shows the morphology of the final printed product 3D printed using P1 as the printing material.

[0135] Then the layer thickness of the final printed product is measured under an optical microscope to obtain the curing depth C of the support. d , critical curing energy E c and penetration depth D p , the results are as follows Figure 2 shown.

[0136] It can be seen that with the increase of UV curing energy, the curing depth of the degradable photocurable resin gradually increases.

[0137] According to the formula (where E is the output energy of the UV lamp), the critical curing energy and penetration depth of the photocurable resin prepared by the present invention can be calculated. That is, the critical curing energy of the photocurable resin prepared by PCL-LA1k is 12.7 mJ / cm 2 .

[0138] Therefore, the degradable photocurable resin containing disulfide bonds provided by the present invention can realize 3D printing without diluent at room temperature;

[0139] And it can achieve fast reaction curing printing at extremely low exposure energy.

[0140] Test Example 2

[0141] The polycaprolactone (PCL1k) and polycaprolactone lipoic acid ester (PCL-LA1k) prepared in the above example were dissolved in deuterated chloroform, and then 1 H NMR spectrum characterization, the results are as follows Figure 3 As shown, Figure 3 PCL tiol 1k is the characterization graph obtained using PCL1k as the test sample; PCL-LA is the characterization graph obtained using PCL-LA1k as the test sample.

[0142] Depend on Figure 3It can be seen that all chemical shifts of the polycaprolactone PCL1k and polycaprolactone lipoate PCL-LA1k provided by the present invention can be well attributed to the corresponding protons on the backbones of the compound polycaprolactone and the compound polycaprolactone lipoate, respectively, thereby confirming the successful synthesis of PCL1k and PCL-LA1k.

[0143] Test Example 3

[0144] The polycaprolactone lipoic acid ester prepared in the above example was used for photocuring kinetic characterization:

[0145] Polycaprolactone lipoate was dissolved in deuterated chloroform to obtain a polycaprolactone lipoate solution, which was then transferred to a silicone mold with a thickness of about 0.5 mm. The upper and lower surfaces of the silicone mold were clamped with two glass plates (2.1 mm thick), and then placed under ultraviolet light (365 nm) for different times (0-30 min), and then placed under an ultraviolet-visible spectrophotometer for band scanning (300-800 nm) to obtain spectra at different light curing times, such as Figure 4 As shown, Figure 4 BAPO in FIG. 5 is the absorption peak of the photoinitiator phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide used.

[0146] Figure 4 It is shown in the figure that under irradiation with a wavelength of 365 nm, the peak of the dithiolane group at 330 nm gradually decreases until it disappears, and the curing time is 30 min at this time, which confirms that within the polycaprolactone lipoic acid ester solution provided by the present invention, as the ultraviolet light is irradiated, the polymer is continuously cross-linked, a cross-linked network is continuously formed, and the cross-linking can be completed within 30 min.

[0147] Preparation Example C

[0148] The polycaprolactone lipoic acid ester prepared in the above-mentioned Example 1, Example 3 and Comparative Examples 1-4 is prepared into a PCL-LA sheet, and the polycaprolactone triacrylate prepared in Comparative Example 5 is prepared into a PCL-TA sheet, specifically comprising:

[0149] 1.5 g of polycaprolactone lipoate or polycaprolactone triacrylate was dissolved in 500 μL of dichloromethane, and 75 μL of a mixed solution of phenyl bis(2,4,6-trimethylbenzoyl)phosphine oxide and dichloromethane (mixing ratio of 300 mg / 1.5 mL) was added and mixed evenly, and transferred to a silicone mold with a thickness of about 0.5 mm. The upper and lower surfaces of the silicone mold were clamped with two glass plates (2.1 mm thick), and then placed under ultraviolet light (365 nm) for 20 minutes (7 cm from the lamp head) for cross-linking. The cross-linked slices were taken out after cooling to room temperature to obtain samples, namely PCL-LA slices (cross-linked PCL-LA1k, cross-linked PCL-LA2k, cross-linked PCL-LA5k, cross-linked PCL-LA6k, cross-linked PCL-LA7k, cross-linked PCL-LA15k) and PCL-TA slices (cross-linked PCL-TA7k) for experimental characterization.

[0150] Test Example 3

[0151] The polycaprolactone, polycaprolactone lipoic acid ester and PCL-LA sheets prepared in the above examples were characterized by thermal analysis, and the results are shown in Table 2;

[0152] It can be seen that with the increase of molecular weight, the melting points of polycaprolactone, polycaprolactone lipoate and PCL-LA sheets all increase continuously. The melting points of PCL and PCL-LA are not much different, while the melting point and crystallinity of PCL-LA sheets decrease significantly.

[0153] Test Example 4

[0154] The PCL-LA sheet and PCL-TA sheet prepared in the above example were cut into discs with a mass of about 10 mg, and an active oxygen elimination experiment was conducted, specifically including:

[0155] Place the disc in a 24-well plate and add 2 mL of 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) solution, the solvent is 80% ethanol and 20% water, and the DPPH concentration is 200 μM. Then place the plate in a 37-degree incubator. Take 100 μL of the solution at regular intervals and measure the absorbance A at 517 nm on a multifunctional microplate reader. 样品 , the group without PCL-LA sheet is A 阳性对照 , and then calculate the active oxygen content at that time point using the following formula:

[0156] %DPPH=(A 阳性对照 -A 样品 ) / A 阳性对照 ×100%;

[0157] The results are as follows Figure 5As shown, it can be seen that as time goes by, the active oxygen content in the system gradually decreases until it disappears. At the same time point, there is no significant difference in the ability of PCL-LA sheets to eliminate active oxygen. However, there is no ability to eliminate active oxygen with PCL-TA sheets. The results show that the disulfide-bonded degradable photocurable resin provided by the present invention has excellent ability to eliminate active oxygen.

[0158] Test Example 5

[0159] The cross-linked PCL-LA1k, cross-linked PCL-LA7k and cross-linked PCL-TA7k prepared in the above examples were cut into discs with a mass of about 20 mg (M0) and subjected to active oxygen degradation experiments:

[0160] The disc was placed in a 24-well plate, 2 mL of degradation solution was added thereto and placed in a 37°C constant temperature shaker for degradation experiments;

[0161] Among them, the degradation solutions are divided into three types: degradation solution I (PBS buffer); degradation solution II (2% H2O2 / 0.01M CoCl2 solution that generates free radicals); degradation solution III (20% H2O2 / 0.1M CoCl2 solution that generates free radicals);

[0162] The disc was taken out and washed three times with ultrapure water, and then freeze-dried and weighed (M t ), and calculate the remaining mass ratio of the disc at different time points = M t / M0×100%, the result is as follows Figure 6 As shown, Figure 6 a is the degradation curve of cross-linked PCL-LA1k in three degradation solutions; Figure 6 b is the degradation curve of cross-linked PCL-LA7k in three degradation solutions; Figure 6 c is the degradation curve of cross-linked PCL-LA1k, cross-linked PCL-LA7k and cross-linked PCL-TA7k in degradation solution III.

[0163] It can be seen that within 10 days, cross-linked PCL-LA1k and cross-linked PCL-LA7k had almost no mass change in PBS buffer, but had obvious changes in the degradation solution rich in active oxygen-generating free radicals, and the higher the active oxygen content, the faster the degradation rate.

[0164] For the same degradation solution, the degradation rates of cross-linked PCL-LA1k and cross-linked PCL-LA7k are much higher than that of cross-linked PCL-TA7k. In addition, the degradation rate of cross-linked PCL-LA1k in Example 1 is much higher than that of cross-linked PCL-LA7k in Comparative Example 3, indicating that the disulfide bond content in the cross-linked network of cross-linked PCL-LA1k is higher. The results show that the disulfide bond-containing degradable photocurable resin provided by the present invention has excellent active oxygen free radical degradability.

[0165] Test Example 6

[0166] The cross-linked PCL-LA1k, cross-linked PCL-LA7k and cross-linked PCL-TA7k prepared in the above examples were cut into discs (6 mm in diameter, 0.5 mm in thickness) for recyclability evaluation:

[0167] The disc was placed in a 20 mL sample bottle, and a chloroform solution containing 1% 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was added. After standing for 1 hour, the remaining mass and morphology of the sample were observed, and the solubility was obtained as the recyclability evaluation.

[0168] The results show that the cross-linked PCL-LA1k disc in Example 1 can be dissolved in a 1% DBU chloroform solution within 1 hour, while the cross-linked PCL-LA7k in Comparative Example 3 takes 3 hours to dissolve in a 1% DBU chloroform solution, and the cross-linked PCL-TA7k in Comparative Example 5 is insoluble in the above solution. The above results show that the disulfide bond-containing degradable photocurable resin provided by the present invention has excellent recyclability.

[0169] Test Example 7

[0170] The cross-linked PCL-LA1k and cross-linked PCL-TA7k prepared in the above examples were cut into discs (6 mm in diameter, 0.5 mm in thickness) for self-healing characterization:

[0171] Cut the disc into two equal parts with a blade and place them on a glass slide. Then:

[0172] Group 1 (DBU, 24 h): 10 μL of DBU was added to the cuts of the two discs, and the discs were covered with glass slides and placed at room temperature for 24 h.

[0173] The second group (80°C, 24 h): the disc was divided into two parts and clamped with glass slides, and placed at 80°C for 24 h;

[0174] Then, the morphology of the cut portions of the first and second groups of wafers after standing were observed under an optical microscope.

[0175] Figure 7 The test results of cross-linked PCL-LA1k in the first group are shown in the figure: PCL-LA sheets can self-heal and repair in the presence of DBU;

[0176] Figure 7 Also shown in the figure are the test results of the cross-linked PCL-LA1k in the second group: PCL-LA sheets were able to achieve self-healing of scratches within 1 day at 80°C.

[0177] However, cross-linked PCL-TA7k could not heal on its own.

[0178] Table 1

[0179] P1 P2 P3 DP1 DP2 DP3 DP4 DP5 Printing Results success success success fail fail fail fail fail

[0180] Table 2

[0181]

[0182]

[0183] From the above results, it can be seen that the disulfide bond-containing degradable photocurable resin provided by the present invention is not only biologically active, but also degradable and recyclable, and can be printed at room temperature without the addition of a diluent, and the printed products can meet the corresponding mechanical properties and precision requirements.

[0184] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. A degradable photocurable resin containing disulfide bonds, characterized in that: The degradable photocurable resin contains polycaprolactone lipoic acid ester and a photoinitiator in a weight ratio of 98-99.5:1; Wherein, the polycaprolactone lipoic acid ester is a compound represented by formula (1); Wherein, R1, R2, and R3 are each independently selected from the group represented by formula (2); Wherein, the value of n is an integer from 1 to 6; The photoinitiator is selected from (2,4,6-trimethylbenzoyl)diphenylphosphine oxide and / or photoinitiator 784.

2. The degradable photocurable resin according to claim 1, wherein: The polycaprolactone lipoic acid ester is a compound represented by formula (3); Here, the value of n is an integer from 1 to 6.

3. The degradable photocurable resin according to claim 1 or 2, wherein: The weight ratio of the polycaprolactone lipoic acid ester to the photoinitiator is 98.5-99:

1.

4. The degradable photocurable resin according to claim 1, wherein: The polycaprolactone lipoic acid ester is a product obtained by contacting polycaprolactone with a solvent, lipoic acid, a condensing agent, and 4-dimethylaminopyridine, and the operation of the contact reaction includes: (1) mixing the polycaprolactone and the solvent for a first time for 20-60 min at 15-25° C. and a rotation speed of 400-800 rpm to obtain a mixture I; (2) mixing the mixture I with the thioctic acid, the 4-dimethylaminopyridine, and the condensing agent for a second time at 15-25° C. and a rotation speed of 400-800 rpm under light-proof conditions for 18-24 hours to obtain the polycaprolactone thioctic ester after purification; Wherein, the number average molecular weight of the polycaprolactone is 400-2000; The solvent is selected from at least one of dichloromethane, tetrahydrofuran, dimethylformamide and toluene.

5. The degradable photocurable resin according to claim 4, wherein: The condensing agent is at least one of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, N,N-dicyclohexylcarbodiimide, and 1,3-diisopropylcarbodiimide; and / or The solvent is dichloromethane; and / or The photoinitiator is phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide.

6. The degradable photocurable resin according to claim 4 or 5, wherein: The molar ratio of the polycaprolactone to the lipoic acid is 1:3-4.

7. The degradable photocurable resin according to claim 4 or 5, wherein: For every 1 mmol of the polycaprolactone, the volume of the solvent is 1-15 mL, the weight of the condensing agent is 3-4 mmol, and the weight of the 4-dimethylaminopyridine is 3-4 mmol.

8. A method for preparing a degradable photocurable resin containing disulfide bonds, characterized in that: include: Mixing the polycaprolactone lipoic acid ester and the photoinitiator according to claim 1 for 60-180 minutes at 15-25° C. and a stirring speed of 400-800 rpm in the dark to obtain the disulfide bond-containing degradable photocurable resin; Wherein, the weight ratio of the polycaprolactone lipoic acid ester to the photoinitiator is 98-99.5:1; The photoinitiator is selected from (2,4,6-trimethylbenzoyl)diphenylphosphine oxide and / or photoinitiator 784.

9. The degradable photocurable resin containing disulfide bonds prepared by the method according to claim 8.

10. Use of the disulfide bond-containing degradable photocurable resin according to claim 1 or 9 in the field of 3D printing materials.

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