Programmable hydrogel, preparation method thereof and application thereof in preparing medical self-expanding stent

Abstract

The present invention relates to a programmable hydrogel, a preparation method thereof and its application in the preparation of a medical self-expanding stent, and belongs to the field of biomedical material technology. In order to solve the problem that existing programmable hydrogels cannot meet the requirement of mild induced stimulation of biomaterials, the present invention provides a programmable hydrogel, wherein formaldehyde-modified xylan is mixed with gelatin to prepare a gel, a shaped product is prepared by 3D printing or mold shaping, and the product is immersed in a salt solution for salting out to obtain a programmable hydrogel. The present invention utilizes the Hofmeister effect to make the editable hydrogel exhibit ion stimulation response and shape memory characteristics, and can achieve self-expansion under mild stimulation of low-concentration ion solution or distilled water. The editable hydrogel provided by the present invention meets the requirements of simple biomaterial preparation, suitable mechanical strength, mild induced stimulation, non-toxicity, and good biocompatibility, and has great application prospects in the preparation of self-expanding artificial stents.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedical materials, and in particular relates to a programmable hydrogel, a preparation method thereof, and an application thereof in preparing a medical self-expanding stent. Background Art

[0002] Hydrogels are polymer networks composed of physically or covalently cross-linked polymer chains in aqueous solution. Because their structure is similar to the highly hydrated composition of the human body, they have been widely used in biomedicine, such as tissue engineering scaffolds, implantable devices, and drug delivery. Programmable hydrogels are a class of hydrogel materials that can sense external stimuli and convert them into mechanical outputs. Their stimulus responses can be categorized into humidity, pH, temperature, light, electric, and magnetic field responses, depending on their characteristics. Programmable hydrogels can significantly change volume or shape in response to various external stimuli. As the most important smart material, they have been widely used in fields such as soft robotics, artificial muscles, and smart valves.

[0003] Vascular stents are a type of balloon angioplasty procedure that expands arteries to treat coronary, renal, and aortic diseases. Traditional commercial stents are subject to unintended elongation, deformation, damage, or failure due to the complex design and operation procedures. If programmable hydrogels can be used as stent materials, such as rapidly self-expanding vascular stents, they could offer a viable option for further biomedical applications.

[0004] The basic requirements for viable biomaterials are simple preparation, mild induced stimulation, and non-toxicity. However, the current induced stimulation methods of programmable hydrogels are too complex to meet the requirements of biomaterial vascular stents. Summary of the Invention

[0005] In order to solve the problem that existing programmable hydrogels cannot meet the requirement of mild stimulation induced by biomaterials, the present invention provides a programmable hydrogel, a preparation method thereof, and an application thereof in the preparation of a medical self-expanding stent.

[0006] The technical solution of the present invention:

[0007] A method for preparing a programmable hydrogel comprises the following steps:

[0008] Step 1, preparing an aldehyde xylan solution with a concentration of 1 wt.% to 15 wt.%;

[0009] Step 2: mixing the aldehyde-xylan solution obtained in step 1 with a gelatin solution having a concentration of 5 wt.% to 15 wt.% in a certain volume ratio to obtain a GEL / Xyl-CHO gel;

[0010] Step 3: Using the GEL / Xyl-CHO gel obtained in step 2 as a material, 3D printing is performed to obtain a 3D printed product, or the GEL / Xyl-CHO gel is poured into a mold to be shaped to obtain a shaped product;

[0011] Step 4: Immerse the 3D printed product or shaped product obtained in step 3 in a salt solution for salting out to obtain a programmable hydrogel.

[0012] Furthermore, the preparation method of the aldehyde-xylan solution in step 1 is:

[0013] Materials were prepared according to the mass volume ratio of xylan, deionized water, sodium periodate, and ethylene glycol of 2-4 g:200-400 ml:5-10 g:2-5 ml. Xylan was dissolved in deionized water at room temperature, and then sodium periodate was added to obtain a reaction mixture system. The obtained reaction mixture system was stirred in the dark at 30-50° C. under closed conditions; then ethylene glycol was added, and the reaction was terminated after stirring for 1 hour. The obtained reaction product was dialyzed in the dark for 60-75 hours. The dialyzed product was freeze-dried and ground to obtain an aldolized xylan sample. The aldolized xylan sample was dissolved in deionized water and ultrasonically treated for 15-30 minutes to obtain an aldolized xylan solution.

[0014] Furthermore, the molecular weight of the xylan is 280-950 Mw, and the molecular weight of the gelatin is 10,000-70,000 Mw.

[0015] Furthermore, the volume ratio of the aldehyde-xylan solution to the gelatin solution in step 2 is 1-5:1-3.

[0016] Furthermore, the structure layer height of the printer for 3D printing in step 3 is set to 0.2-0.4 mm, the speed is set to 300-360 mm / min, and the processing temperature is 6-30°C.

[0017] Furthermore, the salt solution in step 4 is one of sodium sulfate solution, potassium sulfate solution, sodium chloride solution or ammonium sulfate solution; the concentration of the salt solution is 20wt.% to 30wt.%, the salt solution is a clear solution obtained by ultrasonic treatment for 20 to 55 minutes, and the immersion time is 1 to 3 hours.

[0018] A programmable hydrogel prepared by a method for preparing a programmable hydrogel can self-swell in distilled water or a salt solution with a concentration lower than 5 wt.%.

[0019] A method for preparing a programmable hydrogel and application of the programmable hydrogel prepared in the preparation of a medical self-expanding stent.

[0020] Furthermore, the medical self-expanding stent is a self-expanding vascular stent; the self-expanding vascular stent includes a coronary vascular stent, a cerebral vascular stent, a renal artery vascular stent, an aorta vascular stent, a venous vascular stent and a peripheral vascular stent.

[0021] Furthermore, the self-expanding vascular stent is prepared by pouring the GEL / Xyl-CHO gel into a mold for shaping, cutting the resulting shaped product into a long strip, naturally curling and deforming the resulting long strip to form a spirally curled three-dimensional stent structure, immersing the three-dimensional stent structure in a saline solution for salting out, thereby obtaining a self-expanding vascular stent; the self-expanding vascular stent is capable of self-expanding within 60 seconds under the stimulation of distilled water or a saline solution with a concentration of less than 5 wt.%, and after expansion, forms a spiral tubular structure with a hollow interior.

[0022] Beneficial effects of the present invention:

[0023] The present invention utilizes the Hofmeister effect to enable the editable hydrogel to exhibit ion stimulation response and excellent shape memory properties, and can achieve self-expansion under slight stimulation of low-concentration ion solution or distilled water, meeting the requirement of slight induced stimulation of biomaterials.

[0024] The mechanical properties of the editable hydrogel of the present invention have been significantly improved. The present invention uses aldehyde-modified xylan as a biological cross-linking agent, and utilizes the aldehyde groups in the aldehyde-modified xylan to react with the amino groups in gelatin to produce a Schiff base reaction. Based on the Schiff base, hydrogen bond interaction, the enhancement of the aldehyde-modified xylan nanoparticles in the polymer network, and the mechanical robustness of the aldehyde-modified xylan and gelatin, the mechanical properties of the editable hydrogel of the present invention are enhanced. The tensile strength of the GEL / Xyl-CHO gel prepared by the present invention is 11.02 kPa, which is 53.9% higher than that of gelatin; the toughness is 311.38 kJ·m -3 , which is enhanced by 265.81% compared with gelatin; the compressive Young's modulus is 23.99kPa, which is enhanced by 8.86% compared with gelatin.

[0025] Based on the reversible Schiff base crosslinked network formed by the editable hydrogel of the present invention, the editable hydrogel prepared by the present invention exhibits excellent room-temperature self-healing properties. The xylan material used in the present invention is derived from corn cobs, and gelatin is a natural biopolymer. Therefore, the editable hydrogel produced has excellent biocompatibility and conforms to the ecological concept of green environmental protection.

[0026] The editable hydrogel provided by the present invention can be used as a 3D printing composite wire to prepare 3D printed products with high mechanical strength, self-repair, biocompatibility and ion stimulation responsive shape memory properties.

[0027] Cytotoxicity and compatibility tests show that the editable hydrogel provided by the present invention is safe and non-toxic, and can meet the requirements of simple biomaterial preparation, appropriate mechanical strength, mild shape memory induction stimulation, non-toxicity, and good biocompatibility. It has great application prospects in the preparation of various self-expanding artificial stents in the biomedical field, and is particularly suitable for the preparation of self-expanding vascular stents. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is a photo of the self-expandable vascular stent prepared in Example 1 before expansion;

[0029] Figure 2 This is a photo of the self-expanding vascular stent prepared in Example 1 after self-expanding for 10 seconds under mild stimulation of a low-concentration saline solution;

[0030] Figure 3 This is a photo of the self-expanding vascular stent prepared in Example 1 after self-expanding for 60 seconds under mild stimulation of a low-concentration saline solution;

[0031] Figure 4 This is a display of the effect of the snowflake structure 3D printed product prepared in Example 2;

[0032] Figure 5 This is a diagram showing the effect of the spider web structure 3D printed product prepared in Example 3;

[0033] Figure 6 This is a diagram showing the effect of the hollow cylindrical 3D printed product prepared in Example 4;

[0034] Figure 7 2 is a comparison diagram of the tensile stress-strain curves of the GEL / Xyl-CHO gel obtained in step 2 of Example 2;

[0035] Figure 8 2 is a comparison diagram of the compressive stress-strain curves of the GEL / Xyl-CHO gel obtained in step 2 of Example 2;

[0036] Figure 9 is a histogram of the compressive elastic modulus of the GEL / Xyl-CHO gel obtained in step 2 of Example 2;

[0037] Figure 10 is a histogram of the tensile toughness of the GEL / Xyl-CHO gel obtained in step 2 of Example 2;

[0038] Figure 11 This is a diagram showing the self-healing effect of the shaped product obtained in step 3 of Example 1 within 24 hours. DETAILED DESCRIPTION

[0039] The technical solution of the present invention is further described below with reference to the embodiments, but is not limited thereto. Any modification or equivalent replacement of the technical solution of the present invention without departing from the spirit and scope of the technical solution of the present invention shall be included in the scope of protection of the present invention. The process equipment or devices not specifically noted in the following examples are all conventional equipment or devices in the art. Unless otherwise specified, the raw materials used in the examples of the present invention can be obtained commercially; unless otherwise specified, the technical means used in the examples of the present invention are all conventional means well known to those skilled in the art.

[0040] Example 1

[0041] This embodiment provides a programmable hydrogel self-expanding vascular stent and a preparation method thereof.

[0042] The specific preparation method of this embodiment includes the following steps:

[0043] Step 1: Dissolve 3 g of xylan in 200 ml of deionized water at room temperature, then add 5 g of sodium periodate to obtain a reaction mixture. The reaction mixture is stirred in the dark at 40°C under closed conditions for 6 hours. Then, add 4 ml of ethylene glycol and terminate the reaction after mechanical stirring for 1 hour. The resulting reaction product is dialyzed in the dark for 70 hours. The dialyzed product is freeze-dried to obtain an aldehyde-modified xylan material, Xyl-CHO. The obtained aldehyde-modified xylan material, Xyl-CHO, is ground into a powder and stored in the dark. The aldehyde-modified xylan powder is dissolved in deionized water and ultrasonically treated for 30 minutes to obtain an aldehyde-modified xylan solution with a concentration of 12 wt.%.

[0044] Step 2: Add 12 g of gelatin to 100 ml of deionized water and stir magnetically in an oil bath at 50°C until dissolved to prepare a gelatin solution with a concentration of 12 wt.%. The aldehyde-modified xylan solution obtained in step 1 was mixed with the gelatin solution in a volume ratio of 1:1 to obtain a GEL / Xyl-CHO gel.

[0045] Step 3: Pour the GEL / Xyl-CHO gel obtained in Step 2 into a mold to shape the resulting shaped product. The resulting shaped product is 4 mm thick and is cut into strips with a width of 8 mm. The resulting strips are naturally curled and deformed to obtain a spirally curled three-dimensional scaffold structure.

[0046] Step 4: Prepare a 25 wt.% sodium sulfate solution at room temperature, ultrasonicate for 20 min to obtain a clean solution, and immerse the three-dimensional stent structure obtained in step 3 in the 25 wt.% sodium sulfate solution for 2 h to obtain a programmable hydrogel, i.e., a self-expanding vascular stent. The specific structure is as follows: Figure 1 shown.

[0047] The self-expanding vascular stent prepared in this example was immersed in a sodium sulfate solution with a concentration of 2 wt.%. The self-expanding vascular stent rapidly expanded under the induction stimulation of the low concentration salt solution. After 10 seconds of stimulation, the self-expanding effect was as follows: Figure 2 As shown, the self-expansion effect after 60s of stimulation is as follows Figure 3 It can be seen that the self-expanding vascular stent prepared in this embodiment can complete self-expansion within 60 seconds and form a spiral tubular structure with a hollow interior after expansion.

[0048] The xylan material used in this example was purchased from Shanghai MacLean Biochemical Technology Co., Ltd. and was derived from corn cobs, with a content of 90% and a molecular weight range of 280 to 950 Mw. The gelatin material used in this example had a molecular weight of 10,000 to 70,000 Mw.

[0049] Example 2

[0050] This embodiment provides a programmable hydrogel and a preparation method thereof.

[0051] The specific preparation method of this embodiment includes the following steps:

[0052] Step 1: Dissolve 2 g of xylan in 250 ml of deionized water at room temperature, then add 6 g of sodium periodate to obtain a reaction mixture. The reaction mixture is stirred in the dark at 30°C for 4 hours under closed conditions. 2 ml of ethylene glycol is then added, and the reaction is terminated after mechanical stirring for 1 hour. The resulting reaction product is dialyzed in the dark for 60 hours. The dialyzed product is freeze-dried to obtain an aldehyde-modified xylan material, Xyl-CHO. The resulting aldehyde-modified xylan material, Xyl-CHO, is ground into a powder and stored in the dark. The aldehyde-modified xylan powder is dissolved in deionized water to prepare an aldehyde-modified xylan solution having a concentration of 10 wt.%.

[0053] Step 2: Add 8 g of gelatin to 80 ml of deionized water and stir magnetically in an oil bath at 40°C until dissolved to prepare a gelatin solution with a concentration of 10 wt.%. The aldehyde-modified xylan solution obtained in step 1 was mixed with the gelatin solution in a volume ratio of 1:1 to obtain a GEL / Xyl-CHO gel.

[0054] Step 3: Print the 3D scaffold structure using the ink writing 3D printer DIW with the GEL / Xyl-CHO gel obtained in step 2 as the 3D printing filament. The printer structure layer height is set to 0.2 mm, the speed is set to 300 mm / min, and the processing temperature is 6 ° C. The printed product in this embodiment is a snowflake structure, such as Figure 4 shown.

[0055] Step 4: Prepare a 25 wt.% sodium sulfate solution at room temperature, ultrasonicate for 20 min to obtain a clean solution, and immerse the 3D printed product obtained in step 3 in a 25 wt.% sodium sulfate solution for 1 h to obtain a programmable hydrogel with high mechanical strength, self-healing, biocompatibility, and low-concentration ion stimulus-responsive shape memory properties.

[0056] The xylan material used in this example was purchased from Shanghai MacLean Biochemical Technology Co., Ltd. and was derived from corn cobs, with a content of 90% and a molecular weight range of 280 to 950 Mw. The gelatin material used in this example had a molecular weight of 10,000 to 70,000 Mw.

[0057] Example 3

[0058] This embodiment provides a programmable hydrogel and a preparation method thereof.

[0059] The specific preparation method of this embodiment includes the following steps:

[0060] Step 1: 3.5 g of xylan was dissolved in 300 ml of deionized water at room temperature, and then 7 g of sodium periodate was added to obtain a reaction mixture. The reaction mixture was stirred in the dark at 45° C. under closed conditions for 6 hours. 3 ml of ethylene glycol was then added, and the reaction was terminated after mechanical stirring for 1 hour. The resulting reaction product was dialyzed in the dark for 68 hours. The dialyzed product was freeze-dried to obtain an aldehyde-modified xylan material, Xyl-CHO. The obtained aldehyde-modified xylan material, Xyl-CHO, was ground into a powder and stored in the dark. The aldehyde-modified xylan powder was dissolved in deionized water to prepare an aldehyde-modified xylan solution with a concentration of 12 wt.%.

[0061] Step 2: Add 10 g of gelatin to 100 ml of deionized water and stir magnetically in an oil bath at 50°C until dissolved to prepare a gelatin solution with a concentration of 10 wt.%. The aldehyde-modified xylan solution obtained in step 1 was mixed with the gelatin solution in a volume ratio of 1:1 to obtain a GEL / Xyl-CHO gel.

[0062] Step 3: Print the 3D scaffold structure using the ink writing 3D printer DIW with the GEL / Xyl-CHO gel obtained in step 2 as the 3D printing filament. The printer structure layer height is set to 0.3 mm, the speed is set to 320 mm / min, and the processing temperature is 20 ° C. The printed product in this embodiment is a spider web structure, such as Figure 5 shown.

[0063] Step 4: Prepare a 23 wt.% sodium sulfate solution at room temperature, ultrasonicate for 30 min to obtain a clean solution, and immerse the 3D printed product obtained in step 3 in a 23 wt.% sodium sulfate solution for 2 h to obtain a programmable hydrogel with high mechanical strength, self-healing, biocompatibility, and low-concentration ion stimulus-responsive shape memory properties.

[0064] The xylan material used in this example was purchased from Shanghai MacLean Biochemical Technology Co., Ltd. and was derived from corn cobs, with a content of 90% and a molecular weight range of 280 to 950 Mw. The gelatin material used in this example had a molecular weight of 10,000 to 70,000 Mw.

[0065] Example 4

[0066] This embodiment provides a programmable hydrogel and a preparation method thereof.

[0067] The specific preparation method of this embodiment includes the following steps:

[0068] Step 1: Dissolve 4 g of xylan in 200 ml of deionized water at room temperature, then add 10 g of sodium periodate to obtain a reaction mixture. The reaction mixture is stirred in the dark at 50° C. under closed conditions for 8 hours. Then, add 5 ml of ethylene glycol, and terminate the reaction after mechanical stirring for 1 hour. The resulting reaction product is dialyzed in the dark for 75 hours. The dialyzed product is freeze-dried to obtain an aldehyde-modified xylan material, Xyl-CHO. The obtained aldehyde-modified xylan material, Xyl-CHO, is ground into a powder and stored in the dark. The aldehyde-modified xylan powder is dissolved in deionized water to prepare an aldehyde-modified xylan solution with a concentration of 15 wt.%.

[0069] Step 2: Add 11 g of gelatin to 100 ml of deionized water and stir magnetically in an oil bath at 60°C until dissolved to prepare a gelatin solution with a concentration of 11 wt.%. The aldehyde-modified xylan solution obtained in step 1 was mixed with the gelatin solution in a volume ratio of 1:1 to obtain a GEL / Xyl-CHO gel.

[0070] Step 3: Print the 3D scaffold structure using the ink writing 3D printer DIW with the GEL / Xyl-CHO gel obtained in step 2 as the 3D printing filament. The printer structure layer height is set to 0.4 mm, the speed is set to 360 mm / min, and the processing temperature is 30 ° C. The printed product in this embodiment is a hollow cylindrical structure, such as Figure 6 shown.

[0071] Step 4: Prepare a 20 wt.% sodium sulfate solution at room temperature, ultrasonicate for 55 min to obtain a clean solution, and immerse the 3D printed product obtained in step 3 in a 20 wt.% sodium sulfate solution for 3 h to obtain a programmable hydrogel with high mechanical strength, self-healing, biocompatibility, and low-concentration ion stimulus-responsive shape memory properties.

[0072] The xylan material used in this example was purchased from Shanghai MacLean Biochemical Technology Co., Ltd. and was derived from corn cobs, with a content of 90% and a molecular weight range of 280 to 950 Mw. The gelatin material used in this example had a molecular weight of 10,000 to 70,000 Mw.

[0073] In the present invention, aldehyde-modified xylan is used as a biocrosslinking agent. The aldehyde groups in the aldehyde-modified xylan react with the amino groups in the gelatin to form a Schiff base reaction, thereby enhancing the mechanical properties of the aldehyde-modified crosslinked hydrogel. The mechanical properties of the GEL / Xyl-CHO gel obtained in step 2 of Example 2 were tested, and the results were as follows: Figure 7-10 As shown, the mechanical properties of the GEL / Xyl-CHO gel prepared in the present invention are superior to those of gelatin. The GEL / Xyl-CHO gel prepared in the present invention has a tensile strength of 11.02 kPa, a 53.9% increase compared to gelatin; a toughness of 311.38 kJ·m⁻³, a 265.81% increase compared to gelatin; and a compressive Young's modulus of 23.99 kPa, an 8.86% increase compared to gelatin.

[0074] Based on the reversible Schiff base crosslinking network formed by aldehyde-modified xylan and gelatin, the GEL / Xyl-CHO gel-formed products have good room temperature self-healing properties. The GEL / Xyl-CHO gel prepared in Example 1 was poured into a mold to form the product. The formed product was cut with a knife and the degree of crack healing over time was observed under an optical microscope. Figure 11 The following diagrams show the self-healing effect of the shaped product obtained in step 3 of Example 1 within 24 hours. Figure a shows a crack that has just been cut, Figure b shows the effect of self-healing for 6 hours, Figure c shows the effect of self-healing for 18 hours, and Figure d shows the effect of self-healing for 24 hours. It can be seen from the figure that the crack gradually shortens with the passage of time and is completely healed after 24 hours.

[0075] Example 5

[0076] This embodiment provides a programmable hydrogel scaffold and a preparation method thereof.

[0077] The specific preparation method of this embodiment includes the following steps:

[0078] Step 1: Dissolve 3 g of xylan in 200 ml of deionized water at room temperature, then add 5 g of sodium periodate to obtain a reaction mixture. The reaction mixture is stirred in the dark at 40°C under closed conditions for 6 hours. Then, add 4 ml of ethylene glycol and terminate the reaction after mechanical stirring for 1 hour. The resulting reaction product is dialyzed in the dark for 70 hours. The dialyzed product is freeze-dried to obtain an aldehyde-modified xylan material, Xyl-CHO. The obtained aldehyde-modified xylan material, Xyl-CHO, is ground into a powder and stored in the dark. The aldehyde-modified xylan powder is dissolved in deionized water and ultrasonically treated for 30 minutes to obtain an aldehyde-modified xylan solution with a concentration of 12 wt.%.

[0079] Step 2: Add 12 g of gelatin to 100 ml of deionized water and stir magnetically in an oil bath at 50°C until dissolved to prepare a gelatin solution with a concentration of 12 wt.%. The aldehyde-modified xylan solution obtained in step 1 was mixed with the gelatin solution in a volume ratio of 5:3 to obtain a GEL / Xyl-CHO gel.

[0080] Step 3: Pour the GEL / Xyl-CHO gel obtained in Step 2 into a mold to shape the resulting shaped product. The resulting shaped product is 2 mm thick and cut into strips with a width of 5 mm. The resulting strips are naturally curled to form a spirally curled three-dimensional scaffold structure.

[0081] Step 4: Prepare a 20 wt.% potassium sulfate solution at room temperature, ultrasonicate for 20 minutes to obtain a clean solution, and immerse the three-dimensional stent structure obtained in step 3 in the 20 wt.% potassium sulfate solution for 2 hours to obtain a programmable hydrogel, i.e., a self-expanding vascular stent.

[0082] The self-expanding vascular stent prepared in this example can be rapidly self-expanded under the stimulation of the low-concentration salt solution when immersed in a sodium sulfate solution with a concentration of 3 wt.%.

[0083] The xylan material used in this example was purchased from Shanghai MacLean Biochemical Technology Co., Ltd. and was derived from corn cobs, with a content of 90% and a molecular weight range of 280 to 950 Mw. The gelatin material used in this example had a molecular weight of 10,000 to 70,000 Mw.

[0084] Example 6

[0085] This embodiment provides a programmable hydrogel scaffold and a preparation method thereof.

[0086] The specific preparation method of this embodiment includes the following steps:

[0087] Step 1: Dissolve 3 g of xylan in 200 ml of deionized water at room temperature, then add 5 g of sodium periodate to obtain a reaction mixture. The reaction mixture is stirred in the dark at 40°C under closed conditions for 6 hours. Then, add 4 ml of ethylene glycol and terminate the reaction after mechanical stirring for 1 hour. The resulting reaction product is dialyzed in the dark for 70 hours. The dialyzed product is freeze-dried to obtain an aldehyde-modified xylan material, Xyl-CHO. The obtained aldehyde-modified xylan material, Xyl-CHO, is ground into a powder and stored in the dark. The aldehyde-modified xylan powder is dissolved in deionized water and ultrasonically treated for 30 minutes to obtain an aldehyde-modified xylan solution with a concentration of 12 wt.%.

[0088] Step 2: Add 12 g of gelatin to 100 ml of deionized water and stir magnetically in an oil bath at 50°C until dissolved to prepare a gelatin solution with a concentration of 12 wt.%. The aldehyde-modified xylan solution obtained in step 1 was mixed with the gelatin solution in a volume ratio of 3:2 to obtain a GEL / Xyl-CHO gel.

[0089] Step 3: Pour the GEL / Xyl-CHO gel obtained in Step 2 into a mold to shape the resulting shaped product. The resulting shaped product is 3 mm thick and is cut into strips with a width of 4 mm. The resulting strips are naturally curled and deformed to obtain a spirally curled three-dimensional scaffold structure.

[0090] Step 4: Prepare a 30 wt.% sodium chloride solution at room temperature, ultrasonicate for 20 min to obtain a clean solution, and immerse the three-dimensional stent structure obtained in step 3 in the 30 wt.% sodium chloride solution for 2 h to obtain a programmable hydrogel, i.e., a self-expanding vascular stent.

[0091] The self-expanding vascular stent prepared in this example was immersed in a sodium sulfate solution with a concentration of 4 wt.%, and was able to rapidly self-expand under the stimulation induced by the low-concentration salt solution.

[0092] The xylan material used in this example was purchased from Shanghai MacLean Biochemical Technology Co., Ltd. and was derived from corn cobs, with a content of 90% and a molecular weight range of 280 to 950 Mw. The gelatin material used in this example had a molecular weight of 10,000 to 70,000 Mw.

[0093] Example 7

[0094] This embodiment provides a programmable hydrogel scaffold and a preparation method thereof.

[0095] The specific preparation method of this embodiment includes the following steps:

[0096] Step 1: Dissolve 3 g of xylan in 200 ml of deionized water at room temperature, then add 5 g of sodium periodate to obtain a reaction mixture. The reaction mixture is stirred in the dark at 40°C under closed conditions for 6 hours. Then, add 4 ml of ethylene glycol and terminate the reaction after mechanical stirring for 1 hour. The resulting reaction product is dialyzed in the dark for 70 hours. The dialyzed product is freeze-dried to obtain an aldehyde-modified xylan material, Xyl-CHO. The obtained aldehyde-modified xylan material, Xyl-CHO, is ground into a powder and stored in the dark. The aldehyde-modified xylan powder is dissolved in deionized water and ultrasonically treated for 30 minutes to obtain an aldehyde-modified xylan solution with a concentration of 12 wt.%.

[0097] Step 2: Add 12 g of gelatin to 100 ml of deionized water and stir magnetically in an oil bath at 50°C until dissolved to prepare a gelatin solution with a concentration of 12 wt.%. The aldehyde-modified xylan solution obtained in step 1 was mixed with the gelatin solution in a volume ratio of 2:1 to obtain a GEL / Xyl-CHO gel.

[0098] Step 3: Pour the GEL / Xyl-CHO gel obtained in Step 2 into a mold to shape the resulting shaped product. The resulting shaped product is 3 mm thick and is cut into strips with a width of 6 mm. The resulting strips are naturally curled to form a spirally curled three-dimensional scaffold structure.

[0099] Step 4: Prepare a 20 wt.% ammonium sulfate solution at room temperature, ultrasonicate for 20 minutes to obtain a clean solution, and immerse the three-dimensional stent structure obtained in step 3 in the 20 wt.% ammonium sulfate solution for 2 hours to obtain a programmable hydrogel, i.e., a self-expanding vascular stent.

[0100] The self-expanding vascular stent prepared in this example was immersed in distilled water and was able to rapidly self-expand under the slight induction stimulation of the distilled water.

[0101] The xylan material used in this example was purchased from Shanghai MacLean Biochemical Technology Co., Ltd. and was derived from corn cobs, with a content of 90% and a molecular weight range of 280 to 950 Mw. The gelatin material used in this example had a molecular weight of 10,000 to 70,000 Mw.

Claims

1. A method for preparing a programmable hydrogel, characterized in that: The steps include: Step 1, preparing an aldehyde xylan solution with a concentration of 1wt% to 15wt%; The preparation method of the aldehyde-xylan solution is as follows: Prepare materials according to the mass volume ratio of xylan, deionized water, sodium periodate, and ethylene glycol of 2-4 g:200-400 ml:5-10 g:2-5 ml, wherein the molecular weight of the xylan is 280-950 Mw; dissolve the xylan in deionized water at room temperature, then add sodium periodate to obtain a reaction mixture system, and stir the reaction mixture system in a closed environment at 30-50° C. in the dark for 4-8 hours; then add ethylene glycol, stir for 1 hour, and terminate the reaction. The reaction product is dialyzed in the dark for 60-75 hours, and the dialyzed product is freeze-dried and ground to obtain an aldolized xylan sample. The aldolized xylan sample is dissolved in deionized water and ultrasonically treated for 15-30 minutes to obtain an aldolized xylan solution; Step 2: mixing the aldehyde-xylan solution obtained in step 1 with a gelatin solution having a concentration of 5 wt% to 15 wt% at a volume ratio of 1 to 5:1 to 3, wherein the gelatin has a molecular weight of 10,000 to 70,000 Mw, to obtain a GEL / Xyl-CHO gel; Step 3: Using the GEL / Xyl-CHO gel obtained in step 2 as a material, 3D printing is performed to obtain a 3D printed product, or the GEL / Xyl-CHO gel is poured into a mold to be shaped to obtain a shaped product; Step 4: Immerse the 3D printed product or shaped product obtained in step 3 in a salt solution for salting out. The salt solution is one of sodium sulfate solution, potassium sulfate solution, sodium chloride solution, or ammonium sulfate solution. The concentration of the salt solution is 20 wt% to 30 wt%. The salt solution is a clear solution obtained by ultrasonic treatment for 20 to 55 minutes. The immersion time is 1 to 3 hours to obtain a programmable hydrogel.

2. The method for preparing a programmable hydrogel according to claim 1, wherein: The printer structure layer height of the 3D printing in step 3 is set to 0.2~0.4mm, the speed is set to 300~360mm / min, and the processing temperature is 6~30℃.

3. A programmable hydrogel prepared by the method for preparing a programmable hydrogel according to claim 1 or 2, characterized in that: The programmable hydrogel can self-swell in distilled water or a saline solution with a concentration of less than 5 wt%.

4. Use of the programmable hydrogel prepared by the method for preparing a programmable hydrogel according to claim 1 or 2 in preparing a medical self-expanding stent.

5. The use of the programmable hydrogel according to claim 4 in preparing a medical self-expanding stent, characterized in that: The medical self-expanding stent is a self-expanding vascular stent; the self-expanding vascular stent includes a coronary vascular stent, a cerebral vascular stent, a renal artery vascular stent, an aorta vascular stent, a venous vascular stent and a peripheral vascular stent.

6. Use of the programmable hydrogel according to claim 5 in preparing a medical self-expanding stent, characterized in that: The self-expanding vascular stent is prepared by pouring the GEL / Xyl-CHO gel into a mold for shaping, cutting the resulting shaped product into a long strip, naturally curling and deforming the resulting long strip to obtain a spirally curled three-dimensional stent structure, and immersing the three-dimensional stent structure in a saline solution for salting out to obtain a self-expanding vascular stent. The self-expanding vascular stent is capable of self-expanding within 60 seconds under the stimulation of distilled water or a saline solution with a concentration of less than 5wt%, and after expansion, forms a spiral tubular structure with a hollow interior.

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