A 4D-printable hydrogel precursor composition, a hydrogel with programmable shape memory effect, and a preparation method thereof

Abstract

The present invention relates to a 4D-printable hydrogel precursor composition, a hydrogel having a programmable shape memory effect, and a preparation method thereof. The hydrogel precursor composition of the present invention comprises aramid nanofibers, a monomer containing a carboxylic acid group, a crosslinking agent containing metal ions, a water-soluble photoinitiator, and water.

Description

Technical Field

[0001] The present invention relates to the fields of advanced manufacturing and materials, and particularly to a hydrogel precursor composition capable of 4D printing, a hydrogel with programmable shape memory effect, and a preparation method thereof. Background Art

[0002] Shape memory hydrogels are a class of intelligent materials that can fix a temporary shape and spontaneously return to the initial shape by forming or breaking reversible crosslinks when subjected to external stimuli. Shape memory hydrogels usually have two types of network structures, namely, an irreversible crosslinking network that maintains the initial shape and a dynamic crosslinking network that provides reversible molecular switches to fix the temporary shape. Among them, common types of reversible molecular switches include supramolecular interactions such as metal ion coordination, hydrogen bonding, host-guest interactions, and dynamic covalent bonds, and can induce the shape fixation and recovery of shape memory hydrogels through various stimuli such as pH, temperature, and chemicals. For hydrogels with a three-dimensional network structure assembled only by dynamic non-covalent bonds between long-chain molecules without a covalent crosslinking network, they can be called supramolecular hydrogels.

[0003] Para-aramid nanofibers (ANF) are the nanoscale version of poly(p-phenyleneterephthalamide) fibers (PPTA) and have excellent mechanical properties. ANF will break amide bonds and release free radicals under ultraviolet light irradiation to generate more active sites, which is beneficial for ANF to bind with other matrices and serve as an effective reinforcing phase of hydrogel composites.

[0004] Currently, the research on shape memory hydrogels mainly focuses on three directions: high-strength and tough shape memory hydrogels, multi-stimulus responsive shape memory hydrogels, and multifunctional shape memory hydrogels. Due to the excellent properties of shape memory hydrogels such as biocompatibility, responsiveness to external stimuli, and mechanical properties close to biological tissues, they have broad application prospects in the fields of biomedicine, flexible electronic devices, etc.

[0005] However, the shape memory hydrogels printed by mask-projected microstereolithography technology have weak mechanical properties, low printing resolution, single functional characteristics, and complex and time-consuming post-treatment processes, which limit their applications in the fields of biomedicine and flexible electronics. Summary of the Invention

[0006] Problems to be Solved by the Invention

[0007] The existing 4D-printable shape memory hydrogels in the prior art have problems of weak mechanical properties, single functional characteristics, and difficulty in achieving high-resolution printing.

[0008] The object of the present invention is to provide a hydrogel precursor composition which can be made into a hydrogel by 4D printing (such as surface projection microstereolithography technology), and the obtained hydrogel has high strength and toughness, and can also have characteristics such as programmable shape memory effect.

[0009] Solution for solving the problem

[0010] In view of the above problems, the inventors of the present invention have conducted long-term and in-depth research and found that on the basis of toughening the hydrogel with aramid nanofibers, calcium acetate is further introduced, and the carboxyl group forms a dynamic complex with calcium ions and acetate ions to endow the hydrogel with a programmable shape memory effect.

[0011] Specifically, the present invention solves the problems of the present invention through the following solutions.

[0012] [1] A hydrogel precursor composition, which comprises aramid nanofibers, a monomer containing a carboxylic acid group, a crosslinking agent containing metal ions, a water-soluble photoinitiator and water, and optionally contains a light absorber.

[0013] [2] The hydrogel precursor composition according to claim 1, wherein the content of the aramid nanofibers is 0-1 wt%; the content of the monomer containing a carboxylic acid group is 10-50 wt%; the content of the crosslinking agent containing metal ions is 1-10 wt%; the content of the water-soluble photoinitiator is 0.1-1.5 wt%; the content of the water is 30-80 wt%; the content of the light absorber is 0-0.1 wt%;

[0014] Preferably, the weight ratio of the monomer to the crosslinking agent is 1:(0.05-0.5);

[0015] Preferably, the weight ratio of the monomer to the photoinitiator is 1:(0.005-0.1).

[0016] [3] The hydrogel precursor composition according to [1] or [2], wherein,

[0017] the aramid nanofibers are para-aramid nanofibers, with an average diameter of 10-500 nm and an aspect ratio of 2000-4000;

[0018] the monomer is one or more of (meth)acrylic acid and its derivatives, preferably acrylic acid;

[0019] the metal ions in the crosslinking agent are zirconium ions or aluminum ions; the crosslinking agent is preferably one or more selected from zirconium oxychloride octahydrate, zirconium chloride and aluminum oxide hexahydrate;

[0020] The water-soluble photoinitiator is one or more selected from water-soluble aromatic ketones, polycyclic aromatic hydrocarbons, polysilanes, acylphosphonates, azo compounds, and metal-organic complex initiators; preferably a water-soluble azo initiator, more preferably azodiisobutylamidine hydrochloride;

[0021] The light absorber is one or more of quinoline yellow, sudan red, methyl red, and brilliant green.

[0022] [4]. The preparation method of the hydrogel precursor composition according to any one of [1] to [3] includes the following steps:

[0023] Mix aramid nanofibers with water and stir to obtain an aqueous dispersion of aramid nanofibers;

[0024] Mix the aqueous dispersion of aramid nanofibers with a carboxylic acid group-containing monomer, a metal ion-containing crosslinking agent, a water-soluble photoinitiator, and optionally a light absorber to obtain the hydrogel precursor composition.

[0025] [5] A supramolecular hydrogel comprising aramid nanofibers and a crosslinked polymer, and at least part of the aramid nanofibers are covalently bonded to the crosslinked polymer, and the crosslinked structure in the crosslinked polymer is formed by coordination of carboxyl groups in the polymer with metal ions.

[0026] [6] A hydrogel having a programmable shape memory effect, comprising aramid nanofibers, a crosslinked polymer, and calcium acetate, and at least part of the aramid nanofibers are covalently bonded to the crosslinked polymer, and the crosslinked structure in the crosslinked polymer is formed by coordination of carboxyl groups in the polymer with metal ions;

[0027] Optionally, the hydrogel includes a dynamic complex formed by carboxyl groups with calcium ions and acetate ions.

[0028] [7] The hydrogel according to [5] or [6], wherein the aramid nanofibers are para-aramid nanofibers, with an average diameter of 10 to 500 nm and an aspect ratio of 2000 to 4000; the content of the aramid nanofibers is 0 to 1 wt%;

[0029] The content of the crosslinked polymer is 11 to 60 wt%; the crosslinked polymer contains one or more structural units derived from monomers selected from (meth)acrylic monomers, and a crosslinked structure formed by the coordination bond between the carboxyl group in the polymer and metal ions; preferably, the crosslinked polymer is formed by polymerizing a raw material composition containing a monomer with a carboxylic acid group and a crosslinking agent containing metal ions, the monomer is one or more selected from (meth)acrylic acids; the metal ion in the crosslinking agent is a zirconium ion; the crosslinking agent is preferably zirconium oxychloride octahydrate and / or zirconium chloride; the weight ratio of the monomer to the crosslinking agent is 1:(0.05 to 0.5); the polymerization is preferably photoinitiated polymerization.

[0030] [8] The hydrogel having a programmable shape memory effect according to [6], wherein the content of calcium acetate is 0.1 to 10 wt%, preferably 1 to 8 wt%.

[0031] [9] The method for preparing a supramolecular hydrogel according to [5], which includes the step of irradiating the hydrogel precursor composition according to any one of [1] to [3] with light;

[0032] Preferably, the hydrogel precursor composition is poured into a mold and then irradiated with light; or the light irradiation is carried out while performing 3D or 4D printing on the hydrogel precursor composition;

[0033] Preferably, the light irradiation is carried out using light with a wavelength of 365 to 405 nm;

[0034] Preferably, the light irradiation is carried out by digital light processing technology (DLP) of stereolithography.

[0035]

[10] The method for preparing a hydrogel having a programmable shape memory effect according to [6], which includes the following steps:

[0036] Contact the supramolecular hydrogel described in [5] with an aqueous alkali solution, and then contact it with an aqueous solution containing calcium acetate;

[0037] Preferably, the contact time with the aqueous alkali solution is 0.5 to 30 minutes, preferably 1 to 20 minutes;

[0038] Preferably, the contact time with the aqueous solution containing calcium acetate is 1 to 168 hours, preferably 3 to 48 hours, more preferably 4 to 20 hours;

[0039] Preferably, the contact is carried out by immersing the hydrogel described in [5] in the aqueous alkali solution or the aqueous solution containing calcium acetate;

[0040] Preferably, the concentration of calcium acetate in the aqueous solution containing calcium acetate is 0.01 to 2 mol / L.

[0041]

[11] A vascular stent having a tubular structure, the wall of the tubular structure being reticular and comprising a hydrogel having a programmable shape memory effect according to [6].

[0042]

[12] The vascular stent according to

[11] , wherein the wall further comprises one or more components selected from the following: biocompatible substances, X-ray contrast agents, drugs.

[0043]

[13] The vascular stent according to

[11] or

[12] , wherein the outer diameter of the tubular structure is 2 - 30 mm; the length of the tubular structure is 5 - 30 mm, and the thickness of the wall is 0.1 - 2 mm.

[0044]

[14] A method for preparing the vascular stent according to any one of

[11] -

[13] , comprising the following steps:

[0045] (I) While performing 3D or 4D printing on the hydrogel precursor composition according to any one of [1] - [3], irradiating with light to obtain a stent precursor having a tubular structure;

[0046] (II) Contacting the stent precursor with an aqueous alkali solution, and then contacting it with an aqueous solution containing calcium acetate.

[0047]

[15] The method for preparing the vascular stent according to

[14] , further comprising the following step:

[0048] Coating the inner surface and / or outer surface of the stent with a composition comprising one or more components selected from biocompatible substances, X-ray contrast agents, drugs after (II);

[0049] Preferably, the coating is carried out by dipping or spraying.

[0050]

[16] Use of the vascular stent according to

[11] -

[13] in the preparation of medical devices for treating cardiovascular diseases.

[0051] Effects of the Invention

[0052] The present invention can achieve the following beneficial effects:

[0053] The supramolecular hydrogel of the present invention is a photo-curable supramolecular hydrogel composite material strengthened by para-aramid nanofibers. Para-aramid nanofibers are prone to photo-aging and fracture to form free radicals under ultraviolet light irradiation, and can improve the strength, toughness and elongation at break of the hydrogel through covalent cross-linking points, hydrogen bonds and long-chain entanglements. This hydrogel material can in-situ form a high-strength, high-toughness and highly stretchable hydrogel after photo-curing, without complex and time-consuming post-treatment processes, overcoming the weaknesses of current photo-curable hydrogels with low strength and poor fracture toughness.

[0054] The supramolecular hydrogel of the present invention is completely composed of a physical cross-linking network coordinated by metal ions and does not contain an irreversible covalent cross-linking network. After being soaked in a calcium acetate solution, it can quickly obtain programmable shape memory ability, overcoming the weaknesses of the current shape memory hydrogels with irreversible covalent cross-linking networks, resulting in limited recovery ability and difficulty in meeting sensor applications.

[0055] The hydrogel precursor composition of the present invention can be used to prepare complex three-dimensional structures based on DLP printers for 4D printing. The prepared structures have excellent mechanical properties, programmable shape memory effects, high resolution, electrical conductivity and other properties or characteristics at the same time. It overcomes the weaknesses of current DLP-printed hydrogels with poor mechanical properties and single functional characteristics.

[0056] The hydrogel precursor composition of the present invention can be used to prepare biomedical and flexible electronic devices such as vascular stents and skin patches through 4D printing, and has broad application scenarios and great application potential.

[0057] The vascular stent of the present invention has a programmable shape memory effect, can be easily implanted into blood vessels with a small outer diameter of the contour, and can restore the initial shape with a larger diameter after the dormant period to play a role in supporting blood vessels. Description of the Drawings

[0058] Figure 1 Stress-strain curves of hydrogel composite materials with four different aramid fiber contents prepared in step (3) of Example 1;

[0059] Figure 2 Fracture energy diagrams of hydrogel composite materials with four different aramid fiber contents prepared in step (4) of Example 1;

[0060] Figure 3 Shows the minimum resolution that can be achieved by the hydrogel composite material printed by DLP photo-curing in Example 2;

[0061] Figure 4 Physical photos of the three-dimensional structure hydrogel composite material printed by DLP photo-curing in Example 2;

[0062] Figure 5Schematic diagram of the shape fixation and recovery processes of the programmable shape memory hydrogel composite material obtained in Example 3;

[0063] Figure 6 Schematic diagram of the crosslinking mechanism of the hydrogel in the preferred implementation of the present invention.

[0064] Figure 7 a) shows a physical photograph of the vascular stent obtained in Example 4;

[0065] Figure 7 b) shows the deformation process of the vascular stent obtained in Example 4;

[0066] Figure 7 c) shows a schematic diagram of the process of the vascular stent obtained in Example 4 gradually recovering to its original shape after being implanted into a blood vessel. Detailed implementation mode

[0067] Hereinafter, the content of the present invention will be described in detail. The description of the technical features recorded below is based on the representative implementation modes and specific examples of the present invention, but the present invention is not limited to these implementation modes and specific examples.

[0068] <Terms and definitions>

[0069] In this specification, the term "alkyl" includes linear, branched or cyclic alkyl, unless otherwise clearly stated.

[0070] In this specification, a "monomer" refers to a compound capable of undergoing a polymerization reaction, and its molecular weight is 500 or less, for example, 400 or less, or for another example, 300 or less, and more specifically, 200 or less, 100 or less.

[0071] In this specification, the numerical range expressed as "numerical value A to numerical value B" refers to a range including the endpoint numerical values A and B.

[0072] In this specification, the numerical range expressed as "above" or "below" refers to a numerical range including this number.

[0073] In this specification, the meaning expressed by "can" includes both the meaning of performing a certain treatment and the meaning of not performing a certain treatment.

[0074] In this specification, the use of "optionally" or "optional" means that certain substances, components, execution steps, applied conditions, etc. are used or not used.

[0075] In this specification, the unit names used are all international standard unit names, and unless otherwise specifically stated, the "%" used represents weight or mass percentage content.

[0076] In this specification, the "preferred embodiments", "embodiments", etc. mentioned refer to the specific elements related to the embodiment (for example, features, structures, properties, and / or characteristics) are included in at least one of the embodiments described herein, and may or may not be present in other embodiments. Additionally, it should be understood that the elements can be combined in various embodiments in any suitable manner.

[0077] <Hydrogel precursor composition>

[0078] One object of the present invention is to provide a hydrogel precursor composition, which comprises aramid nanofibers, a monomer containing a carboxylic acid group, a crosslinking agent containing metal ions, a water-soluble photoinitiator, and water, and optionally further comprises a light absorber.

[0079] The hydrogel precursor composition of the present invention contains a water-soluble photoinitiator, and thus can be cured by light irradiation, so that complex three-dimensional structures can be fabricated by using techniques such as 3D and 4D printing. And during the light irradiation process, the amide bonds on the surface of the aramid nanofibers break to form free radicals, which can form covalent bonds with the crosslinked polymer formed by the monomer and the crosslinking agent, thereby obtaining a more excellent toughening effect.

[0080] In one embodiment, the aramid nanofibers are para-aramid nanofibers. The para-aramid nanofibers are composed of poly(p-phenylene terephthalamide) with liquid crystallinity, and its molecular chains are more regularly arranged and have higher strength, so it is preferred.

[0081] In one embodiment, the average diameter of the aramid nanofibers is 10 - 500 nm, preferably 10 - 300 nm, more preferably 10 - 100 nm, and the aspect ratio of the aramid nanofibers is 2000 - 4000, preferably 3000 - 4000. The length of the aramid nanofibers is 20 - 1200 μm, preferably 30 - 800 μm, more preferably 30 - 500 μm. By using aramid nanofibers with an average diameter and aspect ratio within the above ranges, a better toughening effect can be obtained. And the longer the length of the aramid nanofibers and the smaller the diameter, the better the toughening effect on the hydrogel.

[0082] In one embodiment, in the hydrogel precursor composition of the present invention, the content of the aramid nanofibers is 0.001 to 1 wt%, preferably 0.002 to 0.9 wt%, more preferably 0.003 to 0.8 wt%, further preferably 0.004 to 0.75 wt%, still preferably 0.005 to 0.7 wt%, 0.006 to 0.65 wt%, 0.007 to 0.6 wt%, 0.008 to 0.55 wt%, 0.009 to 0.5 wt%, 0.01 to 0.45 wt%, 0.015 to 0.4 wt%, 0.02 to 0.375 wt%, such as 0.03 wt%, 0.04 wt%, 0.05 wt%, 0.06 wt%, 0.07 wt%, 0.08 wt%, 0.09 wt%, 0.1 wt%, 0.12 wt%, 0.14 wt%, 0.16 wt%, 0.18 wt%, 0.20 wt%, 0.22 wt%, 0.24 wt%, 0.26 wt%, 0.28 wt%, 0.30 wt%, 0.32 wt%, 0.34 wt%, 0.36 wt%. By making the content of the aramid nanofibers within the above range, an excellent strengthening effect can be obtained, and at the same time, it can be ensured that the hydrogel precursor composition has a suitable viscosity for 3D printing processing. If the content of the aramid nanofibers is too large, the viscosity of the hydrogel precursor composition will be too large, affecting its application in 3D printing; if the content of the aramid nanofibers is too small, sufficient strengthening effect cannot be obtained, and the strength of the hydrogel is insufficient to meet the requirements.

[0083] In a specific embodiment, the aramid nanofibers can be commercially obtained through conventional channels, including but not limited to the para-aramid nanofibers of Shandong Polyarylene New Materials Co., Ltd. used in the following examples.

[0084] In one embodiment, the monomer is one or more of (meth)acrylic acid and its derivatives, preferably acrylic acid.

[0085] In one embodiment, in the hydrogel precursor composition of the present invention, the content of the carboxylic acid group-containing monomer is 10 to 50 wt%, preferably 12 to 48 wt%, 14 to 46 wt%, 16 to 44 wt%, 18 to 42 wt%, 20 to 40 wt%, 21 to 38 wt%, 22 to 36 wt%, 23 to 34 wt%, 24 to 32 wt%, 25 to 30 wt%, 26 to 29 wt%, 27 to 28 wt%.

[0086] In one embodiment, in the hydrogel precursor composition of the present invention, the metal ion in the crosslinking agent is zirconium ion; the crosslinking agent is preferably zirconium oxychloride octahydrate and / or zirconium chloride.

[0087] In one embodiment, in the hydrogel precursor composition of the present invention, the content of the crosslinking agent is 1-10 wt%, preferably 1.5-9 wt%, 2-8 wt%, 2.5-7 wt%, 3-6 wt%, 3.5-5.5 wt%, 4-5 wt%.

[0088] Preferably, the weight ratio of the monomer to the crosslinking agent is 1:(0.05-0.5), preferably 1:(0.07-0.4), 1:(0.09-0.3), 1:(0.1-0.25), 1:(0.15-0.2).

[0089] In one embodiment, in the hydrogel precursor composition of the present invention, the water-soluble photoinitiator is one or more selected from water-soluble aromatic ketones, polycyclic aromatic hydrocarbons, polysilanes, acylphosphonates, azo compounds and metal organic complex initiators; preferably a water-soluble azo initiator, more preferably azobisisobutyramidine hydrochloride.

[0090] In one embodiment, in the hydrogel precursor composition of the present invention, the content of the water-soluble photoinitiator is 0.1-1.5 wt%, preferably 0.2-1.4 wt%, 0.3-1.3 wt%, 0.4-1.2 wt%, 0.45-1.1 wt%, 0.5-1.0 wt%, 0.55-0.9 wt%, 0.6-0.8 wt%, and also for example 0.7 wt%.

[0091] Preferably, the weight ratio of the monomer to the photoinitiator is 1:(0.005-0.1), preferably 1:(0.01-0.08), 1:(0.015-0.06), 1:(0.02-0.04), 1:(0.022-0.03).

[0092] In one embodiment, in the hydrogel precursor composition of the present invention, the content of water is 30-80 wt%, 40-78 wt%, 50-76 wt%, 60-75 wt%, 65-70 wt%.

[0093] In one embodiment, in the hydrogel precursor composition of the present invention, the content of the light absorbent is 0-0.1 wt%, preferably 0.001-0.5 wt%, 0.005-0.1 wt%, 0.008-0.015 wt%, 0.01-0.012 wt%.

[0094] In one embodiment, the hydrogel precursor composition of the present invention may further comprise one or more other components selected from dyes, pigments, polymerization inhibitors, other polymerization initiators, light stabilizers, heat stabilizers, biocompatible substances, X-ray contrast agents, drugs, etc. In a preferred embodiment, the hydrogel precursor composition of the present invention further comprises a light absorber, preferably a water-soluble light absorber, and the light absorber may be selected from one or more of quinoline yellow, sudan red, methyl red, and brilliant green.

[0095] In one embodiment, based on the total mass of the hydrogel precursor composition, the content of other components is 0.001 wt% to 1 wt%, for example, 0.003 wt% to 0.5 wt%, and for another example, 0.005 wt% to 0.1 wt%.

[0096] One object of the present invention is to provide a method for preparing the hydrogel precursor composition of the present invention, which comprises the following steps:

[0097] Mix aramid nanofibers with water and stir to obtain an aqueous dispersion of aramid nanofibers;

[0098] Mix the aqueous dispersion of aramid nanofibers with a carboxylic acid group-containing monomer, a metal ion-containing crosslinking agent, and a water-soluble photoinitiator to obtain the hydrogel precursor composition.

[0099] In one embodiment, in the aqueous dispersion of aramid nanofibers, the content of aramid nanofibers is 0.001 to 1 wt%, preferably an amount such that the hydrogel precursor composition satisfies the content range of aramid nanofibers described above for the hydrogel precursor composition.

[0100] There is no particular limitation on the water used for preparing the aqueous dispersion of aramid nanofibers in the present invention. From the perspective of avoiding introducing impurities into the hydrogel, deionized water or distilled water is preferably used.

[0101] In the aqueous dispersion of aramid nanofibers obtained by the preparation method of the present invention, the aramid nanofibers are uniformly dispersed, and there is no obvious layering phenomenon after standing for 30 days.

[0102] In one embodiment, mix the aqueous dispersion of aramid nanofibers with a carboxylic acid group-containing monomer, a metal ion-containing crosslinking agent, and a water-soluble photoinitiator, and stir to obtain the hydrogel precursor composition.

[0103] For the stirring in the preparation method of the present invention, any stirring method known in the art can be used, including but not limited to mechanical stirring, magnetic stirring, and ultrasonic dispersion, etc., and magnetic stirring is preferred. Stirring is preferably carried out under light-shielded conditions to avoid the aging of aramid nanofibers under light.

[0104] Preferably, the stirring time is 0.1 hour or more, 0.3 hour or more, 0.5 hour or more, 0.7 hour or more, 0.8 hour or more, 0.9 hour or more, 1 hour or more.

[0105] For the aramid nanofibers, monomers, crosslinking agents, initiators, etc. used in the preparation method of the present invention, refer to the corresponding descriptions of the hydrogel precursor composition above.

[0106] The present invention also correspondingly relates to a hydrogel precursor composition obtained by the preparation method of the present invention.

[0107] <Supramolecular hydrogel>

[0108] One object of the present invention is to provide a supramolecular hydrogel, which comprises aramid nanofibers and a crosslinked polymer, and at least part of the aramid nanofibers are covalently bonded to the crosslinked polymer, and the crosslinked structure in the crosslinked polymer is formed by the coordination of carboxyl groups in the polymer with metal ions.

[0109] Regarding the characteristics of the aramid nanofibers in the supramolecular hydrogel of the present invention, refer to the description above.

[0110] In one embodiment, in the supramolecular hydrogel of the present invention, the content of the crosslinked polymer is 11-60 wt%, preferably 13-55 wt%, more preferably 15-50 wt%, and further preferably 18-45 wt%.

[0111] In one embodiment, the crosslinked polymer comprises structural units derived from one or more monomers selected from (meth)acrylic monomers, and a crosslinked structure formed by coordination bonds of carboxyl groups in the polymer with metal ions.

[0112] Preferably, the crosslinked polymer is formed by polymerization of a raw material composition comprising a monomer containing a carboxylic acid group and a crosslinking agent containing a metal ion. The characteristics of the monomer containing a carboxylic acid group and the crosslinking agent containing a metal ion can be referred to the description above.

[0113] The polymerization is preferably photoinitiated polymerization. Regarding the characteristics of the photoinitiator, refer to the description above.

[0114] One object of the present invention is to provide a preparation method of the supramolecular hydrogel of the present invention, which comprises the step of irradiating the hydrogel precursor composition of the present invention with light.

[0115] In one embodiment, the light irradiation is carried out using ultraviolet light with a wavelength of 365-405 nm. The specific wavelength can be selected according to the specific photoinitiator.

[0116] In one embodiment, the hydrogel precursor composition of the present invention is poured into a mold, and then the light irradiation is carried out. There are no particular limitations on the size, shape, and material of the mold, and those skilled in the art can specifically select according to actual needs. The material of the mold is preferably polytetrafluoroethylene, and more preferably has a cover made of transparent acrylic material to ensure the shape of the obtained hydrogel.

[0117] In one embodiment, using a digital light processing technology for surface projection photopolymerization (such as projection microstereolithography (PμSL)) and other 3D printing technologies, the hydrogel of the present invention is prepared from the hydrogel precursor composition of the present invention. The layer thickness selected for the digital light processing technology of surface projection photopolymerization 3D printing is 20 - 60 μm, preferably 30 - 50 μm, more preferably 35 - 45 μm; the ultraviolet light wavelength is 365 - 405 nm, and the ultraviolet light intensity is 40 - 80 mW / cm 2 , preferably 50 - 70 mW / cm 2 , more preferably 55 - 65 mW / cm 2 ; the exposure time for each layer is 20 - 50 s, preferably 25 - 35 s.

[0118] When photocuring and printing the hydrogel precursor composition of the present invention using the digital light processing technology for surface projection photopolymerization, the characteristic width of the single-pixel grid printed is 20 μm or less, preferably 18 μm or less, 16 μm or less, 14 μm or less, 13 μm or less.

[0119] The present invention correspondingly relates to a hydrogel obtained by the preparation method of the present invention.

[0120] The supramolecular hydrogel of the present invention has excellent mechanical properties. In one embodiment, the tensile strength of the hydrogel is 1000 kPa or more, preferably 1500 kPa or more, more preferably 1600 kPa or more, further preferably 1700 kPa or more, and even more preferably 18000 kPa or more. There is no particular limitation on the upper limit of the tensile strength, which is usually 3000 kPa or less, or 2500 kPa or less. The tensile strength of the aramid nanofiber toughened supramolecular hydrogel of the present invention is 1.1 - 10 times that of the original hydrogel, such as 1.2 - 8 times, such as 1.3 - 7 times, and also such as 1.4 - 6 times, and also such as 5 times, 4 times, 3 times, 2 times.

[0121] Herein, the "original hydrogel" refers to a hydrogel having the same composition and content as the aramid nanofiber toughened supramolecular hydrogel of the present invention, except that the aramid nanofiber dispersion liquid is replaced with the same content of water during preparation.

[0122] In one embodiment, the fracture energy of the supramolecular hydrogel of the present invention is 1000 J / m 2Above, preferably 1500 J / m 2 Above, more preferably 1600 J / m 2 Above, further preferably 1700 J / m 2 Above, even more preferably 1800 J / m 2 Above. There is no particular limitation on the upper limit of the fracture energy, which is usually 5000 J / m 2 Below, or 4500 J / m 2 Below, or 4000 J / m 2 Below, or 3000 J / m 2 Below.

[0123] The fracture energy of the aramid nanofiber-reinforced supramolecular hydrogel of the present invention is 1.5 to 15 times that of the original hydrogel, for example, 1.6 to 12 times, for example, 1.7 to 10 times, 1.8 to 8 times, 1.9 to 6 times, 2 to 4 times.

[0124] In one embodiment, the elongation at break of the supramolecular hydrogel of the present invention is 560% or more, preferably 570% or more, more preferably 580% or more, still preferably 590% or more, and further preferably 600% or more.

[0125] The elongation at break of the aramid nanofiber-reinforced supramolecular hydrogel of the present invention is 1.05 times or more, preferably 1.08 times or more, more preferably 1.1 times or more, for example, 1.2 times or more, 1.3 times or more, 1.4 times or more of the original hydrogel.

[0126] <Hydrogel with programmable shape memory effect>

[0127] An object of the present invention is to provide a hydrogel with a programmable shape memory effect, which comprises aramid nanofibers, a crosslinked polymer, and calcium acetate, and at least a part of the aramid nanofibers is covalently bonded to the crosslinked polymer, and the crosslinked structure in the crosslinked polymer is formed by the coordination of carboxyl groups in the polymer with metal ions;

[0128] Optionally, the hydrogel includes a dynamic complex formed by carboxyl groups with calcium ions and acetate ions.

[0129] Regarding the characteristics of the aramid nanofibers and crosslinked polymers in the hydrogel with a programmable shape memory effect of the present invention, refer to the above description.

[0130] In one embodiment, the content of calcium acetate is 0.1 to 10 wt%, preferably 1 to 8 wt%, more preferably 1.5 to 7 wt%, 2 to 6.5 wt%, 2.5 to 6 wt%, 3 to 5.5 wt%, 4 to 4.5 wt%.

[0131] An object of the present invention is to provide a method for preparing a hydrogel with programmable shape memory effect of the present invention, which comprises the following steps:

[0132] Contact the supramolecular hydrogel of the present invention with an aqueous alkali solution, and then contact it with an aqueous solution containing calcium acetate.

[0133] By contacting the supramolecular hydrogel with an aqueous alkali solution, at least part of the cross-linked structure in the cross-linked polymer is released, that is, at least part of the carboxyl groups coordinated with metal ions in the cross-linking agent are re-converted into free carboxyl groups.

[0134] Preferably, the contact time with the aqueous alkali solution is 0.5 to 30 minutes, preferably 1 to 20 minutes, such as 10 minutes.

[0135] Preferably, the aqueous alkali solution is an aqueous solution of sodium hydroxide or potassium hydroxide, and the concentration of the alkali is preferably 0.01 to 2 mol / L, preferably 0.05 to 1.8 mol / L, 0.1 to 1.6 mol / L, 0.2 to 1.5 mol / L, 0.3 to 1.4 mol / L, 0.4 to 1.3 mol / L, 0.5 to 1.2 mol / L, 0.6 to 1.1 mol / L, 0.7 to 1 mol / L, 0.8 to 0.9 mol / L.

[0136] Preferably, after contacting with the aqueous alkali solution, the hydrogel is contacted with water to remove the alkali therein. The contact time with water is 0.5 to 30 minutes, preferably 1 to 20 minutes, such as 10 minutes.

[0137] The above-mentioned contact with the aqueous alkali solution and contact with water are preferably carried out by immersing the supramolecular hydrogel in the aqueous alkali solution or water.

[0138] By contacting with an aqueous solution containing calcium acetate after contacting with the aqueous alkali solution, calcium acetate enters the network of the hydrogel, and carboxyl groups form dynamic complexes with calcium ions and acetate ions, thereby endowing the hydrogel with programmable shape memory effect.

[0139] Calcium acetate is a calcium salt with inverse solubility. When the hydrogel network containing carboxyl groups contains sufficient calcium acetate, carboxyl groups form dynamic complexes with calcium ions and acetate ions (–COO-...Ca 2+...-OOCCH3). Among them, the acetic acid group is prone to form hydrophobic aggregates and undergo dehydration at high temperatures, inducing phase separation in the hydrogel network and causing the hydrogel to transform from a rubber state to a glass state; when the temperature returns to room temperature, free water will diffuse back into the polymer network and dissolve the polymer chains, and the hydrogel will turn back from the glass state to the rubber state. Such reversible thermosetting dominated by internal mass diffusion endows the hydrogel with programmable shape memory characteristics: the hydrogel can be fixed into a temporary shape when heated, and after being transferred to room temperature, it will first experience a "dormant period" and then return to its original shape. By adjusting the shaping time in hot water, a programmable shape recovery process with different "dormant period" durations can be achieved.

[0140] The hydrogel with programmable shape memory effect of the present invention has a programmable cold-induced shape memory effect. When placed in hot water, it can significantly harden and be fixed into a temporary shape. After being transferred to cold water, it will first experience a "dormant period" and then gradually return to its original shape. By adjusting the shaping time in hot water, a programmable shape recovery process with different "dormant period" durations can be achieved.

[0141] Preferably, the contact time with the aqueous solution containing calcium acetate is 1 to 168 hours, preferably 3 to 48 hours, more preferably 4 to 20 hours, such as 1 to 48 hours, 3 to 40 hours, etc.

[0142] Preferably, the contact is carried out by immersing the supramolecular hydrogel of the present invention in the aqueous solution containing calcium acetate.

[0143] Preferably, the concentration of calcium acetate in the aqueous solution containing calcium acetate is 0.01 to 2 mol / L, preferably 0.05 to 1.8 mol / L, 0.1 to 1.6 mol / L, 0.2 to 1.5 mol / L, 0.3 to 1.4 mol / L, 0.4 to 1.3 mol / L, 0.5 to 1.2 mol / L, 0.6 to 1.1 mol / L, 0.7 to 1 mol / L, 0.8 to 0.9 mol / L.

[0144] In one embodiment, the preparation method of the hydrogel with programmable shape memory effect further includes the step of immersing the hydrogel after contact with the aqueous solution containing calcium acetate in water.

[0145] Preferably, the immersion time in water is 1 to 24 hours, preferably 6 to 18 hours, and more preferably the time for the hydrogel to reach swelling equilibrium.

[0146] The present invention also correspondingly relates to a double-network hydrogel obtained by the preparation method of the present invention.

[0147] Figure 6It shows the crosslinking and shape memory effect mechanism of the hydrogel with programmable shape memory effect in the preferred embodiment of the present invention. The hydrogel network is physically crosslinked by ion coordination formed by long chains of polyacrylic acid and zirconium ion aggregates. Additional covalent crosslinking points, long-chain entanglements and hydrogen bonds are generated between the para-aramid fibers and the hydrogel polymer chains to form a hybrid network, effectively improving the mechanical properties of the supramolecular hydrogel. Subsequently, contacting with sodium hydroxide solution can remove the coordination of some zirconium ions and carboxyl groups, while contacting with calcium acetate solution can make the calcium ions in calcium acetate form coordination with carboxyl groups. Since acetic acid groups form hydrophobic aggregates at high temperatures, inducing phase separation of the hydrogel network, the hydrogel can be fixed into a temporary shape when heated, and after being transferred to room temperature, it first undergoes a "dormant period" and then returns to its initial shape, and a programmable shape recovery process with different "dormant period" durations can be achieved by adjusting the shaping time in hot water. It should be noted that the shape transformation kinetics of this hydrogel is dominated by the mass diffusion of internal free water, rather than the heat transfer of ordinary shape memory polymers. Since the redistribution of internal water is a slow, transport-limited process, the recovery of the macroscopic shape will be dominated by mass diffusion and exhibit a controllable "dormant period" for programming.

[0148] The programming temperature (i.e., the temperature for fixing its shape) of the hydrogel with programmable shape memory effect of the present invention is above 70 °C, preferably above 75 °C, more preferably above 80 °C, still more preferably above 85 °C, for example, above 90 °C.

[0149] The programming time (i.e., the time for the hydrogel to be at the programming temperature) of the hydrogel with programmable shape memory effect of the present invention is 1 - 3600 s, preferably 1 - 1800 s, more preferably 1 - 600 s, still more preferably 1 - 500 s, 2 - 400 s, 3 - 350 s, 4 - 300 s, 5 - 200 s, 6 - 150 s, 7 - 100 s, 8 - 80 s, 9 - 70 s, 10 - 65 s.

[0150] The "dormant period" of the hydrogel with programmable shape memory effect of the present invention can be 1 - 3600 s, preferably 1 - 1800 s, more preferably 1 - 600 s, still more preferably 1 - 500 s, 2 - 400 s, 3 - 350 s, 4 - 300 s, 5 - 200 s, 6 - 150 s, 7 - 100 s, 8 - 80 s, 9 - 70 s, 10 - 65 s.

[0151] <Vascular stent and its preparation method>

[0152] The present invention also relates to a vascular stent having a tubular structure, the wall of the tubular structure being reticular and containing the hydrogel with programmable shape memory effect of the present invention.

[0153] In one embodiment, the wall further comprises one or more components selected from the following: biocompatible substances, X-ray contrast agents, drugs, so that the vascular stent of the present invention has more abundant functions.

[0154] In the case of containing biocompatible substances, the vascular stent of the present invention has more excellent biocompatibility, thus avoiding adverse reactions such as rejection reactions and inflammatory reactions after implantation.

[0155] In the case of containing X-ray contrast agents, the vascular stent of the present invention can be visualized under X-ray irradiation, so that it can be detected by a variety of detection means, and effects such as visual implantation can also be achieved.

[0156] In the case of containing drugs, the vascular stent of the present invention can further have functions such as drug delivery and drug sustained release. There is no particular limitation on the specific drug, for example, it can be various drugs for treating cardiovascular and cerebrovascular diseases.

[0157] Since the tube wall contains the hydrogel with programmable shape memory effect of the present invention, the vascular stent of the present invention correspondingly has a programmable shape memory effect. For example, the vascular stent of the present invention can be folded so that the diameter of the outer contour of its cross-section (the cross-section perpendicular to the axial direction) (the distance between the two points with the largest distance on the outer contour) is smaller than the diameter of the original tubular structure, and then the folded shape is fixed at a higher temperature. Since the folded shape has a smaller outer contour diameter, it is beneficial to smoothly implant the vascular stent into the blood vessel. After being implanted into the blood vessel, the temperature decreases, and the vascular stent of the present invention restores its initial shape (the shape before folding) after experiencing a dormant period, so as to play a role in supporting the blood vessel.

[0158] There is no particular limitation on the folding method. For example, it can be flattened along the radial direction to obtain a sheet structure composed of two tube walls, and then the sheet structure is folded; or multiple parallel lines on the tube wall along the axial direction can be recessed towards the center.

[0159] The present invention has no particular limitation on the outer diameter of the tubular structure of the vascular stent, which can be determined according to the diameter of the specific blood vessel to be implanted. For example, when implanting into an artery, it usually should have a larger diameter, and for a vein, the diameter is smaller.

[0160] Preferably, the outer diameter of the tubular structure of the vascular stent of the present invention is 2 - 30 mm, preferably 2.5 - 20 mm, more preferably 3 - 15 mm, and also such as 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, etc.

[0161] The present invention has no particular limitation on the length of the vascular stent, which can be determined according to specific requirements. In one embodiment, the length of the tubular structure of the vascular stent of the present invention is 5 to 30 mm, preferably 6 to 28 mm, more preferably 7 to 25 mm, further preferably 8 to 20 mm, and also for example 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, etc.

[0162] The present invention has no particular limitation on the wall thickness of the tubular structure of the vascular stent, which can be determined according to specific requirements. In one embodiment, the thickness of the wall of the tubular structure of the vascular stent of the present invention is 0.1 to 2 mm, preferably 0.2 to 1.5 mm, more preferably 0.3 to 1 mm, further preferably 0.4 to 0.7 mm, and also for example 0.5 mm, 0.6 mm, etc.

[0163] For the specific structure of the network constituting the tube wall, such as the shape and size of the mesh holes, the cross-sectional shape and size of the wire, etc., the present invention has no particular limitation and can be any suitable shape and size known in the art. For example, it can be Figure 7 the shape with diamond-shaped mesh holes formed by wires intersecting at a certain angle with the axial direction as shown.

[0164] Those skilled in the art can understand that the above description of the composition and properties of the hydrogel with programmable shape memory effect of the present invention is also applicable to the vascular stent of the present invention.

[0165] An object of the present invention is to provide a method for preparing the vascular stent of the present invention, which comprises the following steps:

[0166] (I) While performing 3D or 4D printing on the hydrogel precursor composition of the present invention, irradiating with light to obtain a stent precursor with a tubular structure;

[0167] (II) Contacting the stent precursor with an aqueous alkali solution, and then contacting with an aqueous solution containing calcium acetate.

[0168] The details and preferred schemes described above for the preparation method of the hydrogel with programmable shape memory effect of the present invention are also applicable to the preparation method of the vascular stent of the present invention.

[0169] In one embodiment, the method for preparing the vascular stent of the present invention further comprises the following steps:

[0170] Coating the inner surface and / or outer surface of the vascular stent obtained in step (II) with a composition containing one or more components selected from biocompatible substances, X-ray contrast agents, and drugs.

[0171] Preferably, the coating is carried out by dipping or spraying, preferably by electrostatic spraying.

[0172] Preferably, the composition further contains a suitable solvent, such as water, ethanol, etc.

[0173] The present invention also correspondingly relates to the use of the vascular stent of the present invention in the preparation of medical devices for treating cardiovascular diseases.

[0174] Examples

[0175] In order to make the objectives, technical solutions and advantages of the present invention more clear and understandable, the embodiments of the present invention will be further described in detail below in conjunction with the drawings and examples. It should be understood that the following detailed description of the examples and the drawings are used to exemplarily illustrate the principles of the present invention and cannot be used to limit the scope of the present invention. In addition, without conflict, the embodiments of the present invention described below and the features in the embodiments can be combined with each other.

[0176] The descriptions of the raw materials and instruments used in the following examples are as follows:

[0177] Para-aramid nanofibers: The manufacturer is Shandong Jufang New Materials Co., Ltd., with a diameter between 10 and 100 nm and a length between 30 and 300 μm;

[0178] AAPH: The manufacturer is Shanghai Aladdin Biochemical Technology Co., Ltd., with the product number G2319363;

[0179] DLP light-curing printer: The manufacturer is Chongqing MoFang Precision Technology Co., Ltd. (BMF PrecisionTech Inc.), and the equipment model is microArch S240.

[0180] Example 1

[0181] (1) Take different contents of para-aramid nanofibers and disperse them in water through a fiber defibrator to obtain uniform dispersions with para-aramid fiber mass concentrations of 0.114 wt%, 0.229 wt%, and 0.343 wt%, respectively.

[0182] (2) Mix the aramid fiber dispersion in step (1) with the acrylic hydrogel precursor. The mass of the aramid fiber dispersion is 28 g, and the mass of the acrylic hydrogel precursor is 12 g. The acrylic hydrogel precursor consists of acrylic acid, zirconium oxychloride octahydrate, and photoinitiator AAPH. The mass of acrylic acid is 10 g, the mass of zirconium oxychloride octahydrate is 1.76 g, and the mass of AAPH is 0.24 g. The mass ratio of acrylic acid to zirconium oxychloride octahydrate is 1:0.176, and the mass ratio of acrylic acid to AAPH is 1:0.024. Stir with a magnetic stirrer for more than 1 hour in a light-shielded environment to form a uniform hydrogel precursor solution. The aramid fiber contents in the finally obtained hydrogel precursor solution are 0.08 wt%, 0.16 wt%, and 0.24 wt%.

[0183] In addition, according to the above method, use deionized water to replace the aramid fiber dispersion to prepare a group of hydrogel precursor solutions without aramid fibers as a control. The proportion of deionized water is 70 wt%, and the formulation of the acrylic hydrogel precursor is the same as above.

[0184] (3) Fill the four hydrogel precursor solutions prepared in step (2) into a polytetrafluoroethylene mold conforming to the dumbbell-shaped specimen of Type 4 in GB / T528-2009, cover it with a transparent acrylic plate, and place it in an ultraviolet lamp box. Irradiate it with 405 nm ultraviolet light for 5 min to obtain four hydrogel composites with different aramid fiber contents.

[0185] (4) Fill the four hydrogel precursor solutions prepared in step (2) into a rectangular mold with dimensions of 25 mm × 20 mm × 0.8 mm, cover it with a transparent acrylic plate, and place it in an ultraviolet lamp box. Irradiate it with 405 nm ultraviolet light for 4 min to obtain four hydrogel composites with different aramid fiber contents.

[0186] (5) Conduct uniaxial tensile tests on the cured dumbbell-shaped specimens in step (3), and conduct Rivlin-Thomas fracture tests and fatigue cyclic loading tests on the cured rectangular specimens in step (4) according to the methods described in the literature Nature, 2012, 489(7414):133-136 and the literature Extreme Mechanics Letters, 2017, 15:91-96.

[0187] Figure 1The stress-strain curves of the hydrogel composites with four different aramid fiber contents obtained in step (3) are shown. It can be seen that the strengths of the hydrogel composites with aramid fiber contents of 0.08wt%, 0.16wt%, and 0.24wt% are 1.76 Mpa, 1.85 Mpa, and 1.75 Mpa respectively. Compared with the strength of the hydrogel without aramid fiber (1.19 Mpa), they are increased by 47%, 55%, and 46% respectively. The elongation at break are 616%, 771%, and 829% respectively. Compared with the elongation at break of the hydrogel without aramid fiber (558%), they are increased by 10%, 38%, and 49% respectively, indicating that after adding aramid fiber, the increase in strength is not accompanied by a decrease in elongation at break.

[0188] Figure 2 The fracture energy change curves of the hydrogel composites with four different aramid fiber contents obtained in step (4) are shown. It can be seen that the fracture energies of the hydrogel composites with aramid fiber contents of 0.08wt%, 0.16wt%, and 0.24wt% are 1901 J / m 2 、2384 J / m 2 、2714 J / m 2 respectively, which are increased to 2.3, 2.9, and 3.3 times of the fracture energy of the hydrogel without aramid fiber (816 J / m 2 ).

[0189] Example 2

[0190] (1) Use a fiber defibrillator to disperse para-aramid nanofibers in water to obtain a uniform dispersion with a para-aramid fiber mass concentration of 0.114wt%.

[0191] (2) Mix the aramid fiber dispersion in step (1) with the acrylic hydrogel precursor. The mass of the aramid fiber dispersion is 28 g, and the mass of the acrylic hydrogel precursor is 12 g. The acrylic hydrogel precursor consists of acrylic acid, zirconium oxychloride octahydrate, and the photoinitiator AAPH. The mass of acrylic acid is 10 g, the mass of zirconium oxychloride octahydrate is 1.76 g, and the mass of AAPH is 0.24 g. The mass ratio of acrylic acid to zirconium oxychloride octahydrate is 1:0.176, and the mass ratio of acrylic acid to AAPH is 1:0.024. Add 4 mg of quinoline yellow to the above mixture. Stir with a magnetic stirrer for more than 1 hour in a light-shielded environment to form a uniform hydrogel precursor solution.

[0192] (3) Transfer the hydrogel precursor solution prepared in step (2) to the liquid tank of a DLP light-curing printer, set the slice layer thickness to 40 μm, the ultraviolet light wavelength to 405 nm, and the ultraviolet light intensity to 58 mW / cm 2, the exposure time of the bottom layer is 35 s, and the exposure time of the remaining layers is 30 s. A high-resolution, high-strength and tough supramolecular hydrogel structure is obtained by printing.

[0193] Figure 3 It shows the minimum resolution that can be achieved by the DLP photocuring printed hydrogel composite material. The minimum width of the single-pixel grid feature printed is about 13 μm.

[0194] Figure 4 It shows a photo of the high-resolution hydrogel three-dimensional structure printed by DLP photocuring.

[0195] Example 3

[0196] (1) Use a fiber defibrillator to disperse para-aramid nanofibers in water to obtain a uniform dispersion with a para-aramid fiber mass concentration of 0.114 wt%.

[0197] (2) Mix the aramid fiber dispersion in step (1) with the acrylic hydrogel precursor. The mass of the aramid fiber dispersion is 28 g, and the mass of the acrylic hydrogel precursor is 12 g. The acrylic hydrogel precursor consists of acrylic acid, zirconium oxychloride octahydrate, and the photoinitiator AAPH. The mass of acrylic acid is 10 g, the mass of zirconium oxychloride octahydrate is 1.76 g, and the mass of AAPH is 0.24 g. The mass ratio of acrylic acid to zirconium oxychloride octahydrate is 1:0.176, and the mass ratio of acrylic acid to AAPH is 1:0.024. Stir with a magnetic stirrer for more than 1 hour in a light-shielded environment to make the above mixture form a uniform hydrogel precursor solution.

[0198] (3) Fill the hydrogel precursor solution prepared in step (2) into a rectangular mold with dimensions of 25 mm × 2 mm × 1 mm, cover it with a transparent acrylic plate, and place it in an ultraviolet lamp box. Irradiate it with 405 nm ultraviolet light for 5 min to obtain a supramolecular hydrogel composite material.

[0199] (4) Immerse the hydrogel composite material cured in step (3) in 1 M sodium hydroxide solution for 5 min to remove part of the coordination of zirconium ions and carboxyl groups, and immerse it in deionized water for 5 min to remove sodium hydroxide. Subsequently, transfer the hydrogel into 1 M calcium acetate solution and soak it for 12 h, and then transfer it into deionized water and soak it to reach swelling equilibrium, and a hydrogel composite material with a programmable shape memory effect can be obtained.

[0200] (5) Apply an external force to the shape - memory supramolecular hydrogel obtained after soaking in calcium acetate in step (4), divide it into four groups, bend each group by 180° and soak them in hot water at 90 °C for 15 s, 30 s, 45 s, and 60 s respectively (programming time). After removing the external force, it is found that the shape of the hydrogel is fixed and significant hardening occurs. Transfer it to cold water at 20 °C, and the hydrogel will first experience a "dormant period" of about 5 s and then gradually recover to the initial shape after the soaking treatment in step (4).

[0201] (6) Step (5) can be repeated multiple times in a cycle.

[0202] Figure 5 The schematic diagram of the hydrogel composite material with the programmable shape - memory effect and the curve of the shape - recovery ratio varying with time at different programming times are shown. It can be found that the hydrogel can achieve shape fixation at a higher temperature and cold - induced shape recovery, and it will experience a delayed - recovery "dormant period" before shape recovery. The length of this "dormant period" changes with the programming time in hot water. Therefore, the supramolecular hydrogel composite material has a programmable and delay - recoverable shape - memory effect.

[0203] Example 4:

[0204] (1) Use a fiber defibrillator to disperse para - aramid nanofibers in water to obtain a uniform dispersion with a para - aramid fiber mass concentration of 0.114 wt%.

[0205] (2) Mix the aramid fiber dispersion in step (1) with the acrylic hydrogel precursor. The mass of the aramid fiber dispersion is 28 g, and the mass of the acrylic hydrogel precursor is 12 g. The acrylic hydrogel precursor consists of acrylic acid, zirconium oxychloride octahydrate, and the photo - initiator AAPH. The mass of acrylic acid is 10 g, the mass of zirconium oxychloride octahydrate is 1.76 g, and the mass of AAPH is 0.24 g. The mass ratio of acrylic acid to zirconium oxychloride octahydrate is 1:0.176, and the mass ratio of acrylic acid to AAPH is 1:0.024. Stir the above mixture with a magnetic stirrer for more than 1 hour in a light - shielded environment to form a uniform hydrogel precursor solution.

[0206] (3) Transfer the hydrogel precursor solution prepared in step (2) to the liquid tank of a DLP stereolithography 3D printer, set the slice layer thickness to 40 μm, the ultraviolet light wavelength to 405 nm, the ultraviolet light intensity to 58 mW / cm 2 , the bottom - layer exposure time to 35 s, and the exposure time of the remaining layers to 30 s to print a high - resolution three - dimensional vascular stent precursor.

[0207] (4) Immerse the printed vascular stent precursor in step (3) in a 1M sodium hydroxide solution for 5 min to remove part of the coordination between zirconium ions and carboxyl groups, and then immerse it in deionized water to remove sodium hydroxide. Subsequently, transfer it to a 1M calcium acetate solution and immerse it for 12 h, and finally transfer it to deionized water for soaking to reach swelling equilibrium, obtaining a hydrogel vascular stent with programmable shape memory effect.

[0208] (5) Apply an external force to the hydrogel vascular stent obtained in step (4), fold it and immerse it in hot water at 90 °C for 15 s, then remove the external force. It is found that the shape of the stent is fixed and significant hardening occurs. Transfer it to cold water at 20 °C. The stent first undergoes a "dormant period" of about 5 s, and then gradually returns to its original shape.

[0209] (6) Step (5) can be repeated multiple times in a cycle.

[0210] Figure 7 a) of shows a physical photo of the vascular stent obtained in this embodiment; Figure 7 b) of shows the deformation process of the vascular stent obtained in this embodiment; Figure 7 c) of shows a schematic diagram of the process of the vascular stent obtained in this embodiment gradually recovering to its original shape after being implanted into a blood vessel.

[0211] It can be seen from Figure 7 that, relying on excellent printing resolution and programmable shape memory effect, the vascular stent of the present invention has a delicate customizable structure, can be conveniently implanted into a blood vessel in a folded form, and delays the recovery to the original shape to fit the inner wall of the blood vessel to provide support. The vascular stent of the present invention has the application potential for treating cardiovascular diseases such as arterial atherosclerosis.

[0212] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, and improvements made within the spirit and principle of the present invention shall be included within the scope of the claims of the present invention.

[0213] Industrial applicability

[0214] The hydrogel precursor composition and hydrogel of the present invention have broad application prospects in the fields of biomedicine and flexible electronics.

Claims

1. A hydrogel with programmable shape memory effect, characterized in that: The invention comprises aramid nanofibers, a cross-linked polymer and calcium acetate, wherein at least a portion of the aramid nanofibers are connected to the cross-linked polymer by covalent bonds, and a cross-linked structure in the cross-linked polymer is formed by the coordination of carboxyl groups in the polymer and metal ions; The hydrogel includes a dynamic complex formed by carboxyl groups and calcium ions and acetate ions; The aramid nanofiber is a para-aramid nanofiber with an average diameter of 10 to 500 nm and an aspect ratio of 2000 to 4000; the content of the aramid nanofiber is 0.001 to 1 wt%; The content of the cross-linked polymer is 11 to 60 wt %; the cross-linked polymer comprises one or more structural units derived from (meth) acrylic acid monomers, and a cross-linked structure formed by coordination bonds between carboxyl groups in the polymer and metal ions; the metal ions are zirconium ions; The content of calcium acetate is 0.1-10wt%.

2. The hydrogel with programmable shape memory effect according to claim 1, characterized in that: The cross-linked polymer is formed by polymerizing a raw material composition comprising a monomer containing a carboxylic acid group and a cross-linking agent containing a metal ion, wherein the monomer is one or more selected from (meth)acrylic acid; the cross-linking agent is zirconium oxychloride octahydrate and / or zirconium chloride; the weight ratio of the monomer to the cross-linking agent is 1:(0.05-0.5); and the polymerization is photoinitiated polymerization.

3. The hydrogel with programmable shape memory effect according to claim 1 or 2, characterized in that: The content of calcium acetate is 1-8wt%.

4. The hydrogel with programmable shape memory effect according to claim 2, characterized in that: The monomer is acrylic acid.

5. A method for preparing a hydrogel having a programmable shape memory effect according to any one of claims 1 to 4, characterized in that: The following steps are involved: irradiating the hydrogel precursor composition with light to obtain a supramolecular hydrogel; and contacting the obtained supramolecular hydrogel with an aqueous alkali solution, and then contacting it with an aqueous solution containing calcium acetate; The hydrogel precursor composition comprises aramid nanofibers, a monomer containing a carboxylic acid group, a cross-linking agent containing a metal ion, a water-soluble photoinitiator and water, and optionally further comprises a light absorber.

6. The preparation method according to claim 5, characterized in that: The hydrogel precursor composition is poured into a mold and then the light irradiation is performed; or the light irradiation is performed while the hydrogel precursor composition is 3D or 4D printed.

7. The preparation method according to claim 5, characterized in that: The light irradiation is performed using light with a wavelength of 365 to 405 nm.

8. The preparation method according to claim 5, characterized in that: The light irradiation is performed by digital light processing (DLP) technology of surface projection photocuring.

9. The preparation method according to claim 5, characterized in that: The contact time with the alkaline aqueous solution is 0.5 to 30 minutes.

10. The preparation method according to claim 9, characterized in that: The contact time with the alkaline aqueous solution is 1 to 20 minutes.

11. The preparation method according to claim 5, characterized in that: The contact time with the aqueous solution containing calcium acetate is 1 to 48 hours.

12. The preparation method according to claim 11, characterized in that: The contact time with the aqueous solution containing calcium acetate is 4 to 20 hours.

13. The preparation method according to claim 5, characterized in that: The contacting is performed by immersing the supramolecular hydrogel in an alkaline aqueous solution or an aqueous solution containing calcium acetate.

14. The preparation method according to claim 13, characterized in that: The concentration of calcium acetate in the aqueous solution containing calcium acetate is 0.01-2 mol / L.

15. A vascular stent, characterized in that: The tubular structure has a tubular structure, the wall of which is mesh-shaped, and contains the hydrogel with programmable shape memory effect according to any one of claims 1 to 4.

16. The vascular stent according to claim 15, characterized in that: The wall further comprises one or more components selected from the group consisting of: biocompatible materials, X-ray contrast agents, and drugs.

17. The vascular stent according to claim 15 or 16, characterized in that: The outer diameter of the tubular structure is 2-30 mm; the length of the tubular structure is 5-30 mm, and the wall thickness is 0.1-2 mm.

18. A method for preparing a vascular stent according to any one of claims 15 to 17, characterized in that: The following steps are involved: (I) 3D or 4D printing the hydrogel precursor composition while irradiating light to obtain a scaffold precursor having a tubular structure; (II) contacting the scaffold precursor with an aqueous alkaline solution and then contacting it with an aqueous solution containing calcium acetate; The hydrogel precursor composition comprises aramid nanofibers, a monomer containing a carboxylic acid group, a cross-linking agent containing a metal ion, a water-soluble photoinitiator and water, and optionally further comprises a light absorber.

19. The preparation method according to claim 5 or 18, characterized in that: In the hydrogel precursor composition, the content of the aramid nanofiber is 0.001-1wt%; the content of the monomer containing the carboxylic acid group is 10-50wt%; the content of the cross-linking agent containing the metal ion is 1-10wt%; the content of the water-soluble photoinitiator is 0.1-1.5wt%; the content of water is 30-80wt%; and the content of the light absorber is 0-0.1wt%.

20. The preparation method according to claim 5 or 18, characterized in that: The weight ratio of the monomer to the water-soluble photoinitiator is 1:(0.005-0.1).

21. The preparation method according to claim 5 or 18, characterized in that: The water-soluble photoinitiator is one or more selected from water-soluble aromatic ketones, condensed aromatic hydrocarbons, polysilanes, acylphosphonates, azos and metal organic complex initiators.

22. The preparation method according to claim 5 or 18, characterized in that: The water-soluble photoinitiator is a water-soluble azo initiator.

23. The preparation method according to claim 5 or 18, characterized in that: The water-soluble photoinitiator is azobisisobutylamidine hydrochloride.

24. The preparation method according to claim 5 or 18, characterized in that: The light absorber is one or more of quinoline yellow, Sudan red, methyl red and brilliant green.

25. The method for preparing a vascular stent according to claim 18, characterized in that: It also includes the following steps: After the step (II), the inner surface and / or outer surface of the stent is coated with a composition comprising one or more components selected from the group consisting of biocompatible substances, X-ray imaging agents, and drugs.

26. The method for preparing a vascular stent according to claim 25, characterized in that: The coating is performed by dipping or spraying.

27. The preparation method according to claim 5 or 18, characterized in that: The method also includes preparing the hydrogel precursor composition, wherein the preparation of the hydrogel precursor composition includes the following steps: Mixing aramid nanofibers with water and stirring to obtain an aqueous dispersion of aramid nanofibers; The aqueous dispersion of aramid nanofibers is mixed with a monomer containing a carboxylic acid group, a cross-linking agent containing a metal ion, a water-soluble photoinitiator and an optional light absorber to obtain the hydrogel precursor composition.

28. Use of the vascular stent according to any one of claims 15 to 17 in preparing a medical device for treating cardiovascular diseases.

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