CN115044213B

CN115044213B - Hydrogel with controllable surface microstructure and preparation method thereof

Info

Publication number: CN115044213B
Application number: CN202210903603.7A
Authority: CN
Inventors: 冷劲松; 耿强旺; 张风华; 刘彦菊
Original assignee: Harbin Institute of Technology
Current assignee: Harbin Institute of Technology
Priority date: 2022-07-28
Filing date: 2022-07-28
Publication date: 2023-07-18
Anticipated expiration: 2042-07-28
Also published as: CN115044213A

Abstract

The invention provides a hydrogel with a controllable surface microstructure and a preparation method thereof, and relates to the technical field of hydrogel preparation. The substrate with the micropattern structure is prepared by adopting the shape memory material, the micropattern can be regulated and controlled by a physical heating method, and the disappearance or reproduction of the micropattern can be effectively controlled, so that the proliferation, differentiation, orientation or directional migration behavior of cells can be regulated and controlled. In addition, the shape of the micro-pattern structure is controlled by adopting a physical heating mode, which is beneficial to in-vivo application and simplified operation difficulty.

Description

Hydrogel with controllable surface microstructure and preparation method thereof

Technical Field

The invention relates to the technical field of hydrogel preparation, in particular to a hydrogel with a controllable surface microstructure and a preparation method thereof.

Background

Hydrogel is a polymer material with a stable three-dimensional network structure which only swells in water but does not dissolve in water. Its three-dimensional network is generally composed of two parts: hydrophilic groups such as hydroxyl, carboxyl, amine, etc., and hydrophobic groups such as alkyl, etc. Hydrogels have been widely used in biomedical fields because of their good biocompatibility, flexibility, and low cytotoxicity, such as: drug loading, postoperative adhesion resistance, tissue engineering scaffolds, and the like. Compared with the traditional high molecular scaffold material, the property of the hydrogel tissue engineering scaffold is closer to the tissue environment in a organism, and the hydrogel tissue engineering scaffold is used as a high molecular functional material integrating water absorption, water retention and controlled release, can well transfer and supply nutrition to cells and regulate the growth and differentiation of the cells; meanwhile, the compound can be used as a drug and growth factor slow release system to better simulate various physical and chemical environments in organisms. In addition, the hydrogel has excellent plasticity, can form a fine structure with high bionic performance through a micropattern die-building or three-dimensional printing mode, effectively plays a role in physical guidance, and regulates and controls the actions of cell adhesion, spreading, differentiation and the like. For example, macrophages exhibit a time shift from the M1 phenotype (from the time of injury to 3 days after injury) to the M2 phenotype during normal wound healing and tissue regeneration in vivo. M1 type macrophages secrete high levels of potent angiogenic factors, vascular endothelial growth factors and pro-inflammatory cytokines, while M2a type macrophages secrete high levels of potent mitogens, platelet-derived growth factors and pro-fibrotic chemokines. The loss of M1 macrophage behavior or the premature appearance of M2a will lead to delayed wound healing, severe or even pathological fibrosis, so that both macrophages M1 and M2 are important and need to play their own roles at the appropriate time. Micropatterning the surface of the hydrogel can cause the cells to exhibit a desired phenotype (e.g., M1 or M2 type) and retain it for a sustained period of time, thereby facilitating repair of the injury and tissue regeneration.

At present, many studies indicate that micropatterning of biological materials has a great impact on regulating cellular behavior. For example Luo Yiyun et al manipulate macrophage phenotype by ultraviolet induced dynamic Arg-Gly-Asp (RGD) pattern, polyethylene glycol-dithiol/polyethylene glycol-norbornene (PEG-SH/PEG-Nor) hydrogels with dynamic RGD surface were prepared, after 365nm ultraviolet irradiation, uniform RGD surface was transformed into RGD pattern surface, inducing macrophage transformation from round to elongated morphology, followed by pro-inflammatory to anti-inflammatory phenotype. It is difficult to apply to the body because it needs to be irradiated with ultraviolet light to undergo a chemical reaction to form a form having a micropatterned structure. For example, li Guicai et al prepare Polyacrylamide (PAM) hydrogel with surface micropatterns to effectively regulate the directional growth of schwann cells, but the solution cannot realize the regulation of the surface micropatterns, is difficult to promote the transformation of cells to different types, and limits the application of the surface micropatterns.

Disclosure of Invention

Aiming at the problems in the prior art, the invention aims to provide hydrogel with a controllable surface microstructure and a preparation method thereof.

In order to achieve the above object, the present invention is specifically achieved by the following techniques:

the invention provides a hydrogel with a controllable surface microstructure, which comprises a substrate, wherein the substrate has a shape memory function and an initial shape and a temporary shape, the substrate is used for being converted from the temporary shape to the initial shape under the stimulation of external conditions, the surface of the substrate is a plane under the temporary shape, and a micropattern is formed on the surface of the substrate under the initial shape.

Further, the micropattern is an array of protrusions.

Further, the protrusions are one or more of strip-shaped protrusions, cube-shaped protrusions, frustum-shaped protrusions, columnar protrusions, hemispherical protrusions and water-drop-shaped protrusions.

Further, the protrusions are strip-shaped protrusions, the strip-shaped protrusions are distributed in parallel at intervals, and downward concave grooves are formed between two adjacent strip-shaped protrusions.

Further, micro-channels are formed on the surface of the bulge and/or the bottom of the groove, and a plurality of micro-channels are arranged in parallel at intervals.

Further, the hydrogel further comprises a surface layer, wherein the surface layer is arranged on one surface of the substrate with the micropattern, and the surface layer is made of raw materials including gelatin.

In addition, the invention provides a preparation method of the hydrogel with the controllable surface microstructure, which comprises the following steps:

s1, dissolving gelatin, acrylamide, tannic acid, a cross-linking agent and an initiator to obtain a pre-reaction solution;

s2, pouring the pre-reaction liquid into a mold, and heating to solidify the pre-reaction liquid to obtain the substrate with the micropattern structure.

Further, in the pre-reaction liquid, the mass ratio of the gelatin, the acrylamide, the tannic acid, the cross-linking agent and the initiator is 1:1-2:0.005-0.015:0.001-0.1:0.0001-0.01.

Further, the cross-linking agent is N, N-methylene acrylamide; the initiator is a thermal initiator.

Further, the method also comprises the following steps:

and S3, adding gelatin into deionized water for dissolution, then dripping gelatin solution onto the surface of the substrate with the micropattern structure until a flat surface is formed, and then cooling to obtain the hydrogel with the gelatin surface layer.

The substrate with the micropattern structure is prepared by adopting the shape memory material, the micropattern can be regulated and controlled by a physical heating method, and the disappearance or reproduction of the micropattern can be effectively controlled, so that the proliferation, differentiation, orientation or directional migration behavior of cells can be regulated and controlled. In addition, the shape of the micro-pattern structure is controlled by adopting a physical heating mode, which is beneficial to in-vivo application and simplified operation difficulty.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for the description of the embodiments will be briefly described below, and it is apparent that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.

FIG. 1 is a schematic illustration of the structure of a hydrogel with controllable surface microstructure in an initial shape according to an embodiment of the present invention;

FIG. 2 is a schematic illustration of the structure of a hydrogel with controllable surface microstructure in a temporary shape according to an embodiment of the invention;

FIG. 3 is a scanning electron microscope image of a hydrogel with a controllable surface microstructure in an initial shape according to an embodiment of the invention;

FIG. 4 is a scanning electron microscope image of a hydrogel with a controllable surface microstructure in a temporary shape according to an embodiment of the present invention;

FIG. 5 is a schematic illustration of the structure of a hydrogel with controllable surface microstructure in an initial shape according to another embodiment of the invention;

FIG. 6 is a schematic view of a configuration of a protrusion and micro-channel mating in accordance with an embodiment of the present invention;

FIG. 7 is a diagram showing a preparation mechanism of a base material according to an embodiment of the present invention;

FIG. 8 is a diagram showing a shape memory deformation process of a base material according to an embodiment of the present invention;

FIG. 9 is a graph showing stress-strain curves of hydrogels prepared using different ratios of gelatin and acrylamide according to an embodiment of the present invention.

Detailed Description

In order to make the above objects, features and advantages of the present invention more comprehensible, technical solutions in specific embodiments accompanied with figures are described clearly and completely below. It will be apparent that the described embodiments are only some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to fall within the scope of the invention.

It should be noted that technical terms used in the specification and the claims of the present invention should be construed as having a general meaning as understood by those having ordinary skill in the art to which the present invention pertains. As used in the specification and in the claims, the terms "comprises," "comprising," or the like are intended to cover the inclusion of a feature or element that is "comprising" or "comprises" or "comprising" followed by the recited feature or element and equivalents thereof, but do not exclude other features or elements. The terms "connected" or "connected," and the like, are not limited to physical or mechanical connections, nor to direct or indirect connections.

It is to be understood that all numbers expressing quantities, percentages, and other values used in the present invention are to be understood as being modified in all instances by the term "about". Accordingly, unless indicated otherwise, the numerical parameters set forth in the specification and claims are approximations that may vary depending upon the desired properties sought to be obtained. Each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

An embodiment of the present invention provides a hydrogel with a controllable surface microstructure, see fig. 1-2 and fig. 5, where the hydrogel includes a substrate having a shape memory function and having an initial shape and a temporary shape, where the substrate is used to transition from the temporary shape to the initial shape under an external condition stimulus, and where the surface of the substrate is planar (see fig. 2) and where the surface of the substrate is formed with a micropattern (see fig. 1 and fig. 5, where a gray solid indicates a micropattern).

In the context of the present invention, the term "shape memory" refers to a material or article having an initial shape that changes its initial shape upon stimulation by external conditions (e.g., temperature, light, current, solvent, or ionic strength) and sets to form a temporary shape from which it returns to its initial shape upon response to an external stimulus. Glass transition temperature (T) of shape memory material _g ) The following is a hard material as long as the temperature does not rise to its T _g This shape can be maintained all the time.

It is noted that in the context of the present invention, the surface of the substrate refers to the side on which cells are oriented, propagated, differentiated or adhered for growing the cells.

In this embodiment, when no micropattern is required to be displayed, the substrate in the temporary shape can be formed by heating to a temperature above the glass transition temperature (Tg) of the substrate and applying an external force to flatten the micropattern on the surface, and after the temperature is reduced to its deformation temperature, the external force is removed to maintain the temporary shape. When the micropattern is required to be developed, the substrate can be automatically restored to the original shape by reheating to above Tg. Fig. 1-4 show the deformation process of the substrate, respectively, wherein fig. 1 and 3 show the substrate morphology in the initial shape and fig. 2 and 4 show the substrate morphology in the temporary shape. The substrate with the micropattern structure is prepared by adopting the shape memory material, the micropattern can be regulated and controlled by a physical heating method, and the disappearance or reproduction of the micropattern can be effectively controlled, so that the proliferation, differentiation, orientation and/or directional migration behavior of cells can be regulated and controlled. In addition, the shape of the micro-pattern structure is controlled by adopting a physical heating mode, which is beneficial to in-vivo application and simplified operation difficulty.

Optionally, the micropattern is an array of protrusions. Specifically, the protrusions are one or more of strip-shaped (or long rectangular body), cube-shaped, frustum-shaped, columnar, spherical, water-drop-shaped and other three-dimensional protrusions.

When the protrusions are strip-shaped protrusions, referring to fig. 1 and 3, the strip-shaped protrusions are distributed in parallel at intervals, and a downward concave groove is formed between two adjacent strip-shaped protrusions. The grooves and the protrusions are sequentially arranged to form array distribution. The introduction of the raised structures helps direct the directional growth and alignment of cells, such as macrophages, along the direction of the protrusions.

The above characteristics can be applied to the field of injury treatment or tissue engineering. Specifically, before the hydrogel is implanted into a body, the hydrogel is heated and the surface of the hydrogel is converted into a planar structure under the action of external force, so that the shape memory substrate is in a temporary shape, then the hydrogel is implanted into the body, macrophages are polarized into M1 type on the smooth substrate surface, the functions of secreting pro-inflammatory cytokines, chemotactic factors and the like are exerted, the hydrogel participates in forward immune response, plays the role of immune monitoring, and the hydrogel is heated until the hydrogel reaches T after about 3 days after injury _g Above, the substrate automatically restores to the original shape, the micropattern appears, at the moment, the strip-shaped bulges induce the cells to generate contact guiding effect, the cells are guided to move along the bulge orientation, elongation and orientation, macrophages are polarized into M2 type, and the inflammatory factors are expressed to play roles in inhibiting inflammatory reaction and tissue repair, so that the tissue injury repair is quickened. Thus, the life of macrophages can be better completed by controlling the disappearance or recurrence of micropatterns.

It should be noted that the hydrogels with the above structure can also be used to regulate the polarization of other cells with oriented structures, such as blood-profound cells and stem cells.

When the protrusions are other than stripe-shaped protrusions, for example, referring to fig. 5, the protrusions are arranged at intervals, so that proteins are conveniently attached to the surface of the micropattern, and cell adhesion can be increased.

The above characteristics are applicable to the field of targeted therapy. Specifically, the hydrogel is placed in a body, a certain time and a certain distance are needed for the hydrogel to reach the lesion position, if the columnar bulge structure on the surface of the substrate is directly exposed in the body, cells at other parts can be adhered early, but the shape memory substrate is adopted, before implantation, the surface of the hydrogel is converted into a planar structure, the adhesion of the cells can be reduced, and after reaching the lesion position, the hydrogel is heated at the position, so that the shape memory substrate is restored to the original shape, and at the moment, the columnar bulge is exposed, and the effect of targeted treatment can be well achieved.

Optionally, micro-channels are formed on the surface of the protrusion (i.e. the surface not contacted with the substrate) and/or the bottom of the groove, and a plurality of micro-channels are arranged in parallel and at intervals to form a stripe array. Fig. 6 is a schematic view showing the structure of a micro channel, taking an example that the micro channel is disposed on a protrusion.

The micro-channels are provided on the protrusions and/or grooves, and have micro-nano dimensions, and the micro-channels have a width of 1-10 μm, a depth of 50-200nm, and a pitch of 5-20 μm, for example.

The micro-nano micro-channel has stronger contact guiding effect, is more beneficial to the growth of macrophages into M2 type along micro-stripes, increases the induced orientation sites of the macrophages in a limited space, and is beneficial to the improvement of the quantity of the M2 macrophages. In addition, the cell adhesion sites are increased, and the adhesion between the substrate and the cells can be enhanced. In order to better improve the cell adsorption efficiency, the micro-channel can also be provided with small bulges or a structure combining the small bulges and the micro-channel.

In order to provide good compatibility of the substrate material with the cells, the cells are easily combined with the substrate, and thus the cell behavior is better regulated, optionally the substrate is made of raw materials including gelatin, acrylamide and tannic acid. The preparation method comprises the following steps:

s2, pouring the pre-reaction liquid into a mold, and heating to solidify the pre-reaction liquid to obtain the substrate, wherein the substrate is in an initial state.

Gelatin facilitates cell adhesion, spreading, proliferation, etc. In the embodiment, the gelatin with good biocompatibility is taken as a base material, the acrylamide and the tannic acid are introduced, and the acrylamide is crosslinked and copolymerized under the action of an initiator and a crosslinking agent to form a polyacrylamide crosslinked network, as shown in fig. 7, the network structure (light gray curve in fig. 7) is inserted in a spiral structure (dark gray curve in fig. 7) of the gelatin, the gelatin spiral network serves as a soft segment, the acrylamide serves as a hard segment, meanwhile, the tannic acid has rich hydrogen bond forming groups, and can respectively form hydrogen bonds with the gelatin and the acrylamide to play a role of crosslinking points (positions shown by black dots in fig. 7), so that on one hand, the base material with a shape memory function is formed, and the glass transition temperature is as low as 40-45 ℃ to facilitate in vivo regulation; on the other hand, the gelatin spiral network and the polyacrylamide cross-linked network are connected to form a three-dimensional network space structure, so that the strength of the material is greatly enhanced, and the mechanical tensile strength of the material can be improved from less than 0.01MPa of gelatin to 0.1-0.5MPa. In addition, the gelatin can be prevented from melting at high temperature in the heating process, and the stability of the substrate is improved. Tannic acid can also increase the antibacterial property of the material.

The step S1 specifically comprises the following steps: adding gelatin, acrylamide, tannic acid and a cross-linking agent into deionized water, heating to 50-70 ℃ and stirring, stopping heating when the gelatin, the acrylamide and the tannic acid are completely dissolved until the solution is transparent, cooling to room temperature, then adding an initiator, and stirring uniformly to obtain a pre-reaction solution.

The step S2 specifically comprises the following steps: pouring the pre-reaction liquid into a mould, heating to 80 ℃, carrying out curing reaction for 1h, and then standing at 0 ℃ for 30min to obtain the substrate. The mold has a pattern structure matched with the micropattern to form a substrate with the micropattern when the material is cured, the micropattern and the substrate being integrally formed.

Wherein, in the pre-reaction liquid, the mass ratio of the gelatin, the acrylamide, the tannic acid, the cross-linking agent and the initiator is 1:1-2:0.005-0.01:0.001-0.1:0.0001-0.01. Illustratively, when gelatin is 1 part, acrylamide is 1-2 parts, tannic acid is 0.005-0.01 parts, cross-linking agent is 0.001-0.1 parts, and initiator is 0.0001-0.01 parts.

In the invention, the spiral network of gelatin and the polyacrylamide cross-linked network are matched and are mutually contained, so that the invention has good mechanical properties. When the content of the helical network of the gelatin is high, the content of the polyacrylamide cross-linked network is low, or when the content of the helical network of the gelatin is low, the content of the polyacrylamide cross-linked network is low, the coordination effect between the two networks is reduced. The acrylamide with proper content is favorable for forming a polyacrylamide cross-linked network with higher content, is favorable for matching with a spiral network of gelatin, and is further favorable for improving mechanical strength. Referring to fig. 9, the abscissa in fig. 9 is Strain (Stress), and the ordinate is Stress (unit is MPa), and different proportions of gelatin and acrylamide are used, specifically, the mass ratio of gelatin to acrylamide is sequentially from 1:1 to 1:1.9, the mechanical strength tends to increase and decrease. Preferably, the mass ratio of the gelatin to the acrylamide is 1:1.5-1.9. In some embodiments, the mass ratio may be 1:1.5, 1:1.7 or 1:1.9. more preferably 1:1.7.

preferably, the mass ratio of the gelatin, the acrylamide, the tannic acid, the cross-linking agent and the initiator is 1:1.5-1.9:0.01:0.005-0.05:0.0005-0.005.

Alternatively, the crosslinking agent may facilitate the crosslinking reaction of acrylamide, including but not limited to N, N-methylene acrylamide, which is a commonly used crosslinking agent for acrylamide AM.

Alternatively, the initiator is a thermal initiator for initiating the cross-linking polymerization of the acrylamide at a temperature sufficient to effect cross-linking polymerization of the acrylamide, including but not limited to one or more of ammonium persulfate, sodium persulfate, potassium persulfate, hydrogen peroxide, and benzoyl peroxide.

Illustratively, a base material having a glass transition temperature of 45 ℃ was prepared from 1 part of gelatin, 1.7 parts of acrylamide, 0.01 part of tannic acid, 0.01 part of N, N' -methylenebisacrylamide, and 0.001 part of potassium persulfate as raw materials. Fig. 8 shows a shape memory deformation process of the base material. The initially shaped substrate was immersed in deionized water at 70 ℃ for 20s, shaped by applying an external force, then maintained and placed at 0 ℃ for 20s to reduce the temperature below the glass transition temperature, and then removed to maintain the temporary shape. Subsequently, the temporarily shaped substrate was placed in deionized water at 45 ℃ for 20s, which was restored to the original shape.

Optionally, the hydrogel further comprises a surface layer, wherein the surface layer is arranged on one surface of the substrate with the micropattern, and the surface layer is made of a raw material comprising gelatin.

When the composite material is applied to the field of injury treatment or tissue engineering, compared with a substrate material formed by a composite system of gelatin, acrylamide and tannic acid, the surface layer material adopts a gelatin system, and has an excellent effect of promoting macrophage to M1 type polarization. That is, before the hydrogel is implanted into a body, the surface of the substrate is covered with a gelatin surface layer, at this time, gelatin can more effectively promote the differentiation of macrophages into M1 type, after the M1 type macrophages realize the function, the gelatin surface layer is heated to above the glass transition temperature of the substrate, at this time, the gelatin surface layer melts, takes away the M1 type macrophages attached to the gelatin surface layer, and flows away under the flushing of blood. Meanwhile, the substrate is restored to the original shape with the micropattern, so that the polarization of the new-born macrophages to the M2 type is promoted, and the polarization efficiency of the macrophages with different types can be improved through the synergistic effect of the gelatin surface layer and the shape memory substrate, and the damage repair efficiency is obviously improved. When the gel is used as the directional treatment field, before reaching a lesion site, the gel surface layer is covered to reduce the cell viscosity of a non-lesion site, and adhered non-lesion cells can be removed by melting the gel surface layer, so that the directional fixed-point treatment is more effectively realized. In addition, the gelatin surface layer is adopted, has higher binding force with the substrate, is beneficial to the integration of the substrate and the surface layer, and avoids the problem of interface separation or layering. This is because hydrogel is required to be soaked in alcohol or water in advance for disinfection or purification of hydrogel when it is implanted in vivo, unreacted small molecules are exchanged away in the synthesis process, if the upper and lower layers are layered, the upper and lower layers are separated in the soaking process, so that the covering effect of the surface layer is lost, and 90% of the blood is water after the hydrogel is implanted in vivo, and the risk is also faced, so that the application effect of the surface layer material is lost. The upper layer and the lower layer of the invention adopt gelatin systems which are integrated, thus solving the layering problem.

Optionally, the surface layer also comprises K-carrageenan, and the surface layer is prepared by mixing the K-carrageenan with gelatin such as tuna gelatin, so that a surface layer material with a melting point of about 42 ℃ can be obtained, and the influence of body temperature fluctuation on the surface layer structure can be avoided.

Specifically, the preparation method of the surface layer comprises the following steps: adding gelatin into deionized water, heating to 50-70deg.C, stirring until gelatin is completely dissolved, cooling to below 40deg.C when the solution becomes completely transparent, dripping gelatin solution onto the surface of the substrate with surface micropattern until a flat surface is formed, and standing at 0deg.C for 30min to obtain hydrogel with gelatin surface layer.

Another embodiment of the present invention provides a method for preparing a hydrogel with a controllable surface microstructure as described above, comprising the steps of preparing a substrate with a micropatterned structure, specifically comprising the following steps:

s2, pouring the pre-reaction liquid into a mold, and heating to solidify the pre-reaction liquid to prepare the substrate with the micropattern structure.

The preparation method of the hydrogel with the controllable surface microstructure is the same as that of the hydrogel with the controllable surface microstructure in the prior art, and is not described herein.

Further, the preparation of the surface layer is also included, and the description is omitted here.

Although the present disclosure is disclosed above, the scope of the present disclosure is not limited thereto. Various changes and modifications may be made by one skilled in the art without departing from the spirit and scope of the disclosure, and these changes and modifications will fall within the scope of the disclosure.

Claims

1. A hydrogel with a controllable surface microstructure, comprising a substrate, wherein the substrate has a shape memory function and has an initial shape and a temporary shape, the substrate is used for being converted from the temporary shape to the initial shape under the stimulation of external conditions, the surface of the substrate is a plane under the temporary shape, and a micropattern is formed on the surface of the substrate under the initial shape;

the surface layer is arranged on one surface of the substrate with the micropattern, and is made of raw materials including gelatin; the surface layer melts when the substrate transitions from the temporary shape to the initial shape under an external condition stimulus;

the preparation method of the hydrogel with the controllable surface microstructure comprises the following steps:

s2, pouring the pre-reaction liquid into a mold, and heating to solidify the pre-reaction liquid to obtain a substrate with a micropattern structure;

the cross-linking agent is N, N-methylene acrylamide; the initiator is a thermal initiator;

the preparation method of the hydrogel with the controllable surface microstructure further comprises the following steps:

2. The surface-microstructured hydrogel of claim 1, wherein the micropattern is an array of protrusions.

3. The surface microstructure-controllable hydrogel of claim 2, wherein the protrusions are one or more of bar-shaped protrusions, cube-shaped protrusions, frustum-shaped protrusions, columnar protrusions, hemispherical protrusions, and water-drop-shaped protrusions.

4. The surface microstructure controllable hydrogel of claim 3, wherein the protrusions are in the form of strips, the strips being spaced apart in parallel, and wherein a downwardly concave channel is formed between two adjacent strips.

5. The surface microstructure controllable hydrogel of claim 4, wherein the surface of the strip-shaped protrusions and/or the bottoms of the grooves are provided with micro-channels, and a plurality of the micro-channels are arranged in parallel at intervals.

6. The surface microstructure-controllable hydrogel of claim 1, wherein the mass ratio of the gelatin, the acrylamide, the tannic acid, the cross-linking agent, and the initiator in the pre-reaction solution is 1:1-2:0.005-0.015:0.001-0.1:0.0001-0.01.