Hydrogel material with skin-like mechanical property and preparation method thereof

Abstract

The invention discloses a hydrogel material with skin-like mechanical properties and a preparation method thereof, and belongs to the technical field of functional polymer materials. The preparation method comprises the following steps: reacting an amino acid monomer with acryloyl chloride under an alkaline condition to synthesize a vinylated amino acid monomer, and carrying out photo-initiated random copolymerization on the vinylated amino acid monomer and an acrylamide monomer to form a hydrogel material with regulation and control mechanical properties. The optimal process conditions are determined by changing the types, the components and the dialysis environment of the monomers, and the mechanical properties of the prepared hydrogel can be regulated and controlled in a large range.

Description

Technical Field

[0001] The invention relates to the technical field of functional polymer materials, and in particular to a hydrogel with skin-like mechanical properties and a preparation method thereof. Background Art

[0002] Skin-like materials are synthetic materials that mimic the structure and properties of animal skin, and have the characteristics of softness, stretchability, breathability and wear resistance. Skin-like materials have broad application prospects in the fields of medicine, robotics, flexible electronics, smart textiles, etc., and have become one of the hot areas of material science research. At present, the design of soft materials with skin-like mechanical properties can be done by studying the structure and properties of animal skin, obtaining inspiration and imitating its design, such as scales, hair, stratum corneum, etc. On the other hand, the combination design of polymer materials can be used to design materials with skin-like properties by taking advantage of the characteristics and interactions of different polymer materials.

[0003] Skin tissues are mainly composed of proteins, lipids, water, minerals, vitamins and other compounds. Amino acids are the basic building blocks of proteins. Due to their amino, carboxyl and chiral carbon, they exhibit unique hydrophilicity, net charge, stereoregularity and other functions when they constitute proteins, greatly enriching the structure and biological functions of proteins.

[0004] Inspired by the structure of skin-like tissue, we introduced amino acid units into synthetic polymers and designed hydrogel materials with skin-like mechanical properties.

[0005] There are two main methods for preparing hydrogels with excellent mechanical properties: Method 1, synthesizing polyamino acids through condensation reaction or amino acid anhydride ring-opening polymerization. The polyamino acids synthesized by this method are similar in structure to natural polypeptides, and therefore have physical properties similar to proteins. However, the synthesis of polyamino acids using this method is complicated and cumbersome, the conditions are harsh, and the synthesized products usually do not have high molecular weight and strong mechanical properties, so there are limitations in application; Method 2, polymerizing monomers containing amino acids to synthesize polymers containing amino acid side chains, or modifying reactive polymer functional groups with amino acid functional groups (carboxylic acids, amines, thiols, hydroxyls, etc.) to synthesize polymers containing amino acid side chains. Although the polymers synthesized by this method do not have the structure of natural polypeptides (such as α and β helices), they have more significant stimulus responsiveness to external environmental conditions (such as pH value, temperature, and metal ion complexing ability). At the same time, due to the hydrogen bonds, hydrophilic and hydrophobic interactions, electrostatic interactions, etc. between amino acid groups, the prepared polymer materials have better mechanical properties.

[0006] In summary, it is necessary to develop new hydrogels with skin-like mechanical properties and their preparation methods to solve the problems in existing processes such as complex and cumbersome reactions, harsh conditions, and the products do not have high molecular weight and strong mechanical properties. Summary of the invention

[0007] In view of the problems existing in the prior art, the present invention provides a hydrogel material with skin-like mechanical properties and a preparation method thereof. Amino acid monomers and acryloyl chloride are reacted under alkaline conditions to synthesize vinylized amino acid monomers, and the amino acid monomers are randomly copolymerized with acrylamide monomers by light initiation to form a hydrogel material with adjustable mechanical properties. The present invention determines the optimal process conditions by changing the type of monomers, the composition of the components and the dialysis environment thereof. The mechanical properties of the prepared hydrogel can be adjusted over a wide range, such as the fracture strain can be adjusted from 50% to 2000%, the fracture stress can be adjusted from 0.009MPa to 3MPa, and the Young's modulus can be adjusted from 0.003MPa to 30MPa. This performance is comparable to that of biological tissue skin. This hydrogel material with widely adjustable mechanical properties is expected to be used in the fields of biomedical tissue engineering, wearable electronic products, flexible devices, etc. The method of the present invention has a simple process, the raw materials are cheap and easy to obtain, there is no biological toxicity, and it is conducive to process mass production.

[0008] To achieve the above object, the present invention adopts the following technical solutions:

[0009] On the one hand, the present invention provides a hydrogel material with skin-like mechanical properties, wherein the hydrogel material is obtained by reacting monomer one and monomer two in the presence of a crosslinking agent and an initiator, and further dialyzing.

[0010] Furthermore, the monomer one is a vinylated amino acid monomer. Furthermore, the amino acid is selected from at least one of glutamic acid, lysine and valine. Furthermore, the preparation process of the vinylated amino acid monomer is as follows: it is obtained by further treating the amino acid and acryloyl chloride under alkaline conditions. Furthermore, the alkalinity refers to adjusting the pH to 10-12 with sodium hydroxide. Furthermore, during the reaction, acryloyl chloride is added dropwise to control the reaction rate. Furthermore, the post-treatment refers to stirring the reaction to completion after the acryloyl chloride is added dropwise, adding acid to terminate the reaction, filtering, washing and freeze-drying. Taking valine as an example, the specific reaction formula is as follows:

[0011]

[0012] Among them, Acryloyl chloride: acryloyl chloride; Valine: valine; acidification: acidification; DN-acryloyl valinamide: vinylated valine monomer.

[0013] Furthermore, the second monomer is an acrylamide monomer. Furthermore, the second monomer is selected from at least one of acrylamide, methacrylamide, and N,N-dimethylacrylamide.

[0014] Furthermore, the cross-linking agent is N,N'-methylenebisacrylamide (MBAA), and the initiator is one of azobisisobutyronitrile (AIBN) and dioxoglutaric acid (α-keto).

[0015] Furthermore, the reaction requires the use of an organic solvent, and further, the organic solvent is selected from at least one of dimethyl sulfoxide (DMSO), N,N'-dimethylformamide (DMF), and anhydrous ethanol. Further, the reaction refers to the formation of monomer 1 and monomer 2 by random copolymerization.

[0016] Furthermore, the dialysate used in the dialysis is selected from at least one of a 0.9wt% sodium chloride solution, a hydrochloric acid solution with a pH of 1 to 6, and deionized water.

[0017] Further, by weight, the ratio of the monomer 1, the monomer 2, the crosslinking agent, and the initiator is (0-100 parts): (0-100 parts): (0-50 parts): (0-5 parts). Further, by weight, the ratio of the monomer 1, the monomer 2, the crosslinking agent, and the initiator is (40-90%): (1-60 parts): (0.01-20 parts): (0.01-0.5 parts). Further, by weight, the ratio of the monomer 1, the monomer 2, the crosslinking agent, and the initiator is (40-90%): (9-50 parts): (0.01-2.5 parts): (0.01-0.1 parts). Further, by weight, the ratio of the monomer 1, the monomer 2, the crosslinking agent, and the initiator is 70 parts: 30 parts: 2.5 parts: 0.1 parts.

[0018] In another aspect, the present invention provides a method for preparing the hydrogel material having skin-like mechanical properties according to the present invention, comprising the following steps:

[0019] (1) Preparation of Monomer 1: reacting an amino acid monomer with a vinylating agent to obtain Monomer 1;

[0020] (2) Preparation of hydrogel: Monomer 1 and monomer 2 obtained in step (1) are reacted in the presence of a crosslinking agent and an initiator, and further dialyzed to obtain a hydrogel.

[0021] Furthermore, the preparation process of the monomer one is as follows: it is obtained by further treating an amino acid and acryloyl chloride after reacting under alkaline conditions. Furthermore, the alkalinity refers to adjusting the pH to 10-12 with sodium hydroxide. Furthermore, during the reaction, acryloyl chloride is added dropwise to control the reaction rate. Furthermore, the post-treatment refers to stirring the reaction to completion after the acryloyl chloride is added dropwise, adding acid to terminate the reaction, filtering, washing, and freeze-drying. The temperature during the reaction is 0°C to 40°C (further 25-35°C), and the temperature during the acryloyl chloride addition process is controlled at 0 to 5°C. The freeze-drying temperature is controlled at -30°C. The acid is hydrochloric acid, and the pH of the acid-terminating reaction is 2 to 3. Furthermore, the preparation steps of the monomer one are as follows: dissolving the amino acid monomer in deionized water, adding sodium hydroxide to adjust the pH value to 10-12, adding acryloyl chloride dropwise at 0-5°C, stirring for reaction for 2 hours and then reacting at room temperature for 1 hour; then adding hydrochloric acid to adjust the pH value to 2-3, stirring for reaction for 1 hour, filtering out the solid precipitate, washing with deionized water to obtain a crude product (white solid); freeze-drying it at -30°C for 24 hours to obtain a vinylated amino acid monomer, namely monomer one.

[0022] Further, the preparation process of the hydrogel is as follows: first, monomer one, monomer two, crosslinking agent and initiator are mixed, and the mixture is stirred and dissolved in an organic solvent; gas replacement is performed after degassing; the solution is transferred to a transparent mold, and placed under a UV lamp under nitrogen protection for polymerization reaction; the organic gel in the transparent mold is taken out, placed in a dialysate for replacement, and the dialysate is replaced every day to obtain a hydrogel. Further, the hydrogel is a pH-responsive hydrogel with adjustable performance based on amino acid derivatives. Further, the weight percentage of monomer one and monomer two in the mixture is 10-50%, further 30%, 40%, etc. Further, the polymerization reaction time is 4-8 hours, preferably 4, 6, 8 hours. Further, the replacement time is 7-14 days, further 7 days, 10 days, 12 days or 14 days. Further, the number of times the dialysis solution is replaced every day is 1-2 times. Further, the dialysate dosage is about 300-600ml. The amount of the organic solvent is about 50%-100% of the weight of the reaction system.

[0023] In one aspect, the present invention provides a hydrogel material having skin-like mechanical properties, having the following chemical structure:

[0024]

[0025] , wherein n and m are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.

[0026] On the other hand, the present invention provides an application of a hydrogel material with skin-like mechanical properties in biomedical tissue engineering, wearable electronic products and flexible devices.

[0027] In summary, the present invention includes the following beneficial technical effects:

[0028] 1. The present invention uses cheap, readily available, biocompatible amino acids as base materials, has a simple process, is easy to operate, has a high yield, can be produced in large quantities, and has good performance. As a new material, it will have broad application prospects.

[0029] 2. The present invention can achieve regulation of the mechanical properties of the hydrogel by changing the ratio of the two monomers: taking the acid solution dialysis environment of pH = 2 as an example, the gel with different monomer ratios has a fracture strain ranging from 50% to 2000%, a fracture stress ranging from 0.15MPa to 3MPa, a Young's modulus ranging from 0.15M Pa to 30MPa, and a water content ranging from 90wt% to 25wt%, and its modulus and water content are comparable to those of human tissue skin.

[0030] 3. The present invention can achieve regulation of the mechanical properties of skin-like hydrogels by changing the dialysis environment of the gel: taking a 60% monomer-ratio component as an example, the gel in different dialysis solutions has a fracture strain varying from 250% to 2000%, a fracture stress varying from 0.009MPa to 3MPa, and a Young's modulus varying from 0.003MPa to 1.5MPa, and its fracture stress and fracture strain are comparable to those of human tissue skin. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 Hydrogel samples;

[0032] Figure 2 The change curve of NAV ratio and water content in hydrogel samples;

[0033] Figure 3 Mechanical curve of the sample dialyzed in acid solution at pH = 2. Where (Norminal strain: nominal strain; Norminal stress: nominal stress) DETAILED DESCRIPTION

[0034] In order to enable those skilled in the art to better understand the technical solution of the present invention, some non-limiting embodiments are further disclosed below to further illustrate the present invention in detail.

[0035] The reagents used in the present invention can be purchased from the market or prepared by the method described in the present invention.

[0036] In the present invention, min means minute; h means hour; g means gram; mL means milliliter; and mg means milligram.

[0037] 1. Moisture content

[0038] Take the hydrogel sample after dialysis equilibrium, wipe off the surface moisture, and weigh it to obtain the mass of the hydrogel m0. Then put the gel into a freeze dryer and freeze-dry it at -50℃ for 24 hours, and weigh it to obtain the mass of the dry gel m t The moisture content is given by the formula W = (m0-m t ) / m0 is obtained.

[0039] 2. Fracture strain

[0040] The hydrogel was cut into a national standard dumbbell shape and subjected to a tensile performance test using a universal mechanical testing machine in a humid environment. The test speed was 50 mm / min and the sensor was 100 N. The ratio of the displacement value of the hydrogel sample at break to the original length was expressed as a percentage (%).

[0041] 3. Fracture stress

[0042] The hydrogel was cut into a national standard dumbbell shape and subjected to a tensile performance test using a universal mechanical testing machine in a humid environment. The test speed was 50 mm / min and the sensor was 100 N. The maximum tensile stress that the hydrogel sample could withstand was expressed in MPa.

[0043] 4. Young's modulus

[0044] The hydrogel was cut into a national standard dumbbell shape and subjected to a tensile performance test using a universal mechanical testing machine in a humid environment. The test speed was 50 mm / min and the sensor was 100 N. The hydrogel would undergo brittle fracture, and the strain and stress in the initial stage of loading were in direct proportion (i.e., in accordance with Hooke's law), and the proportionality coefficient was called Young's modulus.

[0045] Example 1

[0046] Preparation of monomer 1: Dissolve 2.9 g of amino acid monomer in 10 ml of deionized water, adjust the pH to 10 with sodium hydroxide solution (10%), add 2 ml of acryloyl chloride dropwise at 0°C, stir for 2 hours, and return to room temperature for 1 hour.

[0047] 1% hydrochloric acid solution was added to adjust the pH value to 2, and the mixture was stirred for reaction for 1 hour. The solid precipitate was filtered out by suction and washed with deionized water three times to obtain a crude product (white solid). The crude product was freeze-dried at -30°C for 24 hours to obtain monomer 1.

[0048] Example Amino acid monomers Monomer Yield 1-1 Glutamate Vinylated Glutamic Acid Monomer 60％ 1-2 Lysine Vinylated lysine monomer 65％ 1-3 Valine Vinylated valine monomer 59％

[0049] Example 2

[0050] Preparation of hydrogel: First, mix monomer 1, monomer 2 (total monomer concentration is 1.5M / ml), crosslinker and initiator, and stir to dissolve in an organic solvent. After degassing, transfer the solution to a glove box, replace the gas with nitrogen for half an hour, and then transfer the solution to a transparent glass mold with a pipette. Place it under ultraviolet light under nitrogen protection for 4-8 hours for polymerization reaction. Finally, take out the organic gel in the glass mold from the glove box, place it in the dialysate for replacement for 7-14 days, and change the dialysate 1-2 times a day to obtain the hydrogel material.

[0051]

[0052]

[0053]

[0054] The present invention can achieve regulation of the mechanical properties of the hydrogel by changing the ratio of the two monomers: in the dialysis environment of an acid solution with a pH of 2, it can be seen that the gels with different monomer ratios have a fracture strain ranging from 50% to 2000%, a fracture stress ranging from 0.15MPa to 3MPa, a Young's modulus ranging from 0.15M Pa to 30MPa, and a water content ranging from 90wt% to 25wt%, and their modulus and water content are comparable to those of human tissue skin.

[0055]

[0056]

[0057] The present invention can achieve regulation of the mechanical properties of skin-like hydrogels by changing the dialysis environment of the gel: from the results of a 60% monomer-ratio component, it can be seen that the fracture strain of the gel in different dialysis solutions varies from 250% to 2000%, the fracture stress varies from 0.009MPa to 3MPa, and the Young's modulus varies from 0.003MPa to 1.5MPa, and its fracture stress and fracture strain are comparable to those of human tissue skin.

[0058] Example 3

[0059] Characterization of hydrogel materials with skin-like mechanical properties

[0060] 1. Moisture content

[0061] Take the hydrogel sample after dialysis equilibrium, wipe off the surface moisture, and weigh it to obtain the mass of the hydrogel m0. Then put the gel into a freeze dryer and freeze-dry it at -50℃ for 24 hours, and weigh it to obtain the mass of the dry gel m t The moisture content is given by the formula W = (m0-m t) / m0, the water content of the skin-like hydrogel material depends on the content of vinylated valine monomer in the sample. The experimental results are as follows Figure 2 shown.

[0062] from Figure 2 It can be seen that as the content of vinylated valine monomer increases from 0 to 60% during the preparation of the hydrogel, the water content gradually decreases; but when the content of vinylated valine monomer reaches 60%, the water content reaches the lowest; when the content of vinylated valine monomer is increased again (60-100%), the water content of the gel will gradually increase again.

[0063] 2. Mechanical properties

[0064] The hydrogel was cut into a national standard dumbbell shape and subjected to a tensile performance test using a universal mechanical testing machine in a humid environment. The test speed was 50 mm / min and the sensor was 100 N. The tensile mechanical properties of the skin-like hydrogel material depended on the content of vinylated valine monomers in the sample. The experimental results are shown in Figure 2. Figure 3 shown.

[0065] Through the analysis of the test results of the above examples, it can be seen that the mechanical properties of the hydrogel are closely related to the content of vinylated valine. When the content of vinylated valine monomer is less than 0.4, the gel is in a highly swollen state, and the interaction force between the molecular chains is small, so it exhibits the characteristics of rubber materials and has a weak modulus, fracture stress and fracture strain. When the content of vinylated valine monomer is between 0.4 and 0.8, the hydrogel shrinks, and the hydrogen bonds and hydrophobic associations formed inside the molecular chain are stretched, so that the gel has a larger fracture strain and fracture stress. Continuing to increase the content of vinylated valine monomer (0.9-1.0), the gel will undergo brittle fracture, and the fracture strain and fracture stress are low.

[0066] The present invention develops a hydrogel material with skin-like mechanical properties, which has similar mechanical properties to human skin, such as water content, Young's modulus, tensile strength, etc.; it can be used in various environments (pH value and temperature) and can meet the requirements for gel performance in different occasions.

[0067] The above embodiment is a method for preparing a skin-like hydrogel provided by the present invention, but the implementation method of the present invention is not limited to the above implementation example, and any other changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principle of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

[0068] The method of the present invention has been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the methods and applications described herein within the content, spirit and scope of the present invention to implement and apply the technology of the present invention. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters. It is particularly important to point out that all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention.

Claims

1. A hydrogel material with skin-like mechanical properties, characterized in that: The hydrogel material is prepared by reacting monomer 1 and monomer 2 in the presence of a crosslinking agent and an initiator, and further dialyzing; The first monomer is a vinylated amino acid monomer, and the second monomer is an acrylamide monomer.

2. The hydrogel material according to claim 1, characterized in that: The amino acid is selected from at least one of glutamic acid, lysine and valine.

3. The hydrogel material according to claim 1, characterized in that: The preparation process of the vinylated amino acid monomer is as follows: the amino acid and acryloyl chloride are reacted under alkaline conditions and then further treated to obtain the monomer.

4. The hydrogel material according to claim 1, characterized in that: The second monomer is selected from at least one of acrylamide, methacrylamide and N,N-dimethylacrylamide.

5. The hydrogel material according to claim 1, characterized in that: The cross-linking agent is N,N'-methylenebisacrylamide, and the initiator is one of azobisisobutyronitrile and dioxoglutaric acid.

6. The hydrogel material according to claim 1, characterized in that: The reaction requires the use of an organic solvent, and the organic solvent is selected from at least one of dimethyl sulfoxide, N,N'-dimethylformamide, and anhydrous ethanol.

7. The hydrogel material according to claim 1, characterized in that: The dialysate used in the dialysis is selected from at least one of a 0.9wt% sodium chloride solution, a hydrochloric acid solution with a pH of 1 to 6, and deionized water.

8. The hydrogel material according to claim 1, characterized in that: In terms of weight, the ratio of the monomer 1, the monomer 2, the crosslinking agent and the initiator is (0 to 100 parts): (0 to 100 parts): (0 to 50 parts): (0 to 5 parts).

9. A method for preparing the hydrogel material according to any one of claims 1 to 8, comprising the following steps: (1) Preparation of Monomer 1: reacting an amino acid monomer with a vinylating agent to obtain Monomer 1; (2) Preparation of hydrogel: Monomer 1 and monomer 2 obtained in step (1) are reacted in the presence of a crosslinking agent and an initiator, and further dialyzed to obtain a hydrogel.

10. Use of the hydrogel material according to any one of claims 1 to 8 in the preparation of biomedical tissue engineering, wearable electronic products and flexible devices.

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