CN110845743B - Quadruple hydrogen bond-based polyamino acid-based self-healing hydrogel and preparation method thereof - Google Patents

Abstract

The invention relates to a poly amino acid-based self-healing hydrogel based on quadruple hydrogen bonds, which takes poly amino acid as a main body material, takes biodegradable high-molecular poly L-glutamic acid (PLGA) as an example, carries out modification and modification on the poly L-glutamic acid by using aminated polyethylene glycol (HAPEG) and methacrylate-based polyethylene glycol (MAPEG), introduces 2-ureido- [ 4-hydrogen ] -pyrimidinone (UPy), obtains single-network self-healing hydrogel S- (PLGA-MAPEG-HAPEG) -g-UPy based on quadruple hydrogen bonds, and has excellent self-healing performance and shear thinning performance; after ultraviolet irradiation, the mechanical property of the double-network D- (PLGA-MAPEG-HAPEG) -g-UPy hydrogel is obviously improved. The double-network hydrogel has good biocompatibility and stability. The hydrogel-cell compound is injected under the skin of a mouse and self-heals to form a whole after illumination, and the self-healing hydrogel based on the polyamino acid developed by the invention is proved to have potential application value in the field of tissue engineering.

Description

Quadruple hydrogen bond-based polyamino acid-based self-healing hydrogel and preparation method thereof

Technical Field

The invention belongs to the technical field of biomedical high polymer materials, and particularly relates to a poly amino acid-based self-healing hydrogel based on quadruple hydrogen bonds and a preparation method thereof.

Background

The self-healing hydrogel is a novel intelligent material, has physical and chemical properties similar to natural extracellular matrix, high water retention rate and an adjustable network structure, can automatically heal after being damaged by the outside, recovers the original performance, and is a tissue engineering scaffold material with application prospect.

The nature of self-healing hydrogels is a dynamic bonding chemistry, which can be divided into two broad categories depending on the type of bonding: chemically cross-linked self-healing hydrogels and physically cross-linked self-healing hydrogels. The chemical self-healing hydrogel is formed by dynamic covalent bond crosslinking, and common dynamic covalent bonds include a sulfur-sulfur bond (disulfide bond), a carbon-nitrogen bond (acylhydrazone bond/imine bond), a boron-oxygen bond (phenylboronate), a cyclohexene bond (reversible Diels-Alder reaction) and a reversible free radical reaction. However, the application of the chemically crosslinked self-healing hydrogel is greatly limited because the chemically crosslinked hydrogel can be automatically repaired without external stimulation, and the application range of the hydrogel is greatly expanded because external stimulation is usually required to trigger a reversible reaction, for example, the exchange reaction of phenylboronate needs to be triggered by acid, the reversible Diels-Alder reaction needs to be triggered by heat, and the like. The physical cross-linked hydrogel is formed by cross-linking of non-covalent supermolecule action among polymer molecular chains, does not need to add a cross-linking agent, does not have large volume change in the sol-gel conversion process, and the dynamic nature of the physical cross-linked hydrogel endows the hydrogel with shear thinning and self-healing performance, can effectively solve a large amount of loss caused by too slow gelling time, and can heal into a complete gel after injection by utilizing the self-healing performance, so the physical cross-linked hydrogel has important application in the field of biomedicine. The non-covalent interaction is also called supramolecular interaction, and common supramolecular interaction comprises metal ion complexation, host-guest interaction, electrostatic interaction, hydrophobic interaction, hydrogen bond interaction and the like. Among them, hydrogen bonding is the most extensive physical action in nature, and is the most important driving force for macromolecular self-assembly, ureido pyrimidinone (UPy) is the most widely studied hydrogen bonding group, can be introduced into polymer through the reaction of isocyanate and hydroxyl or amino, and is widely applied in the fields of supramolecular polymer and biomedicine by virtue of its strong binding constant and simple synthesis and modification method.

At present, most of self-healing hydrogels usually adopt non-degradable high molecular materials as matrixes, such as polyacrylate, poly-N-isopropylacrylamide and high molecular weight polyethylene glycol, which are not degraded, difficult to absorb or discharge outside bodies and difficult to meet the requirement of biodegradation of tissue engineering scaffold materials; in addition, the dynamic reversible crosslinking nature of self-healing hydrogels affects hydrogel stability. Therefore, research on preparing self-healing hydrogel with biodegradability and good stability is an important research subject.

Disclosure of Invention

One of the purposes of the invention is to provide a polyamino acid-based self-healing hydrogel based on quadruple hydrogen bonds.

The second purpose of the invention is to provide a preparation method of the self-healing hydrogel.

Amino acids, which are compounds in which hydrogen atoms on carbon atoms of carboxylic acids are substituted with amino groups, are mostly α -amino acids, and polyamino acids, such as poly-L-glutamic acid (PLGA), polyaspartic acid, polylysine, and the like, have excellent biocompatibility and biodegradability that cannot be achieved by general polymers. PLGA is a biodegradable polypeptide artificially synthesized through amido bonds, and the degradation product of PLGA is amino acid required by human body, so that inflammation reaction caused by too low local pH in the human body can be avoided. In addition, the PLGA side chain has free carboxyl group, can be functionalized to endow the material with new functions, and is an ideal tissue engineering material.

The invention takes polyamino acid as a main material, takes biodegradable high molecular PLGA as an example, carries out modification on the polyamino acid and the PLGA, such as amination polyethylene glycol (HAPEG), methacrylate-based polyethylene glycol (MAPEG) and UPy, and prepares single-network self-healing hydrogel S- (PLGA-MAPEG-HAPEG) -g-UPy based on quadruple hydrogen bonds through regulation design on a hydrogel precursor structure; on the basis, secondary crosslinking is initiated by light to obtain the double-network hydrogel D- (PLGA-MAPEG-HAPEG) -g-UPy.

According to the principle, the invention adopts the following technical scheme:

a poly amino acid-based self-healing hydrogel based on quadruple hydrogen bonds is characterized in that the self-healing hydrogel takes poly amino acid as a main body material, takes aminated polyethylene glycol (HAPEG), methacrylate-based polyethylene glycol (MAPEG) and ureido pyrimidone (UPy) as functional components, and realizes single-network self-healing hydrogel S- (PLGA-MAPEG-HAPEG) -g-Upy through the quadruple hydrogen bonds; the molar ratio of the polyamino acid, aminated polyethylene glycol (HAPEG), methacrylate-based polyethylene glycol (MAPEG) and ureidopyrimidone is 1:20-60:70-30:1-10; the self-healing hydrogel has the following solid contents: 2 to 20 percent.

The polyamino acid is: poly-L-glutamic acid (PLGA), polyaspartic acid, polylysine, and the like.

The method for preparing the quadruple hydrogen bond-based polyamino acid-based self-healing hydrogel is characterized by comprising the following specific steps:

a. dissolving polyamino acid, methacrylate-based polyethylene glycol and aminated polyethylene glycol in dimethyl sulfoxide, fully dissolving, sequentially adding dimethylaminopyridine serving as a stabilizer and 1-ethyl- (3-dimethylaminopropyl) carbonyl diimine hydrochloride (EDC & HCl) serving as an activating agent, wherein the feeding ratio is carboxyl in the polyamino acid: dimethylaminopyridine: 1-ethyl- (3-dimethylaminopropyl) carbonyldiimine hydrochloride =1:1-1.5:1-2; reacting for 2-3 days at room temperature, dialyzing, freezing and drying to obtain a white flocculent intermediate product PLGA-MAPEG-HAPEG; then dissolving ureido pyrimidone in anhydrous N, N-Dimethylformamide (DMF), dispersing at 90 ℃, adding an intermediate product PLGA-MAPEG-HAPEG after uniform dispersion, and reacting for 1-2 days to obtain yellow viscous liquid; precipitating in glacial ethyl ether to obtain a light yellow precipitate, and vacuum drying for 1 day after suction filtration to obtain a light yellow hydrogel precursor PLGA-MAPEG-HAPEG-UPy; the dosage of the ureido pyrimidone is 1 to 10 percent of the polyamino acid;

b. dissolving a photoinitiator in phosphate buffer solution PBS to prepare PBS buffer solution with the concentration of 0.1% w/v;

c. adding the PBS buffer solution obtained in the step b into the hydrogel precursor PLGA-MAPEG-HAPEG-UPy obtained in the step a to obtain hydrogel S- (PLGA-MAPEG-HAPEG) -g-UPy; fully dissolving and permeating in a constant temperature box at 37 ℃, and then irradiating for 5 min under an ultraviolet lamp to obtain the double-network hydrogel D- (PLGA-MAPEG-HAPEG) -g-UPy.

c. Preparing a PBS buffer solution with the concentration of I2959 photoinitiator being 0.1% w/v; taking a hydrogel precursor PLGA-MAPEG-HAPEG-UPy, adding PBS buffer solution to prepare hydrogel S- (PLGA-MAPEG-HAPEG) -g-UPy, mixing with cells, and uniformly dispersing (cell density 5 × 10) ⁵ /ml) is injected subcutaneously by mice, then irradiated for 5 min under an ultraviolet lamp, and the gel-cell compound is self-healed into a whole to obtain the double-network hydrogel D-(PLGA-MAPEG-HAPEG) -g-UPy-cell complex.

The initiator is as follows: azodiisobutyronitrile, 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropiophenone.

The application of the polyamino acid-based self-healing hydrogel based on the quadruple hydrogen bonds as a cell carrier in the wrapping and transferring of cells.

The hydrogel S- (PLGA-MAPEG-HAPEG) -g-UPy of the invention is mixed with cells and uniformly dispersed (the cell density is 5 multiplied by 10) ⁵ And/ml), sucking by using a 1ml syringe without a needle, matching with a 26# needle, injecting to the subcutaneous part of the mouse, and irradiating for 5 min under an ultraviolet lamp to self-heal the gel-cell compound into a whole to obtain the double-network hydrogel D- (PLGA-MAPEG-HAPEG) -g-UPy-cell compound.

The hydrogel disclosed by the invention expands the biocompatibility and stability on the basis of the good self-healing performance of the common self-healing hydrogel, improves the mechanical property to a certain extent, can be used as a cell carrier for wrapping and transferring cells, and has potential application value in the field of tissue engineering.

Drawings

The invention will be briefly described below with reference to the accompanying drawings.

FIG. 1 is a graph showing the dynamic characteristics of the S- (PLGA-MAPEG-HAPEG) -g-UPy hydrogel prepared according to the present invention. In the strain-modulus curve, as shown in fig. 1a, the hydrogel is subjected to a cyclic alternating strain test, and is sequentially cyclically alternated for 4 times, and the hydrogel after each failure can still maintain the original modulus, which indicates that the hydrogel has good self-healing performance. As measured by viscosity-shear rate, the hydrogel decreased in viscosity with increasing shear rate, showing shear-thinning behavior, as shown in fig. 1 b.

FIG. 2 is a graph showing the change in the viscoelastic properties of D- (PLGA-MAPEG-HAPEG) -g-UPy hydrogels at different MAPEG grafting ratios; wherein a is the viscoelastic property characterization of the S- (PLGA-MAPEG-HAPEG) -g-UPy single-network hydrogel under different MAPEG grafting rates; and b represents the viscoelastic property of the D- (PLGA-MAPEG-HAPEG) -g-UPy double-network hydrogel under different MAPEG grafting rates, and compared with the single-network hydrogel, the mechanical property of the double-network hydrogel is improved by introducing the second network.

FIG. 3 is a graph showing the stability of D- (PLGA-MAPEG-HAPEG) -g-UPy hydrogel in PBS and cell culture medium (DMEM). Wherein a shows that after the hydrogel is soaked in PBS for 35 days, the MAPEG grafting rate is 35%, the mass of the hydrogel is remained by 20%, and other proportions are close to 0%, which indicates that when the MAPEG grafting rate is 35%, the double-network D- (PLGA-MAPEG-HAPEG) -g-UPy hydrogel has the optimal stability and is degraded slowest. When the hydrogel was soaked in DMEM for 35 days, the hydrogel with 35% MAPEG grafting still had a complete profile.

FIG. 4 shows in vitro injection and photocrosslinking experiments of hydrogel-loaded cells. Wherein a is a single network (before illumination), b is a double network (after illumination), and c is the survival condition of cells; 1ml of S- (PLGA-MAPEG 35% -HAPEG 9%) -g-UPy3% self-healing hydrogel was mixed with cells (cell density 5X 10) ⁵ /ml), mice were injected subcutaneously and secondarily photo-crosslinked to obtain a double-crosslinked hydrogel-cell complex. According to confocal observation, the gel-cell compound is self-healed into a whole after injection and illumination, and the cell survival rate is 87%, so that the hydrogel constructed by the invention has good self-healing performance and biocompatibility, and can be used as a new material for tissue engineering.

Detailed Description

The present invention is further illustrated, but is not limited, by the following examples.

The first embodiment is as follows:

weighing 0.5g of PLGA, dissolving in 50ml of DMSO at room temperature, adding 2.12g of HAPEG and 3.22g of MAPEG after complete dissolution, sequentially adding 0.20g of DMAP and 0.40g of EDC & HCL after full dissolution, reacting for 2 days at room temperature, dialyzing, freezing and drying to obtain 0.39g of white flocculent intermediate product PLGA-MAPEG18% -HAPEG9%. And then dissolving 0.21g of UPyHDI in a small amount of anhydrous DMF, dispersing at 90 ℃, adding the intermediate product PLGA-MAPEG18% -HAPEG9% after uniform dispersion, and reacting for 24 hours to obtain yellow viscous liquid. Precipitating in glacial ethyl ether to obtain a light yellow precipitate, and vacuum drying for 1 day after suction filtration to obtain light yellow hydrogel precursors PLGA-MAPEG18% -HAPEG9% -UPy3%. A PBS solution of photoinitiator I2959 at a concentration of 0.1% w/v was prepared. Taking 0.1g hydrogel precursor PLGA-MAPEG18% -HAPEG9% -UPy3 percent, adding 1.9ml of PBS buffer solution to obtain hydrogel S- (PLGA-MAPEG 18-HAPEG 9%) -g-UPy3 percent, wherein the storage modulus is 800Pa, the compressive strength is 800Pa, and the hydrogel repeatedly undergoes gel-sol transition through multiple alternating strain cycle tests to show good self-healing performance; the viscosity of the hydrogel is reduced from 6 kPa.s to 10 with the increase of the shear rate ^-4 kpa.s, exhibits shear thinning behavior. And (3) carrying out ultraviolet irradiation for 5 min to obtain the double-network hydrogel D- (PLGA-MAPEG 18% -HAPEG 9%) -g-UPy3% with the mass concentration of 5%, wherein the storage modulus is 1500Pa, and the compressive strength is 2000 Pa. The hydrogel was stable in cell culture for 14 days. 5% of hydrogel S- (PLGA-MAPEG 18% -HAPEG 9%) -g-UPy3% in mass concentration is used for wrapping cells, subcutaneous injection and secondary photocrosslinking are carried out on mice, the gel-cell compound is self-healed into a whole, the cell survival rate is 86%, and the hydrogel is verified to have good self-healing performance and biocompatibility.

The second embodiment:

weighing 0.5g of PLGA, dissolving in 50ml of DMSO at room temperature, adding 2.12g of HAPEG and 4.33g of MAPEG after complete dissolution, sequentially adding 0.20g of DMAP and 0.40g of EDC & HCL after full dissolution, reacting for 2 days at room temperature, dialyzing, freezing and drying to obtain 0.37g of white flocculent intermediate product PLGA-MAPEG25% -HAPEG9%. And then dissolving 0.21g of UPyHDI in a small amount of anhydrous DMF, dispersing at 90 ℃, adding the intermediate product PLGA-MAPEG25% -HAPEG9% after uniform dispersion, and reacting for 24 hours to obtain yellow viscous liquid. And precipitating in glacial ethyl ether to obtain a light yellow precipitate, and performing suction filtration and vacuum drying for 1 day to obtain light yellow hydrogel precursors PLGA-MAPEG25% -HAPEG9% -UPy3%. A PBS solution of photoinitiator I2959 at a concentration of 0.1% w/v was prepared. Taking 0.1g of hydrogel precursor PLGA-MAPEG25% -HAPEG9% -UPy3%, adding 3.33ml of PBS buffer solution to prepare hydrogel S- (PLGA-MAPEG 25% -HAPEG 9%) -g-UPy3%, wherein the storage modulus and the compressive strength are 600Pa and 700 Pa, and the hydrogel shows good self-healing performance through multiple alternating strain cycle tests; the viscosity of the hydrogel is reduced from 5 kPa.s to 10 with the increase of the shear rate ^-4 kpa.s, exhibits shear thinning behavior. Ultraviolet irradiation is carried out for 5 min, and the double-network hydrogel D- (PLGA-MAPEG 25% -HAPEG 9%) -g-UPy3% with the mass concentration of 3% is obtained, the storage modulus is 1000Pa, and the compressive strength is 1000Pa1800Pa, the hydrogel was stable in the culture for 16 days. 3% of hydrogel S- (PLGA-MAPEG 25% -HAPEG 9%) -g-UPy3% of mass concentration is used for wrapping cells, subcutaneous injection and secondary photocrosslinking are carried out on mice, the gel-cell compound is self-healed into a whole, the cell survival rate is 83%, and the hydrogel is verified to have good self-healing performance and biocompatibility.

Example three:

weighing 0.5g of PLGA, dissolving in 50ml of DMSO at room temperature, adding 2.12g of HAPEG and 5.43g of MAPEG after complete dissolution, sequentially adding 0.20g of DMAP and 0.40g of EDC & HCL after complete dissolution, reacting for 2 days at room temperature, dialyzing, freezing and drying to obtain a white flocculent intermediate product 0.41g of PLGA-MAPEG35% -HAPEG9%. And then dissolving 0.21g of UPyHDI in a small amount of anhydrous DMF, dispersing at 90 ℃, adding the intermediate product PLGA-MAPEG35% -HAPEG9% after uniform dispersion, and reacting for 24 hours to obtain yellow viscous liquid. Precipitating in glacial ethyl ether to obtain a light yellow precipitate, and vacuum drying for 1 day after suction filtration to obtain a light yellow hydrogel precursor PLGA-MAPEG35% -HAPEG9% -UPy3%. A PBS solution of photoinitiator I2959 at a concentration of 0.1% w/v was prepared. Taking 0.1g of hydrogel precursor PLGA-MAPEG35% -HAPEG9% -UPy3%, adding 0.67ml of PBS buffer solution to obtain hydrogel S- (PLGA-MAPEG 35% -HAPEG 9%) -g-UPy3%, wherein the storage modulus is 1000Pa, the compressive strength is 900Pa, and the hydrogel shows good self-healing performance through multiple alternating strain cycle tests; the viscosity of the hydrogel is reduced from 12 kPa.s to 10 with the increase of the shear rate ^-4 kpa.s, exhibits shear thinning behavior. And (3) carrying out ultraviolet irradiation for 5 min to obtain the double-network hydrogel D- (PLGA-MAPEG 35% -HAPEG 9%) -g-UPy3% with the mass concentration of 15%, and carrying out mechanical property characterization on the double-network hydrogel, wherein the storage modulus is 1800Pa, and the compressive strength is 2500 Pa. The hydrogel was stable in the culture for 35 days. Cells are wrapped by 3% of hydrogel S- (PLGA-MAPEG 35% -HAPEG 9%) -g-UPy by mass concentration, subcutaneous injection and secondary photocrosslinking are carried out on mice, the gel-cell compound is self-healed into a whole, the cell survival rate is 87%, and the hydrogel is verified to have good self-healing performance and biocompatibility.

Example four:

0.5g PLGA was weighed, dissolved in 50ml DMSO at room temperature until completely dissolvedThen, 2.12g HAPEG and 6.54g MAPEG are added, after full dissolution, 0.20g DMAP and 0.40g EDC & HCL are added in turn, the reaction is carried out for 2 days at room temperature, and the white flocculent intermediate product 0.45g PLGA-MAPEG45% -HAPEG9% is obtained after dialysis freeze drying. And then dissolving 0.21g of UPyHDI in a small amount of anhydrous DMF, dispersing at 90 ℃, adding the intermediate product PLGA-MAPEG45% -HAPEG9% after uniform dispersion, and reacting for 24 hours to obtain yellow viscous liquid. And precipitating in glacial ethyl ether to obtain a light yellow precipitate, and performing suction filtration and vacuum drying for 1 day to obtain light yellow hydrogel precursors PLGA-MAPEG45% -HAPEG9% -UPy3%. PBS solution with the concentration of the photoinitiator I2959 being 0.1% w/v was prepared. 0.1g of hydrogel precursor PLGA-MAPEG45% -HAPEG9% -UPy3% is taken, and 0.9ml of PBS buffer solution is added to prepare the hydrogel S- (PLGA-MAPEG 45% -HAPEG 9%) -g-UPy3%. The storage modulus is 600Pa, the compression modulus is also 600Pa, and the hydrogel shows good self-healing performance through multiple alternating strain cycle tests; the viscosity of the hydrogel is reduced from 4 kPa.s to 10 with the increase of the shear rate ^-4 kpa.s, exhibits shear thinning behavior. And (3) carrying out ultraviolet irradiation for 5 min to obtain the double-network hydrogel D- (PLGA-MAPEG 45% -HAPEG 9%) with the mass concentration of 10% -g-UPy3%. And characterizing the mechanical property of the hydrogel, wherein after photo-crosslinking, the storage modulus is 1900Pa, the compressive strength is 5500 Pa, and the hydrogel is stable in a culture solution for 20 days. Cells are wrapped by 10% of hydrogel S- (PLGA-MAPEG 45% -HAPEG 9%) -g-UPy3% by mass concentration, subcutaneous injection and secondary photocrosslinking are carried out on mice, the gel-cell compound is self-healed into a whole, the cell survival rate is 89%, and the hydrogel is verified to have good self-healing performance and biocompatibility.

Example five:

weighing 0.5g of PLGA, dissolving in 50ml of DMSO at room temperature, adding 2.12g of HAPEG and 7.65g of MAPEG after complete dissolution, sequentially adding 0.20g of DMAP and 0.40g of EDC & HCL after full dissolution, reacting for 2 days at room temperature, dialyzing, freezing and drying to obtain 0.40g of white flocculent intermediate product PLGA-MAPEG53% -HAPEG5%. And then dissolving 0.21g of UPyHDI in a small amount of anhydrous DMF, dispersing at 90 ℃, adding the intermediate product PLGA-MAPEG53% -HAPEG5% after uniform dispersion, and reacting for 24 hours to obtain yellow viscous liquid. Precipitating in glacial ethyl ether to obtain light yellow precipitate, vacuum filtering, and vacuum drying for 1 day to obtain light yellowPLGA-MAPEG53% -HAPEG5% -UPy2% as the color hydrogel precursor. A PBS solution of photoinitiator I2959 at a concentration of 0.1% w/v was prepared. Taking 0.1g of hydrogel precursor PLGA-MAPEG53% -HAPEG5% -UPy2%, and adding 0.5ml of PBS buffer solution to obtain hydrogel S- (PLGA-MAPEG 53% -HAPEG 5%) -g-UPy2%, wherein the storage modulus is 1100Pa, the compressive strength is 1000Pa, and the hydrogel shows good self-healing performance through multiple alternating strain cycle tests; the viscosity of the hydrogel is reduced from 2 kPa.s to 10 along with the increase of the shear rate ^-4 kpa.s, exhibits shear thinning behavior. Irradiating for 5 min under an ultraviolet lamp to obtain the double-network hydrogel D- (PLGA-MAPEG 53% -HAPEG 5%) -g-UPy2% with the mass concentration of 20%, and characterizing the mechanical property of the double-network hydrogel, wherein after photo-crosslinking, the storage modulus is 1900Pa, the compression strength is 2600 Pa, and the hydrogel is stable in a culture solution for 15 days. The hydrogel S- (PLGA-MAPEG 53% -HAPEG 5%) -g-UPy2% with mass concentration of 20% is used for wrapping cells, subcutaneous injection and secondary photocrosslinking are carried out on mice, the gel-cell compound is self-healed into a whole, the cell survival rate is 84%, and the hydrogel is verified to have good self-healing performance and biocompatibility.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and should not be taken as limiting the scope of the present invention, which is intended to cover any modifications, equivalents, improvements, etc. within the spirit and scope of the present invention.

Claims (3)

1. A poly amino acid-based self-healing hydrogel based on quadruple hydrogen bonds is characterized in that the self-healing hydrogel takes poly amino acid as a main body material, the poly amino acid is poly L-glutamic acid (PLGA), and takes aminated polyethylene glycol (HAPEG), methacrylate-based polyethylene glycol (MAPEG) and ureido pyrimidone (UPy) as functional components, and single-network self-healing hydrogel S- (PLGA-MAPEG-HAPEG) -g-Upy is realized through the quadruple hydrogen bonds; the molar ratio of PLGA, aminated polyethylene glycol (HAPEG), methacrylate-based polyethylene glycol (MAPEG) and ureido pyrimidone is 1:20-60:70-30:1-10; the self-healing hydrogel has the following solid contents: 2 to 20 percent; on the basis, secondary crosslinking is initiated by light to obtain the double-network hydrogel D- (PLGA-MAPEG-HAPEG) -g-UPy.

2. A method for preparing the quadruple hydrogen bond-based polyamino acid-based self-healing hydrogel according to claim 1, which comprises the following specific steps:

a. dissolving poly-L-glutamic acid (PLGA), methacrylate polyethylene glycol and aminated polyethylene glycol in dimethyl sulfoxide, fully dissolving, sequentially adding dimethylaminopyridine as a stabilizer and 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC & HCl) as an activator, wherein the material ratio is carboxyl in the polyamino acid: dimethylaminopyridine: 1-ethyl- (3-dimethylaminopropyl) carbonyldiimine hydrochloride =1:1-1.5:1-2; reacting for 2-3 days at room temperature, dialyzing, freezing and drying to obtain a white flocculent intermediate product PLGA-MAPEG-HAPEG; then dissolving ureido pyrimidone in anhydrous N, N-Dimethylformamide (DMF), dispersing at 90 ℃, adding an intermediate product PLGA-MAPEG-HAPEG after uniform dispersion, and reacting for 1-2 days to obtain yellow viscous liquid; precipitating in glacial ethyl ether to obtain a light yellow precipitate, and vacuum drying for 1 day after suction filtration to obtain a light yellow hydrogel precursor PLGA-MAPEG-HAPEG-UPy; the dosage of the ureido pyrimidone is 1-10% of the polyamino acid;

b. dissolving a photoinitiator in phosphate buffer solution PBS to prepare PBS buffer solution with the concentration of 0.1% w/v;

c. adding the PBS buffer solution obtained in the step b into the hydrogel precursor PLGA-MAPEG-HAPEG-UPy obtained in the step a to obtain hydrogel S- (PLGA-MAPEG-HAPEG) -g-UPy; fully dissolving and permeating in a constant temperature box at 37 ℃, and then irradiating for 5 min under an ultraviolet lamp to obtain the double-network hydrogel D- (PLGA-MAPEG-HAPEG) -g-UPy.

3. The method for preparing the quadruple hydrogen bond-based polyamino acid-based self-healing hydrogel according to claim 2, wherein the initiator is: azobisisobutyronitrile, 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropiophenone.

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