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CN-118994643-B - Fluorescent self-healing injectable hydrogel and preparation method thereof

CN118994643BCN 118994643 BCN118994643 BCN 118994643BCN-118994643-B

Abstract

The invention discloses a preparation method and application of a fluorescence self-healing injectable hydrogel. The biocompatible fluorescent small molecules are anchored on the polysaccharide macromolecular chains through EDC/NHS coupling reaction, and then in-situ crosslinking is carried out through dynamic imine bonds under physiological conditions, so that the fluorescent self-healing injectable hydrogel is prepared. The fluorescent self-healing injectable hydrogel has self-healing property, injectability, shape adaptability, biodegradability, cell compatibility and tissue compatibility and outstanding fluorescent effect, can be used for nondestructive, in-situ and real-time detection, not only provides a new strategy for synthesizing polysaccharide-based fluorescent self-healing injectable hydrogel under mild conditions, but also provides a new idea for establishing a system model of a minimally invasive interventional treatment technology in-situ real-time monitoring biomedical platform.

Inventors

  • CHEN YONGMEI
  • WEI WEI
  • LI PENGCHENG
  • Tao Ruikai
  • LI JIANHUI
  • Nitake Hideyuki
  • ITO YOSHIKO

Assignees

  • 陕西科技大学

Dates

Publication Date
20260508
Application Date
20240809

Claims (9)

  1. 1. A method for preparing a fluorescence self-healing injectable hydrogel, which is characterized by comprising the following steps: S1, dissolving bioluminescence molecules in 2-morphine ethanesulfonic acid solution, then adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide, stirring and dissolving to obtain mixed solution, adding the 2-morphine ethanesulfonic acid solution of N-carboxyethyl chitosan into the mixed solution, and stirring and reacting to obtain bioluminescence molecules/N-carboxyethyl chitosan polymer; S2, mixing a PBS solution containing the bioluminescent molecules/N-carboxyethyl chitosan polymer with a PBS solution containing oxidized sodium alginate to prepare the fluorescent self-healing injectable hydrogel; The preparation method of the bioluminescent molecule comprises the steps of uniformly mixing citric acid powder and cysteine, heating for reaction, washing a product, and recrystallizing to obtain the bioluminescent molecule.
  2. 2. The preparation method of the fluorescence self-healing injectable hydrogel according to claim 1, wherein the N-carboxyethyl chitosan is prepared by mixing chitosan and acrylic acid and then reacting, wherein the concentration of the chitosan in a mixed solution of the chitosan and the acrylic acid is 5-10 mM, and the concentration of the acrylic acid is 20-25 mM.
  3. 3. The method for preparing the fluorescent self-healing injectable hydrogel according to claim 2, wherein the deacetylation degree of chitosan is 86% -88%, and the molecular weight of chitosan is 2 x 10 5 ~3*10 5 g/mol.
  4. 4. The method for preparing the fluorescent self-healing injectable hydrogel according to claim 1, wherein the amino substitution degree of the N-carboxyethyl chitosan is 48% -50%.
  5. 5. The preparation method of the fluorescence self-healing injectable hydrogel according to claim 1, wherein the oxidized sodium alginate is prepared by mixing sodium periodate with sodium alginate and oxidizing the mixture, wherein the concentration of the sodium alginate is 5.4 x 10 -3 ~1.2*10 -2 g/mL and the concentration of the sodium periodate is 1.0 x 10 -2 ~1.2*10 -2 g/mL in the mixed solution of the sodium periodate and the sodium alginate.
  6. 6. The method for preparing a fluorescence self-healing injectable hydrogel according to claim 5, wherein the viscosity of the sodium alginate is 350-400 mpa.s.
  7. 7. The method for preparing the fluorescent self-healing injectable hydrogel according to claim 1, wherein the oxidation degree of the oxidized sodium alginate is 48% -55%.
  8. 8. The method for preparing the fluorescent self-healing injectable hydrogel according to claim 1, wherein in the step S1, after adding the 2-morphine ethanesulfonic acid solution of N-carboxyethyl chitosan into the mixed solution, the mass fraction of the N-carboxyethyl chitosan is 1.5 wt% -2.5 wt%, and in the step S2, the mass fraction of oxidized sodium alginate in the PBS solution of the oxidized sodium alginate is 0.5 wt% -1.5 wt%.
  9. 9. A fluorescent self-healing injectable hydrogel prepared by the method of any one of claims 1 to 8.

Description

Fluorescent self-healing injectable hydrogel and preparation method thereof Technical Field The invention belongs to the technical field of flexible biological materials, and relates to a fluorescence self-healing injectable hydrogel and a preparation method thereof. Background The biocompatible self-healing injectable hydrogel has wide application prospect in the biomedical field and is characterized in that the biocompatible self-healing injectable hydrogel can spontaneously recover the structure and the function after being damaged, thereby remarkably improving the performance as an intelligent flexible material. As an intelligent multifunctional biological material, the self-healing injectable hydrogel can be combined with a minimally invasive interventional therapy technology, so that the self-healing injectable hydrogel can be widely applied to the fields of tissue engineering, drug/cell delivery, biosensors and the like. The self-healing injectable hydrogel has the advantages of in-situ gel formation in the injector, gel injection at the target site, autonomous healing of gel particles, and remodelling and forming at the target site, and changes the fluid operation method of the traditional injectable hydrogel, namely, filling a precursor solution into the injector, injecting a solution at the target site, and gel formation at the target site. Meanwhile, the self-healing injectable hydrogel overcomes various defects of the traditional injectable hydrogel, such as loss of medicines, cells and the like caused by diffusion before gelation, difficulty in controlling gelation time and potential toxicity of chemical substances (such as monomers, initiators and the like). Despite the advances made, however, conventional self-healing injectable hydrogels still suffer from a lack of in-situ real-time monitoring functionality, limited by the difficulty of non-invasive monitoring and tracking after implantation in the body. To date, in vivo noninvasive and tracking functions remain a major issue with self-healing injectable hydrogels. The fluorescence monitoring technology has the advantages of quick response, high sensitivity, high contrast, no wound and the like, and is convenient for the real-time monitoring of the fluorescence hydrogel. Fluorescent hydrogels with good biocompatibility are of great interest in the biomedical field, and have particular applications in biomedical platforms, such as bioimaging and biomonitoring tracking. Coupling or doping various fluorescent substances (such as lanthanide ions, organic dyes, quantum dots, fluorescent proteins, and metal ligands, etc.) into the hydrogel matrix can impart fluorescent properties to the hydrogel. However, most fluorescent substances have the defects of biotoxicity, poor water solubility, complex preparation process and the like, and the practical application in the biomedical field is greatly limited. The multifunctional fluorescence self-healing injectable hydrogel has great application potential in biomedical platforms for real-time biological imaging monitoring. Although the existing strategies focus on developing various self-healing injectable hydrogels suitable for biomedical fields, there is little research interest in the application of self-healing injectable hydrogels having fluorescence properties, biocompatibility and biodegradability at the same time in biomedical fields. Fluorescent self-healing injectable hydrogels are expected to be monitored in real-time imaging in vivo by non-invasive methods without interfering with the efficacy and safety of the treatment. However, how to develop a simple and effective strategy for fixing biocompatible fluorescent substances in a three-dimensional network structure of a dynamic hydrogel, and to synthesize a fluorescent self-healing injectable hydrogel for a biomedical platform are major problems to be solved by current researchers. Therefore, it is necessary to combine fluorescent substances with excellent biosafety and simple operation with the hydrogel to prepare the fluorescent self-healing injectable hydrogel with excellent fluorescence characteristics and functions (self-healing, injectability, biocompatibility, biodegradability and the like) of the polysaccharide-based dynamic hydrogel, so as to realize non-invasive monitoring and tracking and minimally invasive interventional therapy. Disclosure of Invention Aiming at the problems in the prior art, the invention provides the fluorescent self-healing injectable hydrogel and the preparation method thereof, thereby solving the technical problems of poor biosafety of fluorescent substances, poor fluorescent effect and lack of in-situ real-time monitoring function of the self-healing injectable hydrogel in the prior art. The invention is realized by the following technical scheme: A method for preparing a fluorescence self-healing injectable hydrogel, which comprises the following steps: S1, dissolving bioluminescence molecules in 2-morphine