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CN-119463029-B - Preparation method of reactive hyperbranched polymer hydrogel based on ROS (reactive oxygen species) and hydrogel

CN119463029BCN 119463029 BCN119463029 BCN 119463029BCN-119463029-B

Abstract

The invention provides a preparation method of a hyperbranched polymer hydrogel based on ROS (reactive oxygen species) and the hydrogel, which belong to the technical field of hydrogels, wherein a Michael addition reaction is carried out on double bonds on PEGDA and amine groups of chain aliphatic diamine with ROS scavenging groups in the structure, the obtained hyperbranched polymer PBAE is used as a cross-linking agent, then methacrylic anhydride and HA are subjected to esterification reaction to obtain HAMA, and finally HAMA, AM and PBAE solution are mixed to form the AHP hydrogel through a free radical polymerization one-step method. The AHP hydrogel disclosed by the invention is simple in preparation method, wide in material source, high in production efficiency, good in mechanical property, oxidation resistance and biocompatibility, and easy to produce and prepare on a large scale.

Inventors

  • LIU JIANFENG
  • WU YUANHAO
  • LIU JINJIAN
  • XIA YI

Assignees

  • 中国医学科学院放射医学研究所

Dates

Publication Date
20260508
Application Date
20241023

Claims (3)

  1. 1. The preparation method of the ROS-based responsive hyperbranched polymer hydrogel is characterized by comprising the following steps of: s1, carrying out Michael addition reaction on double bonds on PEGDA and amino groups of chain aliphatic diamine with ROS scavenging groups in the structure, wherein the obtained hyperbranched polymer PBAE is used as a cross-linking agent, the molecular weight range of the PEGDA is 575-700, the chain aliphatic diamine with ROS scavenging groups in the structure is cystamine dihydrochloride, and the molar ratio of carbon-carbon double bonds in the PEGDA to amino active hydrogen in the cystamine dihydrochloride is (1.2-1.25): 1; S2, carrying out esterification reaction on methacrylic anhydride and HA to obtain HAMA, wherein the molar ratio of the methacrylic anhydride to the HA with the solution concentration of 10-20mg/mL is 1 (0.16-0.2), the reaction is kept for 14-18h, the pH value is 8-9, the whole reaction process is carried out on ice and is protected from light, after the reaction is finished, the reacted solution is precipitated by acetone, then washed by methanol, dialyzed and freeze-dried to obtain the HAMA; S3, mixing HAMA, AM and PBAE solution, and forming AHP hydrogel through a free radical polymerization one-step method, wherein HAMA, PBAE, AM is dissolved in deionized water to form gel precursor solution, a photoinitiator is added, free radicals are generated by carbon-carbon double bonds under the action of ultraviolet light initiation through physical blending, the free radicals are polymerized to form the AHP hydrogel, the solid content of HAMA in the gel precursor solution is 1-2%, the solid content of PBAE is 0.1-1%, the solid content of AM is 10-25%, the photoinitiator adopts 2-hydroxy-4' - (2-hydroxyethoxy) -2-methyl propiophenone, and the content of the photoinitiator accounts for 0.1-0.2% of the gel precursor component.
  2. 2. The method for preparing the ROS-responsive hyperbranched polymer hydrogel according to claim 1, wherein in the step S1, cystamine dihydrochloride and PEGDA are respectively added into a round-bottomed flask, a magnetic stirrer is added, triethylamine is added as a catalyst, the reaction is carried out for 4 to 10 hours at 60 to 100 ℃, and then a yellow oily substance PBAE is obtained by precipitation with glacial ethyl ether.
  3. 3. A hydrogel, characterized in that it is manufactured by the method for preparing a ROS-responsive hyperbranched polymer hydrogel according to claim 1 or 2.

Description

Preparation method of reactive hyperbranched polymer hydrogel based on ROS (reactive oxygen species) and hydrogel Technical Field The invention belongs to the technical field of hydrogels, and particularly relates to a preparation method of a hyperbranched polymer hydrogel based on ROS response and the hydrogel. Background Hydrogels (Hydrogel) are a class of extremely hydrophilic three-dimensional network structure gels that swell rapidly in water and in this swollen state can hold large volumes of water without dissolution. Hyaluronic Acid (HA) is a polysaccharide naturally occurring in human tissue, whose hydroxyl groups in the structural side chains can undergo esterification reaction with methacrylic anhydride to form methacryloylated hyaluronic acid (HAMA) with good biosafety. The carbon-carbon double bond in the HAMA structure can be used as a monomer to form hydrogels with various properties through chemical crosslinking with other components, and further the hydrogels can be applied to various fields (Advanced Functional Materials 2020, 30, 2004709; bioactive Materials 2021, 6, 1689-1698). However, the hydrogel formed by independently crosslinking HAMA through free radical polymerization has weaker mechanical property and oxidation resistance, is not only easy to crack, but also can collapse after being dried and aged due to oxidation after being exposed to air for a long time. Disclosure of Invention The invention aims to solve the problem of providing a preparation method of a reactive hyperbranched polymer hydrogel based on ROS and the hydrogel. In order to solve the technical problems, the technical scheme adopted by the invention is that the preparation method of the ROS-based responsive hyperbranched polymer hydrogel comprises the following steps: s1, carrying out Michael addition reaction on double bonds on polyethylene glycol diacrylate (PEGDA) and amine groups of chain aliphatic diamine with ROS scavenging groups (such as TK bond, disulfide bond and diselenide bond) in the structure, and taking the obtained hyperbranched Polymer (PBAE) as a cross-linking agent; s2, performing esterification reaction on methacrylic anhydride and Hyaluronic Acid (HA) to obtain methacryloylated hyaluronic acid (HAMA); S3, taking HAMA as a main monomer and Acrylamide (AM) as a monomer forming a main framework of gel, mixing the HAMA, the AM and a PBAE solution, and forming the AHP hydrogel through a free radical polymerization one-step method. Further, in step S1, the molecular weight of the PEGDA is in the range of 575 to 700. Further, in step S1, the chain aliphatic diamine having ROS scavenging group in the structure is cystamine dihydrochloride. It can be replaced by other chain aliphatic diamine with disulfide bond, selenocyamine dihydrochloride, other chain aliphatic diamine with diselenide bond, and chain aliphatic diamine with thioketal structure. Further, in step S1, the molar ratio of the carbon-carbon double bond in the PEGDA to the amino active hydrogen in the cystamine dihydrochloride is (1.2-1.25): 1. Further, in step S1, cystamine dihydrochloride and PEGDA are respectively added into a round-bottom flask, a magnetic stirrer is added, triethylamine is added as a catalyst, the reaction is carried out for 4 to 10 hours at the temperature of 60 to 100 ℃, and then the yellow oily substance is obtained by precipitation with glacial ethyl ether. Further, in step S2, methacrylic anhydride is added to HA with the concentration of 10-20mg/mL, the molar ratio of HA to methacrylic anhydride is (0.16-0.2): 1, the reaction is kept for 14-18h, the pH value is 8-9, the whole reaction process is carried out on ice and is protected from light, after the reaction is finished, the reacted solution is precipitated by acetone, then washed by methanol, dialyzed and freeze-dried, and HAMA is obtained. Further, in step S3, HAMA, PBAE, AM is dissolved in deionized water to form a gel precursor solution, a photoinitiator is added, and by physical blending, the carbon-carbon double bond generates free radicals under the action of ultraviolet light initiation, and the free radicals polymerize to form the AHP hydrogel. Further, in step S3, the solid content of HAMA in the gel precursor solution is 1-2%, the solid content of PBAE is 0.1-1%, the solid content of AM is 10-25%, and the photoinitiator is 2-hydroxy-4' - (2-hydroxyethoxy) -2-methyl propiophenone, and the content of the photoinitiator is 0.1-0.2% of the gel precursor component. Further, in step S3, a thermal initiator may also be used to generate radicals from the carbon-carbon double bonds, the thermal initiator being ammonium persulfate. It is another object of the present invention to provide an AHP hydrogel obtained by the above preparation method. By adopting the technical scheme, the invention has the following beneficial effects: The invention solves the preparation problem of AHP hydrogel, HAMA and AM are used as monomers, PBAE is used as a cross-linking agen