CN116688222A - Intelligent response hydrogel dressing based on hypoxia exosome and preparation method and application thereof - Google Patents
Intelligent response hydrogel dressing based on hypoxia exosome and preparation method and application thereof Download PDFInfo
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- CN116688222A CN116688222A CN202310761500.6A CN202310761500A CN116688222A CN 116688222 A CN116688222 A CN 116688222A CN 202310761500 A CN202310761500 A CN 202310761500A CN 116688222 A CN116688222 A CN 116688222A
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- sodium alginate
- hypoxia
- exosome
- carboxymethyl chitosan
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- 206010021143 Hypoxia Diseases 0.000 title claims abstract description 63
- 210000001808 exosome Anatomy 0.000 title claims abstract description 63
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- 239000000017 hydrogel Substances 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title claims abstract description 32
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- 239000000661 sodium alginate Substances 0.000 claims abstract description 146
- 229940005550 sodium alginate Drugs 0.000 claims abstract description 146
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims abstract description 94
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- 239000001263 FEMA 3042 Substances 0.000 claims abstract description 63
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 claims abstract description 63
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- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 14
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- ZSKXYSCQDWAUCM-UHFFFAOYSA-N 1-(chloromethyl)-2-dodecylbenzene Chemical compound CCCCCCCCCCCCC1=CC=CC=C1CCl ZSKXYSCQDWAUCM-UHFFFAOYSA-N 0.000 claims description 2
- ILOJFJBXXANEQW-UHFFFAOYSA-N aminooxy(phenyl)borinic acid Chemical compound NOB(O)C1=CC=CC=C1 ILOJFJBXXANEQW-UHFFFAOYSA-N 0.000 claims description 2
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- 238000000605 extraction Methods 0.000 claims description 2
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- JMZFEHDNIAQMNB-UHFFFAOYSA-N m-aminophenylboronic acid Chemical compound NC1=CC=CC(B(O)O)=C1 JMZFEHDNIAQMNB-UHFFFAOYSA-N 0.000 claims description 2
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- UTHULKKJYXJZLV-UHFFFAOYSA-N (3-aminophenoxy)boronic acid Chemical compound NC1=CC=CC(OB(O)O)=C1 UTHULKKJYXJZLV-UHFFFAOYSA-N 0.000 description 14
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- AEMOLEFTQBMNLQ-AZLKCVHYSA-N (2r,3s,4s,5s,6r)-3,4,5,6-tetrahydroxyoxane-2-carboxylic acid Chemical compound O[C@@H]1O[C@@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-AZLKCVHYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/008—Hydrogels or hydrocolloids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0023—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0057—Ingredients of undetermined constitution or reaction products thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/0066—Medicaments; Biocides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/23—Carbohydrates
- A61L2300/232—Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
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- A—HUMAN NECESSITIES
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
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- A—HUMAN NECESSITIES
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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- A61L2300/602—Type of release, e.g. controlled, sustained, slow
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
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- Chemical Kinetics & Catalysis (AREA)
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Abstract
The application provides a preparation method of an intelligent response hydrogel dressing based on a hypoxia exosome, which comprises the steps of carrying out hydroformylation modification by utilizing sodium alginate with high G content, and then carrying out phenylboric acid grafting to prepare phenylboric acid grafted hydroformylation sodium alginate (PBA-OSA); carrying out tannic acid modification by using carboxymethyl chitosan to prepare tannic acid modified carboxymethyl chitosan (TA-CMCS); the intelligent response hydrogel dressing based on the hypoxia exosomes is prepared by utilizing Schiff base reaction between aldehyde groups of PBA-OSA and amino groups of TA-CMCS and boric acid ester bond between phenyl boric acid groups of PBA-OSA and hydroxyl groups of TA-CMCS to form a double-network structure polysaccharide-based hydrogel with adjustable mechanical property and crosslinking density, and loading the hypoxia exosomes from stem cells into the polysaccharide-based hydrogel, has better mechanical strength and flexibility, and releases the hypoxia exosomes as required according to high sugar and oxidative stress level of diabetes wound microenvironment, so as to achieve the purposes of continuously promoting wound blood vessel regeneration and promoting wound healing.
Description
Technical Field
The application belongs to the technical field of biological medicine, and particularly relates to an intelligent response hydrogel dressing based on a hypoxia exosome, and a preparation method and application thereof.
Background
Diabetic foot ulcers (Diabetic foot ulcers, DFUs) are common and serious complications of diabetes, with about 70% of amputation worldwide being caused by DFUs, and there is still a lack of sustained effective treatment. The main factors of difficult healing of diabetic foot ulcers include cell dysfunction, changes in the ability to regenerate blood vessels, and the like. The diabetic patients are easy to develop vascular lesions, the vascular regeneration is damaged, so that the cell proliferation, the extracellular matrix synthesis and the remodeling are blocked, and finally, the chronic wound surface which is difficult to heal is formed. The disorder of macrophages is another key reason that chronic wounds of diabetes are difficult to heal, and is represented by a state that proinflammatory cytokines are highly expressed and anti-inflammatory factors and growth factors are low in level, so that the wounds cannot enter a proliferation stage in an inflammatory stage for a long time. In addition, complicated physiological microenvironments exist on wounds difficult to heal due to diabetes, so that the conventional wound dressing cannot achieve an ideal repairing effect. Therefore, it is necessary to develop a hydrogel dressing capable of integrating the functions of regulating inflammatory reaction and promoting angiogenesis and intelligently responding to the microenvironment of the diabetic wound surface.
Disclosure of Invention
In view of the problem that the conventional wound dressing can not achieve the healing of chronic wounds of diabetes at present, the application provides an intelligent response hydrogel dressing based on a hypoxia exosome, and a preparation method and application thereof.
The application aims to provide an intelligent response hydrogel dressing based on a hypoxia Exosome, which comprises, by mass, 2-6wt% of phenylboronic acid grafted aldehyde sodium alginate (PBA-OSA), 2-6wt% of tannic acid modified carboxymethyl chitosan (TA-CMCS), 0.5-1.0wt% of the hypoxia Exosome, and the balance of water.
In the intelligent response hydrogel dressing based on the hypoxia exosome, the boric acid ester bond formed between the phenylboronic acid grafted aldehyde sodium alginate (PBA-OSA) and the tannic acid modified sodium carboxymethylcellulose (TA-CMCS) can respond to high sugar and hydrogen peroxide (H) in the microenvironment of the diabetic wound surface 2 O 2 ) And scavenging Reactive Oxygen Species (ROS), and can intelligently release the hypoxia exosome according to the microenvironment of the wound surfaceHExo), and the release amount can be matched with the inflammation degree of the wound surface, so as to realize release according to the need; the hypoxia exosome has strong capability of promoting blood vessel regeneration, and can improve the damage of chronic wound surface blood vessel regeneration of diabetes, thereby better promoting wound surface healing; in addition, the modified sodium alginate with high G content has the excellent performance of regulating and controlling macrophage phenotype polarization, can promote macrophages to regulate and control inflammatory reaction to anti-inflammatory phenotype polarization, and can eliminate active oxygen and reduce oxidative stress by intelligently responding to boric acid ester bonds in gel dressing, thereby further regulating and controlling inflammatory reaction, improving wound inflammation microenvironment and promoting wound healing.
The second object of the application is to provide a preparation method of the intelligent response hydrogel dressing based on the hypoxia exosome, which comprises the following steps:
carrying out hydroformylation modification on sodium alginate with high G content (alpha-L-guluronic acid (G)) and further carrying out phenylboric acid grafting to obtain phenylboric acid grafted hydroformylation sodium alginate (OSA); then using carboxymethyl chitosan to carry out Tannic Acid (TA) modification to prepare Tannic acid modified carboxymethyl chitosan; finally, forming a polysaccharide-based hydrogel with a double-network structure and adjustable mechanical properties and crosslinking density by utilizing Schiff base reaction between aldehyde groups of PBA-OSA and amino groups of TA-CMCS and boric acid ester bonds of phenyl boric acid groups of PBA-OSA and hydroxyl groups of TA-CMCS, and loading a hypoxia exosome from a stem cell source into the polysaccharide-based hydrogel to prepare the intelligent response hydrogel dressing based on the hypoxia exosome.
Further, the method comprises the following steps:
step 1) taking sodium alginate with high G content as a raw material, and carrying out oxidation reaction on the sodium periodate under a light-shielding condition to prepare aldehyde sodium alginate with different substitution degrees; then carrying out grafting modification on the aldehyde sodium alginate by using aminophenylboric acid to prepare phenyl boric acid grafted aldehyde sodium alginate;
step 2) using carboxymethyl chitosan as a raw material, and preparing tannic acid modified carboxymethyl chitosan with tannic acid under the catalysis of coupling agents of 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS);
step 3) culturing the well-cultured stem cells under the anoxic condition, and obtaining the hypoxia exosomes through centrifugation, filtration and isolation extraction;
step 4) forming a polysaccharide-based hydrogel with a double-network structure and adjustable mechanical property and crosslinking density by utilizing Schiff base reaction between aldehyde groups of PBA-OSA and amino groups of TA-CMCS and boric acid ester bonds of phenylboronic acid groups of PBA-OSA and hydroxyl groups of TA-CMCS, and loading the hypoxia exosomes into the polysaccharide-based hydrogel to prepare the intelligent response hydrogel dressing based on the hypoxia exosomes.
Further, in the step 1), dispersing sodium alginate with high G content in absolute ethyl alcohol to prepare sodium alginate suspension, then adding sodium periodate solution with the concentration of 6-20wt% to react for 18-32 h under the condition of light shielding, adding glycol with the same mole as sodium periodate to terminate the reaction to obtain a reaction mixture, purifying the reaction mixture, and freeze-drying to prepare the hydroformylation sodium alginate; dissolving the aldehyde sodium alginate in water to prepare an aldehyde sodium alginate solution with the concentration of 3-5 wt%, adding aminophenylboric acid for reaction, filtering after the reaction is finished, and freeze-drying to prepare phenyl boric acid grafted aldehyde sodium alginate;
wherein the molecular weight of the sodium alginate is 4kDa-50kDa, and the M/G ratio is 1:1-1:3;
the mass volume ratio of the sodium alginate to the absolute ethyl alcohol is 1:4g/mL-1:6g/mL;
the mass ratio of the sodium periodate in the sodium periodate aqueous solution to the sodium alginate in the sodium alginate dispersion liquid is 1:1-6:1;
the mass ratio of the aminophenylboric acid to the aldehyde sodium alginate is 1:5-1:10;
the amino phenylboronic acid is any one or more of 2-amino phenylboronic acid, 3-amino phenylboronic acid and 4-amino phenylboronic acid.
Further, in the step 2), carboxymethyl chitosan and tannic acid are dissolved in water, the concentration of the prepared carboxymethyl chitosan solution is 2-4wt%, and then a coupling agent 1-ethyl- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added for catalytic reaction, so that tannic acid modified carboxymethyl chitosan is prepared;
wherein the mass ratio of the carboxymethyl chitosan to the tannic acid is 1:1-1:5;
the molar ratio of EDC to NHS in the coupling agent is 3-5:0.5-2.
Further, in the step 3), the well-cultured stem cells are cultured for 24 hours under the anoxic condition, the cell debris and macromolecular proteins are removed by centrifugation for 30 minutes based on 15000rpm, then the culture is filtered by a 0.22 mu m filter, finally, after centrifugation for 1 hour at 57000rpm by a super centrifuge, the supernatant is taken out, and transparent precipitate at the bottom of the centrifuge tube is collected, so as to obtain the hypoxia exosome;
wherein the stem cells are any one or more of fat stem cells, mesenchymal stem cells and human urine-derived stem cells;
the anoxic condition is that 85-94% of N is used 2 、1%-10% O 2 And 5% CO 2 Is a mixed gas of (a) and (b).
Further, in the step 4), dissolving phenyl boric acid grafted aldehyde sodium alginate in water to prepare phenyl boric acid grafted aldehyde sodium alginate solution with the concentration of 2-6wt%, adding 0.5wt% -1.0wt% of hypoxia exosome, stirring and mixing uniformly, and finally adding tannic acid modified carboxymethyl chitosan for stirring, and reacting to prepare the intelligent response hydrogel dressing based on the hypoxia exosome; wherein the mass ratio of the phenylboronic acid grafted aldehyde sodium alginate to the tannic acid modified carboxymethyl chitosan is 1:1-1:2.
The application further aims to provide an application of the intelligent response hydrogel dressing based on the hypoxia exosome in preparing a medical dressing for promoting the healing of chronic wounds of diabetes.
Compared with the prior art, the application has the beneficial effects that:
1. the intelligent response gel dressing prepared by the application has better mechanical strength and flexibility, and better dressing property with wounds, and solves the defect that most of the current medical dressings are not suitable for various complex wounds.
2. The intelligent response gel dressing prepared by the application has the characteristics of intelligence, can release the hypoxia exosome which is favorable for promoting the regeneration of blood vessels of the wound surface according to the microenvironment of the wound surface as required, and the release amount can be matched with the inflammation degree of the wound surface.
3. The intelligent response gel dressing prepared by the application plays roles in regulating and controlling inflammation and promoting angiogenesis, can promote the repair of chronic wounds of diabetes, and solves the defect that the traditional medical dressing cannot effectively repair the chronic wounds of diabetes.
Detailed Description
The application will be further illustrated with reference to specific examples. It is to be understood that these examples are illustrative of the present application and are not intended to limit the scope of the present application. Furthermore, it should be understood that various changes and modifications can be made by one skilled in the art after reading the teachings of the present application, and such equivalents are intended to fall within the scope of the application as defined in the appended claims.
The raw materials and reagents used in the examples were conventional products which were obtained commercially, unless otherwise specified; the experimental methods for which specific conditions are not specified in the examples are generally in accordance with the conditions conventional in the art or in accordance with the manufacturer's recommendations.
The sodium alginate powder used in the examples was obtained commercially with a purity of 85% sodium alginate and a content of alpha-L-guluronic acid of 80% -50%. In the following examples, "vigorous stirring" means stirring at a speed of 1200rpm to 1800rpm.
Example 1
The preparation method of the intelligent response hydrogel dressing based on the hypoxia exosome of the embodiment comprises the following steps:
(1) Preparation of phenylboronic acid grafted aldehyde sodium alginate: dispersing 10g of sodium alginate with molecular weight of 50kDa in 50ml of absolute ethyl alcohol to obtain sodium alginate dispersion liquid, adding 20% (w/v) sodium periodate aqueous solution containing 60g of sodium periodate into the sodium alginate dispersion liquid, carrying out light-shielding reaction for 4 hours to obtain a reaction product, and purifying and drying the reaction product to obtain the aldehyde sodium alginate. Adding 2g of oxidized sodium alginate into 100ml of deionized water to prepare 2% aldehyde sodium alginate aqueous solution, adding 3-aminophenylboric acid into the aldehyde sodium alginate solution according to the mass ratio of the 3-aminophenylboric acid to the oxidized sodium alginate of 1:5, reacting for 2h, and purifying the reaction product after the reaction is finished to obtain the phenylboric acid grafted aldehyde sodium alginate.
(2) Preparation of tannic acid modified carboxymethyl chitosan: 2g of carboxymethyl chitosan and 10g of tannic acid are dissolved in 100ml of water to obtain the tannic acid modified carboxymethyl chitosan (TA-CMCS), and then a coupling agent of 0.2g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and 0.1-g N-hydroxysuccinimide (NHS) are added to react, and the tannic acid modified carboxymethyl chitosan (TA-CMCS) is prepared by modification under the catalysis of the coupling agent.
(3) The well-cultured stem cells were cultured under anaerobic (94% N2, 1% O2 and 5% CO 2) conditions for 24 hours, the medium was collected, centrifuged at 15000rpm for 30 minutes, cell debris and macromolecular proteins were removed, then filtered with a 0.22 μm filter, finally, after centrifugation at 57000rpm for 1 hour with a ultracentrifuge, the supernatant was taken out, and the transparent precipitate at the bottom of the centrifuge tube was collected to obtain a hypoxia Exosome (HExo).
(4) 2g of phenylboronic acid grafted aldehyde sodium alginate is dissolved in 100ml of water to prepare phenylboronic acid grafted aldehyde sodium alginate solution, 1g of hypoxia exosome is added into the solution to be stirred and mixed uniformly, and finally tannic acid modified carboxymethyl chitosan is added according to the mass ratio of the phenylboronic acid grafted aldehyde sodium alginate of 1:1 to be stirred, and the intelligent response hydrogel dressing can be obtained after the reaction.
Example 2
The preparation method of the intelligent response hydrogel dressing based on the hypoxia exosome of the embodiment comprises the following steps:
(1) Preparation of phenylboronic acid grafted aldehyde sodium alginate: dispersing 10g of sodium alginate with molecular weight of 50kDa in 50ml of absolute ethyl alcohol to obtain sodium alginate dispersion liquid, adding 20% (w/v) sodium periodate aqueous solution containing 60g of sodium periodate into the sodium alginate dispersion liquid, carrying out light-shielding reaction for 4 hours to obtain a reaction product, and purifying and drying the reaction product to obtain the aldehyde sodium alginate. Adding 2g of oxidized sodium alginate into 100ml of deionized water to prepare a 2% aldehyde sodium alginate aqueous solution, adding 3-aminophenylboric acid into the aldehyde sodium alginate solution according to the mass ratio of the 3-aminophenylboric acid to the oxidized sodium alginate of 1:8, reacting for 2 hours, and purifying the reaction product after the reaction is finished to obtain the phenylboric acid grafted aldehyde sodium alginate.
(2) Preparation of tannic acid modified carboxymethyl chitosan: 2g of carboxymethyl chitosan and 10g of tannic acid are dissolved in 100ml of water to obtain the tannic acid modified carboxymethyl chitosan (TA-CMCS), and then a coupling agent of 0.2g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and 0.1-g N-hydroxysuccinimide (NHS) are added to react, and the tannic acid modified carboxymethyl chitosan (TA-CMCS) is prepared by modification under the catalysis of the coupling agent.
(3) The well-cultured stem cells were cultured under anaerobic (94% N2, 1% O2 and 5% CO 2) conditions for 24 hours, the medium was collected, centrifuged at 15000rpm for 30 minutes, cell debris and macromolecular proteins were removed, then filtered with a 0.22 μm filter, finally, after centrifugation at 57000rpm for 1 hour with a ultracentrifuge, the supernatant was taken out, and the transparent precipitate at the bottom of the centrifuge tube was collected to obtain a hypoxia Exosome (HExo).
(4) 2g of phenylboronic acid grafted aldehyde sodium alginate is dissolved in 100ml of water to prepare phenylboronic acid grafted aldehyde sodium alginate solution, 1g of hypoxia exosome is added into the solution to be stirred and mixed uniformly, and finally tannic acid modified carboxymethyl chitosan is added according to the mass ratio of the phenylboronic acid grafted aldehyde sodium alginate of 1:1 to be stirred, and the intelligent response hydrogel dressing can be obtained after the reaction.
Example 3
The preparation method of the intelligent response hydrogel dressing based on the hypoxia exosome of the embodiment comprises the following steps:
(1) Preparation of phenylboronic acid grafted aldehyde sodium alginate: dispersing 10g of sodium alginate with molecular weight of 50kDa in 50ml of absolute ethyl alcohol to obtain sodium alginate dispersion liquid, adding 20% (w/v) sodium periodate aqueous solution containing 60g of sodium periodate into the sodium alginate dispersion liquid, carrying out light-shielding reaction for 4 hours to obtain a reaction product, and purifying and drying the reaction product to obtain the aldehyde sodium alginate. Adding 2g of oxidized sodium alginate into 100ml of deionized water to prepare 2% aldehyde sodium alginate aqueous solution, adding 3-aminophenylboric acid into the aldehyde sodium alginate solution according to the mass ratio of the 3-aminophenylboric acid to the oxidized sodium alginate of 1:10, reacting for 2h, and purifying the reaction product after the reaction is finished to obtain the phenylboric acid grafted aldehyde sodium alginate.
(2) Preparation of tannic acid modified carboxymethyl chitosan: 2g of carboxymethyl chitosan and 10g of tannic acid are dissolved in 100ml of water to obtain the tannic acid modified carboxymethyl chitosan (TA-CMCS), and then a coupling agent of 0.2g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and 0.1-g N-hydroxysuccinimide (NHS) are added to react, and the tannic acid modified carboxymethyl chitosan (TA-CMCS) is prepared by modification under the catalysis of the coupling agent.
(3) The well-cultured stem cells were cultured under anaerobic (94% N2, 1% O2 and 5% CO 2) conditions for 24 hours, the medium was collected, centrifuged at 15000rpm for 30 minutes, cell debris and macromolecular proteins were removed, then filtered with a 0.22 μm filter, finally, after centrifugation at 57000rpm for 1 hour with a ultracentrifuge, the supernatant was taken out, and the transparent precipitate at the bottom of the centrifuge tube was collected to obtain a hypoxia Exosome (HExo).
(4) 2g of phenylboronic acid grafted aldehyde sodium alginate is dissolved in 100ml of water to prepare phenylboronic acid grafted aldehyde sodium alginate solution, 1g of hypoxia exosome is added into the solution to be stirred and mixed uniformly, and finally tannic acid modified carboxymethyl chitosan is added according to the mass ratio of the phenylboronic acid grafted aldehyde sodium alginate of 1:1 to be stirred, and the intelligent response hydrogel dressing can be obtained after the reaction.
Example 4
The preparation method of the intelligent response hydrogel dressing based on the hypoxia exosome of the embodiment comprises the following steps:
(1) Preparation of phenylboronic acid grafted aldehyde sodium alginate: dispersing 10g of sodium alginate with molecular weight of 50kDa in 50ml of absolute ethyl alcohol to obtain sodium alginate dispersion liquid, adding 20% (w/v) sodium periodate aqueous solution containing 60g of sodium periodate into the sodium alginate dispersion liquid, carrying out light-shielding reaction for 4 hours to obtain a reaction product, and purifying and drying the reaction product to obtain the aldehyde sodium alginate. Adding 2g of oxidized sodium alginate into 100ml of deionized water to prepare 2% aldehyde sodium alginate aqueous solution, adding 3-aminophenylboric acid into the aldehyde sodium alginate solution according to the mass ratio of the 3-aminophenylboric acid to the oxidized sodium alginate of 1:10, reacting for 2h, and purifying the reaction product after the reaction is finished to obtain the phenylboric acid grafted aldehyde sodium alginate.
(2) Preparation of tannic acid modified carboxymethyl chitosan: 2g of carboxymethyl chitosan and 6g of tannic acid are dissolved in 100ml of water to obtain the tannic acid modified carboxymethyl chitosan (TA-CMCS), and then a coupling agent of 0.2g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and 0.1-g N-hydroxysuccinimide (NHS) are added to react, and the tannic acid modified carboxymethyl chitosan (TA-CMCS) is prepared by modification under the catalysis of the coupling agent.
(3) The well-cultured stem cells were cultured under anaerobic (94% N2, 1% O2 and 5% CO 2) conditions for 24 hours, the medium was collected, centrifuged at 15000rpm for 30 minutes, cell debris and macromolecular proteins were removed, then filtered with a 0.22 μm filter, finally, after centrifugation at 57000rpm for 1 hour with a ultracentrifuge, the supernatant was taken out, and the transparent precipitate at the bottom of the centrifuge tube was collected to obtain a hypoxia Exosome (HExo).
(4) 2g of phenylboronic acid grafted aldehyde sodium alginate is dissolved in 100ml of water to prepare phenylboronic acid grafted aldehyde sodium alginate solution, 1g of hypoxia exosome is added into the solution to be stirred and mixed uniformly, and finally tannic acid modified carboxymethyl chitosan is added according to the mass ratio of the phenylboronic acid grafted aldehyde sodium alginate of 1:1 to be stirred, and the intelligent response hydrogel dressing can be obtained after the reaction.
Example 5
The preparation method of the intelligent response gel dressing of the embodiment comprises the following steps:
(1) Preparation of phenylboronic acid grafted aldehyde sodium alginate: dispersing 10g of sodium alginate with molecular weight of 50kDa in 50ml of absolute ethyl alcohol to obtain sodium alginate dispersion liquid, adding 20% (w/v) sodium periodate aqueous solution containing 60g of sodium periodate into the sodium alginate dispersion liquid, carrying out light-shielding reaction for 4 hours to obtain a reaction product, and purifying and drying the reaction product to obtain the aldehyde sodium alginate. Adding 2g of oxidized sodium alginate into 100ml of deionized water to prepare 2% aldehyde sodium alginate aqueous solution, adding 3-aminophenylboric acid into the aldehyde sodium alginate solution according to the mass ratio of the 3-aminophenylboric acid to the oxidized sodium alginate of 1:10, reacting for 2h, and purifying the reaction product after the reaction is finished to obtain the phenylboric acid grafted aldehyde sodium alginate.
(2) Preparation of tannic acid modified carboxymethyl chitosan: 2g of carboxymethyl chitosan and 2g of tannic acid are dissolved in 100ml of water to obtain a solution, then a coupling agent of 0.2g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and 0.1-g N-hydroxysuccinimide (NHS) are added to react, and the tannic acid modified carboxymethyl chitosan (TA-CMCS) is prepared by modification under the catalysis of the coupling agent.
(3) The well-cultured stem cells were cultured under anaerobic (94% N2, 1% O2 and 5% CO 2) conditions for 24 hours, the medium was collected, centrifuged at 15000rpm for 30 minutes, cell debris and macromolecular proteins were removed, then filtered with a 0.22 μm filter, finally, after centrifugation at 57000rpm for 1 hour with a ultracentrifuge, the supernatant was taken out, and the transparent precipitate at the bottom of the centrifuge tube was collected to obtain a hypoxia Exosome (HExo).
(4) 2g of phenylboronic acid grafted aldehyde sodium alginate is dissolved in 100ml of water to prepare phenylboronic acid grafted aldehyde sodium alginate solution, 1.0g of hypoxia exosome is added into the solution to be stirred and mixed uniformly, and finally tannic acid modified carboxymethyl chitosan is added according to the mass ratio of the phenylboronic acid grafted aldehyde sodium alginate of 1:1 to be stirred, and the intelligent response hydrogel dressing can be obtained after the reaction.
Example 6
The preparation method of the intelligent response hydrogel dressing based on the hypoxia exosome of the embodiment comprises the following steps:
(5) Preparation of phenylboronic acid grafted aldehyde sodium alginate: dispersing 10g of sodium alginate with molecular weight of 50kDa in 50ml of absolute ethyl alcohol to obtain sodium alginate dispersion liquid, adding 20% (w/v) sodium periodate aqueous solution containing 60g of sodium periodate into the sodium alginate dispersion liquid, carrying out light-shielding reaction for 4 hours to obtain a reaction product, and purifying and drying the reaction product to obtain the aldehyde sodium alginate. Adding 2g of oxidized sodium alginate into 100ml of deionized water to prepare 2% aldehyde sodium alginate aqueous solution, adding 3-aminophenylboric acid into the aldehyde sodium alginate solution according to the mass ratio of the 3-aminophenylboric acid to the oxidized sodium alginate of 1:10, reacting for 2h, and purifying the reaction product after the reaction is finished to obtain the phenylboric acid grafted aldehyde sodium alginate.
(6) Preparation of tannic acid modified carboxymethyl chitosan: 2g of carboxymethyl chitosan and 10g of tannic acid are dissolved in 100ml of water to obtain the tannic acid modified carboxymethyl chitosan (TA-CMCS), and then a coupling agent of 0.2g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and 0.1-g N-hydroxysuccinimide (NHS) are added to react, and the tannic acid modified carboxymethyl chitosan (TA-CMCS) is prepared by modification under the catalysis of the coupling agent.
(7) The well-cultured stem cells were cultured under anaerobic (90% N2, 5% O2 and 5% CO 2) conditions for 24 hours, the medium was collected, centrifuged at 15000rpm for 30 minutes, cell debris and macromolecular proteins were removed, then filtered with a 0.22 μm filter, finally, after centrifugation at 57000rpm for 1 hour with a ultracentrifuge, the supernatant was taken out, and the transparent precipitate at the bottom of the centrifuge tube was collected to obtain a hypoxia Exosome (HExo).
(8) 2g of phenylboronic acid grafted aldehyde sodium alginate is dissolved in 100ml of water to prepare phenylboronic acid grafted aldehyde sodium alginate solution, 1g of hypoxia exosome is added into the solution to be stirred and mixed uniformly, and finally tannic acid modified carboxymethyl chitosan is added according to the mass ratio of the phenylboronic acid grafted aldehyde sodium alginate of 1:1 to be stirred, and the intelligent response hydrogel dressing can be obtained after the reaction.
Example 7
The preparation method of the intelligent response gel dressing of the embodiment comprises the following steps:
(1) Preparation of phenylboronic acid grafted aldehyde sodium alginate: dispersing 10g of sodium alginate with molecular weight of 50kDa in 50ml of absolute ethyl alcohol to obtain sodium alginate dispersion liquid, adding 20% (w/v) sodium periodate aqueous solution containing 60g of sodium periodate into the sodium alginate dispersion liquid, carrying out light-shielding reaction for 4 hours to obtain a reaction product, and purifying and drying the reaction product to obtain the aldehyde sodium alginate. Adding 2g of oxidized sodium alginate into 100ml of deionized water to prepare 2% aldehyde sodium alginate aqueous solution, adding 3-aminophenylboric acid into the aldehyde sodium alginate solution according to the mass ratio of the 3-aminophenylboric acid to the oxidized sodium alginate of 1:10, reacting for 2h, and purifying the reaction product after the reaction is finished to obtain the phenylboric acid grafted aldehyde sodium alginate.
(2) Preparation of tannic acid modified carboxymethyl chitosan: 2g of carboxymethyl chitosan and 10g of tannic acid are dissolved in 100ml of water to obtain the tannic acid modified carboxymethyl chitosan (TA-CMCS), and then a coupling agent of 0.2g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and 0.1-g N-hydroxysuccinimide (NHS) are added to react, and the tannic acid modified carboxymethyl chitosan (TA-CMCS) is prepared by modification under the catalysis of the coupling agent.
(3) The well-cultured stem cells were cultured in the absence of oxygen (85% N) 2 、10% O 2 And 5% CO 2 ) Culturing for 24 hr under conditions, collecting culture medium, centrifuging at 15000rpm for 30min, removing cell debris and macromolecular proteins, filtering with 0.22 μm filter, centrifuging at 57000rpm for 1 hr with ultracentrifuge, collecting supernatant, and collecting transparent precipitate at bottom of centrifuge tube to obtain hypoxia Exosome (HExo).
(4) 2g of phenylboronic acid grafted aldehyde sodium alginate is dissolved in 100ml of water to prepare phenylboronic acid grafted aldehyde sodium alginate solution, 1g of hypoxia exosome is added into the solution to be stirred and mixed uniformly, and finally tannic acid modified carboxymethyl chitosan is added according to the mass ratio of the phenylboronic acid grafted aldehyde sodium alginate of 1:1 to be stirred, and the intelligent response hydrogel dressing can be obtained after the reaction.
Comparative example 1
The preparation method of the intelligent response gel dressing of the embodiment comprises the following steps:
(1) Preparation of phenylboronic acid grafted aldehyde sodium alginate: dispersing 10g of sodium alginate with molecular weight of 50kDa in 50ml of absolute ethyl alcohol to obtain sodium alginate dispersion liquid, adding 20% (w/v) sodium periodate aqueous solution containing 60g of sodium periodate into the sodium alginate dispersion liquid, carrying out light-shielding reaction for 4 hours to obtain a reaction product, and purifying and drying the reaction product to obtain the aldehyde sodium alginate.
(2) Preparation of tannic acid modified carboxymethyl chitosan: 2g of carboxymethyl chitosan and 2g of tannic acid are dissolved in 100ml of water to obtain a solution, then a coupling agent of 0.2g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and 0.1-g N-hydroxysuccinimide (NHS) are added to react, and the tannic acid modified carboxymethyl chitosan (TA-CMCS) is prepared by modification under the catalysis of the coupling agent.
(3) The well-cultured stem cells were cultured in the absence of oxygen (85% N) 2 、10% O 2 And 5% CO 2 ) Culturing for 24 hr under conditions, collecting culture medium, centrifuging at 15000rpm for 30min, removing cell debris and macromolecular proteins, filtering with 0.22 μm filter, centrifuging at 57000rpm for 1 hr with ultracentrifuge, collecting supernatant, and collecting transparent precipitate at bottom of centrifuge tube to obtain hypoxia Exosome (HExo).
(4) 2g of aldehyde sodium alginate is dissolved in 100ml of water to prepare aldehyde sodium alginate solution, 1.0g of hypoxia exosome is added into the solution to be stirred and mixed uniformly, and finally tannic acid modified carboxymethyl chitosan is added into the solution to be stirred according to the mass ratio of the aldehyde sodium alginate grafted with phenyl boric acid of 1:1, and the intelligent response hydrogel dressing can be obtained after the reaction.
Experimental example
To verify whether the intelligent response gel dressing of the present application can achieve the expected effect, mechanical property experiments, slow release experiments, cell proliferation experiments, healing promotion experiments, etc. were performed on the intelligent response gel dressing prepared in examples 1 to 4 and comparative example 1.
1. Experiment of mechanical Properties
Samples of the intelligent response gel dressings of each group of examples 1-4 and comparative example 1 were prepared by using a polytetrafluoroethylene cylindrical die with a height of 1cm and a diameter of 2cm, and after the samples were completely molded, the samples were placed on a sample platform of a universal tester for compression testing at a compression rate of 0.5mm/min until the samples were broken. The compressive strength and elongation at break of each set of smart responsive gel dressings were calculated and the results are set forth in table 1.
Table 1 compressive strength and elongation at break of each set of smart responsive gel dressings
Sample of | Compressive Strength (MPa) | Elongation at break (%) |
Example 1 | 0.2967±0.0021 | 64.81±0.11 |
Experimental example 2 | 0.2870±0.0035 | 63.68±0.079 |
Experimental example 3 | 0.2763±0.0019 | 62.56±0.082 |
Experimental example 4 | 0.2618±0.0013 | 61.79±0.10 |
Example 5 | 0.2485±0.0008 | 60.985±0.035 |
Experimental example 6 | 0.2759±0.0027 | 62.62±0.13 |
Example 7 | 0.2631±0.0004 | 61.93±0.095 |
Comparative example 1 | 0.1011±0.0004 | 48.88±0.02 |
As can be seen from table 1, the smart responsive gel dressings prepared in examples 1 to 4 have better mechanical strength and flexibility than comparative example 1.
2. Sustained release experiments
The prepared intelligent response gel dressings of each group of examples 1-4 and comparative example 1 were added to a high-sugar PBS solution to simulate the microenvironment of the diabetic wound surface. At certain time intervals, the supernatant was collected, ferric chloride solution was added, and fresh high-sugar PBS buffer was added to keep the volume constant. The concentration of HExo released from the hydrogels was analyzed by UV-visible spectroscopy, and the release rates of HExo in each set of smart responsive gel dressings at each time point were calculated and the results are shown in Table 2.
TABLE 2 release rates of HExo at various times in various groups of smart responsive gel dressings
As can be seen from table 2, the smart response gel dressings prepared in examples 1 to 7 have sustained release performance of the hypoxia exosomes, compared to comparative example 1, wherein the smart response gel dressing prepared in example 1 has better sustained release performance.
3. Cell proliferation assay
At the cellular level, to simulate revascularization in high-sugar environments, human Umbilical Vein Endothelial Cells (HUVECs) were treated with glucose (high sugar) for 24h, and a high-sugar human umbilical vein endothelial cell (HG-HUVECs) model was established. The smart responsive gel dressings prepared in each of examples 1-4 and comparative example were co-cultured with high sugar human umbilical vein endothelial cells (HG-HUVECs) and the cell activity of HUVECs was examined by CCK-8 method, and the results are shown in Table 3.
TABLE 3 cell Activity of various groups of Smart response gel dressings on HUVECs
As can be seen from table 3, the smart responsive gel dressings prepared in examples 1 to 5 have better cell proliferation function than comparative example 1.
4. Test experiment for healing promoting performance
36 SD male rats of 200-250 g diabetes model are selected, and the rats are randomly divided into a control group and an experimental group which are 1-5, and 6 rats are selected in each group. The rat is breathed and anesthetized, a circular wound with the diameter of 1cm is formed at the position of the back center of the rat, which is 4cm away from the postaural midline, after skin preparation and sterilization, the wound is treated by the following methods:
experiment group 1: the wound was wrapped with the intelligent response gel dressing of example 1, covering a double layer spun wrap.
Experiment group 2: the wound was wrapped with the intelligent response gel dressing of example 2, covering a double layer spun wrap.
Experiment group 3: the wound was wrapped with the intelligent response gel dressing of example 3, covering a double layer spun wrap.
Experiment group 4: the wound was wrapped with the intelligent response gel dressing of example 4, covering a double layer spun wrap.
Control group: the wound was wrapped with the intelligent response gel dressing of comparative example 1 over a double layer spun yarn.
The intelligent response gel dressing and spinning are changed every 3 days, the wound is cleaned every time the intelligent response gel dressing and spinning are changed, and the wound healing condition is recorded. The wound healing rate of each group of rats at day 14 of wound formation is shown in table 4.
Table 4 wound healing rate of rats of each group on day 14 of wound formation
As can be seen from table 4, the smart response gel dressings prepared in examples 1 to 7 have excellent wound healing properties as compared to comparative example 1, with the smart response gel dressing prepared in example 1 having the best healing promoting effect.
It is to be understood that the above examples of the present application are provided by way of illustration only and not by way of limitation of the embodiments of the present application; other variations or modifications of the various aspects will be apparent to persons skilled in the art from the foregoing description, and it is not necessary or exhaustive of all embodiments; any modification, equivalent replacement, improvement, etc. which come within the spirit and principles of the application are desired to be protected by the following claims.
Claims (8)
1. Intelligent response hydrogel dressing based on hypoxia exosome, its characterized in that: comprises 2 to 6 weight percent of phenylboronic acid grafted aldehyde sodium alginate (PBA-OSA), 2 to 6 weight percent of tannic acid modified carboxymethyl chitosan (TA-CMCS), 0.5 to 1.0 weight percent of hypoxia Exosome (HExo) and the balance of water.
2. The method for preparing the intelligent response hydrogel dressing based on the hypoxia exosome, according to claim 1, is characterized by comprising the following steps:
carrying out hydroformylation modification by utilizing sodium alginate with high G content, and further carrying out phenylboric acid grafting to obtain phenylboric acid grafted hydroformylation sodium alginate (OSA); then using carboxymethyl chitosan to carry out Tannic Acid (TA) modification to prepare Tannic acid modified carboxymethyl chitosan; finally, forming a polysaccharide-based hydrogel with a double-network structure and adjustable mechanical properties and crosslinking density by utilizing Schiff base reaction between aldehyde groups of PBA-OSA and amino groups of TA-CMCS and boric acid ester bonds of phenyl boric acid groups of PBA-OSA and hydroxyl groups of TA-CMCS, and loading a hypoxia exosome from a stem cell source into the polysaccharide-based hydrogel to prepare the intelligent response hydrogel dressing based on the hypoxia exosome.
3. The method for preparing the intelligent response hydrogel dressing based on the hypoxia exosome according to claim 2, which is characterized by comprising the following steps:
step 1) taking sodium alginate with high G content as a raw material, and carrying out oxidation reaction on the sodium periodate under a light-shielding condition to prepare aldehyde sodium alginate with different substitution degrees; then carrying out grafting modification on the aldehyde sodium alginate by using aminophenylboric acid to prepare phenyl boric acid grafted aldehyde sodium alginate;
step 2) using carboxymethyl chitosan as a raw material, and preparing tannic acid modified carboxymethyl chitosan with tannic acid under the catalysis of coupling agents of 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS);
step 3) culturing the well-cultured stem cells under the anoxic condition, and obtaining the hypoxia exosomes through centrifugation, filtration and isolation extraction;
step 4) forming a polysaccharide-based hydrogel with a double-network structure and adjustable mechanical property and crosslinking density by utilizing Schiff base reaction between aldehyde groups of PBA-OSA and amino groups of TA-CMCS and boric acid ester bonds of phenylboronic acid groups of PBA-OSA and hydroxyl groups of TA-CMCS, and loading the hypoxia exosomes into the polysaccharide-based hydrogel to prepare the intelligent response hydrogel dressing based on the hypoxia exosomes.
4. The method for preparing the intelligent response hydrogel dressing based on the hypoxia exosome, according to claim 3, wherein the method comprises the following steps: in the step 1), dispersing sodium alginate with high G content in absolute ethyl alcohol to prepare sodium alginate suspension, then adding sodium periodate solution with the concentration of 6-20wt% to react for 18-32 h under the condition of light shielding, adding glycol with the same mole as sodium periodate to terminate the reaction to obtain a reaction mixture, purifying the reaction mixture, and freeze-drying to prepare aldehyde sodium alginate; dissolving the aldehyde sodium alginate in water to prepare an aldehyde sodium alginate solution with the concentration of 3-5 wt%, adding aminophenylboric acid for reaction, filtering after the reaction is finished, and freeze-drying to prepare phenyl boric acid grafted aldehyde sodium alginate;
wherein the molecular weight of the sodium alginate is 4kDa-50kDa, and the M/G ratio is 1:1-1:3;
the mass volume ratio of the sodium alginate to the absolute ethyl alcohol is 1:4g/mL-1:6g/mL;
the mass ratio of the sodium periodate in the sodium periodate aqueous solution to the sodium alginate in the sodium alginate dispersion liquid is 1:1-6:1;
the mass ratio of the aminophenylboric acid to the aldehyde sodium alginate is 1:5-1:10;
the amino phenylboronic acid is any one or more of 2-amino phenylboronic acid, 3-amino phenylboronic acid and 4-amino phenylboronic acid.
5. The method for preparing the intelligent response hydrogel dressing based on the hypoxia exosome, according to claim 3, wherein the method comprises the following steps: in the step 2), carboxymethyl chitosan and tannic acid are dissolved in water, the concentration of the prepared carboxymethyl chitosan solution is 2-4wt%, and then a coupling agent 1-ethyl- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide are added for catalytic reaction, so that tannic acid modified carboxymethyl chitosan is prepared;
wherein the mass ratio of the carboxymethyl chitosan to the tannic acid is 1:1-1:5;
the molar ratio of EDC to NHS in the coupling agent is 3-5:0.5-2.
6. The method for preparing the intelligent response hydrogel dressing based on the hypoxia exosome, according to claim 3, wherein the method comprises the following steps: in the step 3), the well-cultured stem cells are cultured for 24 hours under the anoxic condition, the collected culture is centrifuged for 25min-35min based on 14000rpm-16000rpm to remove cell fragments and macromolecular proteins, then a 0.2 mu m-0.45 mu m filter is used for filtering, finally, after the centrifugal process is carried out for 1 hour by a ultracentrifuge at 55000rpm-59000rpm, the supernatant is taken out, and transparent precipitate at the bottom of the centrifuge tube is collected to obtain the hypoxia exosomes;
wherein the stem cells are any one or more of fat stem cells, mesenchymal stem cells and human urine-derived stem cells;
the anoxic condition is that 85-94% N is used 2 、1%-10%O 2 And 5% CO 2 Is a mixed gas of (a) and (b).
7. The method for preparing the intelligent response hydrogel dressing based on the hypoxia exosome, according to claim 3, wherein the method comprises the following steps: in the step 4), dissolving phenyl boric acid grafted aldehyde sodium alginate in water to prepare phenyl boric acid grafted aldehyde sodium alginate solution with the concentration of 2-6wt%, adding 0.5wt% -1.0wt% of hypoxia exosome, stirring and mixing uniformly, and finally adding tannic acid modified carboxymethyl chitosan for stirring, and reacting to prepare the intelligent response hydrogel dressing based on the hypoxia exosome; wherein the mass ratio of the phenylboronic acid grafted aldehyde sodium alginate to the tannic acid modified carboxymethyl chitosan is 1:1-1:2.
8. Use of any one of the hypoxia exosome-based smart responsive hydrogel dressings according to claims 1-7 for the preparation of a medical dressing for promoting healing of chronic wounds of diabetes.
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117180493A (en) * | 2023-11-07 | 2023-12-08 | 中日友好医院(中日友好临床医学研究所) | Composite hydrogel dressing and preparation method and application thereof |
Citations (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4948575A (en) * | 1989-01-24 | 1990-08-14 | Minnesota Mining And Manufacturing Company | Alginate hydrogel foam wound dressing |
US20140296496A1 (en) * | 2011-11-07 | 2014-10-02 | Shenyang Kesi High-Technology Co. Ltd. | Method for extracting brown algae polysaccharide via microwave chemical process |
CN110721162A (en) * | 2019-10-14 | 2020-01-24 | 浙江海洋大学 | Preparation method of nano-microspheres with biological activity |
US20210260085A1 (en) * | 2018-06-29 | 2021-08-26 | Shanghai Green Valley Pharmaceutical Co., Ltd. | Composition of alginic oligosaccharic diacids |
US20210361570A1 (en) * | 2020-05-19 | 2021-11-25 | Mcmaster University | In situ gelling polysaccharide-based nanoparticle hydrogel compositions, and methods of use thereof |
CN113941025A (en) * | 2021-10-27 | 2022-01-18 | 四川大学华西医院 | Tissue-adhesive hydrogel and application thereof |
CN114099416A (en) * | 2021-10-28 | 2022-03-01 | 四川大学 | Multifunctional injectable hydrogel with microenvironment response and preparation method and application thereof |
CN114672118A (en) * | 2022-05-05 | 2022-06-28 | 四川大学 | Injectable sodium alginate/polyvinyl alcohol/dopamine-based hydrogel capable of being rapidly recombined in situ |
CN115429931A (en) * | 2022-10-24 | 2022-12-06 | 山东爱基康健康科技有限公司 | Chitosan hydrogel dressing containing exosome and preparation method thereof |
WO2023060747A1 (en) * | 2021-10-11 | 2023-04-20 | 中国科学院深圳先进技术研究院 | Composition and method for 3d printing of living cells |
CN116139331A (en) * | 2023-01-10 | 2023-05-23 | 华南理工大学 | Multifunctional wound repair dressing loaded with bioactive glass and preparation method thereof |
CN116212103A (en) * | 2023-05-11 | 2023-06-06 | 北京康宇建医疗器械有限公司 | Chitosan gel dressing for promoting healing as well as preparation method and application thereof |
CN116271200A (en) * | 2023-01-10 | 2023-06-23 | 华南理工大学 | Nanometer composite wound repair gel for diabetic ulcer and preparation method thereof |
-
2023
- 2023-06-27 CN CN202310761500.6A patent/CN116688222B/en active Active
Patent Citations (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4948575A (en) * | 1989-01-24 | 1990-08-14 | Minnesota Mining And Manufacturing Company | Alginate hydrogel foam wound dressing |
US20140296496A1 (en) * | 2011-11-07 | 2014-10-02 | Shenyang Kesi High-Technology Co. Ltd. | Method for extracting brown algae polysaccharide via microwave chemical process |
US20210260085A1 (en) * | 2018-06-29 | 2021-08-26 | Shanghai Green Valley Pharmaceutical Co., Ltd. | Composition of alginic oligosaccharic diacids |
CN110721162A (en) * | 2019-10-14 | 2020-01-24 | 浙江海洋大学 | Preparation method of nano-microspheres with biological activity |
US20210361570A1 (en) * | 2020-05-19 | 2021-11-25 | Mcmaster University | In situ gelling polysaccharide-based nanoparticle hydrogel compositions, and methods of use thereof |
WO2023060747A1 (en) * | 2021-10-11 | 2023-04-20 | 中国科学院深圳先进技术研究院 | Composition and method for 3d printing of living cells |
CN113941025A (en) * | 2021-10-27 | 2022-01-18 | 四川大学华西医院 | Tissue-adhesive hydrogel and application thereof |
CN114099416A (en) * | 2021-10-28 | 2022-03-01 | 四川大学 | Multifunctional injectable hydrogel with microenvironment response and preparation method and application thereof |
CN114672118A (en) * | 2022-05-05 | 2022-06-28 | 四川大学 | Injectable sodium alginate/polyvinyl alcohol/dopamine-based hydrogel capable of being rapidly recombined in situ |
CN115429931A (en) * | 2022-10-24 | 2022-12-06 | 山东爱基康健康科技有限公司 | Chitosan hydrogel dressing containing exosome and preparation method thereof |
CN116139331A (en) * | 2023-01-10 | 2023-05-23 | 华南理工大学 | Multifunctional wound repair dressing loaded with bioactive glass and preparation method thereof |
CN116271200A (en) * | 2023-01-10 | 2023-06-23 | 华南理工大学 | Nanometer composite wound repair gel for diabetic ulcer and preparation method thereof |
CN116212103A (en) * | 2023-05-11 | 2023-06-06 | 北京康宇建医疗器械有限公司 | Chitosan gel dressing for promoting healing as well as preparation method and application thereof |
Non-Patent Citations (7)
Title |
---|
余幸鸽;林开利;: "基于天然水凝胶的生物材料在骨组织工程中的应用", 中国生物工程杂志, no. 05, 15 May 2020 (2020-05-15) * |
卢洁: "间充质干细胞来源的外泌体治疗糖尿病足溃疡的机制研究进展", 山东医药, vol. 62, no. 32, pages 1 * |
奚望;杨柳;王允山;梁浩;宋淑亮;王伟莉;吉爱国;: "海藻酸钠/壳聚糖蚯蚓蛋白凝胶剂的制备及其对大鼠深Ⅱ度烫伤促愈合作用的研究", 中药材, no. 10, 25 October 2011 (2011-10-25) * |
张振坤;李喆;李亚;王莹莹;王亚苹;周馨魁;马珊珊;关方霞;: "海藻酸盐基水凝胶/敷料在创面愈合中的应用:持续、动态与顺序释放", 中国组织工程研究, no. 04, 14 September 2020 (2020-09-14) * |
李朝富;王艳;赵然尊;龙仙萍;张巍;陈攀科;石蓓;: "骨髓间充质干细胞源外泌体调控心肌微血管内皮细胞增殖的机制研究", 第三军医大学学报, no. 23 * |
熊永红;夏中元;: "外泌体在糖尿病心肌损伤中的作用研究进展", 中华实用诊断与治疗杂志, no. 10 * |
秦益民: "海洋功能性资源技术丛书 海藻源膳食纤维", 31 July 2021, 北京:中国轻工业出版社, pages: 219 - 220 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117180493A (en) * | 2023-11-07 | 2023-12-08 | 中日友好医院(中日友好临床医学研究所) | Composite hydrogel dressing and preparation method and application thereof |
CN117180493B (en) * | 2023-11-07 | 2024-02-06 | 中日友好医院(中日友好临床医学研究所) | Composite hydrogel dressing and preparation method and application thereof |
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