CN-121971690-A - Composite hydrogel for promoting healing of chronic wound surface of diabetes and preparation method thereof

CN121971690ACN 121971690 ACN121971690 ACN 121971690ACN-121971690-A

Abstract

The invention discloses a composite hydrogel for promoting the healing of chronic wound surfaces of diabetes and a preparation method thereof, wherein the method comprises the following steps of (1) preparing black phosphorus nanosheet BPNs suspension; the preparation method comprises the steps of (1) preparing BPNs modified by amino polyethylene glycol, (3) preparing methacryloylated gelatin powder, and (4) preparing composite hydrogel for promoting the healing of chronic wounds of diabetes. According to the invention, the aminated polyethylene glycol is loaded on the black phosphorus nanosheets in an electrostatic self-assembly mode, the composite particles are excellent in oxidation resistance stability and stable and controllable in loading capacity, the polyphosphate released in response to photo-thermal excitation is used as a biological energy precursor, and the adenosine triphosphate in cells is driven to regenerate in situ through phosphoryl transfer reaction mediated by adenylate kinase, so that the energy metabolism disorder of the diabetic wound microenvironment is fundamentally relieved, and migration, endothelial vascularization and tissue remodeling of damaged cells are synergistically promoted, and chronic wound healing is accelerated.

Inventors

HANG FEI
HUANG SIYUAN
MA WEIQIN
LIU YING

Assignees

华南理工大学

Dates

Publication Date: 20260505
Application Date: 20260318

Claims (10)

1. The preparation method of the composite hydrogel for promoting the healing of the chronic wound surface of the diabetes is characterized by comprising the following steps of: (1) Preparing black phosphorus nano-sheet BPNs suspension; (2) Preparation of aminated polyethylene glycol modified BPNs: Adding aminated polyethylene glycol into the black phosphorus nano-sheet BPNs suspension obtained in the step (1), mechanically stirring in a dark place, centrifuging to remove residual massive black phosphorus which is not completely stripped, obtaining uniform and stable aminated polyethylene glycol-black phosphorus composite nano-sheet dispersion, and carrying out vacuum freeze-drying to obtain BPP powder; (3) Preparing methacryloylated gelatin powder; (4) Preparing composite hydrogel for promoting the healing of chronic wound of diabetes: (4-1) adding the BPP freeze-dried powder into a polyphosphate solution, and mechanically stirring in a dark place to obtain an aminated polyethylene glycol-black phosphorus nano-sheet-polyphosphate suspension; (4-2) heating and stirring the photoinitiator and deoxidized ultrapure water in a dark place, adding the methacryloylated gelatin powder obtained in the step (3) after stirring and dissolving, and continuously stirring in a dark place to obtain GelMA prepolymer; And (4-3) blending the aminated polyethylene glycol-black phosphorus nano sheet-polyphosphate suspension obtained in the step (4-1) with the GelMA prepolymer solution obtained in the step (4-2) and uniformly stirring the mixture in a dark place to obtain a composite prepolymer solution, and irradiating the composite prepolymer solution under ultraviolet light to initiate photopolymerization reaction to obtain the composite hydrogel for promoting the healing of the chronic wound surface of diabetes.
2. The method for preparing a composite hydrogel for promoting the healing of chronic wounds of diabetes according to claim 1, wherein the preparation of the black phosphorus nanoplatelets BPNs suspension in step (1) specifically comprises: Firstly, grinding black phosphorus crystals into powder and dispersing the powder into deoxidized ultrapure water, then, carrying out ultrasonic crushing on the mixed solution by using a cell crusher and carrying out ultrasonic treatment by using an ice bath to obtain uniform brown dispersion liquid, and finally, collecting precipitate by centrifugal separation and re-suspending the precipitate in deoxidized ultrapure water to obtain BPNs suspension liquid.
3. The preparation method of the composite hydrogel for promoting the healing of the chronic wound surface of diabetes mellitus, which is characterized by comprising the following steps of (1), wherein the mass volume ratio of black phosphorus crystals to deoxidized ultrapure water is (40-60) mg (50-80) ml, the time of ice bath ultrasonic treatment is 6-12 hours, the on/off period is 2-5 s/2-6 s, the power of a cytobreaker is 600-1000 w, the centrifugal rotating speed is 5000-12000 r/min, the centrifugal time is 15-30 min, the average size of BPNs is 200-400 nm, and the thickness is 2-5 nm.
4. The preparation method of the composite hydrogel for promoting the healing of the chronic wound surface of diabetes mellitus, which is characterized in that in the step (2), the mass ratio of the aminated polyethylene glycol to the black phosphorus nano-sheet BPNs is (50-80) mg (0.8-1.2) mg, the mechanical stirring time is 8-12h, the centrifugal rotating speed is 5000-12000 r/min, and the average size of the obtained BPP composite nano-particles is 350-500 nm.
5. The method for preparing a composite hydrogel for promoting the healing of chronic wounds of diabetes according to claim 1, wherein the preparation of the methacryloylated gelatin powder in step (3) is specifically: Dissolving gelatin powder in deoxidized ultrapure water under water bath heating condition to obtain gelatin solution, dripping methacrylic anhydride, heating and mechanically stirring to react, repeatedly dialyzing with deoxidized ultrapure water after stopping the reaction to obtain methylacrylate gelatin, and lyophilizing to obtain methylacrylate gelatin powder.
6. The preparation method of the composite hydrogel for promoting the healing of the chronic wound surface of diabetes mellitus, which is characterized by comprising the steps of (3) stirring and dissolving gelatin in deoxidized ultrapure water at 40-65 ℃, controlling the reaction temperature to be 40-65 ℃ after the gelatin is dissolved, dropwise adding methacrylic anhydride at the rate of 0.4-1.0 mL/min and stirring and reacting for 4-8 hours, placing the obtained liquid in a 100kDA molecular weight dialysis bag after the reaction is ended, dialyzing for 5-10 days by deoxidized ultrapure water for purification, and then preparing a white sponge-like GelMA product by a vacuum freeze drying technology.
7. The method for preparing the composite hydrogel for promoting the healing of the chronic wound surface of diabetes mellitus, which is characterized in that in the step (4-1), the concentration of the polyphosphoric acid solution in the aminated polyethylene glycol-black phosphorus nano-sheet-polyphosphoric acid suspension is 1.0-2.0 mg/ml, the concentration of the BPP freeze-dried powder is 0.2-1.0 mg/ml, and the mechanical stirring time is 6-12 hours.
8. The method for preparing a composite hydrogel for promoting the healing of chronic wounds of diabetes according to claim 1, wherein in the step (4-2), the photoinitiator is I-2959, the mass-volume ratio of the photoinitiator to deoxidized ultrapure water is 0.2-1.0 mg/ml, the heating temperature is 50-65 ℃, and the mass-volume ratio of the methacryloylated gelatin powder to GelMA prepolymer solution is 0.5-1.0 g/ml.
9. The preparation method of the composite hydrogel for promoting the healing of the chronic wound surface of diabetes mellitus, which is characterized in that in the step (4-3), the volume ratio of the aminated polyethylene glycol-black phosphorus nano sheet-polyphosphate suspension to the GelMA prepolymer solution is (0.5-1.0) (0.8-1.2), the light-shielding stirring time is 3-6 h, and the ultraviolet irradiation time is 120-240 s.
10. The composite hydrogel for promoting the healing of the chronic wound surface of the diabetes, which is characterized by being prepared by the preparation method of the composite hydrogel for promoting the healing of the chronic wound surface of the diabetes according to any one of claims 1-9.

Description

Composite hydrogel for promoting healing of chronic wound surface of diabetes and preparation method thereof Technical Field The invention relates to antibacterial and healing-promoting hydrogel, in particular to composite hydrogel for promoting the healing of chronic wound surfaces of diabetes and a preparation method thereof. Background Chronic wounds of diabetes have become a serious challenge in global clinical medicine due to their complex microenvironment. Compared with the common wound surface, the diabetic wound surface is usually accompanied with serious multi-drug resistant bacterial infection, and the traditional antibiotic therapy is difficult to realize long-acting antibacterial effect and is easy to induce bacterial drug resistance. Black phosphorus has great potential in the field of antibacterial because of its excellent near infrared response photo-thermal and photodynamic properties. However, black phosphorus nanoplatelets are extremely susceptible to oxidative degradation in aqueous environments, resulting in rapid decay of their physicochemical properties, which greatly limits their long-lasting stability in wound dressings. The wound surface of diabetes is in a state of high sugar, hypoxia and energy deficiency for a long time. Most of the existing wound dressings only focus on the removal of external infection, and often neglect the bioenergy metabolic disorder of damaged cells themselves. Studies have shown that intracellular adenosine triphosphate deficiency significantly impedes fibroblast migration and endothelial cell vascularization process, resulting in wound healing arrest. Therefore, the intelligent composite hydrogel dressing which can realize high efficiency, no drug resistance and antibacterial effect and in-situ repair of cell energy metabolism and provide power support for tissue regeneration is developed, and has important scientific significance and application value for clinically treating chronic wound surfaces of diabetes. Disclosure of Invention In order to overcome the defects and shortcomings of the prior art, the invention aims to provide a composite hydrogel for promoting the healing of diabetic chronic wounds and a preparation method thereof, wherein aminated polyethylene glycol is loaded on black phosphorus nano-sheets in an electrostatic self-assembly mode, composite particles are excellent in oxidation resistance stability and stable and controllable in loading capacity, and polyphosphates released in response to photo-thermal excitation are used as bioenergy precursors, and Adenosine Triphosphate (ATP) in-situ regeneration is driven through phosphoryl transfer reaction mediated by adenylate kinase, so that the energy metabolism disorder of the diabetic wound microenvironment is fundamentally relieved, the migration of damaged cells, endothelial vascularization and tissue remodeling are synergistically promoted, and the healing of the chronic wounds is accelerated. The aim of the invention is achieved by the following technical scheme: The invention provides a preparation method of composite hydrogel for promoting the healing of chronic wound surfaces of diabetes, which comprises the following steps: (1) Preparing black phosphorus nano-sheet BPNs suspension; (2) Preparation of aminated polyethylene glycol modified BPNs: Adding aminated polyethylene glycol into the black phosphorus nano-sheet BPNs suspension obtained in the step (1), mechanically stirring in a dark place, centrifuging to remove residual massive black phosphorus which is not completely stripped, obtaining uniform and stable aminated polyethylene glycol-black phosphorus composite nano-sheet dispersion, and carrying out vacuum freeze-drying to obtain BPP powder; (3) Preparing methacryloylated gelatin powder; (4) Preparing composite hydrogel for promoting the healing of chronic wound of diabetes: (4-1) adding the BPP freeze-dried powder into a polyphosphate solution, and mechanically stirring in a dark place to obtain an aminated polyethylene glycol-black phosphorus nano-sheet-polyphosphate suspension; (4-2) heating and stirring the photoinitiator and deoxidized ultrapure water in a dark place, adding the methacryloylated gelatin powder obtained in the step (3) after stirring and dissolving, and continuously stirring in a dark place to obtain GelMA prepolymer; And (4-3) blending the aminated polyethylene glycol-black phosphorus nano sheet-polyphosphate suspension obtained in the step (4-1) with the GelMA prepolymer solution obtained in the step (4-2) and uniformly stirring the mixture in a dark place to obtain a composite prepolymer solution, and irradiating the composite prepolymer solution under ultraviolet light to initiate photopolymerization reaction to obtain the composite hydrogel for promoting the healing of the chronic wound surface of diabetes. Preferably, the preparation of the black phosphorus nano-sheet BPNs suspension in the step (1) specifically comprises: Firstly, grinding black p