CN112876694A - Preparation method and application of acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel - Google Patents
Preparation method and application of acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel Download PDFInfo
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- CN112876694A CN112876694A CN202011223242.9A CN202011223242A CN112876694A CN 112876694 A CN112876694 A CN 112876694A CN 202011223242 A CN202011223242 A CN 202011223242A CN 112876694 A CN112876694 A CN 112876694A
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- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
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- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
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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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
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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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
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- A61L24/0031—Hydrogels or hydrocolloids
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
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- C08F283/00—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G
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Abstract
The invention discloses an acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel and a preparation method and application thereof. According to the invention, the carbon-carbon double bond on the acrylic acid generates free radical polymerization through illumination and the electrostatic complexation between the nitrogen heterocycle of the pyrrolidone and the phenolic hydroxyl group, and the epsilon-polylysine and the acrylic acid are crosslinked together to form the hydrogel with a three-dimensional network structure, so that the hydrogel has the advantages of controllable performance, good biocompatibility, light forming, spectrum antibiosis, adjustable adhesion strength and the like, is mild and controllable in implementation conditions, and can be applied to the field of biomedical materials such as tissue adhesives, medical dressings, tissue engineering materials and the like.
Description
Technical Field
The invention belongs to the field of biomedical high polymer materials, and particularly relates to a photo-crosslinked acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel and a preparation method and application thereof.
Background
For the treatment of wound, the traditional method is mainly surgical suture, however, the method has higher technical literacy requirement for clinical operators, needs higher professional and technical means, may generate side reactions such as inflammatory reaction, secondary infection, scar formation, bacterial breeding and wound edema, and increases economic cost because of the need of drug anesthesia in the wound suture process. Therefore, in order to solve the above defects, it is critical to develop a tissue adhesive to assist in the suture and repair of wounds. The ideal tissue adhesive needs to have high tissue adhesiveness, broad-spectrum antibacterial property, no immunological rejection reaction, biological non-toxicity, high biocompatibility to human tissues, no irritation to human tissues, certain self-adaptive property and the like.
Most of the prior biological adhesives are fibrin glue and cyanoacrylate adhesives, but the biological adhesives have the problems of poor tissue adhesive strength, easy shedding, poor antibacterial performance, certain skin irritation and the like.
The hydrogel is a multifunctional three-dimensional porous scaffold material with high water content and a structure similar to natural soft tissue, can be reasonably modified by utilizing chemically modifiable groups of a high polymer material, can construct an adhesive hydrogel scaffold, and has important application potential in the field of biomedical high polymer materials. Adhesive hydrogels are an important biomaterial and are used in surgical sealants and wound dressings.
Disclosure of Invention
Aiming at the problems of the prior art, the invention provides a photo-crosslinking high-adhesion acrylic acid/epsilon-polylysine antibacterial hydrogel and a preparation method and application thereof.
In order to achieve the purpose, the invention adopts the following technical scheme:
a preparation method of acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel comprises the following steps:
(1) adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) to an ethanol-water solution containing Gallic Acid (GA) for activation; adding epsilon-polylysine (epsilon-PL) for reaction to obtain gallic acid modified epsilon-polylysine polymer which is marked as epsilon-PL-GA;
(2) adding epsilon-PL-GA, epsilon-polylysine, acrylic acid and polyvinylpyrrolidone (PVP) into an aqueous solution containing a photoinitiator to obtain a stock solution; and (3) irradiating the stock solution under ultraviolet light to obtain the acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel.
Preferably, the reaction time in the step (1) is 12-48 h.
Preferably, the volume ratio of ethanol to water in the ethanol-water solution in the step (1) is 5: 1-1: 2.
Preferably, the epsilon-polylysine added in the step (1) is an epsilon-polylysine aqueous solution with the addition concentration of 5-10 g/L.
Preferably, the molecular weight of the epsilon-polylysine in the step (1) is 1000-4000 daltons.
Preferably, the molar ratio of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride to the N-hydroxysuccinimide in the step (1) is 3: 1-1: 3; the molar ratio of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride to the carboxyl groups in the gallic acid is 1: 1-1: 5; the molar ratio of the gallic acid to the amino groups in the epsilon-polylysine is 5: 1-1: 3.
Preferably, in the step (1), after 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide are added to the ethanol-water solution containing gallic acid, the pH of the solution is 4.5 to 5.5.
Preferably, the activation time in the step (1) is 15-90 min.
Preferably, the temperature for activation in the step (1) is 0-30 ℃.
Preferably, step (1) further comprises a step of reaction, dialysis, and freeze-drying.
Preferably, the dialysis time in the step (1) is 1 to 7 days.
Preferably, the lyophilization time in step (1) is 2 days.
Preferably, the photoinitiator in step (2) is alpha-ketoglutaric acid.
Preferably, the mass concentration of the photoinitiator in the stock solution in the step (2) is 0.2%.
Preferably, the mass concentration of acrylic acid in the stock solution in the step (2) is 30%.
Preferably, the mass concentration of the polyvinylpyrrolidone in the stock solution in the step (2) is 0.2-4%.
Preferably, the mass concentration of epsilon-PL-GA in the stock solution in the step (2) is 0.1-1%.
Preferably, the mass concentration of the epsilon-polylysine in the stock solution in the step (2) is 1-10%.
Preferably, the time of the ultraviolet irradiation in the step (2) is 2min to 10 min. Mixing under ultraviolet irradiation to prepare stock solution, and rapidly gelatinizing within a minimum of 2 min.
The invention also provides the acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel prepared by the method.
The invention also provides application of the acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel prepared by the method in the field of biomedical materials.
The application comprises the following steps: preparing medical dressing, tissue engineering material or tissue adhesive.
The invention has the beneficial effects that:
the free radical polymerization is initiated by ultraviolet irradiation, harmful toxic byproducts are hardly generated, the operation is simple, the condition controllability is higher, the gelling mode is simple and convenient, and the hydrogel is regarded as an ideal hydrogel curing means; secondly, the mechanical property of the hydrogel can be enhanced by utilizing the electrostatic complexation between the nitrogen heterocyclic ring of the pyrrolidone and the phenolic hydroxyl, then the adhesion of the tissue part is promoted by utilizing the synergistic action of the acrylic ester which can be modified by N-hydroxysuccinimide and the epsilon-polylysine polymer which can be modified by gallic acid, and finally the purpose of the antibacterial effect of the tissue adhesive is achieved by utilizing the combined action of the gallic acid and the epsilon-polylysine.
The invention takes safe, nontoxic and biodegradable material epsilon-polylysine as a natural antibacterial material, modifies gallic acid on a macromolecular side chain of the material, utilizes the synergistic action of amino cation, phenolic hydroxyl and aromatic heterocycle to achieve the aim of broad-spectrum antibacterial, and has excellent biocompatibility. The method adopts simple and controllable ultraviolet light to initiate free radical polymerization reaction and simple electrostatic complexation, can provide certain mechanical property for hydrogel, can better solve the problem of weak adhesion strength of hydrogel materials due to the special property of gallic acid and N-hydroxysuccinimide modified acrylic ester, and has wide clinical application prospect in the fields of medical dressings and tissue adhesives.
The method adopts a one-step gel forming technology, and has the characteristics of single curing means, excellent biocompatibility and broad-spectrum antibacterial performance and good adhesion strength.
Drawings
FIG. 1 is a graph showing the adhesion test performed on the hydrogel of the present invention in example 9.
FIG. 2 is a tensile test chart of the hydrogel of the present invention.
FIG. 3 is a graph comparing the cell viability of the hydrogels of the present invention and cell culture media.
Detailed Description
The invention will be better understood from the following examples. However, those skilled in the art will readily appreciate that the description of the embodiments is only illustrative of the present invention and should not be taken as limiting the invention as detailed in the claims.
Example 1
(1) Dissolving Gallic Acid (GA) in ethanol-water system at volume ratio of 1:2, stirring thoroughly to dissolve uniformly, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), adjusting pH to 4.5, and stirring and activating at 30 deg.C for 30 min. Adding epsilon-polylysine (epsilon-PL, the molecular weight is 1500 daltons), wherein the mass concentration of the epsilon-PL is 5g/L, and stirring and reacting for 24 hours at the temperature of 30 ℃; the molar ratio of each substance is EDC: GA 1:1, EDC: NHS: 2:1, and GA: epsilon-PL: 1. Transferring the system obtained by the reaction into a dialysis bag, and dialyzing in deionized water for 2 days; and (3) freeze-drying the dialyzed solution for 2 days to obtain a gallic acid modified epsilon-polylysine polymer (epsilon-PL-GA), wherein the grafting rate of the epsilon-PL-GA is 10%.
(2) Adding a gallic acid modified epsilon-polylysine polymer (epsilon-PL-GA), polylysine (epsilon-PL), polyvinylpyrrolidone (PVP) and acrylic acid (Aa) into an aqueous solution containing alpha-ketoglutaric acid, and fully stirring and uniformly mixing to obtain a stock solution; the mass concentration of epsilon-PL-GA in the stock solution is 0.2 percent, the mass concentration of PVP is 2 percent, the mass concentration of epsilon-PL is 4 percent, the mass concentration of Aa is 30 percent, and the mass concentration of alpha-ketoglutaric acid is 0.2 percent, and the stock solution is irradiated for 5min under ultraviolet light to obtain the acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel.
Example 2
(1) Dissolving Gallic Acid (GA) in ethanol-water system at volume ratio of 1:2, stirring thoroughly and dissolving uniformly, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), adjusting pH to 4.8, and activating at 4 deg.C for 90min under stirring. Adding epsilon-polylysine (epsilon-PL, the molecular weight is 3000 daltons), wherein the mass concentration of the epsilon-PL is 5g/L, and stirring and reacting for 24 hours at the temperature of 30 ℃; the molar ratio of each substance is EDC: GA 1:5, EDC: NHS: 1, and GA: epsilon-PL: 5: 1. Transferring the system obtained by the reaction into a dialysis bag, and dialyzing in deionized water for 3 days; and (3) freeze-drying the dialyzed solution to obtain a gallic acid modified epsilon-polylysine polymer (epsilon-PL-GA), wherein the grafting rate of the epsilon-PL-GA is 12%.
(2) Adding a gallic acid modified epsilon-polylysine polymer (epsilon-PL-GA), polylysine (epsilon-PL), polyvinylpyrrolidone (PVP) and acrylic acid (Aa) into an aqueous solution containing alpha-ketoglutaric acid, and fully stirring and uniformly mixing to obtain a stock solution; the mass concentration of epsilon-PL-GA in the stock solution is 0.3 percent, the mass concentration of PVP is 4 percent, the mass concentration of epsilon-PL is 2 percent, the mass concentration of Aa is 30 percent, and the mass concentration of alpha-ketoglutaric acid is 0.2 percent, and the stock solution is irradiated for 2min under ultraviolet light to obtain the acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel.
Example 3
(1) Dissolving Gallic Acid (GA) in an ethanol-water system with a volume ratio of 5:1, stirring thoroughly and dissolving uniformly, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), adjusting pH to 5, and stirring and activating at 0 deg.C for 30 min. Adding epsilon-polylysine (epsilon-PL, the molecular weight is 1000 daltons), wherein the mass concentration of the epsilon-PL is 5g/L, and stirring and reacting for 24 hours at the temperature of 30 ℃; the molar ratio of each substance is EDC: GA 1:1, EDC: NHS: 3:1, and GA: epsilon-PL: 1. Transferring the system obtained by the reaction into a dialysis bag, and dialyzing in deionized water for 1 day; and (3) freeze-drying the dialyzed solution to obtain a gallic acid modified epsilon-polylysine polymer (epsilon-PL-GA), wherein the grafting rate of the epsilon-PL-GA is 10%.
(2) Adding a gallic acid modified epsilon-polylysine polymer (epsilon-PL-GA), polylysine (epsilon-PL), polyvinylpyrrolidone (PVP) and acrylic acid (Aa) into an aqueous solution containing alpha-ketoglutaric acid, and fully stirring and uniformly mixing to obtain a stock solution; the mass concentration of epsilon-PL-GA in the stock solution is 0.1 percent, the mass concentration of PVP is 2 percent, the mass concentration of epsilon-PL is 4 percent, the mass concentration of Aa is 30 percent, and the mass concentration of alpha-ketoglutaric acid is 0.2 percent, and the stock solution is irradiated for 3min under ultraviolet light to obtain the acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel.
Example 4
(1) Dissolving Gallic Acid (GA) in ethanol-water system at volume ratio of 1:2, stirring thoroughly to dissolve uniformly, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), adjusting pH to 4.5, and activating at 30 deg.C for 15 min under stirring. Adding epsilon-polylysine (epsilon-PL, the molecular weight is 1500 daltons), wherein the mass concentration of the epsilon-PL is 5g/L, and stirring and reacting for 12 hours at the temperature of 30 ℃; the molar ratio of each substance is EDC: GA 1:1, EDC: NHS: 2:1, and GA: epsilon-PL: 1: 3. Transferring the system obtained by the reaction into a dialysis bag, and dialyzing in deionized water for 2 days; and (3) freeze-drying the dialyzed solution to obtain a gallic acid modified epsilon-polylysine polymer (epsilon-PL-GA), wherein the grafting rate of the epsilon-PL-GA is 10%.
(2) Adding a gallic acid modified epsilon-polylysine polymer (epsilon-PL-GA), polylysine (epsilon-PL), polyvinylpyrrolidone (PVP) and acrylic acid (Aa) into an aqueous solution containing alpha-ketoglutaric acid, and fully stirring and uniformly mixing to obtain a stock solution; the mass concentration of epsilon-PL-GA in the stock solution is 0.5 percent, the mass concentration of PVP is 0.2 percent, the mass concentration of epsilon-PL is 1 percent, the mass concentration of Aa is 30 percent, and the mass concentration of alpha-ketoglutaric acid is 0.2 percent, and the stock solution is irradiated for 10min under ultraviolet light, thus obtaining the acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel.
Example 5
(1) Dissolving Gallic Acid (GA) in an ethanol-water system with a volume ratio of 2:1, stirring thoroughly and dissolving uniformly, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), adjusting pH to 4.5, and stirring and activating at 15 deg.C for 30 min. Adding epsilon-polylysine (epsilon-PL, the molecular weight is 1500 daltons), wherein the mass concentration of the epsilon-PL is 7g/L, and stirring and reacting for 24 hours at the temperature of 30 ℃; the molar ratio of each substance is EDC: GA 1:1, EDC: NHS: 1:3, and GA: ε -PL: 1. Transferring the system obtained by the reaction into a dialysis bag, and dialyzing in deionized water for 5 days; and (3) freeze-drying the dialyzed solution to obtain a gallic acid modified epsilon-polylysine polymer (epsilon-PL-GA), wherein the grafting rate of the epsilon-PL-GA is 10%.
(2) Adding a gallic acid modified epsilon-polylysine polymer (epsilon-PL-GA), polylysine (epsilon-PL), polyvinylpyrrolidone (PVP) and acrylic acid (Aa) into an aqueous solution containing alpha-ketoglutaric acid, and fully stirring and uniformly mixing to obtain a stock solution; the mass concentration of epsilon-PL-GA in the stock solution is 0.3 percent, the mass concentration of PVP is 4 percent, the mass concentration of epsilon-PL is 4 percent, the mass concentration of Aa is 30 percent, and the mass concentration of alpha-ketoglutaric acid is 0.2 percent, and the stock solution is irradiated for 3min under ultraviolet light, thus obtaining the acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel.
Example 6
(1) Dissolving Gallic Acid (GA) in ethanol-water system at volume ratio of 1:2, stirring thoroughly to dissolve uniformly, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), adjusting pH to 5.5, and stirring and activating at 30 deg.C for 30 min. Adding epsilon-polylysine (epsilon-PL, the molecular weight is 4000 daltons), wherein the mass concentration of the epsilon-PL is 5g/L, and stirring and reacting for 48 hours at the temperature of 30 ℃; the molar ratio of each substance is EDC: GA 1:1, EDC: NHS: 2:1, and GA: epsilon-PL: 3: 1. Transferring the system obtained by the reaction into a dialysis bag, and dialyzing in deionized water for 2 days; and (3) freeze-drying the dialyzed solution to obtain a gallic acid modified epsilon-polylysine polymer (epsilon-PL-GA), wherein the grafting rate of the epsilon-PL-GA is 10%.
(2) Adding a gallic acid modified epsilon-polylysine polymer (epsilon-PL-GA), polylysine (epsilon-PL), polyvinylpyrrolidone (PVP) and acrylic acid (Aa) into an aqueous solution containing alpha-ketoglutaric acid, and fully stirring and uniformly mixing to obtain a stock solution; the mass concentration of epsilon-PL-GA in the stock solution is 0.5 percent, the mass concentration of PVP is 1 percent, the mass concentration of epsilon-PL is 8 percent, the mass concentration of Aa is 30 percent, and the mass concentration of alpha-ketoglutaric acid is 0.2 percent, and the stock solution is irradiated under ultraviolet light for 8min to obtain the acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel.
Example 7
(1) Dissolving Gallic Acid (GA) in an ethanol-water system with a volume ratio of 4:1, stirring thoroughly and dissolving uniformly, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), adjusting pH to 4.8, and activating with stirring at 4 deg.C for 60 min. Adding epsilon-polylysine (epsilon-PL, the molecular weight is 1500 daltons), the mass concentration of the epsilon-PL is 10g/L, and stirring and reacting for 36 hours at the temperature of 30 ℃; the molar ratio of each substance is EDC: GA 1:3, EDC: NHS: 1.2:1, and GA: epsilon-PL: 5: 1. Transferring the system obtained by the reaction into a dialysis bag, and dialyzing in deionized water for 7 days; and (3) freeze-drying the dialyzed solution to obtain a gallic acid modified epsilon-polylysine polymer (epsilon-PL-GA), wherein the grafting rate of the epsilon-PL-GA is 14%.
(2) Adding a gallic acid modified epsilon-polylysine polymer (epsilon-PL-GA), polylysine (epsilon-PL), polyvinylpyrrolidone (PVP) and acrylic acid (Aa) into an aqueous solution containing alpha-ketoglutaric acid, and fully stirring and uniformly mixing to obtain a stock solution; the mass concentration of epsilon-PL-GA in the stock solution is 0.3 percent, the mass concentration of PVP is 4 percent, the mass concentration of epsilon-PL is 3 percent, the mass concentration of Aa is 30 percent, and the mass concentration of alpha-ketoglutaric acid is 0.2 percent, and the stock solution is irradiated under ultraviolet light for 4min to obtain the acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel.
Example 8
(1) Dissolving Gallic Acid (GA) in an ethanol-water system with a volume ratio of 4:1, stirring thoroughly and dissolving uniformly, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), adjusting pH to 4.8, and activating with stirring at 4 deg.C for 60 min. Adding epsilon-polylysine (epsilon-PL, the molecular weight is 1500 daltons), the mass concentration of the epsilon-PL is 10g/L, and stirring and reacting for 36 hours at the temperature of 30 ℃; the molar ratio of each substance is EDC: GA 1:3, EDC: NHS: 1.2:1, and GA: epsilon-PL: 5: 1. Transferring the system obtained by the reaction into a dialysis bag, and dialyzing in deionized water for 3 days; and (3) freeze-drying the dialyzed solution to obtain a gallic acid modified epsilon-polylysine polymer (epsilon-PL-GA), wherein the grafting rate of the epsilon-PL-GA is 14%.
(2) Adding a gallic acid modified epsilon-polylysine polymer (epsilon-PL-GA), polylysine (epsilon-PL), polyvinylpyrrolidone (PVP) and acrylic acid (Aa) into an aqueous solution containing alpha-ketoglutaric acid, and fully stirring and uniformly mixing to obtain a stock solution; 1% of epsilon-PL-GA, 0.5% of PVP, 10% of epsilon-PL, 30% of Aa and 0.2% of alpha-ketoglutaric acid in the stock solution, and irradiating the stock solution for 3min under ultraviolet light to obtain the adhesive acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel.
Example 9: adhesion Performance evaluation test
The adhesion performance of the adhesive acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel is evaluated by adopting a CMT2103 type universal tester (America Meits MTS company), namely, the mechanical energy is represented by the compression performance. The specific experimental steps are as follows: the test gel was applied to fresh pig skin at a drawing speed of 10mm/min, and the results are shown in Table 1. Compared with commercial tissue adhesive fibrin glue, the hydrogel prepared by the invention has good tissue adhesion; in addition, for a more visual appearance of the adhesion properties of the hydrogel, the pig skin adhesion test using the hydrogel is shown in FIG. 1, and the adhesion properties of the hydrogel are shown in FIG. 2 (FIG. 2 shows that the hydrogel is stretched after being squeezed by hand, and thus, the adhesion properties are high).
TABLE 1 evaluation of hydrogel adhesion Properties at different monomer ratios
| Sample (wt%) | Adhesion Strength (kPa) |
| Fibrin glue | 4.8±0.6 |
| 30％Aa/2％PVP/4％PL/0.1％PL-GA | 6±1.4 |
| 30％Aa/2％PVP/4％PL/0.2％PL-GA | 8±2.4 |
| 30％Aa/4％PVP/4％PL/0.3％PL-GA | 15±1.2 |
| 30％Aa/4％PVP/3％PL/0.3％PL-GA | 13±1.5 |
| 30％Aa/4％PVP/2％PL/0.3％PL-GA | 12±2.6 |
Example 10: evaluation of cytotoxicity
Cell compatibility of the acrylic acid/epsilon-polylysine antibacterial adhesion hydrogel is evaluated by dead-live staining, and an experimental object is a mouse fibroblast (L929). The specific experimental operation steps are as follows: (1) culturing L929 cells in high-glucose DMEM medium containing 10% fetal calf serum and 1% double antibody, and standing at 37 deg.C and 5% CO2Culturing in incubator until cell confluence rate reaches above 85%, digesting with trypsin, centrifuging, and adjusting cell density to 5 × 10 with culture medium5cell/mL of cell suspension; (2) then inoculating the L929 cells into a 24-pore plate, wherein each pore is 200 mu L, placing the plate in a cell culture box, and culturing overnight until the plate is completely attached to the wall; sucking out original culture solution, and respectively adding 1mL of leaching liquor of acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel, blank reference solution (namely fresh complete culture medium) and leaching liquor of GelMA hydrogel with the same concentration, wherein each group contains 3 parallel samples; (4) adding AO/EB staining working solution into each hole according to the proportion of adding 40 microliter into each milliliter at three time points of 24 hours, 48 hours and 72 hours respectively, placing the mixture in a constant temperature incubator at 37 ℃ for 5 minutes, and observing the fluorescent stained cells under a fluorescent inverted microscope. Observing the cell morphology of the stained cells under a fluorescence microscope, wherein the living cells present a green normal structure; the dead cells appeared as orange-red pyknosisOr a bead-like structure. FIG. 3 shows that the present invention shows higher cell survival rate compared to Gel-MA Gel and cell culture medium DMEM.
Note: preparing a dyeing working solution: mixing the Acridine Orange (AO) solution and the Ethidium Bromide (EB) solution according to the volume ratio of 1:1 to obtain a working solution which is prepared on site. The concentration of AO and EB solution in the experiment is 100 mug/ml respectively, and the effect of the experiment is not influenced by the contained stabilizer.
Example 11: evaluation of antibacterial Properties
The invention adopts a nutrient broth dilution method to investigate the antibacterial performance of the acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel. Firstly, hydrogel samples of different monomers are placed in 75% alcohol solution by volume fraction to be soaked for 4 hours to ensure thorough disinfection, then sterile PBS solution is used for washing alcohol in the gel, the hydrogel samples are placed in a 48-hole plate, finally activated bacterial suspension (escherichia coli and bacterial suspension 200 mu L) is dripped on the surface of the hydrogel samples to carry out gel bacteria co-culture for 24 hours, the bacterial samples are added into 300 mu L nutrient broth solution, an ultraviolet spectrophotometer is used for testing absorbance (OD) at a wavelength of 600nm, the experiment result takes untreated bacterial solution as a control group, the calculation formula is (control group OD-experiment group OD)/control group OD multiplied by 100% to calculate the bacteriostasis result, each group of experiments are carried out for 3 times, and the experiment result is shown in Table 2.
TABLE 2 evaluation of the antimicrobial Properties of hydrogels with different monomer ratios
| Sample (wt%) | Escherichia coli (%) | Staphylococcus aureus (%) |
| 30％Aa | 3.12±0.11 | 2.12±0.23 |
| 30％Aa/2％PVP/4％PL/0.1％PL-GA | 75.63±6.17 | 64.65±1.26 |
| 30％Aa/2％PVP/4％PL/0.2％PL-GA | 83.32±2.65 | 75.14±3.11 |
| 30％Aa/4％PVP/4％PL/0.3％PL-GA | 87.14±3.64 | 86.24±2.01 |
| 30％Aa/4％PVP/3％PL/0.3％PL-GA | 85.25±2.13 | 82.33±1.21 |
| 30％Aa/4％PVP/2％PL/0.3％PL-GA | 79.29±4.17 | 79.22±3.41 |
In conclusion, the acrylic acid/epsilon-polylysine is used for preparing the tissue adhesive through the photo-initiated free radical polymerization reaction and the electrostatic complexation, so that the tissue adhesive has better tissue adhesive property, excellent tissue compatibility and stronger broad-spectrum antibacterial property, and is expected to be used as a tissue engineering scaffold such as a skin auxiliary material, a tissue adhesive and a hemostatic material in the later period of clinical application and development.
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| CN117860652A (en) * | 2024-01-15 | 2024-04-12 | 中山大学附属第五医院 | Oral mucosa delivery system, preparation method and application thereof |
| CN118995097A (en) * | 2024-10-15 | 2024-11-22 | 广州富思德新材料科技有限公司 | Water-based adhesive applied to cigarette making and preparation method thereof |
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