CN113274542A

CN113274542A - Hydrogel dressing capable of promoting wound healing

Info

Publication number: CN113274542A
Application number: CN202110175872.1A
Authority: CN
Inventors: 范代娣; 雷桓; 严建亚
Original assignee: Shaanxi Giant Biogene Technology Co ltd; Northwestern University
Current assignee: Shaanxi Giant Biogene Technology Co ltd; Northwestern University
Priority date: 2021-02-09
Filing date: 2021-02-09
Publication date: 2021-08-20

Abstract

The invention discloses a hydrogel dressing capable of promoting wound healing. The hydrogel dressing comprises 1-15 parts by weight of polyvinyl alcohol, 0.3-10 parts by weight of tannic acid, 0.1-10 parts by weight of borax, 0.1-10 parts by weight of Van's recombinant collagen and the balance of water (based on 100 parts by weight of the hydrogel dressing), wherein the weight ratio of the borax to the tannic acid is 1: 3 or more. The invention provides a self-adaptive polyvinyl alcohol hydrogel dressing which can coexist with Van's recombinant collagen and tannic acid and can jointly play a function.

Description

Hydrogel dressing capable of promoting wound healing

Technical Field

The technology relates to the technical field of biomedical materials, in particular to a polyvinyl alcohol hydrogel dressing capable of promoting wound healing.

Background

Polyvinyl alcohol hydrogels are often used as matrix materials for wound dressings, however, wound dressings based on polyvinyl alcohol hydrogels are often morphologically fixed, are not adaptive, can only cover the surface of a wound, and cannot be used inside deep and irregular wounds. It should be noted that the adaptivity of hydrogel materials means that the hydrogel is at the critical point of the fluid and gel, and its shape can change spontaneously to accommodate external conditions, such as irregular or deep and complex wounds.

Tannic acid is a weakly acidic polyphenol compound having strong adhesiveness and particularly enhancing cell adhesion and proliferation, and the high adhesiveness of tannic acid is attributed to an active catechol group which promotes cell adhesion by binding to reactive groups (amino group, carboxyl group and catechol group) on the cell membrane. Tannic acid also has excellent antioxidant, antibacterial, anti-inflammatory and hemostatic properties as well as good biodegradability. Tannic acid has been added to polyvinyl alcohol hydrogels to make polyvinyl alcohol hydrogel medical dressings containing tannic acid.

The van-type recombinant collagen is invented by the professor of the van generation of the university of northwest China (see the Chinese patent application publication specification CN1371919A), has a triple-chain and triple-helix structure, and is a recombinant collagen with high biocompatibility. The van der wae recombinant collagen can promote cell growth, provide nutrition for cells, promote the proliferation of skin fibroblasts and the expression of collagen in skin tissues, so that the van der wae recombinant collagen has good performance of promoting wound healing, and is widely applied to the fields of medical treatment and cosmetology at present. Researchers always expect that tannic acid and van der waals recombinant collagen can be added into polyvinyl alcohol hydrogel and are endowed with adaptivity, so that multiple functions (adaptivity, oxidation resistance, antibacterial property, anti-inflammatory property and hemostatic property and wound healing promotion) are exerted, and the polyvinyl alcohol hydrogel medical dressing with higher performance is prepared.

However, the above expectations of researchers have not been met for at least the following reasons: 1. no matter what method is adopted to prepare the polyvinyl alcohol hydrogel containing the tannic acid in the prior art, the gel fraction is very low, namely, a large amount of water is discharged out of the system in the preparation process, so that the prepared hydrogel has low water content and hard texture, and has self-adaptive performance; 2. tannin can cause the aggregation of Van's recombinant collagen molecules to cause precipitation, so that the Van's recombinant collagen molecules and the precipitation can not effectively coexist in a polyvinyl alcohol hydrogel system and can not play a role together.

Disclosure of Invention

In view of the above-mentioned problems of the prior art, it is an object of the present invention to provide an adaptive polyvinyl alcohol hydrogel dressing in which both van-type recombinant collagen and tannic acid can coexist and function together.

The inventor has intensively studied and found that by adding a certain amount of borax (the weight ratio of borax to tannic acid is more than 1: 3) into a polyvinyl alcohol hydrogel containing recombinant collagen and tannic acid, the Van's recombinant collagen and the tannic acid can stably coexist in a polyvinyl alcohol hydrogel system to play a function together, and the polyvinyl alcohol hydrogel also has adaptability. Moreover, the borax provides an ion conductor, so that the polyvinyl alcohol hydrogel can be endowed with conductivity, and the polyvinyl alcohol hydrogel dressing disclosed by the invention can be used in combination with an electrical stimulation therapy, so that a better effect of promoting wound healing is obtained.

Namely, the present invention comprises:

1. a hydrogel dressing comprising, based on 100 parts by weight of the hydrogel dressing:

wherein the weight ratio of borax to tannic acid is 1: 3 or more.

As the upper limit of the weight ratio of borax to tannic acid, 5: 1 or 3: 1 or 2: 1 or 1: 1. optionally, other ingredients may or may not be included in the hydrogel dressing of the present invention.

Preferably, the lower limit of the weight ratio of borax to polyvinyl alcohol may be, for example, 1: 10 or 1: the upper limit may be, for example, 1: 3 or 1: 5.

2. in the hydrogel dressing, the polyvinyl alcohol is 2 to 10 parts by weight, preferably 5 to 10 parts by weight.

3. In the hydrogel dressing, the tannin accounts for 0.5-5 parts by weight, and preferably 1-3 parts by weight.

4. In the hydrogel dressing, the borax is 0.2-5 parts by weight, preferably 0.5-3 parts by weight.

5. The hydrogel dressing is prepared from the Van's recombinant collagen 0.5-5 parts by weight, preferably 1-2 parts by weight.

6. In the hydrogel dressing, the weight average molecular weight of the polyvinyl alcohol is 89000-98000Da, and the alcoholysis degree is greater than 99%.

7. The hydrogel dressing described above, for use in promoting wound healing.

8. The method for producing a hydrogel dressing according to item 1, comprising the steps of:

5) preparing a polyvinyl alcohol solution with a certain concentration (for example, 3-17 wt%);

6) preparing a borax solution with a certain concentration (for example, 1-5 wt%);

7) preparing a tannic acid solution with a certain concentration (for example, 1-20 wt%);

8) preparing a van-type recombinant collagen solution with a certain concentration (for example, 1-15 wt%);

uniformly mixing the borax solution prepared in the step 2) with the tannic acid solution prepared in the step 3), adding the Van's recombinant collagen solution prepared in the step 4) to obtain a solution A, adding a proper amount of the solution A into the polyvinyl alcohol solution prepared in the step 1), adding a certain amount of water according to needs, stirring uniformly, standing at room temperature for swelling for a certain time (for example, 24 hours), and thus obtaining the hydrogel dressing in the item 1; alternatively, the first and second electrodes may be,

uniformly mixing the borax solution prepared in the step 2) with the Van's recombinant collagen solution prepared in the step 4), adding the tannic acid solution prepared in the step 3) to obtain a solution B, adding a proper amount of the solution B into the polyvinyl alcohol solution prepared in the step 1), adding a certain amount of water according to needs, uniformly stirring, standing at room temperature for swelling for a certain time (for example, 24 hours) to obtain the hydrogel dressing in the item 1; alternatively, the first and second electrodes may be,

mixing the polyvinyl alcohol solution prepared in the step 1) with the van's recombinant collagen solution prepared in the step 4) to obtain a solution C, uniformly mixing the borax solution prepared in the step 2) with the tannic acid solution prepared in the step 3) to obtain a solution D, finally mixing the solution C with the solution D, adding a certain amount of water according to needs, uniformly stirring, standing at room temperature for swelling for a certain time (for example, 24 hours) to obtain the hydrogel dressing in the item 1.

9. Use of the aforementioned hydrogel dressing for the manufacture of a hydrogel dressing for promoting wound healing. The hydrogel dressing is self-adaptive, conductive, self-healing, antibacterial and anti-inflammatory, has self-healing, self-adaptive and conductive performances, has a free radical clearance rate of over 80 percent, a bacteriostatic rate on staphylococcus aureus and escherichia coli of over 90 percent, and has good wound hemostasis and repair effects and anti-inflammatory performance.

10. The use of the foregoing, wherein the wound healing promoting hydrogel dressing is used in combination with electrical stimulation therapy. The hydrogel dressing is a self-adaptive conductive hydrogel, can repair wounds in a combined treatment mode of electric stimulation therapy and promote wound healing, and has the action mechanism that: down-regulating inflammation, resisting bacteria, increasing tissue oxygenation, reducing wound blood flow, promoting angiogenesis, and promoting fibroblast proliferation.

Drawings

FIG. 1 is a graph showing the morphology of the hydrogels of examples 1 to 4 and comparative examples 1 to 3.

FIG. 2 is a diagram showing a possible and impracticable preparation scheme of the hydrogel of the present invention.

Fig. 3 is a graph showing the appearance and self-healing performance of the hydrogel of example 5.

FIG. 4 is a diagram showing the manner of internal bonding of the hydrogel of example 5.

FIG. 5 is a graph showing the adaptivity of the hydrogel of example 5.

Fig. 6 is a graph showing the electrical conductivity of the hydrogel of example 5.

Fig. 7 is a graph showing the oxidation resistance of the hydrogel of example 5.

FIG. 8 is a graph showing the antibacterial properties of the hydrogel of example 5.

FIG. 9 is a graph showing the hepatic hemostatic performance of the hydrogel of example 5.

Figure 10 is a graph showing the anti-inflammatory properties (IL-6 levels) of the hydrogel of example 5.

Figure 11 is a graph showing the full-thickness dermal wound repair performance of the hydrogel of example 5.

Fig. 12 is a diagram showing the hemostatic repair mechanism of deep wounds by an adaptive conductive hydrogel.

FIG. 13 is a graph showing the gel-forming state and gel fraction for the hydrogels of examples 1-4 and comparative examples 1-3.

Detailed Description

The present invention will be further described with reference to specific examples for better illustrating the objects, technical solutions and advantages of the present invention.

As an example of the present invention, the weight average molecular weight of the polyvinyl alcohol was 89000-98000Da, and the alcoholysis degree was more than 99%. The molecular weight of the van-type recombinant collagen is 96000 Da. The molecular weight of tannic acid is 1700 Da.

Gel fraction-weight of hydrogel produced/total weight of charge

Comparative example 1

1) Weighing polyvinyl alcohol, dissolving in deionized water, heating to 90 ℃ to completely dissolve the polyvinyl alcohol, and preparing into 10 weight percent PVA solution.

2) Weighing tannic acid, dissolving in deionized water, and performing ultrasonic treatment to completely dissolve the tannic acid to obtain a solution with a weight percentage of 4%.

3) Weighing human-like collagen, dissolving in deionized water, and dissolving in a constant-temperature water bath at 37 deg.C to obtain 8 wt% solution.

4) The scheme is as follows: adding 10 parts by weight of the tannic acid solution prepared in the step 2) into 10 parts by weight of the Van's recombinant collagen solution prepared in the step 3) to obtain a solution A, adding the solution A into 50 parts by weight of the polyvinyl alcohol solution prepared in the step 1), adding 30 parts by weight of water, stirring uniformly, standing at room temperature for swelling for 24 hours to obtain the hydrogel of the comparative example 1.

The hydrogel of comparative example 1 was measured to have a gel fraction of 2.8%, and the resulting hydrogel was hard in texture and not adaptive. It can be seen from the observation that a large amount of aqueous liquid is also present in the system.

Comparative example 2

2) Weighing borax, dissolving in deionized water, and performing ultrasonic treatment to completely dissolve borax to prepare a 0.167 wt% solution.

3) Weighing tannic acid, dissolving in deionized water, and performing ultrasonic treatment to completely dissolve the tannic acid to obtain a solution with a weight percentage of 4%.

4) Weighing human-like collagen, dissolving in deionized water, and dissolving in a constant-temperature water bath at 37 deg.C to obtain 8 wt% solution.

5) And (2) uniformly mixing 30 parts by weight of the borax solution prepared in the step 2) with 10 parts by weight of the tannic acid solution prepared in the step 3), adding 10 parts by weight of the Van's recombinant collagen solution prepared in the step 4) to obtain a solution A, adding the solution A into 50 parts by weight of the polyvinyl alcohol solution prepared in the step 1), uniformly stirring, standing at room temperature and swelling for 24 hours to obtain the hydrogel in the comparative example 2.

The hydrogel of comparative example 2 was measured to have a gel fraction of 1.9%, and the resulting hydrogel was hard in texture and not adaptive. It can be seen from the observation that a large amount of thick liquid is also present in the system.

Comparative example 3

2) Borax is weighed and dissolved in deionized water, and the borax is completely dissolved by ultrasonic waves to prepare a solution with the weight percent of 2.67%.

3) Tannic acid was weighed and dissolved in deionized water (40 ℃) and ultrasonically treated to be completely dissolved to prepare a 32 weight percent solution.

5) Uniformly mixing 30 parts by weight of the borax solution prepared in the step 2) with 10 parts by weight of the Van's recombinant collagen solution prepared in the step 4), adding 10 parts by weight of the tannic acid solution prepared in the step 3) to obtain a solution B, adding the solution B into 50 parts by weight of the polyvinyl alcohol solution prepared in the step 1), uniformly stirring, standing at room temperature and swelling for 24 hours to obtain the hydrogel in the comparative example 3.

It was observed that a mixture of two hydrogels was actually formed in the system, one hydrogel with a hard texture, one with a soft texture, and the system was not homogeneous.

Example 1

3) Weighing tannic acid, dissolving in deionized water, and performing ultrasonic treatment to completely dissolve the tannic acid to obtain 8 wt% solution.

5) Uniformly mixing 30 parts by weight of the borax solution prepared in the step 2) with 10 parts by weight of the van der-type recombinant collagen solution prepared in the step 4), adding 10 parts by weight of the tannic acid solution prepared in the step 3) to obtain a solution B, adding the solution B into 50 parts by weight of the polyvinyl alcohol solution prepared in the step 1), uniformly stirring, standing at room temperature and swelling for 24 hours to obtain the hydrogel in the embodiment 1. The gel fraction was determined to be greater than 90%.

Example 2

3) Weighing tannic acid, dissolving in deionized water, and performing ultrasonic treatment to completely dissolve the tannic acid to obtain a 16 wt% solution.

5) Mixing 50 parts by weight of the polyvinyl alcohol solution prepared in the step 1) with 10 parts by weight of the Van's recombinant collagen solution prepared in the step 4) to obtain a solution C, uniformly mixing 30 parts by weight of the borax solution prepared in the step 2) with 10 parts by weight of the tannic acid solution prepared in the step 3) to obtain a solution D, finally mixing the solution C with the solution D, uniformly stirring, standing at room temperature for swelling for 24 hours to obtain the hydrogel of the embodiment 2. The gel fraction was determined to be greater than 90%.

Example 3

3) Weighing tannic acid, dissolving in deionized water, and performing ultrasonic treatment to completely dissolve the tannic acid to obtain a 24 wt% solution.

5) And (2) uniformly mixing 30 parts by weight of the borax solution prepared in the step 2) with 10 parts by weight of the tannic acid solution prepared in the step 3), adding 10 parts by weight of the Van's recombinant collagen solution prepared in the step 4) to obtain a solution A, adding the solution A into 50 parts by weight of the polyvinyl alcohol solution prepared in the step 1), uniformly stirring, standing at room temperature, and swelling for 24 hours to obtain the hydrogel of the embodiment 3. The gel fraction was determined to be greater than 90%.

Example 4

2) Borax is weighed and dissolved in deionized water, and the borax is completely dissolved by ultrasonic waves to prepare a solution with the weight percent of 5.52.

5) Uniformly mixing 30 parts by weight of the borax solution prepared in the step 2) with 10 parts by weight of the van der-type recombinant collagen solution prepared in the step 4), adding 10 parts by weight of the tannic acid solution prepared in the step 3) to obtain a solution B, adding the solution B into 50 parts by weight of the polyvinyl alcohol solution prepared in the step 1), uniformly stirring, standing at room temperature and swelling for 24 hours to obtain the hydrogel of the embodiment 4. The gel fraction was determined to be greater than 90%.

FIGS. 1 and 13 are photographs showing the hydrogels prepared in examples 1 to 4 and comparative examples 1 to 3, and it is understood that the hydrogels of examples 1 to 4 were uniform without formation of precipitates, while the hydrogels of comparative examples 1 to 3 were non-uniform with formation of precipitates. Further, the self-adaptability of the hydrogels prepared in examples 1 to 4 and comparative examples 1 and 2 was measured as in item (3) of example 5 described below, and the results showed that the hydrogels of examples 1 to 4 were self-adaptive, while the hydrogels of comparative examples 1 and 2 were not self-adaptive. The hydrogel of comparative example 3 was not a homogeneous system and was not able to determine its adaptivity.

Furthermore, the inventors have found through extensive experimental studies that the contact between polyvinyl alcohol and tannic acid must be performed in the presence of borax during the preparation of the hydrogel of the present invention, otherwise flocs appear in the prepared hydrogel (the addition of borax is not reversible), resulting in non-uniformity of the system (fig. 2).

Example 5

The preparation method of the hydrogel of this example includes the following steps:

based on 100 parts by weight of the hydrogel

2) Weighing borax, dissolving in deionized water, and performing ultrasonic treatment to completely dissolve the borax to prepare a solution with the weight percent of 3.

3) Weighing tannic acid, dissolving in deionized water, and performing ultrasonic treatment to completely dissolve the tannic acid to obtain a 10 wt% solution.

4) Weighing human-like collagen, dissolving in deionized water, and dissolving in 37 deg.C constant temperature water bath to obtain 10 wt% solution.

5) And (2) uniformly mixing 30 parts by weight of the borax solution prepared in the step 2) with 10 parts by weight of the tannic acid solution prepared in the step 3), adding 10 parts by weight of the Van's recombinant collagen solution prepared in the step 4) to obtain a solution A, adding the solution A into 50 parts by weight of the polyvinyl alcohol solution prepared in the step 1), uniformly stirring, standing at room temperature, and swelling for 24 hours to obtain the hydrogel of the embodiment 5.

The hydrogel prepared in example 5 of the present invention was subjected to performance testing and specifications.

(1) Appearance and self-healing performance: the hydrogel of example 5 appeared pale yellow in appearance. The self-healing performance is shown in fig. 3, after the hydrogel of example 5 is dyed by rhodamine B and alcian blue dyes respectively, two hydrogels with different colors are put together and can self-heal within 30s without external force, and the self-healing mechanism is dynamic borate bond formed between hydroxyl of PVA (or TA) and borate. Upon contact, the reestablishment of dynamic bonds can occur at the interface of the two hydrogels. The resulting hydrogel can be stretched and the contacting portions completely coalesced because due to the sufficient number of free hydroxyl groups and borate on the hydrogel surface, borate bonds and hydrogen bonds can be established at the interface of the contacts.

(2) Crosslinking mode of hydrogel internal network: neat PVA in fig. 4a, characteristic peaks show: tensile vibration peak of-OH is 3300cm^-1The stretching vibration peak of the-CH alkyl group is 2940-2905cm^-1Here, the stretching vibration peak of the-CO secondary alcohol was 1086cm^-1To (3). A symmetrical C-C stretching vibration peak at 1142cm was observed^-1This is characteristic of semi-crystalline PVA. The condensation reaction of PVA and boric acid generates characteristic peaks of boric acid ester bond: at 1430cm^-1And 1337cm^-1The peak at (A) is B-O-C asymmetric stretching relaxation at 1123cm^-1And 1129cm^-1The peak at (A) is B-O-C tensile vibration. And the PVA main chain is 1094cm^-1The characteristic absorption (corresponding to the stretching vibration of C-O-C) disappears in the binding spectrum of PVA and boric acid, indicating that the condensation reaction of PVA and boric acid generates a borate bond. In FIG. 4b, at 1429cm^-1And 1334cm^-1The peak at (A) is the asymmetric tensile relaxation of B-O-C and at 1284cm^-1、1196cm^-1And 1130cm^-1The peak at (A) is due to the stretching vibration of B-O-C. The results show that cross-linking between TA and borax forms boronate coordination bonds. In fig. 4c, characteristic peaks for TA: 3600 and 3100cm^-1The wide band in the range is due to TAAnd (3) extending phenolic hydroxyl. The peak characteristic of the C ═ O bond of HLC is 1637cm^-1The absorption peak of the aromatic C ═ O bond of TA at 1611cm^-1After HLC and TA binding, only 1628cm^-1A peak was observed indicating that two C ═ O bonds overlap and that a hydrogen bond exists between HLC and TA. The ligation of PVA and TA is shown in FIG. 4 d: the peak of-OH stretching vibration of PVA was shifted, the peak was shortened and broadened, and the peak of main stretching vibration of CH was relatively moved by the occurrence of hydrogen bond crosslinking (2942.2 cm)^-1→2908.91cm^-1；1661.71cm^-1→1606.25cm^-1；1331.84cm^-1→1315.92cm^-1；678.73cm^-1→505.91cm^-1) Indicating that there is hydrogen bonding cross-linking between PVA and TA. FIG. 4e shows the connection pattern of PVA and HLC, and the characteristic peak of-OH tensile vibration of PVA (3314 cm)^-1) And the bending vibration peak of CH-OH (1450 cm)^-1) Relative displacement occurs, indicating that there is hydrogen bonding cross-linking between the molecules.

(3) Self-adaptive performance: as shown in FIG. 5, the hydrogel of example 5 can move along the natural force of gravity and surface tension, a glass bead with a diameter of 8mm is placed in a beaker, the hydrogel is placed on the surface of the glass bead, the hydrogel slowly moves downwards (under the action of gravity), and after 8min the glass bead is swallowed and finally completely fills the narrow space around the bead, indicating its automatic mobility.

(4) Conductivity: as shown in FIG. 6, the hydrogel of example 5 can illuminate an LED lamp, indicating that the hydrogel has a high electrical conductivity. The conductivity of the hydrogel can be measured by a Tektronix DMM6500 instrument. Indicating that the hydrogel has good conductivity.

(5) Oxidation resistance: free radicals play a crucial role in all stages of wound healing. Topical application of free radical scavenging materials has been shown to accelerate wound repair. As shown in FIG. 7, the DPPH in the DPPH solution is reduced to change the color of DPPH from purple to yellow, and the radical scavenging rate of example 5 can reach 91.2%. Hydrogel addition of APTS⁺In solution, APTS⁺The reduced color is changed from green to colorless, and the free radical clearance can reach 88.4 percent. The oxidation resistance of hydrogels is mainly due to tannic acid or polypolyThe phenolic hydroxyl group of the bamine has radical scavenging ability and is a strong radical terminator.

(6) Antibacterial property: to investigate the antibacterial properties of the hydrogel of example 5, we used gram-positive bacteria (staphylococcus aureus) and gram-negative bacteria (escherichia coli) as model bacteria. As shown in FIG. 8, when the aqueous gel and the bacterial liquid were co-cultured and then the bacterial liquid was applied by dilution, the numbers of colonies of the blank group and the aqueous gel group showed a significant difference in order of magnitude at the same dilution ratio. The hydrogel in example 5 has a bacteriostatic rate of 92.4% for staphylococcus aureus and 97.3% for escherichia coli.

(7) Liver hemostasis: the hemostatic effect of the hydrogel of example 5 was evaluated using a rat liver exsanguination model, as shown in FIG. 9, the liver blood of the untreated rats was drained and the amount of bleeding was large (about 630 mg). In contrast, the amount of bleeding from the hydrogel of example 5 was only six percent (about 40mg) of the blank control, and the amount of bleeding from the hydrogel of example 2 was about 50 mg. There was a significant difference in bleeding between the blank control group and the hydrogel group, with P < 0.01.

(8) Anti-inflammatory properties: anti-inflammatory ability of the hydrogel of example 5 to wounds was evaluated by selecting the expression level of the inflammatory factor IL-6. IL-6 is a multifunctional cytokine produced by fibroblasts, monocytes/macrophages, T lymphocytes, B lymphocytes, epithelial cells, keratinocytes, and a variety of neoplastic cells. IL-6 has the ability to modulate immune responses, acute phase responses and plays an important role in the body's immune response against infection. When infection and inflammation occur, IL-6 is produced first and levels rise rapidly, which can peak at 2 h. The liver after the liver hemostasis is placed back into the rat body, suturing is carried out, the damaged part of the liver is taken out again after 24 hours, immunohistochemical staining is carried out, and the blank group is the liver without hydrogel hemostasis. As shown in FIG. 10, the wound IL-6 secretion after hemostasis was much smaller in the hydrogel of example 5 than in the control group, indicating that the hydrogel of example 5 was effective in anti-inflammatory.

(9) Wound repair performance: the hydrogel of example 5 repairs wounds as shown in fig. 11, on day three, the wounds were richer in granulation tissue and healed at a rate far exceeding that of the blank group, whereas the hydrogel of example 5 and ES combined therapy were more effective in repairing the wounds. The wound tissues of the hydrogel and ES combination treatment group of example 5 had completely healed at day 10, while the wound healing rate of the blank group was only 50% and that of the hydrogel group of example 5 was 72%. The hydrogel of example 5 was shown to be effective in promoting wound repair and to be more rapid in combination with ES for wound repair.

(10) Self-adaptive conductive hydrogel repair mechanism: the adaptive property may also be referred to as the mobility of the hydrogel, which is at the critical point for fluids and gels. Can be automatically adjusted according to the irregular shape of the external wound to adapt to the wound surface of the filled wound and meet the fitting of the irregular wound or the deep wound. As shown in fig. 12. The hydrogel in example 5 has certain viscosity, is not easy to fall off, has antibacterial, anti-inflammatory and antioxidant effects, and can effectively stop bleeding. The hydrogel of example 5 can be combined with external applied Electrical Stimulation (ES) to promote wound healing, and its action mechanism includes: down-regulating inflammation, resisting bacteria, increasing tissue oxygenation, reducing wound blood flow, promoting angiogenesis, and promoting fibroblast proliferation.

Finally, it should be noted that while the above describes exemplifying embodiments of the invention with reference to the accompanying drawings, the invention is not limited to the embodiments and applications described above, which are intended to be illustrative and instructive only, and not limiting. Those skilled in the art, having the benefit of this disclosure, may effect numerous modifications thereto without departing from the scope of the invention as defined by the appended claims.

Claims

wherein the weight ratio of borax to tannic acid is 1: 3 or more.

2. The hydrogel dressing according to claim 1, wherein the polyvinyl alcohol is 2 to 10 parts by weight.

3. The hydrogel dressing according to claim 1, wherein the tannic acid is 0.5 to 5 parts by weight.

4. The hydrogel dressing of claim 1, wherein the borax is 0.2-5 parts by weight.

5. The hydrogel dressing according to claim 1, wherein the van der waals recombinant collagen is 0.5-5 parts by weight.

6. The hydrogel dressing of claim 1, wherein the weight average molecular weight of the polyvinyl alcohol is 89000-98000Da and the alcoholysis degree is greater than 99%.

7. The hydrogel dressing of claim 1 for promoting wound healing.

8. The method of making a hydrogel dressing according to claim 1, comprising the steps of:

1) preparing a polyvinyl alcohol solution with a certain concentration;

2) preparing a borax solution with a certain concentration;

3) preparing a tannic acid solution with a certain concentration;

4) preparing a Van's recombinant collagen solution with a certain concentration;

uniformly mixing the borax solution prepared in the step 2) with the tannic acid solution prepared in the step 3), adding the Van's recombinant collagen solution prepared in the step 4) to obtain a solution A, adding a proper amount of the solution A into the polyvinyl alcohol solution prepared in the step 1), adding a certain amount of water according to needs, stirring uniformly, standing at room temperature and swelling for a certain time to obtain the hydrogel dressing of the claim 1; or

Uniformly mixing the borax solution prepared in the step 2) with the Van's recombinant collagen solution prepared in the step 4), adding the tannic acid solution prepared in the step 3) to obtain a solution B, adding a proper amount of the solution B into the polyvinyl alcohol solution prepared in the step 1), adding a certain amount of water according to needs, uniformly stirring, standing at room temperature, and swelling for a certain time to obtain the hydrogel dressing of claim 1; or

Mixing the polyvinyl alcohol solution prepared in the step 1) with the Van's recombinant collagen solution prepared in the step 4) to obtain a solution C, uniformly mixing the borax solution prepared in the step 2) with the tannic acid solution prepared in the step 3) to obtain a solution D, finally mixing the solution C with the solution D, adding a certain amount of water according to needs, uniformly stirring, standing at room temperature and swelling for a certain time to obtain the hydrogel dressing of the claim 1.

9. Use of the hydrogel dressing of claim 1 for the preparation of a hydrogel dressing for promoting wound healing.

10. The use of claim 9, wherein the wound healing promoting hydrogel dressing is used in combination with electrical stimulation therapy.