CN111073001A

CN111073001A - Amphoteric glucan hydrogel and application thereof

Info

Publication number: CN111073001A
Application number: CN201911230399.1A
Authority: CN
Inventors: 魏玉萍; 邱夏; 焦琴; 操礼龙
Original assignee: Tianjin University
Current assignee: Tianjin University
Priority date: 2019-12-04
Filing date: 2019-12-04
Publication date: 2020-04-28

Abstract

The invention provides an amphoteric glucan hydrogel and application thereof; the hydrogel comprises the following components in percentage by mass: 15-40 wt%; a crosslinking agent: 2-10 wt%; the balance of distilled water. Wherein the zwitterionic dextran includes carboxylate betaine dextran and sulfonate betaine dextran. Uniformly mixing the zwitterionic glucan, the cross-linking agent and the distilled water in a centrifugal tube according to the content range of the components, adding a sodium hydroxide solution to adjust the pH value of the system to be 9-10, and carrying out cross-linking reaction to obtain the zwitterionic hydrogel. In order to make the shape of the gel uniform and complete, the precursor solution is transferred to a self-made polytetrafluoroethylene mold to be sized into a shape with proper size for the wound dressing before the gel is formed. The hydrogel has high water content, so that the wound is in a moist environment; the water absorption capacity is strong, and the secreted body fluid can be absorbed at any time, so that excessive effusion does not exist at the wound part; has good biocompatibility and can not cause skin allergy, red swelling and the like.

Description

Amphoteric glucan hydrogel and application thereof

Technical Field

The invention relates to the technical field of macromolecules, and relates to an amphoteric glucan hydrogel and application thereof. In particular to an amphoteric glucan hydrogel composition for wound dressing and application thereof.

Background

The skin, the largest organ of the human body, serves as a medium for the human body to contact the external environment and is also the main natural defense line of the human body, guarding underlying organs and protecting the body from pathogens and microorganisms. Thus, it is directly affected by harmful microorganisms, heat, machinery and chemistry. If the skin is infected by bacterial erosion after being damaged, the local immunity of the human body is reduced, the body fluid is lost, and various complications can be caused.

After the skin is wounded, people can select proper dressings according to different wounds, and the main purposes are to quickly and comprehensively reduce the infection degree of the wound and promote the healing of the wound. The development process of the wound dressing mainly goes through the following three stages: 1. a conventional type dressing; 2. a passive type dressing; 3. a novel dressing. The traditional dressings mainly comprise traditional dressings such as sheep grease, linen and the like and passive dressings such as cotton, gauze, bandages and the like; the novel dressing mainly comprises the following four types: synthetic dressing, biological dressing, tissue engineering wound surface covering and novel biological synthetic dressing. In the healing of common wounds, the synthetic dressing in the novel dressing is relatively mostly hydrogel, and can be promoted to be in more effective contact with the wounds due to the unique soft performance of the hydrogel, and a good moist environment can be provided for the wounds, so that the hydrogel has a good effect of promoting the healing of the wounds.

In 1962, Winter discovered in studies that the epithelialization rate of skin can be increased by 1 time when polyethylene film is used for covering the surface of a pig, and the discovery firstly proves that the moist and breathable wound dressing can accelerate wound healing, in other words, the moist environment can accelerate wound healing compared with the dry environment, so that the discovery makes breakthrough progress on the cognition of the wound healing process.

In general, an ideal medical dressing for wound surface should have the following functions: the moisture absorption and retention performance is good, and the excessive loss of water and body fluid in the body can be prevented; the wound surface can be kept clean and the probability of bacterial infection can be reduced by continuously removing necrotic tissues at the wound surface; the antibacterial and bacteriostatic properties are good, and the wound surface can be effectively prevented from being infected; the dressing can be tightly attached to the wound surface but not adhered to the wound surface; the wound surface is kept moist and is positioned in an environment without effusion; has good biocompatibility and can promote wound healing.

The hydrogel dressing is a novel moist type dressing. The hydrogel dressing generally consists of two parts, namely hydrogel and a base layer, has excellent biocompatibility, is in a three-dimensional network structure formed by crosslinking macromolecular chains of hydrophilic groups, can swell in water due to the hydrophilic groups, and is very soft in texture. Compared with other dressings, the hydrogel material containing the hydrated structure can continuously absorb the exudate of the wound surface and does not pollute the wound surface; the dressing can be continuously used for 3-7 days without replacement, so that the replacement frequency is obviously reduced, and the waste discharge is reduced to reduce the pollution to the environment; meanwhile, the hydrogel dressing can be closely attached to the wound surface without adhesion, so that the opportunity of bacterial breeding can be reduced, and the dressing is easy to replace; various medicines and growth factors can be loaded in the three-dimensional reticular structure, so that the healing of the wound surface is promoted; in addition, the hydrogel is semitransparent, so that doctors can directly observe the healing condition of wounds through the hydrogel, and the use amount of the medicine can be adjusted in time.

Natural polymers are often used to make hydrogel dressings because of their good biocompatibility. Among them, dextran, gelatin, chitosan, hyaluronic acid, pectin, and the like have been studied in many cases. Dextran (Dextran) is a very important natural biological polysaccharide, is easily soluble in water, is formed by dehydration polymerization of glucose units, has three hydroxyl groups on each glucose unit, is easy to modify and crosslink, and can be modified to form hydrogel through chemical crosslinking. In addition, the dextran also has the functions of immunoregulation, anti-tumor, antioxidation, antivirus, etc. Among them, the immunoregulatory function is considered as the most important physiological activity function, and it can activate macrophages, neutrophils and the like, induce cytokine production, promote fibroblast proliferation, effectively enhance the immune system, and is of great interest in infectious diseases and wound treatment. Therefore, the glucan hydrogel with good biocompatibility and biodegradability becomes a hot spot of research, and is a potential ideal wound dressing. Amphoteric glucans are a very important class of polysaccharide derivatives, which are the products of zwitterionic betaine-modified glucans. The results show that the amphoteric polysaccharide has good protein adsorption resistance and immunoregulation function. However, to date, amphoteric dextran hydrogels have been largely unreported for use in wound dressings.

Disclosure of Invention

The invention provides an amphoteric glucan hydrogel and application thereof; preparation of amphoteric dextran hydrogel and application thereof in wound dressing.

Aiming at the defects of the existing dressing material, the invention firstly utilizes a glucan betaine, specifically comprises Carboxyl Betaine (CB) or Sulfobetaine (SB) amphoteric glucan material as the wet hydrogel raw material. As the macromolecules simultaneously have positive and negative charges on the same monomer unit, the macromolecules can be combined with water molecules through the ionic solvation effect, and a large number of water molecules can be bound to enable the water molecules to be retained in a gel network structure, so that the material disclosed by the invention can maintain a good wet environment, and can also keep a certain three-dimensional network shape to ensure good mechanical properties. On the other hand, a large number of hydroxyl groups and zwitterions in the glucan structure of the material form a hydration layer with a synergistic effect on the surface, and the material has strong nonspecific protein adsorption resistance and biocompatibility, so that foreign body rejection and bacterial adhesion can be effectively resisted, and meanwhile, adhesion with wounds can be avoided. The dextran betaine zwitterionic hydrogel used in the invention has outstanding nonspecific protein adsorption resistance, is used for wound dressings, does not adhere to wounds, is easy to remove, and avoids secondary damage to granulation tissues of the wounds; more importantly, the experimental result shows that the glucan zwitterion hydrogel used as the dressing can accelerate the healing speed of the wound; the zwitterionic hydrogel material according to the invention therefore meets the basic requirements of an ideal dressing in all respects.

The invention aims to provide a preparation method of zwitterionic polysaccharide hydrogel.

The invention aims to apply the prepared zwitterionic glucan hydrogel to a wound dressing to obtain the dressing which can prevent wound adhesion and remarkably accelerate the wound healing speed.

The specific technical scheme is as follows:

the invention discloses an amphoteric glucan hydrogel which comprises the following components in percentage by mass:

zwitterionic dextran: 15-40 wt%

A crosslinking agent: 2 to 10 weight percent of a catalyst,

the balance of distilled water.

The content of the dextran betaine zwitterion, the cross-linking agent and the distilled water is 100 wt%, and the zwitterionic dextran material used in the invention is a compound with positive and negative charges on the same monomer, such as betaine modified dextran compounds, including carboxylate betaine dextran and sulfonate betaine dextran.

The amphoteric glucan is carboxyl glucan betaine, and the chemical structural formula is as follows; the degree of substitution of the zwitterion is from 5 to 40%.

The amphoteric glucan is sulfoglucan betaine, and the chemical structural formula is as follows; the degree of substitution of the zwitterion is 5-40%;

the cross-linking agent is borax, N, N-methylene bisacrylamide, N, N-bis (acryloyl) cystamine, sodium tetraborate, ethylene glycol diglycidyl ether and polyethylene glycol diglycidyl ether.

The cross-linking agent used in the invention is N, N-methylene bisacrylamide, sodium tetraborate, ethylene glycol diglycidyl ether, polyethylene glycol diglycidyl ether or N, N-bis (acryloyl) cystamine.

The prepared zwitterionic hydrogel is directly used for wound dressing. Specifically, the zwitterionic glucan, a cross-linking agent and distilled water are uniformly mixed in a centrifugal tube according to the content range of the components, a sodium hydroxide solution is added to adjust the pH value of a system to be 9-10, the zwitterionic hydrogel is obtained through a cross-linking reaction, and then the zwitterionic hydrogel is taken out and placed in a special polytetrafluoroethylene mold to be shaped into a wound dressing with a proper size.

The application of the invention is illustrated as follows: the zwitterionic polysaccharide hydrogel disclosed by the invention acts on a wound independently, and can maintain a moist environment required by wound healing due to the unique hydrophilicity and anti-adsorption capacity without adding other medicines, cells or active factors, so that secondary damage caused by wound adhesion of dressing can be avoided, and the rapid healing of the wound and the effective repair of skin functions can be promoted.

The zwitterionic polysaccharide hydrogel can adopt various crosslinking methods, such as a borax crosslinking method, Michael addition and the like. The borax cross-linking method is adopted, the forming time is short, the borax simultaneously plays a role in sterilization, the possibility of wound infection is reduced, and the dressing is beneficial to keeping the cleanness of the wound and promoting the wound healing after acting on the wound.

The positive progress effects of the invention are as follows: 1) the water content is high, so that the wound is in a moist environment, and meanwhile, the water absorption capacity is strong, and the secreted body fluid can be absorbed at any time, so that excessive effusion does not exist at the wound part; 2) the zwitterionic hydrogel has the advantages of hydrogel, is soft in texture, has good fitting degree with wounds and does not adhere to the wounds; 3) has good biocompatibility, does not cause the problems of skin allergy, red swelling and the like, and can promote the rapid healing of wounds.

The use of the amphoteric dextran hydrogel of the present invention in wound dressing design is based on the following reasons: (1) the matrix material glucan can induce macrophages to gather in an injury area, strengthen wound necrotic tissues and remove the wound necrotic tissues, and prevent bacterial invasion; (2) the hydration layer is formed by the ionization of carboxyl betaine or sulfobetaine zwitterion and the synergistic action of a large number of hydroxyl hydrogen bonds in the glucan structure, so that nonspecific protein adsorption can be effectively resisted, and when the chitosan modified polysaccharide is used for wound dressing, the adsorption of microorganisms and cells on the surface of a wound can be reduced, and inflammatory reaction can be reduced; in addition, zwitterionic dextran has immunoregulatory effects of activating T cells.

The invention has the following effects: the amphoteric glucan hydrogel without any antibiotic drug is used for mouse wound dressing, the mouse wound dressing can be healed in 14 days, and the effect is superior to that of the commercial dressing Duoderms film and unmodified glucan hydrogel. Due to the fact that the amphoteric glucan structure contains zwitterion groups and has a synergistic effect with hydroxyl in the glucan structure, nonspecific protein adsorption can be effectively resisted, inflammatory reaction can be reduced to a great extent, a new application approach is developed for polysaccharide, and the amphoteric glucan structure has important practical significance and wide development prospect. In addition, the amphoteric glucan hydrogel has low cost of raw materials, simple process and good industrial application prospect, and is still not reported in documents at present when being used as a wound dressing.

Drawings

FIG. 1 comparison of wound healing Effect of amphoteric dextran hydrogel and commercial dressing Duoderms film

Detailed Description

Example 1: preparation of dextran Carboxylic acid betaine (Dex-CB) hydrogels

The components in percentage by weight are as follows:

content of carboxybetaine glucan: 40 percent of

Sodium tetraborate: 5 percent of

Distilled water: 55 percent of

Adding 1000mg of carboxyl betaine glucan into a glass bottle containing 0.9mL of deionized water, performing ultrasonic treatment for about 30 minutes until the carboxyl betaine glucan is completely dissolved, adding 0.125g of sodium tetraborate into 0.5mL of water, heating to dissolve the sodium tetraborate, adding the dissolved sodium tetraborate into amphoteric glucan carboxyl betaine aqueous solution, and adjusting the pH of the system to 9 by using 1mol/L NaOH aqueous solution. And performing ultrasonic treatment for 5 minutes to obtain the hydrogel at the bottom of the glass bottle, wherein the hydrogel is transparent in texture and good in flexibility. In order to make the shape of the gel uniform and complete, the precursor solution needs to be transferred to a self-made polytetrafluoroethylene cylindrical mold before the cross-linking agent and the amphoteric carboxylic acid betaine glucan solution are gelatinized, so that a cylindrical gel sheet with a regular and complete shape is obtained.

Example 2: preparation of dextran Carboxylic acid betaine (Dex-CB) hydrogels

The components in percentage by weight are as follows:

amphoteric carboxy betaine glucan content: 15.9 percent

N, N-methylenebisacrylamide: 2.25 percent

Distilled water: 81.85 percent

Adding 0.113g of carboxyl betaine glucan into a glass bottle containing 0.582mL of deionized water, performing ultrasonic treatment for about 30 minutes until the carboxyl betaine glucan is completely dissolved, adding 0.016g of N, N-methylene bisacrylamide, performing constant-temperature reaction at 50 ℃ for 30 minutes, and adjusting the pH value of the system to 10 by using 2mol/L NaOH aqueous solution. Ultrasonic crosslinking was carried out for 5 minutes to obtain a colorless transparent gel. In order to make the gel form uniform and complete, the precursor solution needs to be transferred to a self-made polytetrafluoroethylene cylindrical mold before the cross-linking agent and the amphoteric carboxyl betaine glucan solution are gelatinized, and the mold is sealed and placed in an oven at 50 ℃. After 30 minutes, the reaction is complete, and the gel sheet is carefully peeled off after cooling at room temperature to obtain a cylindrical gel sheet with a regular and complete shape.

Example 3: preparation of dextran Carboxylic acid betaine (Dex-CB) hydrogels

The components in percentage by weight are as follows:

amphoteric carboxy betaine glucan content: 15.7 percent

N, N' -bis (acryloyl) cystamine: 3.88 percent

Distilled water: 80.42 percent

Adding 0.113g of carboxyl betaine glucan into a glass bottle containing 0.578mL of deionized water, carrying out ultrasonic treatment for 30 minutes until the carboxyl betaine glucan is completely dissolved, adding 0.028g of N, N-bis (acryloyl) cystamine, carrying out constant temperature reaction for 30 minutes at 50 ℃, and adjusting the pH of the system to 10 by using 2mol/L NaOH aqueous solution. Ultrasonic crosslinking was carried out for 5 minutes to obtain a colorless transparent gel. In order to make the gel form uniform and complete, the precursor solution needs to be transferred to a self-made polytetrafluoroethylene cylindrical mold before the cross-linking agent is gelatinized with the amphoteric carboxylic betaine solution, and the mold is sealed and placed in an oven at 50 ℃. After 30 minutes, the reaction is complete, and the gel sheet is carefully peeled off after cooling at room temperature to obtain a cylindrical gel sheet with a regular and complete shape.

Example 4: preparation of dextran Sulfonyl betaine (Dex-SB) hydrogel

The components in percentage by weight are as follows:

preparation content of amphoteric dextran sulfonic acid betaine water gel: 25 percent of

Sodium tetraborate: 5 percent of

Distilled water: 70 percent of

Amphoteric dextran sulfobetaine 1000mg was added to a glass vial containing 2.0mL deionized water and sonicated for 30 minutes until completely dissolved. 0.2g of sodium tetraborate is added into 0.8mL of water, heated and dissolved, then added into an amphoteric dextran sulfonic acid group betaine aqueous solution, and the pH value of the system is adjusted to 9 by using a 1mol/L NaOH aqueous solution. And carrying out ultrasonic crosslinking for 5 minutes to obtain the formed hydrogel. The obtained zwitter-ion hydrogel is transparent in texture and good in flexibility. In order to make the shape of the gel uniform and complete, the precursor solution needs to be transferred to a self-made polytetrafluoroethylene cylindrical mold before the cross-linking agent and the amphoteric sulfobetaine dextran solution are gelatinized, so as to obtain a cylindrical gel sheet with a regular and complete shape.

Example 5: preparation of amphoteric dextran Sulfonyl betaine (Dex-SB) hydrogel

The components in percentage by weight are as follows:

amphoteric sulfobetaine glucan content: 15.9 percent

N, N-methylenebisacrylamide: 2.25 percent

Distilled water: 81.85 percent

Adding 0.113g of amphoteric dextran sulfobetaine into a glass bottle containing 0.582mL of deionized water, carrying out ultrasonic treatment for 30 minutes until the amphoteric dextran sulfobetaine is completely dissolved, adding 0.016g of N, N-methylene bisacrylamide, reacting at the constant temperature of 50 ℃ for 30 minutes, and adjusting the pH value of the system to 10 by using 2mol/L NaOH aqueous solution. Ultrasonic crosslinking was carried out for 5 minutes to obtain a colorless transparent gel. In order to make the gel form uniform and complete, the polymer precursor solution needs to be transferred into a self-made polytetrafluoroethylene cylindrical mold before the cross-linking agent and the amphoteric sulfobetaine dextran solution are gelatinized, and the mold is sealed and placed in an oven at 50 ℃. After 30 minutes, the reaction is complete, and the gel sheet is carefully peeled off after cooling at room temperature to obtain a cylindrical gel sheet with a regular and complete shape.

Example 6: preparation of amphoteric dextran Sulfonyl betaine (Dex-SB) hydrogel

The components in percentage by weight are as follows:

amphoteric dextran sulfobetaine content: 15.70 percent

N, N' -bis (acryloyl) cystamine: 3.88 percent

Distilled water: 80.42 percent

Adding 0.578mL of deionized water into a glass bottle, adding 0.113g of amphoteric dextran sulfate betaine, performing ultrasonic treatment for about 30 minutes until the amphoteric dextran sulfate betaine is completely dissolved, adding 0.028g of N, N-methylene bisacrylamide, performing constant temperature reaction at 50 ℃ for 30 minutes, and adjusting the pH value of the system to 10 by using 2mol/L NaOH aqueous solution. Ultrasonic crosslinking was carried out for 5 minutes to obtain a colorless transparent gel. In order to make the gel form uniform and complete, the polymer precursor solution needs to be transferred into a self-made polytetrafluoroethylene cylindrical mold before the cross-linking agent and the amphoteric sulfobetaine dextran solution are gelatinized, and the mold is sealed and placed in an oven at 50 ℃. After 30 minutes, the reaction is complete, and the gel sheet is carefully peeled off after cooling at room temperature to obtain a cylindrical gel sheet with a regular and complete shape.

Example 7: preparation of Dextran (Dextran) hydrogel

The components in percentage by weight are as follows:

content of glucan: 40 percent of

Sodium tetraborate: 10 percent of

Distilled water: 50 percent of

Add 1000mg of dextran to a glass vial containing 0.8mL of deionized water and sonicate for 30 minutes until completely dissolved. 0.25g of sodium tetraborate is added into 0.45mL of water, heated and dissolved, then added into a glucan water solution, and the pH of the system is adjusted to 9 by using a 1mol/L NaOH water solution. And carrying out ultrasonic crosslinking for 5 minutes to obtain the formed hydrogel. The obtained hydrogel has transparent texture and good flexibility. In order to make the gel form uniform and complete, the precursor solution needs to be transferred to a self-made polytetrafluoroethylene cylindrical mold before the cross-linking agent and the glucan solution are gelatinized, so as to obtain a cylindrical gel sheet with a regular and complete shape.

In the preparation process, the raw material proportion can be changed to prepare the hydrogel with different solid contents. The effects of the obtained glucan hydrogel, carboxyl betaine glucan hydrogel and sulfobetaine glucan hydrogel when used in a mouse wound dressing are shown in figure 1, and the effects of the carboxyl betaine glucan hydrogel and the sulfobetaine glucan hydrogel are obviously superior to those of unmodified glucan hydrogel and commercialized dressing Duoderms film.

The techniques disclosed and suggested in this invention can be implemented by those skilled in the art by appropriately changing the raw materials and process parameters by referring to the contents of the text. While the methods and products of the present invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and products described herein may be made and equivalents employed to practice the techniques of the present invention without departing from the spirit and scope of the invention. It is expressly intended that all such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and content of the invention.

Thirdly, establishing animal model

Mouse model: anesthetizing a mouse with the weight of 20-24g, depilating the back of the mouse with depilatory cream, disinfecting the mouse with an alcohol cotton ball, wiping the mouse dry after wiping the mouse with normal saline, using a biological sampler with the diameter of 5mm to excise the skin on the back of the mouse according to the current clinical practice experience to form a circular open wound with the diameter of 5mm, and then applying a corresponding dressing. Among them, control group 1 was a Duoderm dressing, a dressing produced by the united states of america, which was the first dressing to use hydrocolloid technology, and also a dressing that is the first choice for clinically treating chronic wounds such as bedsores at present. Control 2 was Dextran hydrogel, which is a non-zwitterionic hydrogel material. Experimental group 1 is a zwitterionic dextran Dex-CB hydrogel. Experimental group 2 was a zwitterionic dextran Dex-SB hydrogel.

Healing effect: the healing results of the mice are shown in the attached figure, when the mice burn for 3 days, the wounds begin to shrink gradually, the wound areas of the zwitterionic carboxylic acid betaine glucan (Dex-CB) hydrogel and the zwitterionic sulfobetaine glucan (Dex-SB) hydrogel are faster than those of two control groups of Dextran and Duoderm hydrogel dressings, and the wound areas measured at the same time points are small. From day 8 onwards, the mouse burn wounds using Duoderm and using Dextran hydrogel also started to heal gradually, but the healing speed was significantly slower than in the two experimental groups using zwitterionic hydrogel. The mouse burn wounds of the Dex-CB and Dex-SB hydrogel groups were close to healing, the wounds were covered by neogenetic epithelial tissue, in contrast to the wounds of the Dextran and Duoderm groups which were not yet completely closed, the wound centers appeared reddish, and the neogenetic epithelial tissue was thinner. The mouse burn wounds were healed by Dex-CB and Dex-SB hydrogel groups on day 14.

The mice using the zwitterionic hydrogel dressing had advanced wound healing time and faster hair growth around the wound, with significantly less scar tissue from the new skin than the control, compared to the mice using the Dextran, Duoderm hydrogel dressing, indicating that the zwitterionic hydrogel dressing significantly increased the rate of wound healing.

The above examples are only for illustrating the technical idea and solutions of the present invention and should not be construed as limiting the scope of the present invention, and all equivalent changes and available modifications made according to the spirit of the present invention should be regarded as the protection content of the present invention.

Claims

1. An amphoteric dextran hydrogel; the paint is characterized by comprising the following components in percentage by mass:

amphoteric glucan: 15 to 40 weight percent of the total weight of the alloy,

a crosslinking agent: 2 to 10 weight percent of a catalyst,

the balance of distilled water.

2. A hydrogel according to claim 1; the amphoteric glucan is carboxyl glucan betaine, and the chemical structural formula is as follows; the degree of substitution of the zwitterion is from 5 to 40%.

3. A hydrogel according to claim 1; the amphoteric glucan is characterized in that the amphoteric glucan is sulfoglucan betaine, and the chemical structural formula is as follows; the degree of substitution of the zwitterion is 5-40%;

4. a hydrogel according to claim 1; the cross-linking agent is N, N-methylene bisacrylamide, sodium tetraborate, ethylene glycol diglycidyl ether, polyethylene glycol diglycidyl ether or N, N-bis (acryloyl) cystamine.

5. The amphoteric dextran hydrogel of claim 1 for use in a wound dressing.

6. The application of claim 5, wherein the zwitterionic glucan hydrogel is prepared by uniformly mixing the zwitterionic glucan, the cross-linking agent and distilled water in a centrifugal tube according to the content range of the components, adding a sodium hydroxide solution to adjust the pH value of the system to 9-10, and performing cross-linking reaction. In order to achieve uniform and complete gel morphology, the precursor solution needs to be transferred to a self-made polytetrafluoroethylene mold to be sized into a shape of a proper size for use in a wound dressing before the cross-linking agent is gelled with the amphoteric dextran solution.