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CN-121987844-A - Double-layer hydrogel dressing for chronic wound diagnosis and treatment and preparation method thereof

CN121987844ACN 121987844 ACN121987844 ACN 121987844ACN-121987844-A

Abstract

The invention discloses a double-layer hydrogel dressing for chronic wound diagnosis and treatment and a preparation method thereof. The dressing is formed by compounding a pH response monitoring layer and an anti-inflammatory and antibacterial treatment layer. The monitoring layer is loaded with bromothymol blue, can generate visual color response according to pH change of the wound microenvironment to realize real-time infection monitoring, and the treatment layer takes a methacryloylated gelatin/sodium alginate dual-network as a base material, is loaded with quercetin liposome and copper ions, and has long-acting anti-inflammatory and efficient antibacterial functions. The invention enhances the mechanical property of the hydrogel by constructing a double-network structure, and in-vitro experiments prove that the hydrogel has excellent pH visual response performance and broad-spectrum killing capability on various pathogenic bacteria. The invention integrates real-time diagnosis and treatment functions, and has important application prospect in the aspects of accurate management and healing promotion of diabetes chronic wounds.

Inventors

  • ZHANG LING
  • Diao Zhenkang
  • HUANG SHIQI

Assignees

  • 四川大学

Dates

Publication Date
20260508
Application Date
20260403

Claims (10)

  1. 1. A double-layer hydrogel dressing, which is characterized by comprising a treatment layer and a monitoring layer which are arranged in a stacked manner; wherein the treatment layer is prepared by first crosslinking and solidifying treatment layer prepolymer liquid containing methacryloylated gelatin (GelMA), sodium Alginate (SA), photoinitiator phenyl (2, 4, 6-trimethylbenzoyl) lithium phosphate (LAP) and Quercetin Liposome (QLs); The monitoring layer is prepared from a monitoring layer prepolymer solution containing GelMA, a photoinitiator LAP and bromothymol blue (BTB) through second crosslinking and curing, and is laminated on the surface of the treatment layer and forms an integrated composite structure with the treatment layer; The treatment layer is also loaded with copper ions )。
  2. 2. The double-layer hydrogel dressing of claim 1, wherein in the treatment layer prepolymer liquid, the mass volume percentage of the methacryloylated gelatin is 5-15%, the mass volume percentage of the sodium alginate is 0.1-2%, the concentration of the quercetin liposome is 0.5-5 mg/mL, and the final concentration of the photoinitiator phenyl (2, 4, 6-trimethylbenzoyl) lithium phosphate is 0.2-0.3%; In the monitoring layer prepolymer liquid, the mass volume percentage of the methacryloyl gelatin is 5-15%, the mass volume percentage of the bromothymol blue is 0.03-0.08%, and the final concentration of the photo initiator phenyl (2, 4, 6-trimethylbenzoyl) lithium phosphate is 0.2-0.3%.
  3. 3. The bilayer hydrogel dressing of claim 1, wherein the thickness ratio of the therapeutic layer to the monitoring layer is 0.5-1.5:1.
  4. 4. The bilayer hydrogel dressing according to claim 1, wherein the copper ions are carried by immersing the therapeutic layer in a copper salt solution, the copper salt solution being a copper chloride solution having a concentration of 30-100 mM, the immersion time being 5-15 minutes.
  5. 5. The dual-layer hydrogel dressing of claim 1, wherein the first cross-linking curing is performed by using a 405 nm blue light source with an illumination intensity of 15-25 mW/cm2 for 30-90 seconds, and the second cross-linking curing is performed by using a 405 nm blue light source with an illumination intensity of 15-25 mW/cm2 for 80-120 seconds.
  6. 6. The bilayer hydrogel dressing according to any one of claims 1 to 7 wherein the bilayer hydrogel dressing has at least one of the following properties: (1) Visual color response from yellow to green is presented within the pH range of 4.0-8.0; (2) The compression strength is improved by more than 30 percent compared with that of single GelMA hydrogel; (3) The antibacterial rate to gram-negative bacteria and/or gram-positive bacteria is more than 99%.
  7. 7. A method of preparing a bilayer hydrogel dressing according to any one of claims 1 to 6, comprising the steps of: Preparing a treatment layer prepolymer, namely dissolving GelMA and SA in deionized water, heating and stirring until the GelMA and SA are dissolved, adding LAP, adding QLs suspension, and uniformly mixing to obtain the treatment layer prepolymer; Preparing monitoring layer prepolymer liquid, namely dissolving GelMA in deionized water, adding LAP, adding BTB solution, and uniformly mixing to obtain the monitoring layer prepolymer liquid; Injecting the pre-polymerization liquid of the treatment layer into a mold, and performing first crosslinking and curing by irradiation of a first light source to enable the treatment layer to reach a primary crosslinking state; copper ion loading, namely immersing one side of a treatment layer of the double-layer hydrogel into copper salt solution to ensure that the monitoring layer is not contacted with the solution, taking out after the soaking treatment, and washing to obtain the double-layer hydrogel dressing loaded with copper ions.
  8. 8. The preparation method of the ultraviolet curing adhesive is characterized in that 405 nm blue light sources are adopted for the first crosslinking curing, the illumination intensity is 15-25 mW/cm < 2 >, the illumination time is 30-90 seconds, 405 nm blue light sources are adopted for the second crosslinking curing, the illumination intensity is 15-25 mW/cm < 2 >, and the illumination time is 80-120 seconds.
  9. 9. The preparation method according to claim 7, wherein the copper salt solution is a copper chloride solution, the concentration is 30-100 mM, and the soaking time is 5-15 minutes.
  10. 10. Use of a bilayer hydrogel dressing according to any one of claims 1 to 6 or a bilayer hydrogel dressing prepared by a method according to any one of claims 7 to 9 in the preparation of a wound dressing, a skin tissue engineering scaffold, a surgical incision protection material or a drug delivery vehicle.

Description

Double-layer hydrogel dressing for chronic wound diagnosis and treatment and preparation method thereof Technical Field The invention relates to the technical field of biomedical materials, in particular to an intelligent visual antibacterial anti-inflammatory hydrogel for wound surface management and a preparation method thereof. The hydrogel is formed by SA and GelMA composite crosslinking, and is loadedAnd the pH indicator is used for monitoring the wound microenvironment in real time and playing an antibacterial and anti-inflammatory role. Background Wound healing is a complex physiological process involving multiple stages of hemostasis, inflammation, proliferation, and tissue remodeling. In this process, dynamic changes in the wound microenvironment have a significant impact on the healing process. The pH value is used as a key microenvironment index, and regular change is shown in different healing stages, wherein the normal healing acute wound is usually slightly acidic (pH 5.5-6.5) due to weak acidic barrier and lactic acid accumulation of skin horny layer, and when the wound is subjected to bacterial infection, bacterial metabolic activity generates alkaline metabolites such as ammonia or ischemia and hypoxia of the local tissues due to inflammatory reaction, so that the pH value of the microenvironment is often increased to an alkaline range (pH 7.4-8.5). Thus, monitoring wound pH changes in real time may provide an important reference for assessing wound status and determining whether infection has occurred. The traditional wound dressing commonly used in clinic at present mainly comprises gauze, cotton pad, hydrocolloid dressing, alginate dressing and the like. The primary functions of such dressings are limited to physical coverage, exudate absorption and maintenance of a moist environment, which are passive dressings. Although some functional dressings such as silver ion dressing and iodine-containing dressing have certain antibacterial activity, the mechanism of action is single, and mainly depends on sustained release of antibacterial components, and responsive feedback cannot be made according to real-time change of wound microenvironment. Medical staff often need to frequently change dressing and observe wound outward appearance or gather the sample and carry out microorganism culture and judge the infection state through naked eyes, and the former subjectivity is strong and the accuracy is limited, and the latter consumes time, the operation is complicated, is difficult to in time guide clinical intervention. In recent years, intelligent dressings with microenvironment response function are becoming research hotspots. Some studies have attempted to introduce pH indicators into dressing systems to achieve real-time visual monitoring of wound status. However, the existing pH response dressing mostly adopts a single-layer structure, and the indicator is directly loaded in the base material, so that the indicator is easy to leak, has poor response stability and the like. Meanwhile, such dressings generally have only a monitoring function and lack the capability of actively controlling the treatment of the wound microenvironment. In order to realize the antibacterial function, an additional compound antibacterial agent is often needed, but the controlled release of antibacterial components is difficult to realize by simple physical mixing, and mutual interference can exist between different functional layers. In addition, hydrogels are considered ideal wound dressing substrates because of their high water content, good biocompatibility, and three-dimensional network structure similar to natural extracellular matrix. GelMA, which is a photo-crosslinking gelatin derivative, has good biological activity and adjustable mechanical properties, and is widely used in the fields of tissue engineering and drug delivery. However, the mechanical strength of a single GelMA hydrogel is generally low and degrades quickly in a physiological environment, making it difficult to meet the needs of long-term wound coverage. Enhancing the mechanical properties of hydrogels by introducing a second network is an effective strategy to improve this problem. Sodium alginate is used as a natural polysaccharide, can form an ion cross-linked network with divalent metal ions, and can be compounded with a GelMA photo-linked network to construct a double-network hydrogel system, so that the mechanical stability of the material is remarkably improved. In summary, a multifunctional dressing with the functions of monitoring the microenvironment of a wound and actively regulating and controlling is developed, and the problems of poor stability of a monitoring layer, single function of a treatment layer, unstable double-layer combination and the like in the existing dressing are solved, so that the dressing has important clinical application value and research significance. Disclosure of Invention The application discloses a doub