A dual-network composite hydrogel with low-temperature photothermal antibacterial and L-arginine delivery functions and a preparation method and application thereof

Abstract

This invention discloses a dual-network composite hydrogel with both low-temperature photothermal antibacterial and L-arginine delivery functions, its preparation method, and its applications, belonging to the field of biomedical technology. The dual-network composite hydrogel consists of a dual-network gel matrix and mesoporous polydopamine nanoparticles loaded with L-arginine. In the dual-network gel matrix, one network is formed by cross-linking oxidized hyaluronic acid and carboxymethyl chitosan through Schiff base bonds, while the other network is formed by polyvinylpyrrolidone, oxidized hyaluronic acid, and carboxymethyl chitosan through hydrogen bonding. The dual-network composite hydrogel of this invention exhibits excellent tissue adhesion, self-healing ability, and mechanical properties. It can achieve photothermal antibacterial effects through 808 nm near-infrared laser irradiation, while simultaneously releasing L-arginine and scavenging reactive oxygen species, synergistically promoting the healing of infected wounds, and has promising application prospects in the treatment of infected wounds.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to a dual-network composite hydrogel with both low-temperature photothermal antibacterial and L-arginine delivery functions, its preparation method and application, which is particularly suitable for the repair and treatment of bacterial infected wounds. Background Technology

[0002] As the largest organ in the human body, the skin plays vital physiological roles such as barrier protection and temperature regulation. Damage to its integrity makes it susceptible to bacterial infections and oxidative stress imbalances, leading to delayed wound healing. Traditional wound dressings, such as gauze, can only provide basic wound coverage and cannot simultaneously address multiple healing challenges, including infection control, inflammation regulation, and tissue regeneration, resulting in limited clinical effectiveness.

[0003] Photothermal therapy (PTT) has become a research hotspot in the treatment of infected wounds due to its advantages such as being non-invasive, having broad-spectrum antibacterial activity, and being less likely to induce drug resistance. Mesoporous polydopamine nanoparticles (MPDA NPs), as excellent photothermal agents, possess good biocompatibility, strong photothermal stability, and drug delivery capabilities. Their abundant catechol structures on the surface can also scavenge reactive oxygen species (ROS) and alleviate oxidative stress damage. L-arginine, as a key bioactive substance, participates in the synthesis of biomolecules such as nitric oxide and polyamines, and can effectively promote angiogenesis and tissue repair. However, exogenous supplementation suffers from problems such as easy degradation and short duration of action.

[0004] Hydrogel dressings are widely used in wound care due to their three-dimensional network structure similar to the extracellular matrix, high water-holding capacity, and good tissue compatibility. Natural polysaccharide-based hydrogels, such as hyaluronic acid and chitosan derivatives, possess inherent antibacterial and anti-inflammatory properties; however, their single-network structure often suffers from insufficient mechanical strength and poor self-healing ability. Constructing a dual-network structure can significantly improve the mechanical properties of hydrogels, and synergistic loading of photothermal agents and bioactive molecules holds promise for achieving a multifunctional integration of "antibacterial-antioxidant-promoting repair," providing a systematic solution for the healing of infected wounds.

[0005] While some existing composite hydrogels integrate photothermal and drug delivery functions, they still suffer from the following shortcomings: firstly, the loading stability of photothermal agents and drugs is poor; secondly, the mechanical strength and tissue adhesion of the hydrogel are difficult to adapt to the dynamic wound environment; and thirdly, the regulation of different healing stages is not precise enough, failing to achieve the synergistic effects of antibacterial, antioxidant, and tissue regeneration promotion. Therefore, developing a composite hydrogel with excellent mechanical properties and stable photothermal-drug synergistic delivery capabilities has significant clinical application value. Summary of the Invention

[0006] To address the problems existing in the prior art, the present invention aims to provide a dual-network composite hydrogel with both low-temperature photothermal antibacterial and L-arginine delivery functions, as well as its preparation method and application. This hydrogel enhances mechanical properties and self-healing ability through a dual-network structure, and achieves synergistic effects of photothermal antibacterial, ROS scavenging and L-arginine sustained release through MPDA@L-Arg NPs, effectively promoting the healing of infected wounds.

[0007] A dual-network composite hydrogel possessing both low-temperature photothermal antibacterial properties and L-arginine delivery capabilities comprises a dual-network gel matrix and mesoporous polydopamine nanoparticles (MPDA@L-Arg NPs) loaded with L-arginine. In the dual-network gel matrix, one network is formed by cross-linking oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMCS) via Schiff base bonds, endowing the hydrogel with self-healing properties and an antibacterial basis. The other network is formed by polyvinylpyrrolidone (PVP) with OHA and CMCS through hydrogen bonding, significantly enhancing the mechanical strength and stability of the hydrogel. MPDA@L-Arg NPs are dispersed within the dual-network gel matrix, achieving stable L-arginine loading through electrostatic interactions.

[0008] The oxidation degree of the OHA is 25%~30%, which not only retains the biocompatibility of hyaluronic acid, but also forms Schiff base bonds with the amino groups of CMCS through the aldehyde group; the carboxylation degree of CMCS is ≥80%, and the molecular weight is 100 kDa~200 kDa, which has good antibacterial and hemostatic properties; PVP interacts with the polysaccharide chain through hydrogen bonds, which enhances the network density.

[0009] The MPDA@L-Arg NPs have a particle size of 150 nm to 200 nm, possessing a high specific surface area and mesoporous structure, which is beneficial for L-arginine loading; the L-arginine loading is 25% to 30%; the concentration of MPDA@L-Arg NPs in the dual-network composite hydrogel is 0.5 mg / mL to 2.0 mg / mL, which can achieve synergistic regulation of photothermal effect and drug sustained release.

[0010] This invention also provides a method for preparing the above-mentioned dual-network composite hydrogel with both low-temperature photothermal antibacterial and L-arginine delivery functions, specifically including the following steps: Preparation of oxidized hyaluronic acid (OHA): Hyaluronic acid was dissolved in deionized water, and an aqueous solution containing sodium periodate was added. The mixture was stirred in the dark. Ethylene glycol was then added dropwise, and stirring was continued to quench any unreacted sodium periodate. After the reaction was complete, the mixture was dialyzed with deionized water and freeze-dried to obtain OHA with an oxidation degree of 25%–30%. Preparation of MPDA@L-Arg NPs: MPDA NPs were synthesized by emulsion-induced interfacial self-assembly method, dispersed in Tris-HCl solution, L-arginine solution was added, and after electrostatic interaction loading, centrifugation and washing were performed to obtain mesoporous polydopamine nanoparticles loaded with L-arginine, denoted as MPDA@L-Arg NPs. Preparation of dual-network composite hydrogel: CMCS and PVP were added to deionized water and stirred to form a homogeneous solution A; OHA and MPDA@L-Arg NPs were added to deionized water and stirred to form a homogeneous solution B; solutions A and B were mixed and stirred to obtain the dual-network composite hydrogel.

[0011] In the above steps for preparing oxidized hyaluronic acid: the molecular weight of hyaluronic acid is 100 kDa~400 kDa, and the mass ratio of hyaluronic acid to sodium periodate is (1.0~3.0):(0.5~1.5); the reaction time is 4~8 hours with stirring in the dark; after the reaction is completed, the reaction solution is transferred to a dialysis bag with a molecular weight cutoff of 3500 Da and dialyzed with deionized water for 24~48 hours; the freeze-drying temperature is -50℃.

[0012] In the above steps for preparing MPDA@L-Arg NPs: Pluronic F127 and dopamine are dissolved in a mixed solvent of distilled water and ethanol, stirred until homogeneous, and 1,3,5-trimethylbenzene is slowly added dropwise. The mixture is then sonicated for 5-15 minutes to form a stable emulsion. The mass-to-volume ratio of Pluronic F127, dopamine, and 1,3,5-trimethylbenzene is (0.1-0.3) g:(0.1-0.3) g:(0.1-0.3) mL. Ammonia is added dropwise to the emulsion, and the mixture is stirred at room temperature for 2-12 hours. After the reaction, the mixture is centrifuged at 8000-12000 rpm for 10-20 minutes, the precipitate is collected, and the precipitate is sonicated 1-4 times with a mixture of ethanol and acetone for 10-30 minutes each time to obtain MPDA NPs.

[0013] MPDA NPs were dispersed in Tris-HCl solution and ultrasonically dispersed; Tris-HCl solution containing L-arginine (pH=8.5) was added, and the mixture was stirred at room temperature for 12-48 hours. After the reaction was completed, the mixture was centrifuged at 8000 rpm to 12000 rpm for 10-30 minutes and washed with deionized water 1-5 times to obtain MPDA@L-Arg NPs; wherein the mass ratio of MPDA NPs to L-arginine was (5-15):(5-55).

[0014] In the above steps for preparing the dual-network composite hydrogel: CMCS (2.0 wt%~6.0 wt%) and PVP (6.0 wt%~12 wt%) were added to deionized water and stirred at 40℃~80℃ to form a homogeneous solution A; OHA (2.0 wt%~6.0 wt%) and MPDA@L-Arg NPs were added to deionized water and stirred to form a homogeneous solution B; equal volumes of solution A and solution B were mixed and stirred to obtain the dual-network composite hydrogel. The concentration of MPDA@L-Arg NPs in the dual-network composite hydrogel was 0.5 mg / mL~2.0 mg / mL.

[0015] The application of the dual-network composite hydrogel described in this invention in the preparation of therapeutic products for healing infected wounds is particularly suitable for skin defects caused by Staphylococcus aureus and Escherichia coli infections. In use, the composite hydrogel is applied directly to the wound surface, followed by irradiation with an 808 nm near-infrared laser (power density 0.5 W / cm²). 2 ~2.0 W / cm 2 The product kills bacteria through photothermal effects, with an inhibition rate of ≥98% against Staphylococcus aureus and ≥97% against Escherichia coli. At the same time, MPDA NPs remove excess ROS at the wound site and alleviate oxidative stress. L-arginine is continuously released from the hydrogel, providing raw materials for angiogenesis and tissue repair. The three work synergistically to promote wound healing.

[0016] The beneficial effects of this invention are: Synergistic effect of dual network structure: One network formed by Schiff base bonds endows the hydrogel with good self-healing ability and antibacterial basis, while the other network formed by hydrogen bonds significantly improves the mechanical strength and tissue adhesion of the hydrogel, which can adapt to the dynamic wound environment and avoid displacement or detachment.

[0017] Synergistic effects of photothermal-pharmacological-antioxidant action: MPDA@L-Arg NPs combine photothermal antibacterial, ROS scavenging, and L-arginine sustained-release functions. Under 808 nm near-infrared irradiation, they can precisely kill bacteria while alleviating oxidative stress and inflammatory responses, continuously supplying bioactive substances. In an infected wound model, the wound healing rate within 12 days is ≥96%, effectively promoting angiogenesis and collagen deposition, and improving wound healing quality. Attached Figure Description

[0018] Figure 1 SEM images of MPDA NPs (a) and MPDA@L-Arg NPs (b) of the present invention; Figure 2 This is a SEM image of the dual-network composite hydrogel of the present invention. Figure 3 This is a rheological frequency scanning curve of the dual-network composite hydrogel of the present invention; Figure 4 This is a rheological alternating step strain curve of the dual-network composite hydrogel of the present invention. Figure 5 The stress-strain curve of the dual-network composite hydrogel of the present invention is shown. Figure 6 The image shows the adhesion strength results of the dual-network composite hydrogel of the present invention. Figure 7 The photothermal heating curve of the dual-network composite hydrogel of the present invention is shown below. Figure 8 This is a graph showing the photothermal switching cycle performance of the dual-network composite hydrogel of the present invention. Figure 9 This is a diagram illustrating the antioxidant capacity of the dual-network composite hydrogel of the present invention. Figure 10 This is a diagram illustrating the antibacterial effect of the dual-network composite hydrogel of the present invention. Figure 11 This is an in vitro sustained-release curve of L-arginine in the dual-network composite hydrogel of the present invention; Figure 12 This is a diagram illustrating the wound healing effect of the dual-network composite hydrogel of the present invention. Detailed Implementation

[0019] To more clearly demonstrate the objectives, technical solutions, and advantages of this invention, the technical solutions will be described in detail below. Obviously, the described embodiments are only some examples of this invention, not all examples. Based on these embodiments, all other embodiments obtained by those skilled in the art without creative effort should be considered within the scope of protection of this invention.

[0020] Unless otherwise specified in the embodiments, all techniques or conditions employed were conventional methods or based on techniques or conditions described in the literature in this field, or in accordance with product instructions. Reagents and instruments used, unless otherwise specified by manufacturer, were all conventional products that could be purchased through legitimate channels.

[0021] Example 1 Preparation of dual-network composite hydrogels: Preparation of oxidized hyaluronic acid (OHA): 2.0 g of hyaluronic acid (molecular weight 200 kDa) was dissolved in 100 mL of deionized water and stirred until completely dissolved; 10 mL of an aqueous solution containing 1.0 g of sodium periodate was added, and the mixture was stirred in the dark for 6 hours; then 2.4 mL of ethylene glycol was added dropwise, and stirring was continued for 1 hour to quench unreacted sodium periodate; after the reaction was completed, the reaction solution was transferred to a dialysis bag with a molecular weight cutoff of 3500 Da, and dialyzed with deionized water for 48 hours, with the dialysate being replaced every 12 hours; finally, OHA was obtained by freeze-drying, and its oxidation degree was determined to be 28.48% by hydroxylamine hydrochloride titration.

[0022] Preparation of MPDA@L-Arg NPs: 0.2 g Pluronic F127 and 0.1 g dopamine were dissolved in a mixed solvent of 10 mL distilled water and 10 mL ethanol and stirred until homogeneous. 0.2 mL of 1,3,5-trimethylbenzene was slowly added dropwise, and the mixture was sonicated for 10 minutes to form a stable emulsion. 1 mL of ammonia was added dropwise to the emulsion, and the mixture was stirred at room temperature for 4 hours. After the reaction, the mixture was centrifuged at 10,000 rpm for 20 minutes, and the precipitate was collected. The precipitate was washed three times with a mixture of ethanol and acetone (volume ratio 2:1) for 20 minutes each time to obtain MPDA NPs. 10.0 mg of MPDA NPs were dispersed in 10.0 mL Tris-HCl solution (pH 8.5). 1 mL Tris-HCl solution containing 30.0 mg L-arginine was added, and the mixture was stirred at room temperature for 24 hours. After the reaction, the mixture was centrifuged at 10,000 rpm for 20 minutes, and the precipitate was collected. Centrifuge at rpm for 10 minutes, wash three times with deionized water, collect and combine the supernatants after centrifugation, and determine the L-arginine loading to be 28.74% using the Sakaguchi reagent method combined with a UV-Vis spectrophotometer. The precipitate after centrifugation is MPDA@L-Arg NPs, and its particle size was measured to be 187.7 nm. Figure 1 ).

[0023] Preparation of a dual-network composite hydrogel: 4.0 g CMCS and 9.0 g PVP (molecular weight 1300000 Da) were added to 91.5 mL of deionized water and stirred continuously at 60℃ for 2 hours to form a homogeneous solution A; 4.0 g OHA and 100 mg MPDA@L-Arg NPs were added to 91.5 mL of deionized water and stirred to form a homogeneous solution B; equal volumes of solutions A and B were mixed and stirred to obtain the dual-network composite hydrogel. Figure 2 ).

[0024] Example 2 Preparation of single-network composite hydrogels: Each component was weighed according to the mass fraction of the dual-network composite hydrogel in Example 1. CMCS was added to deionized water to form a homogeneous solution A. OHA and MPDA@L-Arg NPs were added to deionized water and stirred to form a homogeneous solution B. Then, solution A and solution B were mixed and stirred to obtain a single-network composite hydrogel.

[0025] Example 3 Hydrogel performance testing: Rheological performance testing: An AR 2000 EX rheometer was used to test 500 µL of the dual-network hydrogel on preheated 34℃ flat plate sensors with a plate gap of 1000 µm. Frequency sweep tests were conducted at a fixed strain of 1%, with a frequency range of 0.1 Hz to 10 Hz; alternating step strain tests were performed between 1% and 600%. Results showed that in the frequency sweep tests, the storage modulus (G') of the dual-network composite hydrogel was consistently higher than the loss modulus (G''), exhibiting a stable elastic gel state; in the alternating step strain tests, G' and G'' recovered to their initial values, demonstrating its excellent self-healing ability. Figure 3 , Figure 4 ).

[0026] Mechanical and adhesive property testing: The hydrogel was formed into cylinders with a diameter of 10 mm and a height of 3 mm. Compressive strength was tested at room temperature using an electronic universal testing machine at a speed of 1 mm / min. The lap shear adhesion strength of the hydrogel was tested using the lap shear mode. Fresh pigskin, after removing excess fat, was processed into 1×3 cm... 2 The sheets were in the form of hydrogel precursor solution applied to the surface of pigskin, and then two pieces of pigskin were placed at a 1×1 cm interval. 2 The overlapping areas were bonded face-to-face. The adhesive strength was measured using an electronic universal testing machine at a beam speed of 10 mm / min. The results showed that the compressive strength of the dual-network composite hydrogel was 62.09±3.48 kPa, and the adhesive strength was 9.67±1.08 kPa, both superior to those of the single-network hydrogel. Figure 5 , Figure 6 ).

[0027] Photothermal performance testing: At room temperature, an 808 nm near-infrared laser was used with a fixed power density of 0.75 W / cm². 2 A hydrogel sample with a diameter of 10 mm and a height of 3 mm was irradiated at a distance of 1 cm from the hydrogel, and the temperature change was recorded using an infrared thermal imager. The results showed that the temperature of the dual-network composite hydrogel rose to 48.6℃ after irradiation for 5 minutes, and there was no significant temperature decay after four consecutive laser switching cycles (5 minutes of irradiation followed by 10 minutes of off-circuit irradiation each time), demonstrating good photothermal stability. Figure 7, Figure 8 ).

[0028] Antioxidant performance test: First, a 0.01 mM DPPH solution was prepared using anhydrous ethanol. Then, 50 mg and 100 mg of the dual-network composite hydrogel samples were immersed in 3 mL of DPPH solution and incubated at 37 °C for 30 min. After incubation, the absorbance of the supernatant was measured at 517 nm using a UV-Vis spectrophotometer. The results showed that the dual-network composite hydrogel had good scavenging ability against DPPH free radicals. Figure 9 ).

[0029] Antibacterial performance test: Staphylococcus aureus and Escherichia coli were used as test strains, and the antibacterial effect was evaluated using the plate count method. A concentration of 1×10⁻⁶ was used. 8 The bacterial suspension (CFU / mL) was mixed with the double-network composite hydrogel sample and co-cultured in a shaker at 37℃ and 180 rpm. After 6 h of incubation, 100 µL of bacterial suspension from each group was evenly spread onto LB nutrient agar plates, and the agar plates were placed in a constant temperature incubator at 37℃ for another 12 h before photographing and recording the results. The results showed that the control group (without gel) had normal colony growth; the gel group without light showed a certain inhibitory effect on both strains; and the group irradiated with 808 nm near-infrared light (0.75 W / cm²) showed a greater inhibitory effect on both strains. 2 After 5 minutes, the composite hydrogel showed an inhibition rate of 98.88% against Staphylococcus aureus and 97.30% against Escherichia coli, demonstrating a significant photothermal antibacterial effect. Figure 10 ).

[0030] Example 4 In vitro drug release assays for L-Arg: The release curve of L-arginine was evaluated using an in vitro extraction method. Two mL of the dual-network composite hydrogel sample was immersed in 6 mL of PBS (pH=7.4, pH=5.5) and continuously shaken at 110 rpm on a 37℃ constant-temperature shaker. Samples were collected at predetermined time points, and an equal volume of fresh PBS was added simultaneously. The concentration of L-arginine was determined using the Sakaguchi reagent method combined with a UV-Vis spectrophotometer, and the cumulative release rate was calculated. The results showed that the hydrogel exhibited long-lasting sustained-release characteristics at pH=7.4 and pH=5.5, with a slightly faster release rate at pH=5.5 (simulating the inflammatory microenvironment of a wound), demonstrating that the hydrogel can achieve stable sustained release of L-arginine. Figure 11 ).

[0031] Example 5 In vivo healing experiments of dual-network composite hydrogels: A full-thickness skin defect model caused by Staphylococcus aureus infection was established using SD rats. After anesthetizing the rats, most of the hair on their backs was shaved. Once the hair was completely removed, a circular wound with a diameter of 10 mm was created on the rat's back, and 20 μL of Staphylococcus aureus suspension (10 μL / 10 ... 7 (CFU / mL), and after 24 hours, the individuals were randomly divided into a blank control group and a composite hydrogel + light irradiation group.

[0032] Administration method: The blank control group received saline treatment for the wound; the composite hydrogel + light irradiation group received a double-network composite hydrogel applied to the wound surface, followed by irradiation with an 808 nm laser for 5 minutes (power density 0.75 W / cm²). 2 Each group was given 200 µL of physiological saline or gel on days 0, 3, 7, and 11 after modeling.

[0033] The results showed that the composite hydrogel + light irradiation group had a significant wound healing effect, with a residual wound area of ​​only 3.4% on day 12, which was significantly lower than that of the blank control group (19.2%). Figure 12 Histological analysis showed that this group had an increased number of new blood vessels and more orderly collagen deposition, confirming that it can effectively promote angiogenesis and inhibit excessive inflammatory response.

[0034] This invention achieves a synergistic effect of photothermal antibacterial activity, ROS scavenging, and L-arginine sustained release by constructing a dual-network structure and loading multifunctional nanoparticles, providing an efficient and safe treatment option for the healing of infected wounds, and has good prospects for clinical application.

[0035] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the present invention.

Claims

1. A dual-network composite hydrogel possessing both low-temperature photothermal antibacterial properties and L-arginine delivery functions, characterized in that, This dual-network composite hydrogel consists of a dual-network gel matrix and mesoporous polydopamine nanoparticles loaded with L-arginine. In the dual-network gel matrix, one network is formed by cross-linking oxidized hyaluronic acid and carboxymethyl chitosan through Schiff base bonds, and the other network is formed by polyvinylpyrrolidone, oxidized hyaluronic acid, and carboxymethyl chitosan through hydrogen bonding. The mesoporous polydopamine nanoparticles loaded with L-arginine are dispersed in the dual-network gel matrix, and the loading of L-arginine is achieved through electrostatic interactions.

2. The dual-network composite hydrogel with both low-temperature photothermal antibacterial and L-arginine delivery functions according to claim 1, characterized in that, The oxidized hyaluronic acid has an oxidation degree of 25%~30%, the carboxylation degree of carboxymethyl chitosan is ≥80%, and the molecular weight is 100 kDa~200 kDa.

3. The dual-network composite hydrogel with both low-temperature photothermal antibacterial and L-arginine delivery functions according to claim 1, characterized in that, The mesoporous polydopamine nanoparticles loaded with L-arginine have a particle size of 150 nm to 200 nm and an L-arginine loading of 25% to 30%; the concentration of the mesoporous polydopamine nanoparticles loaded with L-arginine in the dual-network composite hydrogel is 0.5 mg / mL to 2.0 mg / mL.

4. A method for preparing a dual-network composite hydrogel with both low-temperature photothermal antibacterial and L-arginine delivery functions as described in any one of claims 1-3, characterized in that, Includes the following steps: Preparation of oxidized hyaluronic acid: Hyaluronic acid was dissolved in deionized water, and sodium periodate aqueous solution was added for oxidation in the dark. After the reaction was completed, ethylene glycol was added to quench the unreacted sodium periodate. The oxidized hyaluronic acid was obtained by dialysis purification and freeze drying. Preparation of L-arginine-loaded mesoporous polydopamine nanoparticles: Mesoporous polydopamine nanoparticles were synthesized by emulsion-induced interfacial self-assembly method, dispersed in Tris-HCl solution, L-arginine solution was added, and after electrostatic interaction loading, centrifugation and washing were performed to obtain L-arginine-loaded mesoporous polydopamine nanoparticles, denoted as MPDA@L-Arg NPs. Preparation of dual-network composite hydrogel: Carboxymethyl chitosan and polyvinylpyrrolidone were dissolved in deionized water to form solution A; Oxidized hyaluronic acid and MPDA@L-Arg NPs were dispersed in deionized water to form solution B; solution A and solution B were mixed and allowed to stand at room temperature to form a double-network composite hydrogel.

5. The preparation method according to claim 4, characterized in that, In the preparation of oxidized hyaluronic acid, the mass ratio of hyaluronic acid to sodium periodate is between (1.0~3.0):(0.5~1.5), the oxidation reaction time is 4~8 hours; the molecular weight cutoff of the dialysis bag is 3500 Da, the dialysis time is 24~48 hours; and the freeze-drying temperature is -50℃.

6. The preparation method according to claim 4, characterized in that, In the step of preparing mesoporous polydopamine nanoparticles loaded with L-arginine, the synthesis of mesoporous polydopamine nanoparticles uses Pluronic F127 as a surfactant and 1,3,5-trimethylbenzene as an organic phase. Dopamine is polymerized under alkaline conditions for 2-12 hours. The mass ratio of mesoporous polydopamine nanoparticles to L-arginine is (5-15):(5-55), the loading reaction time is 12-48 hours, and the centrifugation speed is 8000-12000 rpm.

7. The preparation method according to claim 4, characterized in that, In the steps of preparing the dual-network composite hydrogel, the concentration of carboxymethyl chitosan in solution A is 2.0 wt%~6.0 wt%, and the concentration of polyvinylpyrrolidone is 6.0 wt%~12 wt%; the concentration of oxidized hyaluronic acid in solution B is 2.0 wt%~6.0 wt%; and the concentration of MPDA@L-Arg NPs in the dual-network composite hydrogel is 0.5 mg / mL~2.0 mg / mL.

8. The application of the dual-network composite hydrogel with both low-temperature photothermal antibacterial and L-arginine delivery functions as described in any one of claims 1-3 in the preparation of infectious wound healing treatment products.

9. The application according to claim 8, characterized in that, The infected wounds include skin defects caused by Staphylococcus aureus and Escherichia coli infections; the dual-network composite hydrogel achieves photothermal antibacterial activity through 808 nm near-infrared laser irradiation, with an inhibition rate of ≥98% against Staphylococcus aureus and ≥97% against Escherichia coli, while simultaneously releasing L-arginine and scavenging reactive oxygen species, promoting angiogenesis and tissue repair.

Images