Active oxygen response drug-loading MOFs controlled release type hydrogel dressing and preparation method thereof

Abstract

The invention belongs to the field of biomedical materials, and particularly relates to an active oxygen response drug-loading MOFs controlled release type hydrogel dressing and a preparation method thereof. The preparation method comprises the following steps: firstly, reducing ergothioneine and lipoic acid, then adding 4-toluene sulfonic acid and acetone to react, so that thiol groups on the ergothioneine and the lipoic acid react with the acetone to generate an acetone diethyl mercaptan [-S-C (CH3) 2-S-] structure, and finally, carrying out a reaction on the 4-toluene sulfonic acid and the acetone to obtain the ergothioneine derivative. The preparation method comprises the following steps: adding a copper salt precursor, reacting to obtain supramolecular active oxygen response MOFs with a multi-level ROS response characteristic, preparing a PLL-DOPA copolymer from epsilon-polylysine and dopamine, mixing the MOFs with a cellulose derivative and the PLL-DOPA copolymer, stirring, and molding to obtain the hydrogel dressing. The dressing not only can be well adhered to a wound, but also can respond to active oxygen at the wound and weaken oxidative stress injury, and the dressing acts on the chronic wound through multiple effects of oxidation resistance, bacteria resistance and inflammation resistance, so that the rapid healing of the wound is realized.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials, specifically to a controlled-release hydrogel dressing containing reactive oxygen species (ROS) and its preparation method. Background Technology

[0002] Chronic wounds, as pathological wounds that are difficult to heal, not only cause severe local tissue damage but also pose systemic health threats and a significant socioeconomic burden. Persistent, non-healing wounds can develop intractable biofilm infections, leading to tissue necrosis, ulcer enlargement, and even serious complications such as osteomyelitis. The accompanying intense pain, exudation, and foul odor further severely impact the patient's quality of life. These long-term wounds can also cause systemic harm; persistent inflammation may exacerbate cardiovascular disease and metabolic disorders, and infection may even progress to sepsis, endangering life. Moreover, the long-term treatment of chronic wounds imposes a huge economic burden on patients, and the high recurrence rate further exacerbates the consumption of medical resources and the economic pressure on patients. These interconnected harms highlight the urgency of developing novel intelligent treatment solutions. Only by simultaneously addressing local repair and systemic effects through innovative technologies can patient prognosis be effectively improved and the economic burden reduced.

[0003] The core reason why chronic wounds (such as diabetic ulcers and pressure sores) are difficult to heal lies in their unique pathological microenvironment: persistent oxidative stress, bacterial biofilm infection, and impaired cell repair function constitute a vicious cycle. Excessive reactive oxygen species (ROS) not only directly damage cells and the extracellular matrix but also exacerbate inflammatory responses and inhibit growth factor activity. At the same time, biofilms formed by drug-resistant bacteria further hinder immune clearance and drug penetration, while senescent fibroblasts and endothelial cells lose their normal proliferation and angiogenesis capabilities. These three factors are interconnected—ROS promotes the release of inflammatory factors, inflammation exacerbates oxidative stress and inhibits cell function, and infection further increases ROS levels, ultimately leading to a chronic, non-healing stalemate in the wound.

[0004] Currently, commonly used clinical dressings (such as silver ion dressings and hydrocolloid dressings) often only address partial problems and have significant limitations. For example, while silver ion dressings are antibacterial, they cannot regulate oxidative stress, and high concentrations can be toxic to normal cells such as germ cells; growth factor gels can promote repair, but they are easily degraded and ineffective in the complex wound environment; and traditional passive dressings such as gauze cannot intervene in the wound microenvironment. Furthermore, these dressings generally lack dynamic responsiveness—they cannot intelligently adjust drug release based on wound ROS levels, infection severity, or inflammatory status, leading to limited therapeutic effects or increased side effects. Therefore, developing a novel dressing that can simultaneously address multiple pathological mechanisms and possess environmental responsiveness has become an urgent clinical need. Summary of the Invention

[0005] In view of this, the purpose of the present invention is to provide a controlled-release hydrogel dressing of reactive oxygen species (ROS) and its preparation method. The dressing can adhere well to the wound and respond to ROS at the wound site to reduce oxidative stress damage. Through multiple effects of antioxidation, antibacterial and anti-inflammatory on chronic wounds, it can achieve rapid wound healing.

[0006] To address the aforementioned technical problems, this invention provides a method for preparing a controlled-release hydrogel dressing containing reactive oxygen species (ROS) drug-loaded MOFs, the method comprising the following steps:

[0007] S1. Add ergothioneine and lipoic acid to N,N-dimethylformamide, dissolve them completely, adjust the pH to 5-7, add tris(2-carboxyethyl)phosphine, react at room temperature for 10-20 min, add 4-methylbenzenesulfonic acid and acetone, mix thoroughly, react at 4-8℃ for 30-60 min, then add tannic acid, copper salt precursor and water, adjust the pH to 5.0-6.0, incubate at room temperature for 8-12 h, centrifuge, and vacuum dry to obtain supramolecular reactive oxygen species responsive MOF particles;

[0008] S2. ε-polylysine hydrochloride and dopamine hydrochloride were reacted in a triethylamine solution in the dark. After the reaction was complete, the triethylamine and the remaining dopamine hydrochloride were removed by dialysis to obtain the PLL-DOPA copolymer. The triethylamine was used to provide an alkaline environment.

[0009] S3. The supramolecular reactive oxygen species (MOFs) particles are ultrasonically dispersed in water, and the cellulose derivative and the PLL-DOPA copolymer are added and stirred for 5-10 min. The mixture is then incubated at 60-80℃ for 30-60 min to obtain the controlled-release hydrogel dressing of the reactive oxygen species (MOFs).

[0010] In step S1 of some embodiments of the present invention, the molar ratio of ergothioneine, lipoic acid, tannic acid and copper salt precursor is (9-11):(9-11):(4.5-5.5):(2-5).

[0011] In step S1 of some embodiments of the present invention, the molar ratio of thioctic acid to tris(2-carboxyethyl)phosphine is 10:(1.00-1.03).

[0012] In some embodiments of the present invention, the preparation method is characterized in that the copper salt precursor is one or a combination of copper sulfate, copper nitrate and copper chloride.

[0013] In step S2 of some embodiments of the present invention, the mass ratio of ε-polylysine hydrochloride to dopamine hydrochloride is 1:(1.04-1.49).

[0014] In step S2 of some embodiments of the present invention, the viscosity-average molecular weight of the ε-polylysine hydrochloride is 2000-5000.

[0015] In step S2 of some embodiments of the present invention, the concentration of the triethylamine solution is 20-50 g / L.

[0016] In step S2 of some embodiments of the present invention, the molecular weight cutoff for dialysis is 8000-10000.

[0017] In step S2 of some embodiments of the present invention, the temperature of the light-protected reaction is room temperature, and the reaction time is 20-30 hours.

[0018] In step S3 of some embodiments of the present invention, the feed ratio of the supramolecular reactive oxygen species responsive MOF particles, water, cellulose derivative, and PLL-DOPA copolymer is (0.3-0.5)g:100ml:(4-5)g:(2-4)g.

[0019] In step S3 of some embodiments of the present invention, the ultrasonic dispersion power is 100-200W and the time is 5-10min.

[0020] In some embodiments of the present invention, the cellulose derivative is one of hydroxyethyl cellulose, hydroxypropyl methylcellulose, and methylcellulose.

[0021] In a second aspect, the present invention provides a controlled-release hydrogel dressing of reactive oxygen species-responsive drug-loaded MOFs prepared according to the above-described preparation method.

[0022] Compared with the prior art, the present invention has the following technical effects:

[0023] (1) In this invention, ergothioneine and lipoic acid are reduced, and then 4-methylbenzenesulfonic acid and acetone are added to react, so that the thiol (-SH) groups on ergothioneine and lipoic acid react with acetone to generate acetone diethylthiol [-SC(CH3)2-S-]. After adding a copper salt precursor, supramolecular reactive oxygen species (MOFs) with multi-level ROS responsive characteristics are obtained. Then, PLL-DOPA copolymer is prepared by using ε-polylysine and dopamine. Finally, MOFs are mixed with cellulose derivatives and PLL-DOPA copolymer, stirred, and shaped to obtain a hydrogel dressing. Under the action of PLL-DOPA copolymer, the dressing can adhere well to the wound and respond to reactive oxygen species at the wound (which are oxidized by ROS, i.e., consume ROS), reducing oxidative stress damage. At the same time, the released Cu²⁺ and ε-polylysine also have synergistic antibacterial effects. Thus, through multiple effects of antioxidation, antibacterial and anti-inflammatory on chronic wounds, rapid wound healing is achieved.

[0024] (2) The thiol groups (-SH) of the released ergothioneine and lipoic acid can be oxidized to disulfide bonds (-S-S-) by ROS. The released Cu²⁺ forms coordination bonds with the catechol groups (DOPA) of PLL-DOPA, further consolidating the gel structure, realizing the dynamic reorganization of the gel network, and enhancing the adaptive release of the material under inflammatory conditions. (After MOFs are dissociated and the active ingredients are released, Cu²⁺ is captured by the gel network, forming new coordination bonds and reconstructing the gel network. This is called dynamic reorganization.)

[0025] (3) The gel dressing provided by the present invention has excellent adhesion properties. The amino group (-NH3⁺) of ε-polylysine adheres to negatively charged wound tissue through electrostatic interaction. The catechol group of dopamine (DOPA) mimics mussel adhesive protein, forms covalent bonds with amino / thiol groups on the tissue surface, and enhances adhesion through metal coordination (such as with Fe³⁺ in wound exudate) in a wet state. The thiol groups (-SH) of ergothioneine and lipoic acid in MOFs can also undergo dynamic exchange reactions with protein disulfide bonds (-S-S-) in the stratum corneum of the skin, as well as chelate with metal ions, to achieve strong adhesion. Tannic acid enhances the adhesion effect by using its own phenolic hydroxyl, carboxyl, and aromatic ring structure to interact with the amino and carboxyl groups of proteins on the skin surface and the hydrophobic regions of keratin through hydrogen bonding and hydrophobic interaction. Attached Figure Description

[0026] Figure 1 Scanning electron microscope image of the reactive oxygen species-responsive drug-loaded MOFs controlled-release hydrogel dressing prepared in Example 1 after lyophilization;

[0027] Figure 2 The dressings prepared in Examples 1-3 were treated with different H2O2 concentrations for Cu 2+ The cumulative release concentration;

[0028] Figure 3 The cumulative release concentration of free thiol groups in the dressings prepared in Examples 1-3 after treatment with different H2O2 concentrations;

[0029] Figure 4 The changes in storage modulus of dressings prepared in Examples 1-3 and Comparative Examples 1-2 under different H2O2 concentrations;

[0030] Figure 5 The diameter of the inhibition zone against drug-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAO1) in Examples 1-3, Comparative Examples 1-2, and commercial dressings;

[0031] Figure 6 The inhibitory effects of Examples 1-3, Comparative Examples 1-2, and commercial dressings on biofilms of drug-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAO1) were studied.

[0032] Figure 7 The results show the adhesion of Examples 1-3, Comparative Examples 1-2, and commercial dressings to mouse skin and polyurethane films.

[0033] Figure 8 The wound closure rate of chronic wounds in diabetic mice treated with Examples 1-3, Comparative Examples 1-2, and commercial dressings;

[0034] Figure 9 Collagen deposition rates in chronic wounds of diabetic mice treated with Examples 1-3, Comparative Examples 1-2, and commercial dressings. Detailed Implementation

[0035] To further understand the present invention, preferred embodiments of the present invention are described below in conjunction with examples. However, it should be understood that these descriptions are only for further illustrating the features and advantages of the present invention, and not for limiting the scope of the claims of the present invention.

[0036] Example 1

[0037] A reactive oxygen species-responsive drug-loaded MOFs controlled-release hydrogel dressing and its preparation method include the following steps:

[0038] 1. Add 2.29 g (10 mmol) ergothioneine and 2.06 g (10 mmol) lipoic acid to 100 ml DMF, dissolve thoroughly, adjust pH to 6.0, add 0.25 g (1 mmol) TCEP and mix, react at room temperature for 15 min, then add 0.26 g 4-methylbenzenesulfonic acid and 4.41 ml acetone, mix thoroughly, react at 6 °C for 45 min, then add 8.51 g (5 mmol) tannic acid, 0.524 g copper sulfate (3.28 mmol) and 37 ml water, adjust pH to 5.5, incubate at room temperature for 10 h, centrifuge, and vacuum dry to prepare supramolecular reactive oxygen species (MOF) particles;

[0039] 2. 21.3 g of ε-polylysine hydrochloride with a viscosity-average molecular weight of 3500 and 26.5 g of dopamine hydrochloride were added to a 35.4 g / L triethylamine solution and reacted at room temperature in the dark for 25 h. Then, triethylamine and dopamine hydrochloride were removed by dialysis using a dialysis bag with a molecular weight cutoff of 9000 to obtain PLL-DOPA copolymer.

[0040] 3. Add 0.4g of supramolecular reactive oxygen species (MOFs) to 100ml of water, sonicate at 150W for 7min, then add 4.5g of methylcellulose and 3g of PLL-DOPA copolymer and stir for 8min. Pour into a mold, heat to 70℃, incubate for 45min, and demold to obtain a controlled-release hydrogel dressing of reactive oxygen species (MOFs).

[0041] Figure 1 The image shown is a scanning electron microscope image of the freeze-dried reactive oxygen species-responsive drug-loaded MOFs controlled-release hydrogel dressing prepared in this embodiment. It can be observed that the dressing has a three-dimensional mesh-like channel.

[0042] Example 2

[0043] A reactive oxygen species-responsive drug-loaded MOFs controlled-release hydrogel dressing and its preparation method include the following steps:

[0044] 1. Add 2.06 g (9.00 mmol) ergothioneine and 1.86 g (9.00 mmol) lipoic acid to 100 ml DMF, dissolve thoroughly, adjust pH to 5.0, add 0.23 g (0.92 mmol) TCEP and mix, react at room temperature for 10 min, then add 0.23 g 4-methylbenzenesulfonic acid and 3.97 ml acetone, mix thoroughly, react at 4 °C for 60 min, then add 7.66 g (4.50 mmol) tannic acid, 0.375 g (2 mmol) copper nitrate and 30 ml water, adjust pH to 5.0, incubate at room temperature for 8 h, centrifuge, and vacuum dry to prepare supramolecular reactive oxygen species (MOFs) particles;

[0045] 2. 11.0 g of ε-polylysine hydrochloride with a viscosity-average molecular weight of 2000 and 16.4 g of dopamine hydrochloride were added to a 20 g / L triethylamine solution and reacted at room temperature in the dark for 20 h. Then, triethylamine and dopamine hydrochloride were removed by dialysis using a dialysis bag with a molecular weight cutoff of 8000 to obtain PLL-DOPA copolymer.

[0046] 3. Add 0.3g of supramolecular reactive oxygen species (MOFs) to 100ml of water, sonicate at 200W for 5min, then add 4g of hydroxyethyl cellulose and 2g of PLL-DOPA copolymer and stir for 5min. Pour into a mold, heat to 80℃, incubate for 30min, and demold to obtain a controlled-release hydrogel dressing of reactive oxygen species (MOFs).

[0047] Example 3

[0048] A reactive oxygen species-responsive drug-loaded MOFs controlled-release hydrogel dressing and its preparation method include the following steps:

[0049] 1. Add 2.52 g (11.00 mmol) ergothioneine and 2.27 g (11.00 mmol) lipoic acid to 100 ml DMF, dissolve thoroughly, adjust pH to 7.0, add 0.28 g (1.12 mmol) TCEP and mix, react at room temperature for 20 min, then add 0.28 g 4-methylbenzenesulfonic acid and 4.85 ml acetone, mix thoroughly, react at 8 °C for 30 min, then add 9.36 g (5.50 mmol) tannic acid, 0.672 g (5.00 mmol) copper chloride and 40 ml water, adjust pH to 6.0, incubate at room temperature for 12 h, centrifuge, and vacuum dry to prepare supramolecular reactive oxygen species (MOF) particles;

[0050] 2. 33.5 g of ε-polylysine hydrochloride with a viscosity-average molecular weight of 5000 and 34.8 g of dopamine hydrochloride were added to a 50 g / L triethylamine solution and reacted at room temperature in the dark for 30 h. Then, triethylamine and dopamine hydrochloride were removed by dialysis using a dialysis bag with a molecular weight cutoff of 10000 to obtain PLL-DOPA copolymer.

[0051] 3. Add 0.5g of supramolecular reactive oxygen species (MOFs) to 100ml of water, sonicate at 100W for 10min, then add 5g of hydroxypropyl methylcellulose and 4g of PLL-DOPA copolymer and stir for 10min. Pour into a mold, heat to 60℃, incubate for 60min, and demold to obtain a controlled-release hydrogel dressing of reactive oxygen species (MOFs).

[0052] Comparative Example 1 (without MOFs)

[0053] A dressing and its preparation method, comprising the following steps:

[0054] 1. 21.3 g of ε-polylysine hydrochloride with a viscosity-average molecular weight of 3500 and 26.5 g of dopamine hydrochloride were added to a 35.4 g / L triethylamine solution and reacted at room temperature in the dark for 25 h. Then, triethylamine and dopamine hydrochloride were removed by dialysis using a dialysis bag with a molecular weight cutoff of 9000 to obtain PLL-DOPA copolymer.

[0055] 2. Add 4.5g of methylcellulose and 3g of PLL-DOPA copolymer to 100ml of water, stir for 8min, pour into a mold, heat to 70℃, incubate for 45min, and demold to obtain the dressing.

[0056] Comparative Example 2 (without copolymer)

[0057] A dressing and its preparation method, comprising the following steps:

[0058] 1. Add 2.29 g (10 mmol) ergothioneine and 2.06 g (10 mmol) lipoic acid to 100 ml DMF, dissolve them completely, adjust the pH to 6.0, add 0.25 g (1 mmol) TCEP and mix, react at room temperature for 15 min, then add 0.26 g 4-methylbenzenesulfonic acid and 4.41 ml acetone, mix thoroughly, react at 6 °C for 45 min, then add 8.51 g (5 mmol) tannic acid, 0.524 g copper sulfate (3.28 mmol) and 37 ml water, adjust the pH to 5.5, incubate at room temperature for 10 h, centrifuge, and vacuum dry to prepare supramolecular reactive oxygen species (MOFs) particles.

[0059] 2. Add 0.4g of supramolecular reactive oxygen species (MOFs) to 100ml of water, sonicate at 150W for 7min, then add 4.5g of methylcellulose and 3g of gelatin and stir for 8min. Pour into a mold, heat to 70℃, incubate for 45min, and demold to obtain the dressing.

[0060] Experiment 1: ROS-responsive drug release and dynamic gel recombination

[0061] The graded dissociation, controlled drug release, and gel dynamic recombination capabilities of the dressings under ROS conditions were verified. Dressings of equal area from Examples 1-3 and Comparative Examples 1-2 were immersed in PBS containing H2O2 (0.1 mM, 1 mM, and 10 mM), respectively, and shaken at 37°C in the dark to obtain sample solutions for Examples 1-3 and Comparative Examples 1-2. The Cu content in the sample solutions of Examples 1-3 was determined by ICP-OES. 2+ The release, the result is as follows Figure 2 As shown; the release of thiols was determined by detecting free -SH in the sample solutions of Examples 1-3 using the DTNB method, and the results are as follows. Figure 3 As shown; the changes in the storage modulus (G') of the sample solutions in Examples 1-3 and Comparative Examples 1-2 were tested using a rheometer, and the results are as follows. Figure 4 As shown.

[0062] like Figures 2-4 It is evident that the dressings prepared in Examples 1-3 are based on a triple ROS response mechanism: tannic acid-Cu²⁺ coordination bond cleavage, thiol-Cu²⁺ coordination bond dissociation, and acetone diethylthiol cleavage. This allows for the on-demand release of Cu²⁺ and thiol compounds (ergothioneine / lipoic acid) according to environmental ROS levels, and adaptive recombination of the gel network is achieved through dynamic disulfide bond exchange, significantly enhancing the storage modulus G'. In contrast, the comparative examples lacking MOFs or PLL-DOPA cannot achieve controlled drug release and dynamic gel recombination, resulting in a significantly reduced overall therapeutic effect, validating the irreplaceable nature of each component in this design. This dressing overcomes the limitations of traditional materials in wet adhesion, ROS response precision, and multifunctional integration, providing a new strategy for chronic wound treatment.

[0063] Comparative Example 1 lacks MOF structure, thus failing to respond to ROS to release active ingredients and unable to form disulfide crosslinks to achieve dynamic gel recombination. Comparative Example 2 uses gelatin instead of PLL-DOPA, lacking thiol and catechol groups, and cannot form coordination crosslinks between Cu²⁺ and the catechol groups of PLL-DOPA, resulting in ineffective gel structure recombination after thiol release.

[0064] Experiment 2: Synergistic antibacterial properties (against drug-resistant bacteria)

[0065] The antibacterial effects of the dressings in Examples 1-3 and Comparative Examples 1-2, and commercial dressings (Haisihainuo calcium alginate dressing and Haishihuakang hydrocolloid dressing) were verified. An inhibition zone test was used: the agar diffusion method was employed, placing the dressing discs on a plate inoculated with bacterial solution and measuring the diameter of the inhibition zone; the absorbance at 560 nm was measured using the crystal violet staining method to calculate the biofilm content. The results are as follows: Figures 5-6 As shown. Strains selected: drug-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAO1).

[0066] like Figures 5-6It is evident that in the dressing of the examples, MOFs and ε-polylysine exhibit synergistic antibacterial effects. Supramolecular reactive oxygen species (ROS)-responsive MOFs release Cu²⁺ in the wound microenvironment through a tannic acid (TA)-Cu²⁺ coordination structure. Cu²⁺ can disrupt the integrity of bacterial cell membranes, interfere with their respiratory chain function, and induce ROS generation, leading to bacterial oxidative stress death. Furthermore, ergothioneine and lipoic acid loaded in the MOFs further interfere with bacterial metabolism through thiol groups (-SH). ε-polylysine (PLL), as a natural cationic antimicrobial peptide, adsorbs onto the negatively charged bacterial membrane surface through electrostatic interactions, forming pores and causing intracellular leakage. Its amino group (-NH₃⁺) can also neutralize the negative charge in the bacterial biofilm, disrupting biofilm stability. Dopamine (DOPA) in the PLL-DOPA copolymer permeates the biofilm matrix through hydrophobic interactions, while Cu²⁺ released by MOFs degrades extracellular polysaccharides (EPS) in the biofilm, enhancing the permeability of PLL and thus completely removing stubborn biofilms. Comparative Example 1 (without MOFs): Relying solely on the antibacterial effect of PLL, lacking the synergistic effect of Cu²⁺, its ability to penetrate and remove biofilms is limited. Comparative Example 2 (without copolymer): Although MOFs can release Cu²⁺, they lack the membrane-disrupting effect of PLL, resulting in a narrower antibacterial spectrum and inability to effectively break down biofilms. Commercial dressings do not incorporate antibacterial functions, thus exhibiting poor antibacterial effects. In summary, the dressings in these examples achieve highly efficient killing of drug-resistant bacteria and complete inhibition of biofilms through a triple synergistic mechanism of MOFs (metal ion attack) + PLL (physical disruption) + dynamic ROS response, resulting in the largest inhibition zone and the highest biofilm inhibition rate. This multi-target, intelligent response design is significantly superior to commercial dressings (such as calcium alginate or hydrocolloid dressings) in terms of antibacterial function.

[0067] Experiment 3: Wet Adhesion and Repair-Promoting Effect (Animal Model)

[0068] Objective: To verify the multi-mechanism adhesion and chronic wound healing capabilities of dressings from Examples 1-3, Comparative Examples 1-2, and commercial dressings (Haisihainuo calcium alginate dressing and Haishihuakang hydrocolloid dressing). Animal model: Full-thickness skin defect on the back of diabetic mice (db / db). Adhesion was tested after treatment with the dressings, and the results are as follows. Figure 7 As shown: Dressing peel force test (universal testing machine); analysis of wound closure rate and Masson staining statistical collagen deposition rate, results are as follows. Figures 8-9 As shown.

[0069] like Figures 7-9It is evident that the dressings of Examples 1-3 exhibit excellent wet adhesion (high peel strength in rat skin), mild interfacial bonding (low peel strength in polyurethane film), and optimal wound repair effect (rapid healing and high collagen deposition rate). This is attributed to their synergistic effect of multiple mechanisms: First, the PLL-DOPA copolymer forms covalent and metal coordination bonds with tissue through the catechol groups of DOPA, combined with the electrostatic adsorption of ε-polylysine and the hydrogen bonding of tannic acid, achieving strong wet adhesion; Second, MOFs respond to the high ROS environment of the wound by releasing ergothioneine, lipoic acid, and Cu²⁺. Dynamic thiol-disulfide bond exchange enhances adhesion stability, while antioxidants reduce oxidative stress, and Cu²⁺ promotes angiogenesis; In addition, the synergistic antibacterial and biofilm removal effects of PLL and MOFs, the anti-inflammatory and microenvironmental regulation of tannic acid, and the activation of fibroblasts to secrete collagen, along with the mechanical guidance of gel network, lead to orderly collagen deposition. In contrast, Comparative Example 1 (without MOFs) lacked ROS-responsive treatment, Comparative Example 2 (without PLL-DOPA) showed insufficient adhesion, and commercial dressings only provided passive protection; neither could simultaneously address adhesion, infection, and repair issues. The example dressing demonstrates significant advantages in chronic wound healing through a three-pronged strategy of "biomimetic adhesion - intelligent drug release - antibacterial and repair-promoting."

[0070] This invention provides a controlled-release hydrogel dressing with reactive oxygen species (ROS) drug-loaded MOFs and its preparation method. Many methods and approaches exist for implementing this technical solution; the above description is merely a preferred embodiment. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of this invention, and these improvements and modifications should also be considered within the scope of protection of this invention. All components not explicitly stated in this embodiment can be implemented using existing technologies.

Claims

1. A method for preparing a reactive oxygen species-responsive drug-loaded MOFs controlled-release hydrogel dressing, characterized in that, The preparation method includes the following steps: S1. Add ergothioneine and lipoic acid to N,N-dimethylformamide, dissolve them completely, adjust the pH to 5-7, add tris(2-carboxyethyl)phosphine, react at room temperature for 10-20 min, add 4-methylbenzenesulfonic acid and acetone, mix thoroughly, react at 4-8℃ for 30-60 min, then add tannic acid, copper salt precursor and water, adjust the pH to 5.0-6.0, incubate at room temperature for 8-12 h, centrifuge, and vacuum dry to obtain supramolecular reactive oxygen species responsive MOF particles; S2. ε-polylysine hydrochloride and dopamine hydrochloride were reacted in triethylamine solution in the dark. After the reaction was completed, the triethylamine and the remaining dopamine hydrochloride were removed by dialysis to obtain PLL-DOPA copolymer. S3. The supramolecular reactive oxygen species (MOFs) particles are ultrasonically dispersed in water, and the cellulose derivative and the PLL-DOPA copolymer are added and stirred for 5-10 min. Then, the mixture is incubated at 60-80℃ for 30-60 min to obtain the controlled-release hydrogel dressing of the reactive oxygen species (MOFs).

2. The preparation method according to claim 1, characterized in that, In step S1, the molar ratio of ergothioneine, lipoic acid, tannic acid and copper salt precursor is (9-11):(9-11):(4.5-5.5):(2-5).

3. The preparation method according to claim 1, characterized in that, In step S1, the molar ratio of thioctic acid to tris(2-carboxyethyl)phosphine is 10:(1.00-1.03).

4. The preparation method according to claim 1, characterized in that, The copper salt precursor is one or a combination of copper sulfate, copper nitrate and copper chloride.

5. The preparation method according to claim 1, characterized in that, In step S2, the mass ratio of ε-polylysine hydrochloride to dopamine hydrochloride is 1:(1.04-1.49).

6. The preparation method according to claim 1, characterized in that, In step S2, the viscosity-average molecular weight of the ε-polylysine hydrochloride is 2000-5000.

7. The preparation method according to claim 1, characterized in that, In step S2, the reaction is carried out at room temperature in the dark, and the reaction time is 20-30 hours.

8. The preparation method according to claim 1, characterized in that, In step S3, the feeding ratio of the supramolecular reactive oxygen species (MOFs) particles, water, cellulose derivatives, and PLL-DOPA copolymer is (0.3-0.5)g:100ml:(4-5)g:(2-4)g.

9. The preparation method according to claim 1, characterized in that, The cellulose derivative is one of hydroxyethyl cellulose, hydroxypropyl methylcellulose, and methylcellulose.

10. A controlled-release hydrogel dressing of reactive oxygen species-responsive drug-loaded MOFs prepared by the preparation method according to any one of claims 1-9.

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