Method for preparing a methacrylated chitosan / gelatin-based hydrogel wound dressing by 3D printing and applications thereof

Abstract

A method for 3D printing to prepare methacryloyl chitosan / gelatin-based hydrogel wound dressings and its application are disclosed. This invention relates to a method for preparing hydrogel wound dressings and its application. It addresses the problems of high photothermal conversion temperature of existing MXene dressings and rapid bacterial re-proliferation after near-infrared irradiation is turned off. The ZGC composite hydrogel wound dressing of this invention is a multifunctional integrated dressing capable of simultaneously achieving hemostasis, antibacterial, anti-inflammatory, angiogenesis, and cell regeneration, making it particularly suitable for infected wounds. It can exert antibacterial properties through the dual effects of photothermal therapy and photodynamic therapy under near-infrared light activation, and can also interact with Zn. 2+ Synergistic antibacterial effect. This invention's ZGC composite hydrogel wound dressing can be precisely customized and printed according to the shape and depth of the wound using 3D printing technology. This composite dressing enables precise low-temperature photothermal therapy while maintaining Zn... 2+ Sustained release and MXene's physical antibacterial function kill bacteria while protecting normal tissue, significantly improving the healing rate of infected wounds.

Description

Technical Field

[0001] This invention relates to a method for preparing hydrogel wound dressings and their applications. Background Technology

[0002] The treatment of wound infections remains a significant clinical challenge. Bacterial infections not only disrupt tissue repair processes but also trigger persistent inflammatory responses and oxidative stress, severely impacting wound healing. Traditional treatments often have limited effectiveness in complex situations such as multidrug-resistant bacterial infections, hypoxic microenvironments, and immune dysfunction. Studies have shown that excessively high bacterial loads lead to abnormally elevated levels of reactive oxygen species (ROS), thereby disrupting immune homeostasis and inhibiting key repair processes such as collagen synthesis and angiogenesis. Although natural antioxidants such as enzymes and vitamins have been used to alleviate oxidative damage, their poor stability and high cost limit their clinical application.

[0003] Since its advent in the 1980s, 3D printing technology has revolutionized the medical field through continuous evolution. This technology can create personalized, complex, and heterogeneous biological structures and has been successfully applied to the creation of biomimetic medical models, customized implants, tissue-engineered scaffolds, and three-dimensional cellular structures. For example, new methods combining photothermal therapy (PTT), photodynamic therapy (PDT), and sonodynamic therapy (SDT) with tissue-engineered scaffolds, along with functional hydrogels, offer new avenues for the treatment of infected wounds. Among these, novel nanomaterials such as MXenes and metal-organic frameworks (MOFs) have attracted significant attention due to their excellent biocompatibility and tunable photothermal properties. Digital light processing (DLP)-based 3D printing technology can precisely construct three-dimensional scaffolds with uniform nanoparticle distributions, opening new avenues for the development of novel wound dressings with highly effective antibacterial, antioxidant, and regenerative functions. These integrated treatment solutions hold the promise of reducing reliance on antibiotics and playing a crucial role in specific areas. They possess multiple advantages, including effectively disrupting bacterial biofilms, eliminating various pathogens, and completely eradicating bacteria while avoiding the development of drug resistance. MXenes typically have high photothermal conversion temperatures (above 65°C), which may damage surrounding tissues. Furthermore, due to the short-pulse effect of near-infrared radiation, bacteria may rapidly re-multiply after near-infrared irradiation is turned off. Summary of the Invention

[0004] To address the problems of high photothermal conversion temperature and rapid bacterial re-proliferation after near-infrared irradiation is turned off in existing MXene products, this invention proposes a method and application for 3D printing to prepare methacryloyl chitosan / gelatin-based hydrogel wound dressings.

[0005] The method for 3D printing a methacrylamide chitosan / gelatin-based hydrogel wound dressing of the present invention is carried out according to the following steps:

[0006] Step 1: Print the ink sample to be tested:

[0007] The test ink consists of CSMA, GelMA, an initiator, and a light blocker, with deionized water as the solvent. Multiple printing test groups of the test inks are set up, with different molecular weights of CSMA in each group, ranging from 50 to 2000 kDa. Each printing test group contains multiple test inks with different compositions, but the CSMA molecular weight is the same. Multiple CSMA concentrations are selected within each printing test group, ranging from 0.25 mg / mL to 1.25 mg / mL, and multiple GelMA concentrations are selected within the range of 2.5 mg / mL to 7.5 mg / mL. Samples of multiple test inks are then printed.

[0008] The preparation method of CSMA is as follows: prepare a chitosan acetate solution with a concentration of 1.5% mg / mL; then add 2-15 mL of methacrylic anhydride; react for 12 h under light-protected, 40℃ and 300 rpm stirring and shaking conditions; then use a dialysis bag for 3-7 days of purification and dialysis, changing the deionized water every 12 h during the purification and dialysis process; finally, vacuum freeze-dry for 48-72 h.

[0009] The preparation method of the GelMA is as follows: 10g of gelatin is dissolved in 100mL of phosphate buffer solution, and then 8-20mL of methacrylic anhydride is added; after reacting at 50℃ and 300rpm for 2h, 100mL of PBS solution is added for dilution, and the reaction is continued for 10min-30min. After dialysis purification at 40℃ and 300rpm for 5d-7d, the deionized water is replaced every 12h; finally, vacuum freeze-drying is performed for 48h-72h.

[0010] Step 2: Optimization of CSMA molecular weight, CSMA concentration and GelMA concentration in the ink to be tested: Select samples that are printed and tested completely without any breaks, conduct mechanical property tests, select the sample with the highest compressive strength, and the corresponding ink to be tested is the optimized ink.

[0011] Step 3: Screening of power density and crosslinking time:

[0012] ① Using optimized ink, with the same printing power density, and changing the crosslinking time, multiple digital light processing 3D printing test samples were carried out according to the designed printing resolution.

[0013] ② Using optimized ink, with the same crosslinking time, and varying the power density, multiple digital light processing 3D printing test samples were conducted according to the designed printing resolution.

[0014] The printed test specimen is a laser-shaped model with a central circle at its center. Multiple radial lines are arranged in a ring around the central circle, and these radial lines are connected to the central circle.

[0015] ③ Take microscopic images of the multiple printed test specimens obtained in steps ① and ② using an optical microscope, measure the diameter of the central circle of the printed test specimen, the number of radial lines, and the width of the radial lines in the microscopic images, and calculate the test printing resolution p.

[0016] The test printing resolution p is calculated according to Formula 1:

[0017]

[0018] In Formula 1, p is the printing resolution, μm; D is the diameter of the center circle, μm; n is the number of radial lines, units; and h is the width of the radial lines, μm.

[0019] ④ Compare the design printing resolution of the printed test specimen with the test printing resolution p calculated in step ③. The printed test specimen with the test printing resolution closest to the design printing resolution is the optimal specimen. The power density or crosslinking time corresponding to the optimal specimen is the selected optimal power density and crosslinking time.

[0020] Step 4: Preparation of ZTM / GelMA / CSMA composite hydrogel wound dressing:

[0021] ZIF-8 / TA@MXene was added to the optimized ink selected in step two to obtain ZTM / GelMA / CSMA ink. Digital light processing 3D printing was performed according to the rate density and crosslinking time in step three to obtain a three-dimensional connected network or solid structure ZTM / GelMA / CSMA composite hydrogel wound dressing.

[0022] The preparation method of the ZIF-8 / TA@MXene is as follows:

[0023] ① Dissolve 1.6g of lithium fluoride in 20mL of 9mol / L hydrochloric acid for 10-30min; add 1.0g of MAX phase to the solution and react for 24-72h at 35℃-50℃ and 450rpm stirring; after the reaction is complete, centrifuge at 8000rpm for 10min and collect the reaction product; wash the product twice with 1mol / L HCl, then wash the product with deionized water until the pH of the supernatant is 6; shake the reaction product well and centrifuge at 5000rpm for 3-5min, repeating the HCl washing, deionized water washing and centrifugation ten times; then add deionized water and sonicate at below 30℃ for 60-120min, shaking every 5-10min during sonication; finally, centrifuge at 3500rpm for 10-60min and collect the MXene dispersion with a dropper.

[0024] ② Add 50 mg of tannic acid to the dispersion containing 25 mg MXene, stir evenly at room temperature, add 50 mL of Tris-HCl buffer, continue the reaction for 6 h-12 h, and finally wash three times with deionized water to remove unreacted tannic acid to obtain TA@MXene dispersion.

[0025] ③ Disperse the TA@MXene dispersion into 25 mL of 0.026 mol / L zinc acetate methanol solution, stir well, and then add 25 mL of 0.207 mol / L dimethylimidazolium methanol solution dropwise to the reaction solution. Continue the reaction at room temperature for 12-36 h. After completion, centrifuge the sample to collect the product, wash the product three times with deionized water, freeze at -20℃ overnight, and then perform vacuum freeze-drying for 24 h to obtain ZIF-8 / TA@MXene.

[0026] The application of the above-mentioned ZTM / GelMA / CSMA (ZGC) composite hydrogel wound dressing in the preparation of skin wound healing dressings.

[0027] The principle and beneficial effects of this invention are as follows:

[0028] This invention first prepares tannic acid (TA)-coated modified MXene nanosheets (TA@MXene), and then grows a metal-organic framework ZIF-8 in situ on the TA@MXene surface to obtain ZIF-8 / TA@MXene (ZTM). A certain amount of ZTM nanoparticles are uniformly dispersed in a solution of methacrylamide gelatin (GelMA) and methacrylamide chitosan (CSMA) to prepare a printing ink. Finally, a ZTM / GelMA / CSMA (ZGC) composite hydrogel wound dressing is prepared using a digital light processing (DLP) 3D printer.

[0029] 1. This invention, the ZGC composite hydrogel wound dressing, is a multifunctional integrated dressing capable of simultaneously achieving hemostasis, antibacterial, anti-inflammatory, angiogenesis, and cell regeneration, making it particularly suitable for infected wounds. CSMA retains the inherent properties of chitosan, providing antibacterial, hemostatic, and biodegradable functions. GelMA imparts good cell affinity and mechanical adaptability to the dressing, while ZIF-8 / TA@MXene contributes multiple effects such as photothermal antibacterial, photodynamic antibacterial, antioxidant, and angiogenesis promotion. The complementary enhancement and synergistic degradation effects of CSMA and GelMA, through photocrosslinking to form an interpenetrating network (IPN), combine the antibacterial properties of chitosan with the cell affinity of gelatin, while significantly improving mechanical properties (such as compressive strength). The slow degradation of CSMA is matched with the rapid degradation of GelMA, achieving time-sequential regulation of the dressing's mechanical support and drug release. The layered structure of MXene and ZIF-8 particles serve as physical cross-linking points, enhancing the compressive modulus of the hydrogel and making it suitable for dynamic wounds such as joints. Furthermore, through the synergistic photothermal and antibacterial effects of the layered structure of MXene and the ZIF-8 particles, MXene generates heat under near-infrared light, triggering the Zn content in ZIF-8. 2+ The burst release enables "on-demand antibacterial" action, avoiding drug resistance. The phenolic hydroxyl group of TA forms hydrogen bonds with the amino / carboxyl groups of GelMA / CSMA, and simultaneously with the Zn group of ZIF-8. 2+ It coordinates and enhances component compatibility, prevents phase separation, and scavenges ROS under non-photothermal conditions, thereby maintaining cell viability and promoting endogenous cell proliferation to resist oxidative stress at the defect site. Together with the antibacterial properties of chitosan, it optimizes the wound microenvironment.

[0030] Therefore, the hydrogel wound dressing prepared in this invention can exert good antibacterial properties through the dual effects of photothermal therapy (PTT) and photodynamic therapy (PDT) under the activation of near-infrared light, and can also react with Zn. 2+ The dressing has a synergistic antibacterial effect with a bacteriostatic rate of >99%. It also has excellent hemostatic properties and can maintain a moist environment at the wound site, which helps the wound heal.

[0031] 2. The ZGC composite hydrogel wound dressing of this invention can be precisely customized and printed according to the shape and depth of the wound using 3D printing technology. Its three-dimensional interconnected mesh structure combines excellent breathability and healing-promoting capabilities. The hydrogel's mesh structure provides a scaffold for cell migration through a biomimetic extracellular matrix fiber network. Its three-dimensional porous nature maintains a moist healing environment and promotes oxygen exchange, while mechanical adaptation reduces tissue damage and induces angiogenesis. The mesh structure can also load and sustain-release antibacterial agents and growth factors, while the internal interconnected pores allow for immune cell infiltration, thereby synergistically regulating the inflammatory response, promoting tissue regeneration, and significantly accelerating the wound healing process.

[0032] The antibacterial mechanism of ZGC composite hydrogel wound dressing is divided into two modes: photothermal activation and non-photothermal sustained action; under near-infrared light irradiation, MXene(Ti3C2T) x ZTM promotes the generation of reactive oxygen species (ROS) through photothermal heating and oxygen vacancies. After the near-infrared irradiation is turned off, ZTM releases Zn. 2+ MXene nanosheets also possess antibacterial properties. In this invention, MXene nanosheets exhibit a sharp edge structure and mechanical encapsulation. With an atomically thin two-dimensional structure and sharp edges, MXene nanosheets can directly pierce bacterial cell membranes, causing leakage of cell contents and physically disrupting bacterial integrity. MXene nanosheets can adsorb and encapsulate bacteria, hindering their material exchange and metabolic activities, ultimately leading to bacterial death. Therefore, this dressing optimizes breathability and permeability management through 3D printing of porous structures, while utilizing the synergistic effects of photothermal / chemical / physical antibacterial properties and biocompatibility design of nanomaterials to significantly accelerate the healing of infected wounds, providing an integrated solution for intelligent wound care.

[0033] 3. The temperature control mechanism of the ZGC composite hydrogel wound dressing of the present invention includes: (1) active heat dissipation through the high specific heat capacity of the hydrogel and the heat absorption effect of water evaporation; (2) the 3D-printed grid structure increases the heat dissipation area and avoids local overheating; (3) ZIF-8 / TA modification reduces the surface energy of MXene and optimizes photothermal conversion efficiency. Therefore, under near-infrared irradiation, the composite dressing of the present invention can achieve precise low-temperature photothermal therapy while maintaining Zn 2+ Sustained release and MXene's physical antibacterial function kill bacteria (such as Staphylococcus aureus and Escherichia coli) while protecting normal tissue, significantly improving the healing rate of infected wounds. Attached Figure Description

[0034] Figure 1 This diagram illustrates the optimization process of multiple printing test groups and ink mixing ratios for the ink to be tested.

[0035] Figure 2 The hydrogen NMR spectra of gelatin and gelMA are shown.

[0036] Figure 3 The 1H NMR spectra of chitosan and CSMA are shown.

[0037] Figure 4 The image shows the test results for the ink's mechanical properties.

[0038] Figure 5 This is a schematic diagram of a laser-shaped model;

[0039] Figure 6 Printed test specimens obtained by varying the crosslinking time;

[0040] Figure 7Printed test specimens obtained by changing power density;

[0041] Figure 8 Here is a SEM image of MXene;

[0042] Figure 9 TEM image of MXene;

[0043] Figure 10 SEM image of TA@MXene;

[0044] Figure 11 TEM image of TA@MXene;

[0045] Figure 12 SEM image of ZIF-8 / TA@MXene;

[0046] Figure 13 TEM image of ZIF-8 / TA@MXene;

[0047] Figure 14 XRD patterns of MXene and its modified products;

[0048] Figure 15 Photothermal test images of ZGC composite hydrogel wound dressing under near-infrared lasers of different power densities;

[0049] Figure 16 These are photothermal test images of ZGC composite hydrogel wound dressings with different ZTM contents under near-infrared laser light.

[0050] Figure 17 This is a photograph of the three-dimensional interconnected network ZTM / GelMA / CSMA (ZGC) composite hydrogel wound dressing prepared in Example 1;

[0051] Figure 18 The photothermal antibacterial effects of different samples are shown. Detailed Implementation

[0052] The technical solution of the present invention is not limited to the specific embodiments listed below, but also includes any reasonable combination of the specific embodiments.

[0053] Specific Implementation Method 1: The method for preparing methacrylamide chitosan / gelatin-based hydrogel wound dressings by 3D printing in this implementation method is carried out according to the following steps:

[0054] Step 1: Print the ink sample to be tested:

[0055] The test ink consists of CSMA, GelMA, an initiator, and a light blocker, with deionized water as the solvent. Multiple printing test groups of the test inks are set up, with different molecular weights of CSMA in each group, ranging from 50 to 2000 kDa. Each printing test group contains multiple test inks with different compositions, but the CSMA molecular weight is the same. Multiple CSMA concentrations are selected within each printing test group, ranging from 0.25 mg / mL to 1.25 mg / mL, and multiple GelMA concentrations are selected within the range of 2.5 mg / mL to 7.5 mg / mL. Samples of multiple test inks are then printed.

[0056] The preparation method of CSMA is as follows: prepare a chitosan acetate solution with a concentration of 1.5% mg / mL; then add 2-15 mL of methacrylic anhydride; react for 12 h under light-protected, 40℃ and 300 rpm stirring and shaking conditions; then use a dialysis bag for 3-7 days of purification and dialysis, changing the deionized water every 12 h during the purification and dialysis process; finally, vacuum freeze-dry for 48-72 h.

[0057] The preparation method of the GelMA is as follows: 10g of gelatin is dissolved in 100mL of phosphate buffer solution, and then 8-20mL of methacrylic anhydride is added; after reacting at 50℃ and 300rpm for 2h, 100mL of PBS solution is added for dilution, and the reaction is continued for 10min-30min. After dialysis purification at 40℃ and 300rpm for 5d-7d, the deionized water is replaced every 12h; finally, vacuum freeze-drying is performed for 48h-72h.

[0058] Step 2: Optimization of CSMA molecular weight, CSMA concentration and GelMA concentration in the ink to be tested: Select samples that are printed and tested completely without any breaks, conduct mechanical property tests, select the sample with the highest compressive strength, and the corresponding ink to be tested is the optimized ink.

[0059] Step 3: Screening of power density and crosslinking time:

[0060] ① Using optimized ink, with the same printing power density, and changing the crosslinking time, multiple digital light processing 3D printing test samples were carried out according to the designed printing resolution.

[0061] ② Using optimized ink, with the same crosslinking time, and varying the power density, multiple digital light processing 3D printing test samples were conducted according to the designed printing resolution.

[0062] The printed test specimen is a laser-shaped model with a central circle at its center. Multiple radial lines are arranged in a ring around the central circle, and these radial lines are connected to the central circle.

[0063] ③ Take microscopic images of the multiple printed test specimens obtained in steps ① and ② using an optical microscope, measure the diameter of the central circle of the printed test specimen, the number of radial lines, and the width of the radial lines in the microscopic images, and calculate the test printing resolution p.

[0064] The test printing resolution p is calculated according to Formula 1:

[0065]

[0066] In Formula 1, p is the printing resolution, μm; D is the diameter of the center circle, μm; n is the number of radial lines, units; and h is the width of the radial lines, μm.

[0067] ④ Compare the design printing resolution of the printed test specimen with the test printing resolution p calculated in step ③. The printed test specimen with the test printing resolution closest to the design printing resolution is the optimal specimen. The power density or crosslinking time corresponding to the optimal specimen is the selected optimal power density and crosslinking time.

[0068] Step 4: Preparation of ZTM / GelMA / CSMA composite hydrogel wound dressing:

[0069] ZIF-8 / TA@MXene was added to the optimized ink selected in step two to obtain ZTM / GelMA / CSMA ink. Digital light processing 3D printing was performed according to the rate density and crosslinking time in step three to obtain a three-dimensional connected network or solid structure ZTM / GelMA / CSMA composite hydrogel wound dressing.

[0070] The preparation method of the ZIF-8 / TA@MXene is as follows:

[0071] ① Dissolve 1.6g of lithium fluoride in 20mL of 9mol / L hydrochloric acid for 10-30min; add 1.0g of MAX phase to the solution and react for 24-72h at 35℃-50℃ and 450rpm stirring; after the reaction is complete, centrifuge at 8000rpm for 10min and collect the reaction product; wash the product twice with 1mol / L HCl, then wash the product with deionized water until the pH of the supernatant is 6; shake the reaction product well and centrifuge at 5000rpm for 3-5min, repeating the HCl washing, deionized water washing and centrifugation ten times; then add deionized water and sonicate at below 30℃ for 60-120min, shaking every 5-10min during sonication; finally, centrifuge at 3500rpm for 10-60min and collect the MXene dispersion with a dropper.

[0072] ② Add 50 mg of tannic acid to the dispersion containing 25 mg MXene, stir evenly at room temperature, add 50 mL of Tris-HCl buffer, continue the reaction for 6 h-12 h, and finally wash three times with deionized water to remove unreacted tannic acid to obtain TA@MXene dispersion.

[0073] ③ Disperse the TA@MXene dispersion into 25 mL of 0.026 mol / L zinc acetate methanol solution, stir well, and then add 25 mL of 0.207 mol / L dimethylimidazolium methanol solution dropwise to the reaction solution. Continue the reaction at room temperature for 12-36 h. After completion, centrifuge the sample to collect the product, wash the product three times with deionized water, freeze at -20℃ overnight, and then perform vacuum freeze-drying for 24 h to obtain ZIF-8 / TA@MXene.

[0074] This embodiment first prepares tannic acid (TA)-coated modified MXene nanosheets (TA@MXene), and then grows a metal-organic framework ZIF-8 in situ on the TA@MXene surface to obtain ZIF-8 / TA@MXene (ZTM). A certain amount of ZTM nanoparticles are uniformly dispersed in a solution of methacrylamide gelatin (GelMA) and methacrylamide chitosan (CSMA) to prepare a printing ink. Finally, a ZTM / GelMA / CSMA (ZGC) composite hydrogel wound dressing is prepared using a digital light processing (DLP) 3D printer.

[0075] 1. The ZGC composite hydrogel wound dressing of this embodiment is a multifunctional integrated product, capable of simultaneously achieving hemostasis, antibacterial, anti-inflammatory, angiogenesis, and cell regeneration, making it particularly suitable for infected wounds. CSMA retains the inherent properties of chitosan, providing antibacterial, hemostatic, and biodegradable functions. GelMA endows the dressing with good cell affinity and mechanical adaptability, while ZIF-8 / TA@MXene contributes multiple effects such as photothermal antibacterial, photodynamic antibacterial, antioxidant, and angiogenesis promotion. The complementary enhancement and synergistic degradation effects of CSMA and GelMA, through photocrosslinking to form an interpenetrating network (IPN), combine the antibacterial properties of chitosan with the cell affinity of gelatin, while significantly improving mechanical properties (such as compressive strength). The slow degradation of CSMA is matched with the rapid degradation of GelMA, achieving time-sequential regulation of the dressing's mechanical support and drug release. The layered structure of MXene and ZIF-8 particles serve as physical cross-linking points, enhancing the compressive modulus of the hydrogel and making it suitable for dynamic wounds such as joints. Furthermore, through the synergistic photothermal and antibacterial effects of the layered structure of MXene and the ZIF-8 particles, MXene generates heat under near-infrared light, triggering the Zn content in ZIF-8. 2+The burst release enables "on-demand antibacterial" action, avoiding drug resistance. The phenolic hydroxyl group of TA forms hydrogen bonds with the amino / carboxyl groups of GelMA / CSMA, and simultaneously with the Zn group of ZIF-8. 2+ It coordinates and enhances component compatibility, prevents phase separation, and scavenges ROS under non-photothermal conditions, thereby maintaining cell viability and promoting endogenous cell proliferation to resist oxidative stress at the defect site. Together with the antibacterial properties of chitosan, it optimizes the wound microenvironment.

[0076] Therefore, the hydrogel wound dressing prepared in this embodiment can exert good antibacterial properties through the dual effects of photothermal therapy (PTT) and photodynamic therapy (PDT) under the activation of near-infrared light, and can also react with Zn. 2+ It has a synergistic antibacterial effect with a bacteriostatic rate of >99%; the dressing of this embodiment also has excellent hemostatic properties and can maintain a moist environment at the wound site, which helps the wound heal.

[0077] 2. The ZGC composite hydrogel wound dressing described in this embodiment can be precisely customized and printed according to the shape and depth of the wound using 3D printing technology. Its three-dimensional interconnected mesh structure combines excellent breathability and healing-promoting capabilities. The hydrogel's mesh structure provides a scaffold for cell migration through a biomimetic extracellular matrix fiber network. Its three-dimensional porous nature maintains a moist healing environment and promotes oxygen exchange, while mechanical adaptation reduces tissue damage and induces angiogenesis. The mesh structure can also load and sustain-release antibacterial agents and growth factors, while the internal interconnected pores allow for immune cell infiltration, thereby synergistically regulating the inflammatory response, promoting tissue regeneration, and significantly accelerating the wound healing process.

[0078] The antibacterial mechanism of ZGC composite hydrogel wound dressing is divided into two modes: photothermal activation and non-photothermal sustained action; under near-infrared light irradiation, MXene(Ti3C2T) x ZTM promotes the generation of reactive oxygen species (ROS) through photothermal heating and oxygen vacancies. After the near-infrared irradiation is turned off, ZTM releases Zn. 2+ MXene nanosheets also possess antibacterial properties. In this embodiment, the MXene nanosheets exhibit a sharp edge structure and mechanical encapsulation. MXene nanosheets have an atomically thin two-dimensional structure with sharp edges, capable of directly piercing bacterial cell membranes, leading to leakage of cell contents and physically disrupting bacterial integrity. MXene nanosheets can adsorb and encapsulate bacteria, hindering their material exchange and metabolic activities, ultimately causing bacterial death. Therefore, this dressing optimizes breathability and permeability management through 3D printing of a porous structure, while utilizing the synergistic effects of photothermal / chemical / physical antibacterial properties and biocompatibility design of nanomaterials to significantly accelerate the healing of infected wounds, providing an integrated solution for intelligent wound care.

[0079] 3. The temperature control mechanism of the ZGC composite hydrogel wound dressing in this embodiment includes: (1) active heat dissipation through the high specific heat capacity of the hydrogel and the heat absorption effect of water evaporation; (2) the 3D-printed grid structure increases the heat dissipation area and avoids local overheating; (3) ZIF-8 / TA modification reduces the surface energy of MXene and optimizes photothermal conversion efficiency. Therefore, under near-infrared irradiation, the composite dressing in this embodiment can achieve precise low-temperature photothermal therapy while maintaining Zn 2+ Sustained release and MXene's physical antibacterial function kill bacteria (such as Staphylococcus aureus and Escherichia coli) while protecting normal tissue, significantly improving the healing rate of infected wounds.

[0080] Specific Implementation Method Two: This implementation method differs from Specific Implementation Method One in that the initiation concentration in the ink to be tested in step one is 0.25 mg / mL, and the concentration of the light-blocking agent is 0.05 mg / mL.

[0081] Specific Implementation Method 3: This implementation method differs from Specific Implementation Method 1 or 2 in that the sample of the ink to be tested in step 1 is a cylindrical sample with a radius of 2 mm and a height of 4 mm.

[0082] Specific Implementation Method Four: This implementation method differs from one of Specific Implementation Methods One to Three in that the initiator mentioned in step one is lithium phenyl-2,4,6-trimethylbenzoylphosphonate.

[0083] Specific Implementation Method 5: This implementation method differs from one of the specific implementation methods 1 to 4 in that the light-blocking agent mentioned in step 1 is a water-soluble light absorber.

[0084] Specific Implementation Method Six: This implementation method differs from one of Specific Implementation Methods One to Five in that the water-soluble light absorber mentioned in step one is 2-hydroxy-1-(4-sulfonyl-1-naphthezo)naphthalene-6,8-disulfonate trisodium.

[0085] Specific Implementation Method Seven: This implementation method differs from Specific Implementation Methods One to Six in that the wavelength of the light source during the digital light processing 3D printing described in step Three ② is 405nm.

[0086] Specific Implementation Method Eight: This implementation method differs from one of Specific Implementation Methods One to Seven in that the amount of ZIF-8 / TA@MXene added to the ZTM / GelMA / CSMA ink described in step four is 0.8 mg / mL.

[0087] Specific Implementation Method Nine: This implementation method differs from Specific Implementation Methods One to Eight in that: Step Three ③ uses ImageJ software to measure the diameter of the central circle of the printed test specimen, the number of radial lines, and the width of the radial lines.

[0088] Specific Implementation Method 10: Application of ZTM / GelMA / CSMA composite hydrogel wound dressing in the preparation of skin wound healing dressing.

[0089] This embodiment first prepares tannic acid (TA)-coated modified MXene nanosheets (TA@MXene), and then grows a metal-organic framework ZIF-8 in situ on the TA@MXene surface to obtain ZIF-8 / TA@MXene (ZTM). A certain amount of ZTM nanoparticles are uniformly dispersed in a solution of methacrylamide gelatin (GelMA) and methacrylamide chitosan (CSMA) to prepare a printing ink. Finally, a ZTM / GelMA / CSMA (ZGC) composite hydrogel wound dressing is prepared using a digital light processing (DLP) 3D printer.

[0090] 1. The ZGC composite hydrogel wound dressing of this embodiment is a multifunctional integrated product, capable of simultaneously achieving hemostasis, antibacterial, anti-inflammatory, angiogenesis, and cell regeneration, making it particularly suitable for infected wounds. CSMA retains the inherent properties of chitosan, providing antibacterial, hemostatic, and biodegradable functions. GelMA endows the dressing with good cell affinity and mechanical adaptability, while ZIF-8 / TA@MXene contributes multiple effects such as photothermal antibacterial, photodynamic antibacterial, antioxidant, and angiogenesis promotion. The complementary enhancement and synergistic degradation effects of CSMA and GelMA, through photocrosslinking to form an interpenetrating network (IPN), combine the antibacterial properties of chitosan with the cell affinity of gelatin, while significantly improving mechanical properties (such as compressive strength). The slow degradation of CSMA is matched with the rapid degradation of GelMA, achieving time-sequential regulation of the dressing's mechanical support and drug release. The layered structure of MXene and ZIF-8 particles serve as physical cross-linking points, enhancing the compressive modulus of the hydrogel and making it suitable for dynamic wounds such as joints. Furthermore, through the synergistic photothermal and antibacterial effects of the layered structure of MXene and the ZIF-8 particles, MXene generates heat under near-infrared light, triggering the Zn content in ZIF-8. 2+ The burst release enables "on-demand antibacterial" action, avoiding drug resistance. The phenolic hydroxyl group of TA forms hydrogen bonds with the amino / carboxyl groups of GelMA / CSMA, and simultaneously with the Zn group of ZIF-8. 2+ It coordinates and enhances component compatibility, prevents phase separation, and scavenges ROS under non-photothermal conditions, thereby maintaining cell viability and promoting endogenous cell proliferation to resist oxidative stress at the defect site. Together with the antibacterial properties of chitosan, it optimizes the wound microenvironment.

[0091] Therefore, the hydrogel wound dressing prepared in this embodiment can exert good antibacterial properties through the dual effects of photothermal therapy (PTT) and photodynamic therapy (PDT) under the activation of near-infrared light, and can also react with Zn. 2+It has a synergistic antibacterial effect with a bacteriostatic rate of >99%; the dressing of this embodiment also has excellent hemostatic properties and can maintain a moist environment at the wound site, which helps the wound heal.

[0092] 2. The ZGC composite hydrogel wound dressing described in this embodiment can be precisely customized and printed according to the shape and depth of the wound using 3D printing technology. Its three-dimensional interconnected mesh structure combines excellent breathability and healing-promoting capabilities. The hydrogel's mesh structure provides a scaffold for cell migration through a biomimetic extracellular matrix fiber network. Its three-dimensional porous nature maintains a moist healing environment and promotes oxygen exchange, while mechanical adaptation reduces tissue damage and induces angiogenesis. The mesh structure can also load and sustain-release antibacterial agents and growth factors, while the internal interconnected pores allow for immune cell infiltration, thereby synergistically regulating the inflammatory response, promoting tissue regeneration, and significantly accelerating the wound healing process.

[0093] The antibacterial mechanism of ZGC composite hydrogel wound dressing is divided into two modes: photothermal activation and non-photothermal sustained action; under near-infrared light irradiation, MXene(Ti3C2T) x ZTM promotes the generation of reactive oxygen species (ROS) through photothermal heating and oxygen vacancies. After the near-infrared irradiation is turned off, ZTM releases Zn. 2+ MXene nanosheets also possess antibacterial properties. In this embodiment, the MXene nanosheets exhibit a sharp edge structure and mechanical encapsulation. MXene nanosheets have an atomically thin two-dimensional structure with sharp edges, capable of directly piercing bacterial cell membranes, leading to leakage of cell contents and physically disrupting bacterial integrity. MXene nanosheets can adsorb and encapsulate bacteria, hindering their material exchange and metabolic activities, ultimately causing bacterial death. Therefore, this dressing optimizes breathability and permeability management through 3D printing of a porous structure, while utilizing the synergistic effects of photothermal / chemical / physical antibacterial properties and biocompatibility design of nanomaterials to significantly accelerate the healing of infected wounds, providing an integrated solution for intelligent wound care.

[0094] 3. The temperature control mechanism of the ZGC composite hydrogel wound dressing in this embodiment includes: (1) active heat dissipation through the high specific heat capacity of the hydrogel and the heat absorption effect of water evaporation; (2) the 3D-printed grid structure increases the heat dissipation area and avoids local overheating; (3) ZIF-8 / TA modification reduces the surface energy of MXene and optimizes photothermal conversion efficiency. Therefore, under near-infrared irradiation, the composite dressing in this embodiment can achieve precise low-temperature photothermal therapy while maintaining Zn 2+ Sustained release and MXene's physical antibacterial function kill bacteria (such as Staphylococcus aureus and Escherichia coli) while protecting normal tissue, significantly improving the healing rate of infected wounds.

[0095] Example 1

[0096] The method for 3D printing a methacrylamide chitosan / gelatin-based hydrogel wound dressing of the present invention is carried out according to the following steps:

[0097] Step 1: Print the ink sample to be tested:

[0098] The test ink is composed of CSMA (methacrylated chitosan), GelMA (methacrylated gelatin), an initiator, and a light-blocking agent, with deionized water as the solvent. Multiple printing test groups of the test inks were set up, with different molecular weights of CSMA in each group, ranging from 50 to 2000 kDa. Each printing test group contained multiple test inks with different compositions, but the CSMA molecular weight was the same. Multiple CSMA concentrations were selected within each printing test group, ranging from 0.25 mg / mL to 1.25 mg / mL, and multiple GelMA concentrations were selected within the range of 2.5 mg / mL to 7.5 mg / mL. Samples of multiple test inks were then printed. Figure 1 This diagram illustrates the optimization process of multiple printing test groups and ink mixing ratios for the ink to be tested. Figure 1 As shown, when the molecular weight of CSMA is 1000 kDa, the concentration of CSMA is 1.0 mg / mL, and the concentration of GelMA is 7.5 mg / mL, the cylindrical structure of the sample is the most complete and the printing morphology is the best.

[0099] The initiator concentration in the ink to be tested was 0.25 mg / mL, and the light blocker concentration was 0.05 mg / mL.

[0100] The ink sample to be tested is a cylindrical sample with a radius of 2 mm and a height of 4 mm;

[0101] The initiator is lithium phenyl-2,4,6-trimethylbenzoylphosphonate (LAP); the light blocker is a water-soluble light absorber; the water-soluble light absorber is trisodium 2-hydroxy-1-(4-sulfonyl-1-naphthezo)naphthalene-6,8-disulfonate.

[0102] The preparation method of the methacrylamide chitosan (CSMA) is as follows: 1.5 g of chitosan powder is dissolved in 4% (v / v) glacial acetic acid solution to prepare a chitosan acetic acid solution with a concentration of 1.5% mg / mL; then 6 mL of methacrylic anhydride (MA) is added; the reaction is carried out for 12 h under light-protected, 40℃ and 300 rpm stirring and shaking conditions; then purification and dialysis are carried out for 3 days using a dialysis bag with a molecular weight cutoff of 8000-14000, and the deionized water is replaced every 12 h during the purification and dialysis process; finally, the sample is freeze-dried under vacuum for 48 h; and the spongy sample is collected.

[0103] The preparation method of the methacrylamide gelatin (GelMA) is as follows: 10g of gelatin is dissolved in 100mL of phosphate buffered saline (PBS), and then 8mL of methacrylic anhydride is added; after reacting at 50℃ and 300rpm for 2h, 100mL of PBS solution is added for dilution, and the reaction is continued for 10min. Then, the product is purified by dialysis using a dialysis bag with a molecular weight cutoff of 8000-14000 for 7d under stirring at 40℃ and 300rpm, with deionized water replaced every 12h; finally, the product is freeze-dried under vacuum for 48h; and the foamy finished product is collected.

[0104] Figure 2 The hydrogen NMR spectra of gelatin and gelMA are shown. Figure 3 The images show the 1H NMR spectra of chitosan and CSMA; GelMA was prepared by grafting methacrylic anhydride onto gelatin. The preparation of GelMA was characterized using a fully digital NMR spectrometer. Figure 2 As shown: the two characteristic proton peaks of methacrylate in the 1H NMR spectrum are at 5.4 ppm and 5.6 ppm, respectively, confirming the successful preparation of GelMA. Figure 3 As shown, the two characteristic proton peaks of methacrylate in the 1H NMR spectrum of CSMA are at 5.4 ppm and 5.6 ppm, respectively, proving the successful synthesis of CSMA.

[0105] Step 2: Optimization of CSMA molecular weight, CSMA concentration, and GelMA concentration in the ink to be tested: Samples that are printed completely without breaks are selected for mechanical property testing. The sample with the highest compressive strength is selected, and the corresponding ink is the optimized ink. A universal testing machine is used to perform compression tests on the printed cylinders. Figure 4 It can be seen that the CSMA molecular weight is 1000 kDa, the CSMA concentration is 1.0 mg / mL, and the GelMA concentration is 7.5 mg / mL, resulting in the highest compressive strength. The ink gel exhibits the best mechanical properties.

[0106] Step 3: Screening of power density and crosslinking time:

[0107] ① Using optimized ink, the printing power density remains the same (18W / cm²). 2 By changing the crosslinking time, multiple digital light processing 3D printing test samples were performed according to the designed printing resolution. Figure 6 Printed test specimens obtained by varying the crosslinking time;

[0108] ② Using optimized ink, with the same crosslinking time (20s), and varying the power density, multiple digital light processing 3D printing test samples were performed according to the designed printing resolution. Figure 7Printed test specimens obtained by changing power density;

[0109] The printed test specimen is a laser-shaped model. Figure 5 This is a schematic diagram of a laser-shaped model; the center of the laser-shaped model is a central circle, and there are multiple radial lines arranged in a ring around the central circle, which are connected to the central circle; the wavelength of the light source during digital light processing 3D printing is 405nm;

[0110] ③ Take microscopic images of the multiple printed test specimens obtained in steps ① and ② using an optical microscope. Measure the diameter of the central circle of the printed test specimen, the number of radial lines, and the width of the radial lines in the microscopic images using ImageJ software, and calculate the test printing resolution p.

[0111] The test printing resolution p is calculated according to Formula 1:

[0112]

[0113] In Formula 1, p is the printing resolution, μm; D is the diameter of the center circle, μm; n is the number of radial lines, units; and h is the width of the radial lines, μm.

[0114] ④ Compare the designed printing resolution of the printed test specimen with the test printing resolution p calculated in step ③. The printed test specimen with the test printing resolution closest to the designed printing resolution is the optimal specimen. The power density or crosslinking time corresponding to the optimal specimen is the selected optimal power density and crosslinking time. Figure 6 and Figure 7 The crosslinking time can be determined to be 20 seconds, and the power density is 18 W / cm². 2 ;

[0115] Step 4: Preparation of ZTM / GelMA / CSMA (ZGC) composite hydrogel wound dressing:

[0116] ZIF-8 / TA@MXene (ZTM) was added to the optimized ink selected in step two to obtain ZTM / GelMA / CSMA ink. Digital light processing 3D printing was then performed according to the density and crosslinking time in step three to obtain a three-dimensional connected network or solid structure ZTM / GelMA / CSMA (ZGC) composite hydrogel wound dressing. The amount of ZIF-8 / TA@MXene added to the ZTM / GelMA / CSMA ink was 0.8 mg / mL.

[0117] The preparation method of the ZIF-8 / TA@MXene is as follows:

[0118] ① Dissolve 1.6 g of lithium fluoride in 20 mL of 9 mol / L hydrochloric acid for 10 min; add 1.0 g of MAX phase to the solution and react for 24 h at 35 °C and 450 rpm stirring; after the reaction is complete, centrifuge at 8000 rpm for 10 min and collect the reaction product; first wash the product twice with 1 mol / L HCl to remove unreacted HF, then wash the product with deionized water until the pH of the supernatant is 6; then shake the reaction product well and centrifuge at 5000 rpm for 3 min, repeat the HCl washing, deionized water washing and centrifugation ten times to exfoliate the multilayer MXene into MXene nanosheets. Finally, the product becomes viscous and adheres to the bottom of the tube; then add deionized water and sonicate at below 30 °C for 60 min, shaking every 10 min during sonication; finally, centrifuge at 3500 rpm for 60 min and collect the MXene dispersion with a dropper.

[0119] ② Add 50 mg of tannic acid to the dispersion containing 25 mg MXene, stir evenly at room temperature, add 50 mL of Tris-HCl buffer (concentration of 0.1 mol / L, pH of 8.5), continue the reaction for 6 h, and finally wash three times with deionized water to remove unreacted tannic acid to obtain TA@MXene dispersion.

[0120] ③ Disperse the TA@MXene dispersion into 25 mL of 0.026 mol / L zinc acetate methanol solution, stir well, and then add 25 mL of 0.207 mol / L dimethylimidazolium methanol solution dropwise into the reaction solution. Continue the reaction at room temperature for 12 h. After completion, centrifuge the sample to collect the product, wash the product three times with deionized water, freeze at -20℃ overnight, and then freeze-dry under vacuum for 24 h to obtain ZIF-8 / TA@MXene (ZTM).

[0121] Figure 8 Here is a SEM image of MXene; Figure 9 TEM image of MXene; Figure 10 SEM image of TA@MXene; Figure 11 TEM image of TA@MXene; Figure 12 SEM image of ZIF-8 / TA@MXene (ZTM); Figure 13 TEM image of ZIF-8 / TA@MXene (ZTM); Figure 8 The fact that MXene is distributed in sheets indicates that it has been successfully peeled into sheets. Figure 9 This further confirms that MXene is in the form of flakes. Figure 10 Further observation was conducted on the morphology of the MXene sheet structure after TA coating. Figure 11 This further verified that the MXene sheets thickened after TA coating, further proving that the MXene sheets were successfully coated by TA. Figure 12 The successful in-situ growth of ZIF-8 on the TA@MXene surface was verified. Figure 13 This further verifies the successful in-situ growth of ZIF-8 on the TA@MXene surface.

[0122] Figure 14 XRD patterns of MXene and its modified products; XRD characterization of MXene nanosheets and their derivatives as follows: Figure 14 As shown. Compared to the precursor, the diffraction peak of Al at 38.9° (diffraction angle) disappeared in MXene, indicating that Al was etched away. Furthermore, the interaction between solvated Li+ and water during interlayer intercalation caused the diffraction peak at (002) to decrease from 9.5° to 6.2°, proving the successful acquisition of MXene. The XRD pattern of TA@MXene shows that the position of the (002) diffraction peak decreased to 5.7°.

[0123] Figure 15 This image shows the photothermal test results of ZGC composite hydrogel wound dressing under near-infrared lasers of different power densities. The laser's center wavelength was 808 nm. As the laser power density increased, the temperature of the ZGC composite hydrogel wound dressing rose, thus enhancing its photothermal conversion performance and improving its photothermal antibacterial ability. However, excessively high temperatures can burn the wound surface and affect wound healing. Temperatures above 50℃ cause protein denaturation and cell necrosis, delaying normal wound healing. Therefore, a laser power density of 0.8 W / cm² was selected. 2 .

[0124] Figure 16 These are photothermal test images of ZGC composite hydrogel wound dressings with different ZTM contents under near-infrared laser light; the laser's center wavelength is 808 nm. Figure 16 It can be seen that the optimal addition amount of ZIF-8 / TA@MXene in ZTM / GelMA / CSMA ink is 0.8 mg / mL;

[0125] Figure 17 This is a photograph of the three-dimensional interconnected network ZTM / GelMA / CSMA (ZGC) composite hydrogel wound dressing (blood vessels) prepared in Example 1;

[0126] The in vitro antibacterial activity of the composite hydrogel was evaluated, specifically its photothermal properties against Escherichia coli and Staphylococcus aureus. The different samples were grouped as follows: Control was the blank control; GC was the composite hydrogel dressing printed with GelMA / CSMA ink; TGC was the ZIF-8 / GelMA / CSMA composite hydrogel wound dressing; ZGC was the ZTM / GelMA / CSMA composite hydrogel wound dressing; NIR- represented non-near-infrared irradiation, and NIR+ represented near-infrared irradiation; the preparation method of TGC was as follows: ZIF-8 metal-organic framework was added to the solution of photoinitiator and photoblocker described in step (3), with a ZIF-8 metal-organic framework content of 0.6-1.2 mg / ml; then, ZGC composite ink was prepared according to the formulation selected in the above steps, and CSMA and GelMA were dissolved by heating and vortexing; ZGC composite hydrogels were prepared using a DLP 3D printer according to the formulation and printing parameters selected in the above steps.

[0127] Figure 18 The study investigated the photothermal antibacterial effects of different samples. Results showed that the GC-NIR- group hydrogels exhibited antibacterial activity against *Escherichia coli* and *Staphylococcus aureus*, while the TGC-NIR- and ZGC-NIR- groups demonstrated greater ability to reduce microbial viability. Compared to the GC-NIR- group, TGC-NIR- could kill 38.2% of *Staphylococcus aureus* and 40.1% of *Escherichia coli*; ZGC-NIR- could kill 23.4% of *Staphylococcus aureus* and 37.5% of *Escherichia coli*. This was due to the release of Zn... 2+ The antibacterial effect of ions and the excellent photothermal spectroscopy properties of MXene can destroy the structure of liposomes on microbial membranes.

[0128] Following near-infrared irradiation, ZGC-NIR+ showed a significant decrease in microbial activity due to its effective photothermal therapy, effectively killing Staphylococcus aureus (99.9% kill rate) and Escherichia coli (99.9% kill rate). Furthermore, it was observed that the treatment effects of the GC-NIR-, TGC-NIR-, and ZGC-NIR- groups were negligible due to the lack of photothermal treatment. Importantly, some wrinkles and ruptures in the bacterial membrane were observed in ZGC-NIR+, indicating its excellent photothermal bactericidal properties.

Claims

1. A method for 3D printing to prepare a methacrylamide chitosan / gelatin-based hydrogel wound dressing, characterized in that: The method for 3D printing to prepare methacryloyl chitosan / gelatin-based hydrogel wound dressings is carried out according to the following steps: Step 1: Print the ink sample to be tested: The test ink consists of CSMA, GelMA, an initiator, and a light blocker, with deionized water as the solvent. Multiple printing test groups of the test inks were set up, with different molecular weights of CSMA in each group, ranging from 50 to 2000 kDa. Each printing test group contained multiple test inks with different compositions, but all inks in each group had the same CSMA molecular weight. Multiple CSMA concentrations were selected within each printing test group, ranging from 0.25 mg / mL to 1.25 mg / mL, and multiple GelMA concentrations were selected within the range of 2.5 mg / mL to 7.5 mg / mL. Samples of multiple test inks were then printed. The preparation method of CSMA is as follows: prepare a chitosan acetate solution with a concentration of 1.5% mg / mL; then add 2-15 mL of methacrylic anhydride; react for 12 h under light-protected, 40℃ and 300 rpm stirring and shaking conditions; then use a dialysis bag for 3-7 days of purification and dialysis, changing the deionized water every 12 h during the purification and dialysis process; finally, vacuum freeze-dry for 48-72 h. The preparation method of the GelMA is as follows: 10g of gelatin is dissolved in 100mL of phosphate buffer solution, and then 8-20mL of methacrylic anhydride is added; after reacting at 50℃ and 300rpm for 2h, 100mL of PBS solution is added for dilution, and the reaction is continued for 10min-30min. After dialysis purification at 40℃ and 300rpm for 5d-7d, the deionized water is replaced every 12h; finally, vacuum freeze-drying is performed for 48h-72h. Step 2: Optimization of CSMA molecular weight, CSMA concentration and GelMA concentration in the ink to be tested: Select samples that are printed and tested completely without any breaks, conduct mechanical property tests, and select the sample with the highest compressive strength. The corresponding ink to be tested is the optimized ink. Step 3: Screening of power density and crosslinking time: ① Using optimized ink, with the same printing power density, and changing the crosslinking time, multiple digital light processing 3D printing test samples were carried out according to the designed printing resolution. ② Using optimized ink, with the same crosslinking time, and varying the power density, multiple digital light processing 3D printing test samples were performed according to the designed printing resolution. The printed test specimen is a laser-shaped model with a central circle at its center. Multiple radial lines are arranged in a ring around the central circle, and these radial lines are connected to the central circle. ③ Take microscopic images of the multiple printed test specimens obtained in steps ① and ② using an optical microscope, measure the diameter of the central circle of the printed test specimen, the number of radial lines, and the width of the radial lines in the microscopic images, and calculate the test printing resolution p. The test printing resolution p is calculated according to Formula 1: Official 1 In Formula 1, p is the printing resolution, µm; D is the diameter of the center circle, µm; n is the number of radial lines, units; and h is the width of the radial lines, µm. ④ Compare the design printing resolution of the printed test specimen with the test printing resolution p calculated in step ③. The printed test specimen with the test printing resolution closest to the design printing resolution is the optimal specimen. The power density or crosslinking time corresponding to the optimal specimen is the selected optimal power density and crosslinking time. Step 4: Preparation of ZTM / GelMA / CSMA composite hydrogel wound dressing: ZIF-8 / TA@MXene was added to the optimized ink selected in step two to obtain ZTM / GelMA / CSMA ink. Digital light processing was performed for 3D printing according to the rate density and crosslinking time in step three to obtain a three-dimensional connected network or solid structure ZTM / GelMA / CSMA composite hydrogel wound dressing. The preparation method of the ZIF-8 / TA@MXene is as follows: ① Dissolve 1.6g of lithium fluoride in 20mL of 9mol / L hydrochloric acid for 10-30min; add 1.0g of MAX phase to the solution and react for 24-72h at 35℃-50℃ and 450rpm stirring; after the reaction is complete, centrifuge at 8000rpm for 10min and collect the reaction product; wash the product twice with 1mol / L HCl, then wash the product with deionized water until the pH of the supernatant is 6; shake the reaction product well and centrifuge at 5000rpm for 3-5min, repeating the HCl washing, deionized water washing and centrifugation ten times; then add deionized water and sonicate at below 30℃ for 60-120min, shaking every 5-10min during sonication; finally, centrifuge at 3500rpm for 10-60min and collect the MXene dispersion with a dropper. ② Add 50 mg of tannic acid to the dispersion containing 25 mg MXene, stir evenly at room temperature, add 50 mL of Tris-HCl buffer, continue the reaction for 6 h-12 h, and finally wash three times with deionized water to remove unreacted tannic acid to obtain TA@MXene dispersion. ③ Disperse the TA@MXene dispersion into 25 mL of 0.026 mol / L zinc acetate methanol solution, stir well, and then add 25 mL of 0.207 mol / L dimethylimidazolium methanol solution dropwise to the reaction solution. Continue the reaction at room temperature for 12-36 h. After completion, centrifuge the sample to collect the product, wash the product three times with deionized water, freeze at -20℃ overnight, and then freeze-dry under vacuum for 24 h to obtain ZIF-8 / TA@MXene. The ZIF-8 / TA@MXene content in the ZTM / GelMA / CSMA ink is 0.8 mg / mL.

2. The method for preparing methacrylamide chitosan / gelatin-based hydrogel wound dressing by 3D printing according to claim 1, characterized in that: The initiator concentration in the ink to be tested in step one is 0.25 mg / mL, and the light-blocking agent concentration is 0.05 mg / mL.

3. The method for preparing methacrylamide chitosan / gelatin-based hydrogel wound dressing by 3D printing according to claim 1, characterized in that: The ink sample to be tested in step one is a cylindrical sample with a radius of 2 mm and a height of 4 mm.

4. The method for preparing methacrylamide chitosan / gelatin-based hydrogel wound dressing by 3D printing according to claim 1, characterized in that: The initiator mentioned in step one is lithium phenyl-2,4,6-trimethylbenzoylphosphonate.

5. The method for preparing methacrylamide chitosan / gelatin-based hydrogel wound dressing by 3D printing according to claim 1, characterized in that: The light-blocking agent mentioned in step one is a water-soluble light absorber.

6. The method for preparing methacrylamide chitosan / gelatin-based hydrogel wound dressing by 3D printing according to claim 5, characterized in that: The water-soluble light absorber mentioned in step one is trisodium 2-hydroxy-1-(4-sulfonyl-1-naphthezo)naphthalene-6,8-disulfonate.

7. The method for preparing methacrylamide chitosan / gelatin-based hydrogel wound dressing by 3D printing according to claim 1, characterized in that: In step 3②, the wavelength of the light source used in digital light processing 3D printing is 405nm.

8. The method for preparing methacrylamide chitosan / gelatin-based hydrogel wound dressing by 3D printing according to claim 1, characterized in that: Step 3: Measure the diameter of the center circle of the printed test specimen, the number of radial lines, and the width of the radial lines in the microscopic image using ImageJ software.

9. The application of the ZTM / GelMA / CSMA composite hydrogel wound dressing as described in claims 1 to 8 in the preparation of skin wound healing dressings.

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