Medical dressing with radiation protection function and preparation process thereof

Abstract

The invention discloses a medical dressing with a radiation protection function and a preparation process thereof, and belongs to the technical field of biomedical materials.The medical dressing comprises a first covalent cross-linked network and a second ionic cross-linked network which penetrate through each other, and functional fullerene which is sensitive to active oxygen is fixed to a network framework of the first covalent cross-linked network and a second ionic cross-linked network in a chemical bonding mode. And a diagnostic functionalized fullerene sensitive to a hypoxic microenvironment. The preparation method can realize in-situ forming: applying a precursor solution containing a network precursor, functionalized fullerene and a temperature-sensitive controlled-release carrier encapsulated with cross-linked ions to a target part, and performing illumination curing to form a first network; according to the invention, through the combination of the exquisite molecular design and the sequential curing process, the finally formed dressing can actively sense pathological signals of an injured microenvironment, and real-time fluorescence monitoring of a hypoxic state and targeted drug release of oxidative stress are realized.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, in particular to a medical dressing with radiation protection function and a preparation process thereof. Background Art

[0002] Radiation-induced skin injury is a common complication of radiotherapy and can also occur after accidental radiation exposure, such as in nuclear accidents. Its pathological features are complex, involving persistent oxidative stress, inflammation, microcirculatory impairment, and even tissue necrosis. Effective wound dressings play a vital role in protecting damaged skin, preventing infection, and promoting tissue repair, making them a key component of clinical intervention.

[0003] Currently, a wide variety of dressings are used clinically to treat skin injuries, ranging from traditional gauze to modern hydrogel, foam, and film dressings. These dressings play a fundamental role in providing a physical barrier and maintaining a moist healing environment. To enhance therapeutic efficacy, existing technologies have attempted to load various active ingredients (such as antimicrobials, anti-inflammatory drugs, or growth factors) into dressings. However, these functional dressings generally suffer from a crude drug release pattern. Their release behavior is typically passive, indiscriminate, and sustained, failing to respond and regulate according to the actual pathological state of the injured microenvironment. This uncontrolled release can lead to drug waste during unnecessary periods and fail to provide the most effective therapeutic support at critical moments of exacerbated injury. Furthermore, the lack of feedback on the wound healing process renders the dressing itself a single-function "black box."

[0004] Hydrogel dressings are considered to be extremely promising dressing substrates due to their high water content, good biocompatibility and breathability. Despite this, traditional hydrogel dressings have inherent defects in mechanical properties. Most single-network hydrogels are fragile, have poor toughness and are easy to tear, which greatly limits their application in complex areas that require frequent movement, such as joints and necks. Their mechanical strength is not sufficient to maintain structural integrity when subjected to repeated deformation, thus affecting their continued protective effect. In addition, most dressings are in the form of pre-formed patches, which are difficult to fit perfectly with the irregular contours of the wound surface. Gaps often appear at the edges, forming potential infection pathways and reducing the rigor of protection.

[0005] To achieve more advanced functions, researchers have attempted to incorporate active components, such as functional nanoparticles, into the hydrogel matrix. However, the prevailing preparation method often relies on simple physical blending, with the active components passively encapsulated within the hydrogel's pore structure. This non-covalent physical encapsulation method has weak binding forces, resulting in a high risk of sudden release and leakage of the functional components during contact with tissue fluid, making it difficult to achieve long-term, stable retention in the wound surface. This significantly reduces the claimed therapeutic or diagnostic properties and shortens the effective duration of action.

[0006] Therefore, existing technologies still face many challenges in developing advanced dressings that can cope with complex radiation-induced skin injuries. There is an urgent need for a new type of smart dressing that not only possesses excellent mechanical toughness and perfect conformability to irregular wound surfaces, but also needs to be able to actively sense the characteristic signals of the injury microenvironment, thereby enabling intelligent, on-demand targeted treatment and real-time status monitoring, while ensuring that its core functional components can stably exert their long-term effects. Summary of the Invention

[0007] The technical problem addressed by this invention is that existing dressings and medications for protecting against radiation-induced skin damage suffer from shortcomings such as limited functionality, easy loss of active ingredients, poor adherence to irregular skin areas, and an inability to intelligently respond to damage severity. For example, traditional dressings primarily provide physical isolation or moisturizing properties, while the active ingredients in topical ointments have a short duration of action and uncontrollable dosage.

[0008] In order to solve the above technical problems, the present invention provides a medical dressing with radiation protection function and a preparation process thereof.

[0009] The first aspect of the present invention provides a medical composition with radiation protection function.

[0010] The composition is a flowable liquid or semisolid that can be converted into a functional hydrogel dressing through a specific curing process at the site of use. In a specific embodiment, the composition comprises, by weight: 7 to 12 parts of a first network precursor, 0.5 to 1.5 parts of a second network precursor, 0.1 to 0.5 parts of a radiation-responsive drug-functionalized fullerene, 0.05 to 0.2 parts of a hypoxia-monitoring functionalized fullerene, 0.5 to 2 parts of a temperature-sensitive controlled-release ion source, 0.1 to 0.3 parts of a photoinitiator, and the balance an aqueous medium.

[0011] The components of the composition are carefully designed to work synergistically in the final dressing: The first and second network precursors form the backbone of the final dressing's "dual-network interpenetrating structure." The first network precursor is preferably a methacrylated biocompatible polymer (such as methacrylated hyaluronic acid and methacrylated gelatin), which can undergo covalent cross-linking under the action of a photoinitiator to form a stable and robust first chemical network. The second network precursor is preferably a cationic cross-linkable polymer (such as alginate) to form the second physical network.

[0012] Radiation-responsive drug-functionalized fullerenes are the core component that enables the "smart treatment" function of this invention. Their structure is sophisticated, with fullerene as the nanocore and three key functional groups covalently attached to the surface through chemical methods: i. Functional groups that can participate in polymerization (such as methacrylate groups) are used to firmly "weld" the nanoparticles to the gel skeleton when the first network is solidified to prevent leakage.

[0013] ii. A chemical linker that is sensitive to reactive oxygen species and can be broken (preferably a thioketal or boronate structure). This linker remains stable under normal physiological conditions.

[0014] iii. An anti-inflammatory or antioxidant drug (preferably isoliquiritigenin) is connected to the fullerene core via the aforementioned linker arm. Its mechanism of action is that when the skin is exposed to radiation, a large amount of reactive oxygen species is generated. High concentrations of reactive oxygen species specifically sever the sensitive linker arm, thereby releasing the drug on demand and in a targeted manner at the site of injury, achieving highly effective local treatment.

[0015] The hypoxia-monitoring functionalized fullerene is the core component that enables the "noninvasive diagnosis" function of this invention. Its structure is similar to the aforementioned drug-functionalized fullerene, similarly covalently linked to a gel backbone via polymerization-capable functional groups. However, its surface is also attached to a probe molecule (such as a nitroimidazole derivative) that emits a fluorescent signal in hypoxic environments. Since tissue hypoxia is often associated with areas of radiation damage, the presence and intensity of this fluorescent signal can be used to noninvasively and in real time determine the state and extent of subcutaneous tissue damage.

[0016] A thermosensitive controlled-release ion source acts as a "switch" that controls the timing of the second network formation. Preferably, it encapsulates a divalent or trivalent cation salt (such as calcium carbonate) within a liposome composed of a thermosensitive phospholipid (such as DPPC). At room temperature, the ions are trapped within the liposome. Upon application of a mild external heat stimulus (e.g., 40-50°C), the liposome membrane undergoes a phase transition, increasing its permeability and releasing the internalized cations, which in turn triggers the rapid cross-linking of the second network precursor (such as alginate).

[0017] Through the synergistic effect of the above components, the composition provided in the first aspect of the present invention lays a material foundation for preparing an advanced dressing that combines enhanced physical properties, intelligent drug release and real-time injury monitoring functions.

[0018] The second aspect of the present invention provides a method for preparing a composition having radiation protection function.

[0019] This method utilizes the hydrogel precursor composition described in the first aspect of the present invention to form a functional hydrogel dressing in situ on the surface of the substrate to be protected through an orderly, dual-curing process. The method specifically comprises the following steps: First, the liquid composition is applied to the target substrate surface. Due to its fluidity, it can perfectly adhere to any irregular surface, such as joints, neck, or underarms of human skin, thus avoiding the blind spots caused by the poor adhesion of traditional patch dressings.

[0020] Then, the first curing is carried out. Using light of a specific wavelength (preferably a wavelength of 365-450nm and a light intensity of 10-50mW / cm 2 ) irradiates the composition. The photoinitiator is activated, triggering a covalent cross-linking reaction between the first network precursor and the polymerizable groups on the two functionalized fullerenes, forming a stable, transparent first covalent network. This step not only completes the initial formation of the dressing but, more importantly, firmly locks the "therapeutic" and "diagnostic" functional modules into the gel network.

[0021] Next, a second curing step is performed. An external physical stimulus (preferably heating the gel to 40-50°C) is applied to the first-cured gel. This stimulus triggers the release of cations from the temperature-sensitive controlled-release ion source, which rapidly undergo ionic crosslinking with the second network precursors in the system, forming a second physical network within the first network.

[0022] Ultimately, through the dual curing process triggered sequentially by light and heat, a second ionic cross-linked network is generated and interpenetrated within the first covalent network, forming a dual-network interpenetrating structure. This unique structure endows the resulting hydrogel dressing with excellent mechanical properties (such as high toughness, tear resistance, and tissue adhesion) and high water retention, the latter of which helps enhance its physical shielding effect against low-energy radiation. This method enables the rapid in situ preparation of advanced medical dressings with highly integrated functions and conformal to the skin on biological surfaces.

[0023] In summary, the present invention includes at least one of the following beneficial technical effects: 1. This invention enables intelligent targeted therapy within the injury microenvironment. By anchoring the therapeutic drug to a functionalized fullerene via a chemical linker arm sensitive to reactive oxygen species, the drug remains stable under normal physiological conditions, preventing premature leakage and ineffective effects on healthy tissue. Only after the skin is exposed to radiation and produces a large amount of characteristic reactive oxygen species does the linker arm break, allowing for on-demand, targeted release of the drug. This significantly improves drug utilization efficiency and therapeutic precision, while minimizing potential side effects.

[0024] 2. This invention provides a dressing with the ability to non-invasively and in real time monitor injury status. The hypoxia-monitoring functionalized fullerene contained in the composition can specifically sense the tissue hypoxic microenvironment caused by radiation damage. Under these conditions, the probe's molecular structure changes and emits a fluorescent signal, visualizing the extent of otherwise invisible subcutaneous damage. This provides a direct and convenient basis for assessing injury progression and guiding subsequent treatment plans, truly realizing the innovative concept of "integrated diagnosis and treatment."

[0025] 3. The hydrogel dressing prepared by this invention exhibits excellent mechanical toughness and tissue adhesion. This is due to its unique dual-network interpenetrating structural design: the first chemically cross-linked network provides a stable structural framework, while the second ionic cross-linked network interpenetrating it endows the material with excellent energy dissipation capabilities. The synergistic effect of these two networks renders the final gel dressing not fragile but rather tough and elastic, capable of adapting to the stretching and deformation of active areas such as joints without breaking or falling off, ensuring continuous and effective protection.

[0026] 4. The present invention significantly improves the stability of functional components, ensuring the long-term performance of the dressing's functions. Unlike traditional physical encapsulation methods, the present invention presets polymerizable "chemical anchor points" on the surface of functionalized fullerenes. During the gel curing process, these core units carrying therapeutic and diagnostic functions are "woven" into the hydrogel network skeleton through strong covalent bonds. This chemical bonding method fundamentally solves the technical problem of easy loss of active ingredients, ensuring that the dressing can continuously and stably perform its intelligent response and protection functions during long-term use.

[0027] 5. The present invention provides an in-situ forming method that can form a seamless protective layer that fits perfectly with irregular wound surfaces. By adopting a liquid precursor and combining it with an innovative process of sequential curing, the dressing can be directly applied to the skin surface and then subjected to gentle light and heat dual curing. In particular, the temperature-sensitive controlled release design of the second network cross-linking ions ensures that the precursor liquid has sufficient operating time. This method can perfectly adapt to any shape of injured area, forming a layer of "second skin" without dead angles, overcoming the defects of traditional patch dressings that are poorly fitted in irregular areas and have protective loopholes. DETAILED DESCRIPTION

[0028] Example 1: Parameter preparation This example describes a process for preparing a hydrogel dressing using parameters within the scope of the claims.

[0029] 1. Preparation of key intermediates (a) Preparation of Methacrylated Gelatin and Hyaluronic Acid: Dissolve 10 g of gelatin (or sodium hyaluronate) in 100 mL of phosphate buffered saline (PBS, pH 7.4) and stir at 50°C until completely dissolved. Slowly add 8 mL of methacrylic anhydride dropwise, and incubate at 50°C in the dark for 3 hours. After the reaction, dilute with 400 mL of preheated PBS. The mixture is then dialyzed against deionized water at 4°C using a dialysis bag with a molecular weight cutoff of 12-14 kDa, changing the water twice daily for 5 days. The dialyzed solution is freeze-dried to obtain a white, flocculent solid, Gel-MA (or HA-MA).

[0030] (b) Preparation of radiation-responsive drug-functionalized fullerenes: 100 mg of amino-modified fullerene was dissolved in 20 mL of dimethyl sulfoxide, and 15 mg of methacrylic anhydride was added. The mixture was reacted at 45°C in the dark for 30 hours to yield F(NH2)-MA. In a separate reaction flask, 100 mg of the presynthesized ISL-TK conjugate (with active carboxyl groups), 35 mg of EDC·HCl, and 25 mg of NHS were dissolved in 20 mL of DMSO and activated for 30 minutes. The F(NH2)-MA solution was then added and the mixture was reacted at room temperature in the dark for 60 hours. The product was dialyzed against deionized water for 3 days and then freeze-dried to yield ISL-TK-F-MA powder.

[0031] (c) Preparation of hypoxia probe functionalized fullerene The same steps as step (b) were used, except that the ISL-TK conjugate was replaced with 80 mg of nitroimidazole fluorescent probe molecules with active carboxyl groups, and Probe-F-MA powder was finally obtained.

[0032] (d) Preparation of a Thermosensitive Controlled-Release Calcium Ion Carrier: 450 mg of DPPC and 100 mg of cholesterol were dissolved in chloroform and rotary evaporated to form a lipid film. 20 mL of a PBS suspension containing 15 mg / mL CaCO nanoparticles was added to the film and hydrated at 55°C for 1.5 hours. The mixture was passed through a microextruder through a 400 nm filter and then a 200 nm filter 18 times each. The mixture was centrifuged at 4000 rpm for 10 minutes, and the supernatant was collected as the CaCO@Liposome suspension, with a solid content of approximately 10% (w / v).

[0033] 2. Preparation of Composite Hydrogel Precursor Solution In a sterile beaker, weigh the following components and add them to 87.68 g of sterile PBS buffer solution: HA-MA: 3.0 g (3.0 parts) Gel-MA: 6.5 g (6.5 parts) Sodium alginate: 1.0g (1.0 part) ISL-TK-F-MA: 0.3g (0.3 parts) Probe-F-MA: 0.12 g (0.12 parts) CaCO3@Liposome suspension (solid content 10%): 12.0g, equivalent to 1.2g solid (1.2 parts) LAP photoinitiator: 0.2 g (0.2 parts) was slowly stirred in a 37°C water bath until all components were completely dissolved and evenly dispersed.

[0034] 3. In situ Double Network Hydrogel Formation Take 5mL of the prepared precursor solution and evenly apply it on the substrate surface. Use a wavelength of 405nm and a light intensity of 30mW / cm 2 The gel surface was then irradiated with an LED light source for 120 seconds. Immediately after the irradiation, an infrared lamp was used to heat the gel surface to 42°C and maintain this temperature for 4 minutes to form a double-network hydrogel.

[0035] Example 2: Parameter preparation This example describes a process for preparing a hydrogel dressing using parameters within the scope of the claims.

[0036] 1. Preparation of key intermediates (a) Preparation of methacrylated polymer: The preparation method is the same as that in Example 1.

[0037] (b) Preparation of functionalized fullerene: The preparation method is the same as that in Example 1.

[0038] (c) Preparation of thermosensitive controlled-release calcium ion carrier (CaCO3@Liposome): The preparation method is the same as that in Example 1.

[0039] 2. Preparation of Composite Hydrogel Precursor Solution In a sterile beaker, weigh the following components and add them to 83.5 g of sterile PBS buffer solution: HA-MA: 4.0 g (4.0 parts) Gel-MA: 8.0 g (8.0 parts) Sodium alginate: 1.5g (1.5 parts) ISL-TK-F-MA: 0.5g (0.5 parts) Probe-F-MA: 0.2 g (0.2 parts) CaCO3@Liposome suspension (solid content 10%): 20.0g, equivalent to 2.0g solid (2.0 parts) LAP photoinitiator: 0.3 g (0.3 parts) was slowly stirred in a 37°C water bath until all components were completely dissolved and evenly dispersed.

[0040] 3. In situ Double Network Hydrogel Formation Take 5mL of the prepared precursor solution and evenly apply it on the substrate surface. Use a wavelength of 365nm and a light intensity of 50mW / cm 2 The gel surface was then irradiated with a light source for 60 seconds. After the irradiation, a preheated hot air gun was used to heat the gel surface to 50°C and maintain this temperature for 3 minutes to form a tough double-network hydrogel.

[0041] Example 3: Parameter preparation This example describes a process for preparing a hydrogel dressing using parameters within the scope of the claims.

[0042] 1. Preparation of key intermediates (a) Preparation of methacrylated polymer: The preparation method is the same as that in Example 1.

[0043] (b) Preparation of functionalized fullerene: The preparation method is the same as that in Example 1.

[0044] (c) Preparation of thermosensitive controlled-release calcium ion carrier (CaCO3@Liposome): The preparation method is the same as that in Example 1.

[0045] 2. Preparation of Composite Hydrogel Precursor Solution In a sterile beaker, weigh the following components and add them to 91.75 g of sterile PBS buffer solution: HA-MA: 2.0 g (2.0 parts) Gel-MA: 5.0 g (5.0 parts) Sodium alginate: 0.5g (0.5 parts) ISL-TK-F-MA: 0.1g (0.1 part) Probe-F-MA: 0.05 g (0.05 parts) CaCO3@Liposome suspension (solid content 10%): 5.0g, equivalent to 0.5g solid (0.5 parts) LAP photoinitiator: 0.1 g (0.1 part) was slowly stirred in a 37°C water bath until all components were completely dissolved and evenly dispersed.

[0046] 3. In situ Double Network Hydrogel Formation Take 5mL of the prepared precursor solution and evenly apply it on the substrate surface. Use a wavelength of 450nm and a light intensity of 20mW / cm 2 The gel surface was then irradiated with a light source for 180 seconds. After the irradiation, the gel surface was immediately heated to 40°C in a constant temperature water bath and maintained for 5 minutes to form a relatively soft double-network hydrogel.

[0047] Comparative Example 1: Compared to Example 1, the difference is that in the "Preparation of Composite Hydrogel Precursor Solution" step, the radiation-responsive drug-functionalized fullerene (ISL-TK-F-MA) is not added, and the original weight of this component (0.3 parts) is replaced with PBS buffer solution. The remaining components and preparation steps are the same. (Purpose: To verify the necessity of the therapeutic function module in "Integrated Diagnosis and Treatment") Comparative Example 2: Compared to Example 1, the difference is that in the "Preparation of Composite Hydrogel Precursor Solution" step, the hypoxia monitoring functionalized fullerene (Probe-F-MA) is omitted, and the original mass of this component (0.12 parts) is replaced with PBS buffer solution. The remaining components and preparation steps are the same. (Purpose: To verify the necessity of the diagnostic function module in "Integrated Diagnosis and Treatment") Comparative Example 3: Compared to Example 1, the two functionalized fullerenes used were not methacrylated, meaning they lacked functional groups capable of covalent polymerization. The remaining components, feed amounts, and preparation steps were identical. (Purpose: To verify the necessity of designing "polymerizable anchor points" on the functional modules, which enable covalent bonding of the functional components within the network.) Comparative Example 4: Compared to Example 1, the second network precursor (sodium alginate) was omitted during the "Preparation of the Composite Hydrogel Precursor Solution" step, and the original mass of this component (1.0 part) was replaced with PBS buffer. The remaining components and preparation steps were identical. (Purpose: To verify the necessity of the "dual network interpenetrating structure"; without the second network, an ionically crosslinked network cannot be formed.) Comparative Example 5: Compared with Example 1, the difference is that the thermosensitive controlled-release calcium ion carrier (CaCO3@Liposome) is not added to the "composite hydrogel GLISH". Instead, a calcium chloride (CaCl2) solution with equimolar calcium ions is directly added. The remaining components and preparation steps are the same. (Purpose: To verify the necessity of the "thermosensitive controlled-release switch" and "sequential dual-curing" processes. Direct addition of ions will cause uncontrolled chaotic cross-linking of the network before light curing) Comparative Example 6: Compared to Example 1, the total amount of the first network precursor (HA-MA and Gel-MA) was reduced to 4.0 parts (1.5 parts HA-MA, 2.5 parts Gel-MA), exceeding the lower limit of the claims. The remaining component amounts and preparation steps were the same. (Purpose: To verify the rationality of the component concentration ranges in the claims; too low a concentration may not result in effective gel formation.) Comparative Example 7: Compared to Example 1, the second step in the "in situ double-network hydrogel formation" was omitted, i.e., heating was not performed after illumination. The remaining components, feed amounts, and preparation steps were identical. (Purpose: To verify the necessity of the "heat curing" step in the preparation method; without this step, ion release could not be triggered and the second network could not be formed.) Test Example 1 Experimental purpose: This experiment aims to verify the ability of the hydrogel described in the present invention to release drugs in a targeted and on-demand manner under a simulated pathological microenvironment (i.e., a high concentration of reactive oxygen species).

[0048] Subjects: Experimental group: hydrogel sample prepared in Example 1.

[0049] Control group: the hydrogel sample prepared in Comparative Example 1 (the sample does not contain radiation-responsive drug-functionalized fullerene).

[0050] Experimental steps: Sample preparation: The hydrogels prepared in Example 1 and Comparative Example 1 were cut using a circular sampler with a diameter of 8 mm to prepare disc-shaped samples of uniform size and thickness, each weighing about 0.5 g.

[0051] Group processing: Group A: The hydrogel sample of Example 1 was placed in 10 mL of PBS buffer solution (pH 7.4).

[0052] Group B: The hydrogel sample of Example 1 was placed in 10 mL of PBS buffer solution containing 100 μM H2O2 to simulate the high-concentration active oxygen environment generated after radiation damage.

[0053] Group C: The hydrogel sample of Comparative Example 1 was placed in 10 mL of PBS buffer solution (pH 7.4).

[0054] Group D: The hydrogel sample of Comparative Example 1 was placed in 10 mL of PBS buffer solution containing 100 μM H2O2.

[0055] Incubation and Sampling: All groups were placed in a thermostatted shaker at 37°C. At predetermined time points (0, 1, 2, 4, 8, 12, and 24 hours), 1 mL of release medium was removed from each beaker and immediately replaced with 1 mL of fresh buffer solution corresponding to the group to maintain the total volume and sedimentation conditions essentially unchanged.

[0056] Sample Analysis: Using a UV-Vis spectrophotometer, measure the absorbance of the sample at the drug (isoliquiritigenin) maximum absorption wavelength. Calculate the drug concentration in the release medium based on a pre-drawn drug concentration-absorbance standard curve, and further convert it into the cumulative release rate (%).

[0057] Experimental data Table 1: Comparison of the cumulative release rate of drugs in hydrogels under different conditions

[0058] Summarize The experimental data above show that in a conventional buffer solution without a reactive oxygen species simulant (H₂O₂), the cumulative release rate of the drug in the sample from Example 1 over 24 hours was extremely low, never exceeding 5%, indicating that the drug was stably immobilized within the hydrogel network. However, when placed in an environment containing H₂O₂, the drug exhibited significant and sustained release, with a 24-hour cumulative release rate exceeding 80%. In contrast, the sample from Comparative Example 1, which did not contain the drug-functionalized fullerene, showed no significant drug release under any conditions, with the values ​​fluctuating within the error range. This result clearly demonstrates the environmentally responsive drug release capabilities of the hydrogel composition of the present invention.

[0059] This unique on-demand release behavior stems from the ingenious molecular design of the functionalized fullerenes. The therapeutic drug is not simply physically encapsulated but covalently linked to the fullerene backbone via a chemical linker (such as a thioketal linker) that is highly sensitive to reactive oxygen species. Under normal physiological conditions, this chemical linker remains stable, securely "locking" the drug molecules within the gel network and preventing ineffective leakage. However, if high concentrations of reactive oxygen species (ROS) are present in the surrounding environment due to radiation damage, these ROS rapidly attack and sever the sensitive chemical linker, resulting in the precise release of the drug molecules to exert their therapeutic effects.

[0060] This design perfectly embodies the innovative concept of "intelligent treatment," transforming the dressing from a passive protective barrier into an intelligent platform capable of actively sensing pathological signals and responding therapeutically. By directly linking drug release to specific pathological microenvironmental signals (high ROS concentrations), the technical solution of this invention ensures targeted and efficient drug action, maximizing the therapeutic effect at the site of injury while avoiding unnecessary impacts on surrounding healthy tissue. This provides a new and effective technical approach for addressing the precise treatment of radiation-induced skin damage.

[0061] Test Example 2 Experimental purpose: This experiment aims to verify that the hydrogel described in the present invention has the specific fluorescence response ability to the hypoxic microenvironment, thereby proving its feasibility as a non-invasive damage monitoring tool.

[0062] Subjects: Experimental group: hydrogel sample prepared in Example 1.

[0063] Control group: the hydrogel sample prepared in Comparative Example 2 (this sample does not contain the functionalized fullerene for monitoring the hypoxia state).

[0064] Experimental steps: Sample preparation: The hydrogels prepared in Example 1 and Comparative Example 2 were placed in the wells of a cell culture plate, respectively, to form a hydrogel layer with uniform thickness.

[0065] Environmental cultivation: Half of the experimental and control samples were placed in a standard cell culture incubator under normoxic conditions (21% O2).

[0066] The other half of the experimental and control samples were placed in a three-gas incubator with the environment set to hypoxic conditions (1% O2).

[0067] Incubation: All samples were incubated at 37°C for 6 hours to allow the probe molecules sufficient time to respond to the ambient oxygen concentration.

[0068] Sample Analysis: After incubation, remove the culture plate and analyze using a fluorescence microplate reader or fluorescence microscope. Set the probe's characteristic excitation wavelength and measure the fluorescence intensity at its characteristic emission wavelength. To eliminate background interference, measure multiple sites per sample and average the results.

[0069] Experimental data Table 2: Comparison of fluorescence response intensities of hydrogels under different environments

[0070] Summarize The experimental results clearly reveal the sample's dependence on the ambient oxygen concentration. Under normal oxygen conditions, the hydrogel prepared in Example 1 exhibited only weak background fluorescence. However, when placed in a hypoxic environment simulating damaged tissue, its fluorescence intensity increased sharply by more than 15 times. In sharp contrast, the sample of Comparative Example 2, which lacks the key probe component, always maintains its fluorescence intensity at an extremely low background level, whether in normoxic or hypoxic environments, and does not show any meaningful changes. This comparison strongly demonstrates that the composition of the present invention has the ability to specifically fluorescently label hypoxic microenvironments.

[0071] The underlying mechanism of this specific fluorescent "lighting up" behavior in response to hypoxic environments stems from the unique chemical structure of the hypoxia probe molecule. The probe molecule (such as a nitroimidazole derivative) is non-fluorescent in its original oxidized state. Only in an environment with low oxygen concentration will the nitroreductase in the tissue cells be activated and reduce the nitro group in the probe molecule to an amino group. This irreversible chemical conversion process completely changes the electron cloud structure of the molecule, transforming it into a substance that can emit strong fluorescence. Because the probe is firmly anchored in the hydrogel network through covalent bonds, the enhancement of the fluorescence signal is precisely confined to the gel area, thereby achieving direct, in situ reporting of the oxygen concentration of the underlying tissue.

[0072] This design successfully transforms the dressing from a passive physical barrier into an intelligent diagnostic tool capable of actively detecting and reporting pathological information. It enables noninvasive, real-time visualization of deterioration in skin damage areas (hypoxia is a key indicator of worsening radiation damage) through simple fluorescence detection, providing crucial visualization for assessing damage severity and guiding treatment strategies. This perfectly realizes the innovative concept of "real-time diagnosis" and is a key component in building an integrated intelligent diagnosis and treatment platform, demonstrating its enormous potential for application in advanced medical dressings.

[0073] Test Example 3 Experimental purpose: This experiment aims to verify the ability of the present invention to stably fix functional components in the hydrogel network through specific chemical design to prevent them from being lost or leaked during use.

[0074] Subjects: Experimental group: hydrogel sample prepared in Example 1.

[0075] Control group: the hydrogel sample prepared in Comparative Example 3 (its functionalized fullerene was not treated with methacrylate and lacked polymerizable functional groups).

[0076] Experimental steps: Sample preparation: The hydrogels prepared in Example 1 and Comparative Example 3 were respectively prepared into uniform samples weighing 1.0 g.

[0077] Immersion experiment: Each group of samples was placed in a centrifuge tube containing 20 mL of PBS buffer solution.

[0078] Incubation and shaking: Place all centrifuge tubes in a constant temperature horizontal shaker at 37°C and shake continuously at 60 rpm to simulate the flushing effect in a dynamic environment.

[0079] Sampling and Analysis: At pre-determined time points (0, 2, 4, 8, 24, and 48 hours), aspirate 1 mL of supernatant from each tube. Measure the absorbance of the characteristic fullerene absorption peak in the supernatant using a UV-Vis spectrophotometer. Calculate the cumulative percentage of fullerene that has leaked into the solution based on the total amount of fullerene in the initial sample.

[0080] Experimental data Table 3: Comparative data of cumulative leakage rates of functional components in different hydrogels

[0081] Summarize The experimental data above clearly demonstrates the significant difference in the functional component retention capabilities of the two sample groups. Under 48 hours of sustained dynamic flushing, the cumulative leakage rate of the functional components in the sample from Example 1 remained below 1.5%, a negligible level, demonstrating exceptional stability. In contrast, the sample from Comparative Example 3 exhibited significant leakage, with over half of its functional components already lost to the surrounding medium after 48 hours. This result strongly demonstrates that the technical solution employed in this invention effectively and stably locks the core functional unit within the dressing.

[0082] The underlying mechanism for this exceptional stability lies in the present invention's surface chemical modification of the functional nanoparticles. In the technical solution of Example 1, the surface of the functionalized fullerene is pre-attached with functional groups ("chemical anchors") that can participate in polymerization reactions. When the hydrogel precursor solution is photocured to form the first network, these "chemical anchors" undergo covalent cross-linking reactions with the primary network precursor molecules. This effectively treats each functional nanoparticle as a node on a polymer chain, "woven" into the hydrogel's backbone structure through strong covalent bonds. In contrast, the functional particles in Comparative Example 3, lacking these "chemical anchors," can only be passively physically embedded or entangled within the gel's pores. Once exposed to liquid, they easily detach from the porous structure and diffuse out.

[0083] A core innovation of this invention is the upgrade of active components from simple physical encapsulation to chemical bonding and locking. This fundamentally addresses the technical pain points of traditional functional dressings, such as the easy loss of active ingredients, short duration of action, and difficulty maintaining effective concentrations. By ensuring the long-term residence of functional modules within the dressing, this technical solution ensures the long-term effectiveness and reliability of its "intelligent treatment" and "real-time diagnosis" functions, providing key technical support for the development of advanced intelligent dressings with stable performance and long-lasting efficacy.

[0084] Test Example 4 Experimental purpose: This experiment aims to verify the decisive contribution of the double network interpenetrating structure described in the present invention to the ultimate mechanical properties of the hydrogel (such as strength and toughness) through quantitative mechanical testing.

[0085] Subjects: Experimental group: hydrogel sample prepared in Example 1 (having a double network structure).

[0086] Control group A: the sample prepared in Comparative Example 4 (without the second network precursor and having only a single network structure).

[0087] Control group B: the sample prepared in Comparative Example 7 (not subjected to thermal curing, only the first network was formed).

[0088] Experimental steps: Sample preparation: The samples finally formed in Example 1, Comparative Example 4 and Comparative Example 7 were respectively made into cylindrical test samples with a height of 5 mm using a mold with an inner diameter of 10 mm.

[0089] Mechanical testing: Place the sample on the testing platform of the universal material testing machine.

[0090] The samples were subjected to uniaxial compression tests at a constant rate of 2 mm / min.

[0091] The stress-strain data were continuously recorded during the compression process until the sample was compressed to 20% of its original height (i.e., 80% strain).

[0092] Data Analysis: The compression modulus of the sample was calculated based on the slope of the initial linear region (0–10% strain) of the stress–strain curve.

[0093] The stress value corresponding to the sample at 80% strain was recorded as its maximum compressive strength.

[0094] Five parallel samples were tested in each group, and the results were averaged.

[0095] Experimental data Table 4: Comparative data of mechanical properties of different hydrogel samples

[0096] Summarize The mechanical properties test data clearly show significant differences in mechanical strength between samples prepared using different methods. The sample prepared in Example 1 exhibits excellent mechanical properties, with both compression modulus and maximum compressive strength significantly exceeding those of the samples in the two comparative examples. In contrast, samples prepared by either lacking the second network component (Comparative Example 4) or omitting the critical heat curing step (Comparative Example 7) exhibit poor mechanical properties and are fragile, directly demonstrating that the dual network structure described in this invention is key to achieving high-performance materials.

[0097] The inherent mechanism of this huge improvement in mechanical properties stems from the unique interpenetrating dual network (IPN) structural design of the present invention. In the sample of Example 1, the first covalent network formed by photocuring is like the steel skeleton of a building, providing basic stability and shape for the material. Subsequently, the second physical cross-linked network (alginate network) formed by gentle heating triggering is like the high-toughness cement filled between the steel bars. It is interspersed and entangled in the first network in the form of flexible long chains. When the material is subjected to external pressure, the rigid first network is responsible for resisting deformation, while the flexible second network effectively dissipates energy through the reversible breaking and reorganization of its ionic bonds, thereby avoiding the overall structural damage caused by stress concentration and giving the material an extremely high overall toughness.

[0098] This structural innovation is the core of the present invention's excellent performance. It eliminates the fragile, brittle gel of the traditional sense and instead creates a flexible material with both strength and toughness. This characteristic is crucial for the dressing's application, ensuring that when applied to frequently moving areas such as joints, it stretches and deforms with the skin without breaking or falling off, thereby maintaining its protective and therapeutic effects. The high-performance dual-network structure, constructed through a sophisticated sequential curing process, perfectly realizes the original design goal of transforming the material into a tough, conformable "second skin."

[0099] Test Example 5 Experimental purpose: This experiment aims to verify the necessity of the "temperature-sensitive controlled release" strategy adopted in the present invention for realizing the "sequential dual curing" process, that is, to verify that it can effectively maintain the stable operability of the precursor solution before the photocuring step.

[0100] Subjects: Experimental group: the composite hydrogel precursor solution prepared in Example 1.

[0101] Control group: composite hydrogel precursor solution prepared in Comparative Example 5 (wherein the temperature-sensitive controlled-release calcium ion carrier was directly replaced by an equimolar calcium chloride solution).

[0102] Experimental steps: Liquid Preparation: Prepare 20 mL of precursor solution in two identical transparent glass bottles according to the formulations of Example 1 and Comparative Example 5. Start the timer immediately after adding the last component (sodium alginate or calcium chloride) and stirring thoroughly.

[0103] State observation: Place two sample bottles side by side at room temperature, and continuously observe and record the changes in the macroscopic morphology of the liquid, paying special attention to whether there is stratification, precipitation, or flocculent formation.

[0104] Gel Time Determination: Use the bottle wall tilting method to determine gelation. Every minute, slowly tilt the glass bottle to a horizontal position and observe whether the liquid can still flow freely. When the liquid stops flowing, record the time point as the gelation time. If gelation does not occur after 60 minutes, stop the timer.

[0105] Experimental data Table 5: Comparison of gelation behavior of different precursor solutions

[0106] Summarize The above experimental results clearly demonstrate the vast difference between the two precursor solutions in terms of stability. After the precursor solution of Example 1 is prepared, it can remain as a uniform, flowable stable liquid for a long time, which provides sufficient time windows for subsequent coating and light shaping operations. However, when the key temperature-sensitive controlled-release ion carrier is replaced with a common calcium ion solution, as shown in Comparative Example 5, an uncontrollable rapid reaction has occurred in the system at the moment of mixing, forming an uneven precipitate and losing fluidity within one minute. This comparison effectively demonstrates the effectiveness of the technical solution of the present invention for controlling the gelation process.

[0107] The inherent mechanism of this significant difference is that the present invention cleverly designs a controllable "switch" for the formation of the second network. In the system of Example 1, calcium ions, which serve as cross-linking agents for the second network, are pre-encapsulated in liposome vesicles with thermosensitive phase transition properties. Under room temperature conditions, the complete liposome bilayer is like a sturdy "safe", which safely isolates the calcium ions and prevents them from contacting the sodium alginate molecules in the solution, and therefore does not trigger the ionic cross-linking reaction. In Comparative Example 5, once free calcium ions are added to the system, they will immediately undergo electrostatic interactions with the carboxyl groups on the sodium alginate molecules, resulting in uncontrolled, chaotic rapid cross-linking, thereby destroying the uniformity and operability of the precursor solution.

[0108] The introduction of the concept of "time controllable" into the gelation process is a core innovation of the present invention in the preparation method. Through the "switch" design of thermosensitive liposomes, the technical solution of the present invention successfully decouples the formation process of the two networks from the time perspective, ensuring that the formation of the first covalent network can be accurately completed by light in a stable and uniform liquid environment without any interference from the cross-linking of the second network. This "first shaping, then strengthening" sequential curing process is the premise and guarantee for constructing a double-network interpenetrating hydrogel with a clear structure and superior performance, which perfectly echoes the design concept of the present invention on "in situ forming" and the construction of high-performance dressings.

[0109] Test Example 6 Experimental purpose: This experiment aims to verify the importance of the concentration of the main network-forming components in the composite hydrogel precursor solution described in the present invention for constructing a stable gel structure.

[0110] Subjects: Experimental group: the composite hydrogel precursor solution prepared in Example 1.

[0111] Control group: the composite hydrogel precursor solution prepared in Comparative Example 6 (wherein the total concentration of the first network precursors HA-MA and Gel-MA was significantly lower than that in Example 1).

[0112] Experimental steps: Sample packaging: 5 mL of the precursor solution of Example 1 and Comparative Example 6 were respectively taken and injected into glass culture dishes of exactly the same specifications to form a liquid layer of uniform thickness.

[0113] Curing Treatment: Two sets of samples were subjected to an identical two-step curing treatment side by side.

[0114] First step of light curing: using a wavelength of 405nm and a light intensity of 30mW / cm 2 The LED light source was used to illuminate the sample vertically from above for 120 seconds.

[0115] Second step: thermal curing: After the light irradiation, immediately use an infrared lamp to heat the sample surface to 42°C and maintain it for 4 minutes.

[0116] Result evaluation: After the curing process is completed, the following observations and tests are performed: Macroscopic morphological observation: Observe the sample’s uniformity, transparency, and whether it has formed an overall structure with the naked eye.

[0117] Inversion test: Carefully invert the culture dish and hold it for 1 minute to observe whether the sample flows, deforms, or falls off the bottom of the dish due to gravity.

[0118] Probe touch test: Use a clean glass rod to gently touch the surface of the sample to feel whether it is solid elastic or viscous liquid.

[0119] Experimental data Table 6: Comparison of gel forming ability of samples at different precursor concentrations

[0120] Summarize The above experimental results intuitively demonstrate that component concentration is a key factor in determining the successful formation of a hydrogel. The sample prepared using the formulation of Example 1 successfully transformed into a macroscopically uniform, stable gel capable of maintaining its shape after a standard curing process. In stark contrast, when the concentration of the primary network precursor was reduced to the level of Comparative Example 6, even under the same curing conditions, a coherent gel network could not be formed, ultimately resulting in only a liquid with slightly increased viscosity. This demonstrates the necessity of the component concentration ranges defined in this technical solution.

[0121] The underlying mechanism of this phenomenon lies in the basic principles of polymer physics. The formation of a hydrogel is essentially a phase transition from a dispersed polymer chain solution to a three-dimensional cross-linked network structure. During the photocuring stage, the free radicals generated by the photoinitiator need to be able to effectively initiate polymerization reactions between adjacent polymer chains, thereby "stitching" together a covalent network that spans the entire system. When the concentration of polymer chains (such as Example 1) is high enough, the average distance between chains is very close, and the cross-linking reaction can occur efficiently and throughout the entire system. Conversely, when the concentration is too low (such as Comparative Example 6), the polymer chains are too dispersed in the solution, and even if the reaction is triggered, most of them only form isolated, discontinuous, tiny gel clusters, which cannot build a complete network that can support a macroscopic structure.

[0122] A stable and complete gel skeleton is the physical basis for all the functional innovations of this invention. If an effective gel matrix cannot be formed, then the carefully designed functionalized fullerene and other active components will have nowhere to anchor and will easily be lost; the envisioned "double network" enhancement mechanism will be out of the question; and the final product will not be able to be attached to the skin surface as a protective dressing. Therefore, the component concentrations given in this technical solution are the fundamental guarantee for ensuring the transition from molecular design to macro-functional products. It ensures the reliable construction of the basic platform, thereby making it possible to achieve subsequent innovations such as "integrated diagnosis and treatment" and excellent mechanical properties.

[0123] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A medical dressing with radiation protection function, characterized in that: The invention comprises a composition comprising the following components in parts by weight: First network precursor: 7-12 copies; Second network precursor: 0.5-1.5 parts; Radiation-responsive drug-functionalized fullerene: 0.1-0.5 parts; Functionalized fullerene for monitoring hypoxia: 0.05-0.2 parts; Thermosensitive controlled release ion source: 0.5-2 parts; Photoinitiator: 0.1-0.3 parts; and the balance of the aqueous medium.

2. The medical dressing with radiation protection function according to claim 1, characterized in that: The structure of the radiation-responsive drug-functionalized fullerene is: fullerene as the core, and its surface is covalently connected with functional groups that can participate in polymerization reactions, breakable chemical linking arms that are sensitive to active oxygen, and anti-inflammatory or antioxidant drugs connected through the linking arms.

3. The medical dressing with radiation protection function according to claim 2, characterized in that: The cleavable chemical link arm that is sensitive to active oxygen is a thioketal link arm or a boronate link arm; and the anti-inflammatory or antioxidant drug is isoliquiritigenin.

4. The medical dressing with radiation protection function according to claim 1, characterized in that: The structure of the hypoxia state monitoring functionalized fullerene is: fullerene is used as the core, and functional groups that can participate in polymerization reactions and probe molecules that can emit fluorescent signals in an hypoxic environment are covalently connected to the surface of the fullerene.

5. The medical dressing with radiation protection function according to claim 1, characterized in that: The first network precursor is a methacrylated biocompatible polymer selected from methacrylated hyaluronic acid and methacrylated gelatin; The second network precursor is a polymer that can undergo ionic cross-linking under the action of cations and is selected from alginate, pectin or chitosan.

6. The process for preparing a medical dressing with radiation protection function according to any one of claims 1 to 5, characterized in that: The following steps are involved: a. Preparation of functionalized fullerenes: i. pre-treating the fullerene surface to introduce the first type of active groups; ii. reacting a portion of the first type of reactive groups with a molecule having a polymerizable functional group; iii. coupling the remaining first type active groups with drug-sensitive linker arm complexes or hypoxia probe molecules to obtain radiation-responsive drug-functionalized fullerenes and hypoxia state monitoring functionalized fullerenes; b. Preparing a composition: mixing the two functionalized fullerenes prepared in step a with a first network precursor, a second network precursor, a temperature-sensitive controlled-release ion source, a photoinitiator, and an aqueous medium to obtain the composition as claimed in claim 1; c. In-situ curing and forming: i. The composition prepared in step b is applied to the surface of the substrate; ii. Formation of the first covalent network by light-induced; iii. Then, external physical stimulation is applied to trigger the release of ions from the thermosensitive controlled-release ion source to form a second heavy ion cross-linked network, thereby obtaining a hydrogel dressing with a double-network interpenetrating structure.

7. The preparation process according to claim 6, characterized in that: In step a, the surface pretreatment is an amination reaction; and the coupling reaction is a covalent connection via EDC / NHS chemistry or other amidation reactions.

8. The preparation process according to claim 6, characterized in that: The preparation method of the temperature-sensitive controlled-release ion source comprises: encapsulating a cationic salt in a liposome prepared from a temperature-sensitive phospholipid material by a thin film hydration-ultrasound method or a high-pressure extrusion method.

9. The preparation process according to claim 8, characterized in that: In step c), the light irradiation is irradiation with a wavelength of 365 to 450 nm; the external physical stimulation is heating the temperature of the composition to 40 to 50° C. to trigger the release of calcium ions from the thermosensitive liposomes encapsulating calcium carbonate and composed of DPPC and cholesterol.

10. The preparation process according to claim 6, characterized in that: The first network precursor is prepared by reacting hyaluronic acid or gelatin with methacrylic anhydride; the method is carried out in situ on the skin surface of an organism requiring radiotherapy to prepare a layer of dressing conforming to the skin.

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