Oxygen-carrying hydrogel as well as preparation method and application thereof
By optimizing the composition and structure of the oxygen-carrying hydrogel, a single-layer structure oxygen-carrying hydrogel is prepared by using a photocuring process, which solves the problems of unsustainable oxygen release and insufficient mechanical properties, and achieves long-term oxygen release and good biocompatibility, which is suitable for wound healing and skin care.
Patent Information
- Application Number
- CN202510476405.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-16
- Publication Date
- 2025-08-15
AI Technical Summary
The existing oxygen-carrying hydrogels have shortcomings in the sustainability and stability of oxygen release, their biocompatibility and mechanical properties need to be improved, and their preparation methods are complex, which limits their large-scale production and clinical applications.
The oxygen-carrying hydrogel adopts a single-layer structure, consisting of macromonomers, photoinitiators, fluorocarbons, peroxides, emulsified solubilizers and nanoenhancers, is prepared through a photocuring process to form an oxygen-rich solution system, achieving stable loading and continuous release of oxygen, and improving mechanical properties through nanoenhancers.
It has achieved continuous and stable release of oxygen for more than 30 days, and has excellent biocompatibility and mechanical properties, which are suitable for large-scale production and clinical applications.
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Figure BDA0005361458150000121
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of medical polymer materials, and particularly relates to an oxygen-carrying hydrogel and a preparation method and application thereof. Background Art
[0002] Clinically, wound healing is a complex and orderly biological process, influenced by a range of factors, primarily the patient's physical condition and environmental factors related to the wound. The wound microenvironment, in particular, has a significant impact on wound healing. Modern wound healing theory suggests that a closed, aerobic, and moist environment is beneficial for accelerating wound healing.
[0003] As a polymer material with a three-dimensional polymer network structure, hydrogel can absorb large amounts of water molecules. Due to its good biocompatibility, high water absorption, and adjustable mechanical properties, it has been widely studied and applied in the biomedical field. In particular, in wound care and skin care, hydrogel dressings can provide a moist healing environment and promote wound healing. This is because due to the barrier effect between the skin and the wound surface, gaseous oxygen has difficulty entering the human body through the skin and wound exudate. Liquid oxygen formed by oxygen dissolved in water can more easily penetrate the skin barrier than gaseous oxygen and penetrate deep into the wound, thereby increasing the local blood oxygen partial pressure in the wound, improving oxygen supply to the wound tissue, and improving local tissue aerobic metabolism, which is conducive to healing.
[0004] However, traditional oxygen-carrying hydrogels still have some problems and shortcomings in terms of oxygen release, stability and biocompatibility. Traditional oxygen-carrying hydrogels have shortcomings in the continuity and stability of oxygen release. For example, although some hydrogels can release oxygen, the release time is short, usually within 3 days, which cannot meet the long-term wound healing needs. The biocompatibility and mechanical properties of hydrogels are the key to their application in the medical field. Traditional oxygen-carrying hydrogel materials perform well in terms of biocompatibility, but their mechanical properties still need to be improved. For example, some hydrogels will swell significantly after absorbing water, resulting in a decrease in their mechanical strength, affecting their application in wound dressings. In addition, the preparation methods of traditional oxygen-carrying hydrogels often require complex processes and equipment, which limits their large-scale production and clinical applications. For example, the preparation of some hydrogels requires multi-step chemical reactions and strict condition control, which increases production costs and difficulty.
[0005] Therefore, how to improve the sustained oxygen release time and mechanical properties of oxygen-carrying hydrogels remains a technical problem that needs to be solved urgently in this field. Summary of the Invention
[0006] The present invention aims to address at least one of the technical problems existing in the above-mentioned prior art. To this end, the present invention provides an oxygen-carrying hydrogel, a preparation method, and applications thereof. The oxygen-carrying hydrogel of the present invention exhibits good stability, can continuously release oxygen for more than seven days, and has excellent biocompatibility and mechanical properties.
[0007] In a first aspect, the present invention provides an oxygen-carrying hydrogel, which comprises the following raw materials: a macromonomer, a photoinitiator, a fluorocarbon compound, a peroxide, an emulsifying solubilizer, a nano-enhancer and water; and the oxygen-carrying hydrogel has a single-layer structure.
[0008] In some embodiments of the present invention, the oxygen-carrying hydrogel comprises the following raw materials, by weight percentage: 0.5-8% macromonomer, 0.01-0.2% photoinitiator, 4-20% fluorocarbon, 0.5-2% peroxide, 4-25% emulsifying solubilizer, 0.5-6% nanoenhancer and 30-90% water.
[0009] In some embodiments of the present invention, the oxygen-carrying hydrogel comprises the following raw materials, by weight percentage: 1-5% macromonomer, 0.02-0.1% photoinitiator, 10-15% fluorocarbon, 1-1.5% peroxide, 8-15% emulsifying solubilizer, 1-5% nanoenhancer and 50-75% water.
[0010] In some embodiments of the present invention, the macromonomer includes at least one of methacrylated gelatin (Gelma), methacrylated hyaluronic acid (HAMA), and methacrylated chitosan (CSMA).
[0011] In some embodiments of the present invention, the nano-enhancer includes at least one of lithium magnesium silicate, montmorillonite, and magnesium aluminum silicate.
[0012] In some embodiments of the present invention, the photoinitiator comprises at least one of lithium phenyl-2,4,6-trimethylbenzoyl phosphite (LAP), 2-hydroxy-1-(4-(2-hydroxyethoxy)phenyl)-2-methyl-1-propanone (Irgacure 2959), and 1-hydroxycyclohexylphenyl ketone (184).
[0013] In some embodiments of the present invention, the fluorocarbon compound includes at least one of bromooctane, perfluorooctane, perfluorotripropylamine, and perfluorotributylamine.
[0014] In some embodiments of the present invention, the peroxide includes at least one of calcium peroxide and magnesium peroxide.
[0015] In some embodiments of the present invention, the emulsifying solubilizer includes at least one of poloxamer, cyclodextrin, and hydrogenated castor oil.
[0016] In some embodiments of the present invention, the concentration of dissolved oxygen in the oxygen-carrying hydrogel is ≥300 mg / L.
[0017] In a second aspect, the present invention provides a method for preparing the oxygen-carrying hydrogel according to the first aspect of the present invention, comprising the following steps:
[0018] The macromonomer, photoinitiator, fluorocarbon compound, peroxide, emulsifying solubilizer, nano-enhancing agent and water are mixed, stirred, allowed to stand under sealed conditions, and then photocured to obtain the oxygen-carrying hydrogel.
[0019] In some embodiments of the present invention, the method for preparing the oxygen-carrying hydrogel comprises the following steps:
[0020] Adding the nano-enhancer to water and stirring, then adding the emulsifying solubilizer and the fluorocarbon compound and stirring, then adding the macromonomer and the photoinitiator and stirring to obtain a mixed solution;
[0021] adding peroxide to the mixed solution, stirring, and then allowing to stand under sealed conditions, filtering out insoluble matter to obtain an oxygen-enriched solution;
[0022] The oxygen-rich solution is photocured to obtain the oxygen-carrying hydrogel.
[0023] In some embodiments of the present invention, the stirring speed is 200-800 r / min.
[0024] In some embodiments of the present invention, the standing time is 24-72 hours.
[0025] In some embodiments of the present invention, the wavelength of the light curing is 300-400 nm.
[0026] In some embodiments of the present invention, the light intensity of the light curing is 100-500 mW / cm 2 .
[0027] Specifically, many current oxygen-releasing gel dressings use a double-layer or multi-layer structure, with different layers containing different reactants. Each layer is packaged separately before use, and then combined together during use to release oxygen through a diffusion reaction. This type of gel is inconvenient to use, and the preparation process is also cumbersome and complex, requiring the separate preparation of different layer structures and independent packaging. The oxygen-carrying hydrogel of the present invention uses a single-layer structure, containing a stable oxygen-rich solution system. Rather than releasing oxygen through a diffusion reaction, the oxygen is already stably stored in the gel and can be used directly during use.
[0028] Specifically, molecular oxygen dissolved in water is called dissolved oxygen. Under normal circumstances, dissolved oxygen is closely related to the partial pressure of oxygen in the air, atmospheric pressure, water temperature and water quality. At 20°C and 100kPa, the solubility of oxygen in pure water is relatively low, about 9 mg / L of dissolved oxygen. How to effectively load oxygen into the gel is the key to preparing the oxygen-carrying hydrogel of the present invention. The present invention forms an oxygen carrier by combining fluorocarbon compounds with emulsifying solubilizers, so that the generated oxygen is solubilized to form a stable high-concentration oxygen. The oxygen-rich solution prepared by the present invention does not require an external oxygenation step. The system can directly generate oxygen through the reaction. The initial concentration of dissolved oxygen in the gel can reach more than 95 mg / L, and a continuous and stable release of oxygen is achieved. Experimental results show that the oxygen-carrying hydrogel of the present invention can continuously release oxygen for a long time, which is significantly better than the short-term release in the prior art. This is because the gel system can gradually adsorb oxygen from the air.
[0029] Specifically, the present invention utilizes macromolecular monomers and nanoenhancers for crosslinking, eliminating the presence of small-molecule monomers and crosslinkers, resulting in high biosafety and good biocompatibility. Furthermore, the nanoenhanced hydrogel network structure improves the hydrogel's mechanical properties. Experimental results show that the oxygen-carrying hydrogel of the present invention exhibits high tensile strength and elastic modulus, enabling it to better adapt to the complex deformations of wound sites. Furthermore, the nanoenhancer of the present invention also acts as a suspending agent, evenly suspending the peroxide in the mixed liquid system, thereby enabling sufficient contact with water.
[0030] Specifically, the oxygen-carrying hydrogel of the present invention is formed in one step using a photocuring process. The process is simple, low-cost, and does not require complex equipment and strict condition control. The reaction can be carried out at low temperature and room temperature, which is conducive to the loading and stabilization of oxygen.
[0031] The third aspect of the present invention provides use of the oxygen-carrying hydrogel described in the second aspect of the present invention in the preparation of a medicament for promoting wound healing.
[0032] In some embodiments of the invention, the wound comprises an infected diabetic ulcer wound.
[0033] Compared with the prior art, the present invention has the following beneficial effects:
[0034] (1) Sustainability and stability of oxygen loaded by hydrogel: The present invention optimizes the material composition and structural design of the hydrogel, so that the hydrogel can be rich in dissolved oxygen and achieves continuous and stable release of oxygen; the oxygen-carrying hydrogel of the present invention can maintain a high oxygen loading capacity for a long time (more than 30 days), meeting the long-term demand for oxygen during the wound healing process, which significantly improves the application effect of the hydrogel in wound care.
[0035] (2) Enhanced biocompatibility and mechanical properties: The present invention improves the biocompatibility and mechanical properties of the hydrogel by optimizing the material composition and structural design of the hydrogel; the oxygen-carrying hydrogel of the present invention has excellent tensile strength and elastic modulus, and can better adapt to the complex deformation of the wound site; the elongation at break of the hydrogel is 730-850%, and the elastic modulus is 45-51 kPa, which enables the hydrogel to exhibit better performance and effects in applications such as wound dressings and skin care.
[0036] (3) Preparation using an integrated photocuring process: The oxygen-carrying hydrogel of the present invention is primarily prepared using a photocuring process, which is simple, low-cost, and does not require complex equipment or strict control conditions. Through photocuring, a three-dimensional network structure is formed within the hydrogel, which facilitates the loading and release of oxygen. The preparation method of the present invention is more convenient and suitable for large-scale production and clinical application.
[0037] (4) Multifunctionality: The main function of the oxygen-carrying hydrogel of the present invention is to continuously release oxygen to promote wound healing and skin health. While maintaining a high oxygen release capacity, it also has good biocompatibility and mechanical properties, and is suitable for a variety of medical application scenarios. DETAILED DESCRIPTION
[0038] The present invention is further described in detail below by way of specific examples. Unless otherwise specified, the raw materials, reagents, or devices used in the examples are all commercially available or can be obtained by conventional methods. Unless otherwise specified, all experiments or testing methods are conventional methods in the art.
[0039] Example 1
[0040] An oxygen-carrying hydrogel comprises the following raw materials: 0.5 g of GelMA (methacrylated gelatin), 0.5 g of lithium magnesium silicate, 0.01 g of lithium phenyl-2,4,6-trimethylbenzoyl phosphite (LAP), 5 g of fluoctane bromide, 5 g of poloxamer, 0.5 g of calcium peroxide, and 88.49 g of deionized water.
[0041] The preparation method of the oxygen-carrying hydrogel comprises the following steps:
[0042] 1) slowly adding lithium magnesium silicate into deionized water and continuously stirring at 200 r / min to fully dissolve the lithium magnesium silicate to obtain an aqueous solution;
[0043] 2) mixing poloxamer and fluoctane evenly, adding the mixture to the lithium magnesium silicate aqueous solution prepared in step 1) while stirring, and then adding GelMA and LAP, stirring and dissolving the mixture to obtain a mixed solution;
[0044] 3) adding calcium peroxide to the mixed solution of step 2), stirring evenly, and then pouring into a sealed container. The mixture was allowed to stand for 24 hours to allow the system to stabilize, thereby obtaining an oxygen-enriched system. The insoluble matter was then removed by filtration through a filter membrane to obtain an oxygen-enriched solution.
[0045] 4) Pour the oxygen-enriched solution from step 3) into the mold and use a light source with a wavelength of 300 nm and an intensity of 100 mW / cm 2 The oxygen-carrying hydrogel is obtained by irradiating and curing with a UV-LED lamp.
[0046] Performance Testing
[0047] A 0.6 cm thick oxygen-carrying hydrogel was taken as a sample and the following tests 1)-3) were performed.
[0048] 1) Oxygen Release Test: The sample was placed in a sealed container, and the oxygen concentration within the gel was measured using an oxygen sensor electrode placed within the gel. The results showed that the oxygen-carrying hydrogel prepared in this example contained a high and relatively stable dissolved oxygen concentration. The initial oxygen concentration in the gel was 95 mg / L, and the oxygen content after 7 days was 87 mg / L, and after 30 days, the oxygen content was 85 mg / L.
[0049] 2) Mechanical Properties: Mechanical properties testing of the samples was conducted using a universal testing machine. The data showed that the oxygen-carrying hydrogel maintained a moderate tensile strength, with an elongation at break of 730% and an elastic modulus of 50 kPa.
[0050] 3) Biocompatibility testing: Cell culture experiments were conducted to evaluate the toxicity of the hydrogel to fibroblasts. The results showed that the hydrogel had no significant toxicity to fibroblasts, with a cell survival rate greater than 90%.
[0051] Example 2
[0052] An oxygen-carrying hydrogel comprises the following raw materials: 8 g of GelMA, 6 g of lithium magnesium silicate, 0.2 g of 2-hydroxy-1-(4-(2-hydroxyethoxy)phenyl)-2-methyl-1-propanone (Irgacure 2959), 20 g of perfluorooctane, 25 g of cyclodextrin, 2 g of magnesium peroxide, and 38.8 g of deionized water.
[0053] The preparation method of the oxygen-carrying hydrogel comprises the following steps:
[0054] 1) slowly adding lithium magnesium silicate into deionized water and continuously stirring at 300 r / min to fully dissolve the lithium magnesium silicate to obtain an aqueous solution of lithium magnesium silicate;
[0055] 2) After cyclodextrin and perfluorooctane are uniformly mixed, they are added dropwise to the lithium magnesium silicate aqueous solution prepared in step 1) at a rate of 3-5 drops per second while stirring. GelMA and Irgacure 2959 are then added and stirred to dissolve to obtain a mixed solution.
[0056] 3) adding magnesium peroxide to the mixed solution of step 2), stirring evenly, and then pouring into a sealed container. The mixture was allowed to stand for 36 hours to allow the system to stabilize, thereby obtaining an oxygen-enriched system. The insoluble matter was then removed by filtration through a filter membrane to obtain an oxygen-enriched solution.
[0057] 4) Pour the oxygen-enriched solution from step 3) into the mold and use a light source with a wavelength of 400 nm and an intensity of 500 mW / cm 2 The oxygen-carrying hydrogel is obtained by irradiating and curing with a UV-LED lamp.
[0058] Performance Testing
[0059] A 0.6 cm thick oxygen-carrying hydrogel was taken as a sample and the following tests 1)-3) were performed.
[0060] 1) Oxygen Release Test: The sample was placed in a sealed container, and the oxygen concentration within the gel was measured using an oxygen sensor electrode placed within the gel. The results showed that the oxygen-carrying hydrogel prepared in this example contained a high and relatively stable dissolved oxygen concentration. The initial oxygen concentration in the gel was 115 mg / L, and after 7 days, the oxygen content was 105 mg / L, and after 30 days, the oxygen content was 101 mg / L.
[0061] 2) Mechanical Properties: The samples were tested using a universal testing machine. The results showed good tensile strength, with an elongation at break of 840% and an elastic modulus of 45 kPa.
[0062] 3) Biocompatibility testing: Cell culture experiments were used to evaluate the toxicity of the hydrogel to fibroblasts. The results showed that the hydrogel had no significant toxicity to fibroblasts, with a cell survival rate greater than 93%.
[0063] Example 3
[0064] An oxygen-carrying hydrogel comprises the following raw materials: 5g of GelMA, 5g of lithium magnesium silicate, 0.1g of 1-hydroxycyclohexylphenyl ketone (184), 15g of perfluorotripropylamine, 15g of hydrogenated castor oil, 1.5g of calcium peroxide, and 58.4g of deionized water.
[0065] The preparation method of the oxygen-carrying hydrogel comprises the following steps:
[0066] 1) slowly adding lithium magnesium silicate into deionized water and continuously stirring at 250 r / min to fully dissolve the lithium magnesium silicate to obtain an aqueous solution of lithium magnesium silicate;
[0067] 2) After hydrogenated castor oil and perfluorotripropylamine are mixed evenly, they are added dropwise to the lithium magnesium silicate aqueous solution prepared in step 1) at a rate of 2-3 mL per minute while stirring. GelMA and 184 are then added and stirred to dissolve to obtain a mixed solution.
[0068] 3) adding calcium peroxide to the mixed solution of step 2), stirring evenly, and then pouring into a sealed container. The mixture was allowed to stand for 48 hours to allow the system to stabilize, thereby obtaining an oxygen-enriched system. The insoluble matter was then removed by filtration through a filter membrane to obtain an oxygen-enriched solution.
[0069] 4) Pour the oxygen-enriched solution from step 3) into the mold and use a light source with a wavelength of 350 nm and an intensity of 300 mW / cm 2 The oxygen-carrying hydrogel is obtained by irradiating and curing with a UV-LED lamp.
[0070] Performance Testing
[0071] A 0.6 cm thick oxygen-carrying hydrogel was taken as a sample and the following tests 1)-3) were performed.
[0072] 1) Oxygen Release Test: The sample was placed in a sealed container, and the oxygen concentration within the gel was measured using an oxygen sensor electrode placed within the gel. The results showed that the oxygen-carrying hydrogel prepared in this example contained a high and stable dissolved oxygen concentration. The initial oxygen concentration in the gel was 103 mg / L, and after 7 days, the oxygen content was 95 mg / L, and after 30 days, the oxygen content was 91 mg / L.
[0073] 2) Mechanical Properties: The samples were tested using a universal testing machine. The data showed that the oxygen-carrying hydrogel exhibited stable tensile strength, with an elongation at break of 735% and an elastic modulus of 51 kPa.
[0074] 3) Biocompatibility testing: Cell culture experiments were conducted to evaluate the toxicity of the hydrogel to fibroblasts. The results showed that the hydrogel had no significant toxicity to fibroblasts, with a cell survival rate greater than 92%.
[0075] Example 4
[0076] An oxygen-carrying hydrogel comprises the following raw materials: 3 g of GelMA, 3 g of lithium magnesium silicate, 0.05 g of lithium phenyl-2,4,6-trimethylbenzoyl phosphite (LAP), 12 g of perfluorotributylamine, 12 g of poloxamer, 1 g of magnesium peroxide, and 68.95 g of deionized water.
[0077] The preparation method of the oxygen-carrying hydrogel comprises the following steps:
[0078] 1) slowly adding lithium magnesium silicate into deionized water and continuously stirring at 200 r / min to fully dissolve the lithium magnesium silicate to obtain an aqueous solution;
[0079] 2) mixing poloxamer and perfluorotributylamine uniformly, adding the mixture to the lithium magnesium silicate aqueous solution prepared in step 1) while stirring, and then adding GelMA and LAP while stirring to dissolve to obtain a mixed solution;
[0080] 3) adding magnesium peroxide to the mixed solution of step 2), stirring evenly, and then pouring into a sealed container. The mixture was allowed to stand for 72 hours to allow the system to stabilize, thereby obtaining an oxygen-enriched system. The insoluble matter was then removed by filtration using a filter membrane to obtain an oxygen-enriched solution.
[0081] 4) Pour the oxygen-enriched solution from step 3) into the mold and use a light source with a wavelength of 350 nm and an intensity of 400 mW / cm 2 The oxygen-carrying hydrogel is obtained by irradiating and curing with a UV-LED lamp.
[0082] Performance Testing
[0083] A 0.6 cm thick oxygen-carrying hydrogel was taken as a sample and the following tests 1)-3) were performed.
[0084] 1) Oxygen Release Test: The sample was placed in a sealed container, and the oxygen concentration within the gel was measured using an oxygen sensor electrode placed within the gel. The results showed that the oxygen-carrying hydrogel prepared in this example contained a high and relatively stable dissolved oxygen concentration. The initial oxygen concentration in the gel was 98 mg / L, and after 7 days, the oxygen content was 93 mg / L, and after 30 days, the oxygen content was 89 mg / L.
[0085] 2) Mechanical Properties Test: The samples were tested using a universal testing machine. The test results showed that the tensile strength met the requirements, the elongation at break was 850%, and the elastic modulus was 48 kPa.
[0086] 3) Biocompatibility testing: Cell culture experiments were used to evaluate the toxicity of the hydrogel to fibroblasts. The results showed that the hydrogel had no significant toxicity to fibroblasts, with a cell survival rate greater than 93%.
[0087] Comparative Example 1
[0088] A hydrogel comprises the following raw materials: 5 g of GelMA, 0.1 g of 1-hydroxycyclohexylphenyl ketone (184), 1.5 g of calcium peroxide, and 93.4 g of deionized water.
[0089] The method for preparing the hydrogel comprises the following steps:
[0090] 1) Add GelMA and 184 into water and stir to dissolve;
[0091] 2) adding calcium peroxide to the mixed solution of step 1), stirring evenly, and then pouring into a sealed container. The mixture was allowed to stand for 48 hours to allow the system to stabilize, thereby obtaining an oxygen-rich system. The insoluble matter was then removed by filtration through a filter membrane to obtain a solution.
[0092] 3) Pour the solution from step 2) into the mold and use a light source with a wavelength of 350nm and an intensity of 300mW / cm 2 The hydrogel was obtained by irradiating and curing with a UV-LED lamp.
[0093] Performance Testing
[0094] A 0.6 cm thick hydrogel was taken as a sample and the following tests 1) to 3) were performed.
[0095] 1) Oxygen release test: The sample was placed in a sealed container, and the change in oxygen concentration in the gel was measured using an oxygen sensor electrode placed in the gel. Oxygen release test: The sample was placed in a sealed container, and the change in oxygen concentration in the gel was measured using an oxygen sensor electrode placed in the gel. The results showed that the dissolved oxygen concentration of the oxygen-carrying hydrogel prepared in this comparative example was low, wherein the initial oxygen concentration in the gel was 8.3 mg / L, the oxygen carrying capacity after 7 days was 7.9 mg / L, and the oxygen carrying capacity after 30 days was 7.9 mg / L. Compared with Example 3, the oxygen carrying effect was poor, because the oxygen generated by the peroxide diffused into the air and could not be absorbed by the gel system.
[0096] 2) Mechanical Properties: The samples were tested using a universal testing machine. The data showed that the hydrogel had low tensile strength, with an elongation at break of 45% and an elastic modulus of only 3 kPa. Compared with Example 3, the mechanical strength was significantly reduced, and the hydrogel was prone to deformation and rupture under relatively low external forces.
[0097] 3) Biocompatibility testing: Cell culture experiments were conducted to evaluate the toxicity of the hydrogel to fibroblasts. The results showed that the hydrogel had no significant toxicity to fibroblasts, with a cell survival rate greater than 91%.
[0098] Comparative Example 2
[0099] A hydrogel comprises the following raw materials: 5g of GelMA, 5g of lithium magnesium silicate, 0.1g of 1-hydroxycyclohexylphenyl ketone (184), 15g of hydrogenated castor oil, 1.5g of calcium peroxide, and 73.4g of deionized water.
[0100] The method for preparing the hydrogel comprises the following steps:
[0101] 1) slowly adding lithium magnesium silicate into deionized water and continuously stirring at 250 r / min to fully dissolve the lithium magnesium silicate to obtain an aqueous solution of lithium magnesium silicate;
[0102] 2) adding hydrogenated castor oil to the lithium magnesium silicate aqueous solution in step 1) while stirring, then adding GelMA and 184, stirring and dissolving to obtain a mixed solution;
[0103] 3) Calcium peroxide is added to the mixed solution of step 2), stirred evenly, and then poured into a sealed container. The mixture is allowed to stand for 48 hours to allow the system to stabilize, and then filtered through a filter membrane to remove insoluble matter to obtain a solution.
[0104] 4) Pour the solution from step 3) into the mold and use a light source with a wavelength of 350 nm and an intensity of 300 mW / cm 2 The hydrogel was obtained by irradiating and curing with a UV-LED lamp.
[0105] Performance Testing
[0106] A 0.6 cm thick hydrogel was taken as a sample and the following tests 1) to 3) were performed.
[0107] 1) Oxygen Release Test: The sample was placed in a sealed container, and the change in oxygen concentration within the gel was measured using an oxygen sensor electrode placed within the gel. The results showed that the oxygen-carrying hydrogel prepared in this comparative example had a low dissolved oxygen concentration. The initial oxygen concentration in the gel was 8.4 mg / L, the oxygen loading after 7 days was 8.1 mg / L, and the oxygen loading after 30 days was 8 mg / L. Compared with Example 3, the oxygen loading effect was poor, because the oxygen generated by the peroxide diffused into the air and could not be absorbed by the gel system.
[0108] 2) Mechanical Properties: The samples were tested using a universal testing machine. The data showed that the hydrogel maintained a stable tensile strength, with an elongation at break of 728% and an elastic modulus of 44 kPa.
[0109] 3) Biocompatibility testing: Cell culture experiments were conducted to evaluate the toxicity of the hydrogel to fibroblasts. The results showed that the hydrogel had no significant toxicity to fibroblasts, with a cell survival rate greater than 92%.
[0110] Comparative Example 3
[0111] A hydrogel comprises the following raw materials: 5g of GelMA, 5g of lithium magnesium silicate, 0.1g of 1-hydroxycyclohexylphenyl ketone (184), 15g of perfluorotripropylamine, 1.5g of calcium peroxide, and 73.4g of deionized water.
[0112] The method for preparing the hydrogel comprises the following steps:
[0113] 1) slowly adding lithium magnesium silicate into deionized water and continuously stirring at 250 r / min to fully dissolve the lithium magnesium silicate to obtain an aqueous solution of lithium magnesium silicate;
[0114] 2) adding perfluorotripropylamine dropwise to the lithium magnesium silicate aqueous solution prepared in step 1) at a rate of 2-3 mL per minute while stirring, then adding GelMA and 184, stirring and dissolving to obtain a mixed solution;
[0115] 3) Calcium peroxide is added to the mixed solution of step 2), stirred evenly, and then poured into a sealed container. The mixture is allowed to stand for 48 hours to allow the system to stabilize, and then filtered through a filter membrane to remove insoluble matter to obtain a solution.
[0116] 4) Pour the solution from step 3) into the mold and use a light source with a wavelength of 350 nm and an intensity of 300 mW / cm 2 The hydrogel was obtained by irradiating and curing with a UV-LED lamp.
[0117] Performance Testing
[0118] A 0.6 cm thick hydrogel was taken as a sample and the following tests 1) to 3) were performed.
[0119] 1) Oxygen Release Test: The sample was placed in a sealed container, and the change in oxygen concentration within the gel was measured using an oxygen sensor electrode placed within the gel. The results showed that the oxygen-carrying hydrogel prepared in this comparative example had a low dissolved oxygen concentration. The initial oxygen concentration in the gel was 17 mg / L, and the oxygen carrying capacity after 7 days was 15 mg / L, and after 30 days, the oxygen carrying capacity was 15 mg / L. Although the oxygen carrying capacity of this comparative example was higher than that of Comparative Examples 1-3 due to the presence of oxygen-absorbing components in the gel, it was significantly lower than that of Example 3 due to the lack of the oxygen-absorbing micelle structure of Example 3, resulting in limited oxygen absorption capacity.
[0120] 2) Mechanical Properties: The samples were tested using a universal testing machine. The results showed that the hydrogel maintained a stable tensile strength, with an elongation at break of 722% and an elastic modulus of 42 kPa.
[0121] 3) Biocompatibility testing: Cell culture experiments were used to evaluate the toxicity of the hydrogel to fibroblasts. The results showed that the hydrogel had no significant toxicity to fibroblasts, with a cell survival rate greater than 91%.
[0122] Comparative Example 4
[0123] A hydrogel comprises the following raw materials: 5g of GelMA, 5g of lithium magnesium silicate, 0.1g of 1-hydroxycyclohexylphenyl ketone (184), 15g of perfluorotripropylamine, 15g of hydrogenated castor oil, and 59.9g of deionized water.
[0124] The method for preparing the hydrogel comprises the following steps:
[0125] 1) slowly adding lithium magnesium silicate into deionized water and continuously stirring at 250 r / min to fully dissolve the lithium magnesium silicate to obtain an aqueous solution of lithium magnesium silicate;
[0126] 2) After hydrogenated castor oil and perfluorotripropylamine are mixed evenly, they are added dropwise to the lithium magnesium silicate aqueous solution prepared in step 1) at a rate of 2-3 mL per minute while stirring. GelMA and 184 are then added and stirred to dissolve to obtain a mixed solution.
[0127] 3) Pour the mixture from step 2) into the mold and use a light source with a wavelength of 350nm and an intensity of 300mW / cm 2 The hydrogel was obtained by irradiating and curing with a UV-LED lamp.
[0128] Performance Testing
[0129] A 0.6 cm thick hydrogel was taken as a sample and the following tests 1) to 3) were performed.
[0130] 1) Oxygen Release Test: The sample was placed in a sealed container, and the change in oxygen concentration within the gel was measured using an oxygen sensor electrode placed within the gel. The results showed that the oxygen-carrying hydrogel prepared in this comparative example had a low dissolved oxygen concentration, with the initial oxygen concentration in the gel being 8.6 mg / L. After 7 days, the oxygen carrying capacity reached 23 mg / L, and after 30 days, the oxygen carrying capacity reached 25 mg / L. The gradual increase in oxygen carrying capacity in this comparative example is attributed to the oxygen-absorbing micelle structure developed by the present invention, which allows oxygen to be gradually absorbed from the air into the gel.
[0131] 2) Mechanical Properties: The samples were tested using a universal testing machine. The results showed that the hydrogel maintained a stable tensile strength, with an elongation at break of 703% and an elastic modulus of 45 kPa.
[0132] 3) Biocompatibility testing: Cell culture experiments were used to evaluate the toxicity of the hydrogel to fibroblasts. The results showed that the hydrogel had no significant toxicity to fibroblasts, with a cell survival rate greater than 91%.
[0133] By comparing the performance test results of the above examples and comparative examples (see Table 1), it can be seen that the oxygen-carrying hydrogel of the present invention exhibits significant advantages in the sustainability and stability of oxygen release, as well as mechanical properties and biocompatibility, and has broad application prospects.
[0134] Table 1
[0135]
[0136] The above specifically describes the preferred embodiments of the present invention, but the invention is not limited to the embodiments. Those skilled in the art may make various equivalent modifications or substitutions without violating the spirit of the present invention. These equivalent modifications or substitutions are all included in the scope defined by the claims of this application.
Claims
1. An oxygen-carrying hydrogel, characterized in that The oxygen-carrying hydrogel comprises the following raw materials: Macromonomer, photoinitiator, fluorocarbon compound, peroxide, emulsifying solubilizer, nano-enhancing agent and water; the oxygen-carrying hydrogel is a single-layer structure.
2. The oxygen-carrying hydrogel according to claim 1, characterized in that The oxygen-carrying hydrogel comprises the following raw materials by weight percentage: The invention comprises the following components: 0.5-8% macromonomer, 0.01-0.2% photoinitiator, 4-20% fluorocarbon compound, 0.5-2% peroxide, 4-25% emulsifying solubilizer, 0.5-6% nano-enhancing agent and 30-90% water.
3. The oxygen-carrying hydrogel according to claim 1, characterized in that The macromonomer includes at least one of methacrylated gelatin, methacrylated hyaluronic acid, and methacrylated chitosan.
4. The oxygen-carrying hydrogel according to claim 1, characterized in that The nano-enhancer includes at least one of lithium magnesium silicate, montmorillonite, and magnesium aluminum silicate.
5. The oxygen-carrying hydrogel according to claim 1, characterized in that The concentration of dissolved oxygen in the oxygen-carrying hydrogel is ≥300 mg / L.
6. The method for preparing the oxygen-carrying hydrogel according to any one of claims 1 to 5, characterized in that: The following steps are involved: The macromonomer, photoinitiator, fluorocarbon compound, peroxide, emulsifying solubilizer, nano-enhancing agent and water are mixed, stirred, allowed to stand under sealed conditions, and then photocured to obtain the oxygen-carrying hydrogel.
7. The preparation method according to claim 6, characterized in that The standing time is 24-72h.
8. The preparation method according to claim 6, characterized in that The wavelength of the photocuring is 300-400 nm; and / or the light intensity of the photocuring is 100-500 mW / cm 2 .
9. Use of the oxygen-carrying hydrogel according to any one of claims 1 to 5 in the preparation of a medicament for promoting wound healing.
10. The use according to claim 9, characterized in that The wound includes an infected diabetic ulcer wound.
Citation Information
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