Preparation method of medical high-biocompatibility porous hydrogel
By generating a porous structure inside the hydrogel through the Faraday reaction and combining it with UV curing, the problems of monomer residue and excessive hardness in UV-cured hydrogels are solved, and a highly biocompatible porous hydrogel is prepared that can adapt to human activities and promote wound healing.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- ZHEJIANG HANGBIAO MEDICAL PROD CO LTD
- Filing Date
- 2025-09-09
- Publication Date
- 2026-07-21
AI Technical Summary
Existing UV-curable hydrogels contain monomer residues that cause excessive cytotoxicity, and the prepared hydrogels are too hard, making it difficult to adhere to irregular wounds, thus limiting their application in the medical field.
A porous structure is generated inside the hydrogel using the Faraday reaction, combined with UV curing. The highly active redox reaction generated by the electrode reacts with the unpolymerized monomer to prepare a highly biocompatible porous hydrogel, avoiding monomer residue and improving flexibility.
The prepared porous hydrogels exhibit good biocompatibility, flexibility, and strength, adapt to human activities, promote wound healing, and reduce the risk of inflammatory responses.
Abstract
Description
Technical Field
[0001] This invention belongs to the field of medical materials technology, specifically relating to a method for preparing a medical-grade highly biocompatible porous hydrogel. Background Technology
[0002] The preparation process of UV-curable hydrogels mainly relies on the free radical photopolymerization mechanism of monomers. Under ultraviolet irradiation, the photoinitiator rapidly absorbs photon energy, initiating a chain addition polymerization reaction of double bonds in monomer molecules, gradually building a complex three-dimensional network structure. However, due to the complexity of the reaction kinetics and the obstacles to diffusion within the system, this reaction is difficult to achieve complete monomer conversion. A large amount of unpolymerized monomers remain in the final hydrogel system, posing a potential cytotoxicity risk.
[0003] In practical medical applications, this issue presents numerous serious challenges. Taking wound dressings as an example, residual monomers may be continuously released into the tissues surrounding the wound, stimulating immune cells and triggering a strong inflammatory response. This not only delays the normal healing process of the wound but may also increase the risk of wound infection, leading to a decline in the quality of wound healing.
[0004] During the preparation of UV-cured hydrogels, polymerization reactions are accompanied by condensation, resulting in hydrogels with a relatively hard texture. This excessive hardness makes it difficult to achieve a tight and comfortable fit when applied to irregular wounds or tissue defects, failing to provide an ideal healing environment and severely limiting its widespread application in the medical field.
[0005] Therefore, it is urgent to develop a method for preparing medical porous hydrogels that can effectively reduce cytotoxicity while possessing an ideal microstructure and good flexibility. Summary of the Invention
[0006] To address the problems existing in the prior art, this invention provides a method for preparing a medical-grade highly biocompatible porous hydrogel. On the one hand, it can efficiently solve the long-standing industry problem of excessive cytotoxicity caused by monomer residues in traditional UV-cured hydrogels. On the other hand, it also utilizes the unique physicochemical effects of the Faraday reaction to give the hydrogel a porous structure. The porous structure improves the flexibility of the hydrogel, and the presence of pores allows the hydrogel to disperse stress through the micro-deformation of the pores when under stress, avoiding rigid fracture and enabling it to adapt to the activities of different parts of the human body, creating a stable and comfortable environment for wound healing.
[0007] To solve the above technical problems, the present invention adopts the following technical solution:
[0008] A method for preparing a medical-grade highly biocompatible porous hydrogel includes the following steps:
[0009] S1, Preparation of hydrogel photocuring system
[0010] Add the hydrogel monomer, initiator, crosslinking agent, catalyst, and solubilizer to deionized water and stir for 20-30 minutes. Then add the ion source and continue stirring for 5-10 minutes to obtain the hydrogel photocuring system solution.
[0011] Preferably, the hydrogel monomer is one or more selected from acrylic acid, N-vinylpyrrolidone, N,N-dimethylacrylamide, acrylamide, and acrylamide. These monomers, due to their unique chemical structures, can impart diverse properties to the hydrogel in subsequent reactions.
[0012] Preferably, the initiator is 2-hydroxy-2-methyl-1-phenyl-1-propanone or 1-hydroxy-cyclohexyl-phenyl methyl ketone. Under ultraviolet irradiation, they can rapidly absorb photon energy, decompose to generate free radicals, and then initiate a chain addition polymerization reaction of the double bonds in the monomer molecules, thereby accelerating the curing process of the hydrogel system.
[0013] Preferably, the crosslinking agent is N,N-methylenebisacrylamide, which has two polymerizable double bonds in its molecular structure. During monomer polymerization, it can form chemical bonds between different molecular chains to build a three-dimensional network structure, thereby enhancing the mechanical properties and stability of the hydrogel.
[0014] Preferably, the catalyst is tripropylene glycol diacrylate. The addition of the catalyst can accelerate the polymerization reaction rate, optimize the reaction kinetics, and enable the hydrogel to reach the ideal curing state in a shorter time, thereby improving production efficiency.
[0015] Preferably, using glycerol as a solubilizer and water as a base solvent ensures that monomers, initiators, crosslinking agents, etc. are uniformly dispersed in the system, promoting the interaction between the substances. On the other hand, the addition of glycerol can not only adjust the viscosity of the system, but also enhance the flexibility of the hydrogel, making it better adaptable to the needs of different scenarios in practical applications, and ultimately forming a high-performance hydrogel photocuring system.
[0016] Preferably, the ion source is a metal salt; more preferably, the ion source is sodium chloride or potassium chloride.
[0017] To improve the biocompatibility of hydrogels with the human body, a system with an osmotic pressure close to that of the physiological environment was designed. Therefore, the concentration of the ion source was designed to be 0.5 to 2 wt% of the hydrogel photocuring system solution.
[0018] Preferably, the amount of the initiator added is 1-3% of the mass of the hydrogel monomer, the amount of the crosslinking agent added is 0.5-2% of the mass of the hydrogel monomer, and the amount of the catalyst added is 0.1-1% of the mass of the hydrogel monomer.
[0019] Preferably, the mass ratio of the hydrogel monomer, solubilizer and deionized water is 1-1.5:0.8-1.2:9-12.
[0020] S2, Coating
[0021] Hydrogel sheets are produced using a continuous UV-curing hydrogel production line, employing a 365nm wavelength mercury lamp or LED UV lamp as the light source, with the light intensity controlled between 5 and 50 mW / cm². 2 The hydrogel photocuring system solution is uniformly coated onto a continuously moving PET film using a coating equipment. After UV curing, heat dissipation, and winding, a hydrogel sheet is obtained.
[0022] Preferably, the coating rate is 0.5 to 11 m / min.
[0023] S3, Faraday reaction
[0024] Remove the PET film from the hydrogel sheet, then attach the electrodes tightly to both sides of the hydrogel and connect them to a power source to ensure full contact between the electrodes and the surface of the hydrogel. Continuously apply current until a porous structure is formed inside the hydrogel. After the reaction is complete, wash with water 2-3 times to successfully prepare a porous hydrogel.
[0025] Preferably, in the electrode, a titanium sheet is used as the cathode and is attached to the front side of the hydrogel sheet; graphite is used as the anode and is attached to the back side of the hydrogel sheet; the front side of the hydrogel sheet refers to the side that comes into contact with the wound.
[0026] Preferably, the power supply is set to a potential range of -1V to 1V, and the current density is controlled between 1 and 20 mA / cm². 2 The electrolysis time is 20 to 40 minutes.
[0027] Preferably, the porous hydrogel has a porosity greater than 70% and a pore size of approximately 10–100 μm.
[0028] During the Faraday reaction, sodium or potassium ions in the hydrogel sheet migrate towards the cathode, creating a concentration gradient within the hydrogel. Simultaneously, chloride and hydrogen ions in the hydrogel sheet generate a large amount of gas. Utilizing the concentration changes of the gas or substance produced by the Faraday reaction, bubbles are generated and evenly distributed within the hydrogel. This ideal porous hydrogel structure is beneficial for the stability of cells in the three-dimensional space within the hydrogel. Furthermore, the porous structure significantly increases the specific surface area of the hydrogel. In wound dressing applications, the porous structure can better absorb wound exudate, keep the wound moist, promote cell migration and proliferation, thereby accelerating wound healing.
[0029] This invention significantly reduces cytotoxicity. During the Faraday reaction, the highly active oxidation and reduction generated by the electrode can react rapidly and efficiently with the unpolymerized monomers in the UV polymerization, prompting them to re-initiate polymerization and avoiding the adverse effects of residual monomers on the wound.
[0030] By adopting the above technical solution, the technical effect achieved by this invention is as follows:
[0031] 1. Experimental data show that the porous hydrogel prepared by the method of this invention exhibits a relative cell proliferation rate of ≥90% as verified by the MTT assay for cytotoxicity. This fully demonstrates that the hydrogel possesses good biocompatibility and can effectively avoid adverse biological effects such as inflammatory reactions and apoptosis caused by cytotoxicity, providing a solid safety guarantee for its in vitro and in vivo medical applications.
[0032] 2. The preparation process of the present invention is simple, does not use pore-forming agents, and avoids the impact of pore-forming agent residue on the performance of porous hydrogels; the porous hydrogels prepared by the present invention have controllable pore size, high strength, good flexibility, and can adapt to the activities of different parts of the human body. Detailed Implementation
[0033] The present invention will be further illustrated below with reference to specific embodiments.
[0034] Example 1: A method for preparing a medical-grade highly biocompatible porous hydrogel, comprising the following steps:
[0035] S1, Preparation of hydrogel photocuring system
[0036] The hydrogel monomer, initiator, crosslinking agent, catalyst, and solubilizer were added to deionized water and stirred for 25 minutes. Then, an ion source was added and stirring was continued for 10 minutes to obtain the hydrogel photocuring system solution.
[0037] The hydrogel monomers are acrylamide and acrylic acid in a mass ratio of 3:1.
[0038] The initiator is 2-hydroxy-2-methyl-1-phenyl-1-propanone.
[0039] The crosslinking agent is N,N-methylenebisacrylamide.
[0040] The catalyst is tripropylene glycol diacrylate, and the solubilizer is glycerol.
[0041] The ion source is sodium chloride, with a concentration of 1 wt% of the hydrogel photocuring system solution.
[0042] The amount of the initiator added is 2% of the mass of the hydrogel monomer, the amount of the crosslinking agent added is 1.5% of the mass of the hydrogel monomer, and the amount of the catalyst added is 0.5% of the mass of the hydrogel monomer.
[0043] The mass ratio of the hydrogel monomer, solubilizer, and deionized water is 1.2:1:10.
[0044] S2, Coating
[0045] Hydrogel sheets are fabricated using a continuous UV-curing hydrogel production line, employing a 365nm wavelength mercury lamp or LED UV lamp as the light source, with the light intensity controlled at 20mW / cm². 2 The hydrogel photocuring system solution is uniformly coated onto a continuously moving PET film using a coating equipment. After UV curing, heat dissipation, and winding, a hydrogel sheet is obtained.
[0046] The coating rate is 6 m / min and the coating length is 10 m.
[0047] S3, Faraday reaction
[0048] Remove the PET film from the hydrogel sheet, then attach the electrodes tightly to both sides of the hydrogel and connect them to a power source to ensure full contact between the electrodes and the surface of the hydrogel. Continuously apply current until a porous structure is formed inside the hydrogel. After the reaction is complete, wash with water three times to successfully prepare a porous hydrogel.
[0049] In the electrode, a titanium sheet is used as the cathode and is attached to the front side of the hydrogel sheet; graphite is used as the anode and is attached to the back side of the hydrogel sheet; the front side of the hydrogel sheet refers to the side that comes into contact with the wound.
[0050] The power supply is set to a potential range of 1V, and the current density is controlled at 5mA / cm². 2 The electrolysis time is 30 minutes.
[0051] The porous hydrogel has a porosity of 80% and an average pore size of 20 μm.
[0052] Example 2: A method for preparing a medical-grade highly biocompatible porous hydrogel, comprising the following steps:
[0053] S1, Preparation of hydrogel photocuring system
[0054] The hydrogel monomer, initiator, crosslinking agent, catalyst, and solubilizer were added to deionized water and stirred for 20 minutes. Then, an ion source was added and stirring was continued for 5 minutes to obtain the hydrogel photocuring system solution.
[0055] The hydrogel monomers are acrylamide and acrylic acid in a mass ratio of 3:1.
[0056] The initiator is 2-hydroxy-2-methyl-1-phenyl-1-propanone.
[0057] The crosslinking agent is N,N-methylenebisacrylamide.
[0058] The catalyst is tripropylene glycol diacrylate, and the solubilizer is glycerol.
[0059] The ion source is sodium chloride, with a concentration of 0.5 wt% of the hydrogel photocuring system solution.
[0060] The amount of the initiator added is 1% of the mass of the hydrogel monomer, the amount of the crosslinking agent added is 0.5% of the mass of the hydrogel monomer, and the amount of the catalyst added is 0.2% of the mass of the hydrogel monomer.
[0061] The mass ratio of the hydrogel monomer, solubilizer, and deionized water is 1:0.8:9.
[0062] S2, Coating
[0063] Hydrogel sheets are fabricated using a continuous UV-curing hydrogel production line, employing a 365nm wavelength mercury lamp or LED UV lamp as the light source, with the light intensity controlled at 5mW / cm². 2 The hydrogel photocuring system solution is uniformly coated onto a continuously moving PET film using a coating equipment. After UV curing, heat dissipation, and winding, a hydrogel sheet is obtained.
[0064] The coating rate is 0.5 m / min and the coating length is 10 m.
[0065] S3, Faraday reaction
[0066] Remove the PET film from the hydrogel sheet, then attach the electrodes tightly to both sides of the hydrogel and connect them to a power source to ensure full contact between the electrodes and the surface of the hydrogel. Continuously apply current until a porous structure is formed inside the hydrogel. After the reaction is complete, wash twice with water to successfully prepare a porous hydrogel.
[0067] In the electrode, a titanium sheet is used as the cathode and is attached to the front side of the hydrogel sheet; graphite is used as the anode and is attached to the back side of the hydrogel sheet; the front side of the hydrogel sheet refers to the side that comes into contact with the wound.
[0068] The power supply is set to a potential range of -1V, and the current density is controlled at 10mA / cm². 2 The electrolysis time is 20 minutes.
[0069] The porous hydrogel has a porosity of 78% and an average pore size of 45 μm.
[0070] Example 3: A method for preparing a medical-grade highly biocompatible porous hydrogel, comprising the following steps:
[0071] S1, Preparation of hydrogel photocuring system
[0072] The hydrogel monomer, initiator, crosslinking agent, catalyst, and solubilizer were added to deionized water and stirred for 30 minutes. Then, an ion source was added and stirring was continued for 5 minutes to obtain the hydrogel photocuring system solution.
[0073] The hydrogel monomers are acrylamide and acrylic acid in a mass ratio of 3:1.
[0074] The initiator is 2-hydroxy-2-methyl-1-phenyl-1-propanone.
[0075] The crosslinking agent is N,N-methylenebisacrylamide.
[0076] The catalyst is tripropylene glycol diacrylate, and the solubilizer is glycerol.
[0077] The ion source is sodium chloride, with a concentration of 2 wt% of the hydrogel photocuring system solution.
[0078] The amount of the initiator added is 3% of the mass of the hydrogel monomer, the amount of the crosslinking agent added is 2% of the mass of the hydrogel monomer, and the amount of the catalyst added is 1% of the mass of the hydrogel monomer.
[0079] The mass ratio of the hydrogel monomer, solubilizer, and deionized water is 1.5:1.2:12.
[0080] S2, Coating
[0081] Hydrogel sheets are fabricated using a continuous UV-curing hydrogel production line, employing a 365nm wavelength mercury lamp or LED UV lamp as the light source, with the light intensity controlled at 50mW / cm². 2 The hydrogel photocuring system solution is uniformly coated onto a continuously moving PET film using a coating equipment. After UV curing, heat dissipation, and winding, a hydrogel sheet is obtained.
[0082] The coating rate is 11 m / min and the coating length is 10 m.
[0083] S3, Faraday reaction
[0084] Remove the PET film from the hydrogel sheet, then attach the electrodes tightly to both sides of the hydrogel and connect them to a power source to ensure full contact between the electrodes and the surface of the hydrogel. Continuously apply current until a porous structure is formed inside the hydrogel. After the reaction is complete, wash with water three times to successfully prepare a porous hydrogel.
[0085] In the electrode, a titanium sheet is used as the cathode and is attached to the front side of the hydrogel sheet; graphite is used as the anode and is attached to the back side of the hydrogel sheet; the front side of the hydrogel sheet refers to the side that comes into contact with the wound.
[0086] The power supply is set to a potential range of 0.5V, and the current density is controlled at 15mA / cm². 2 The electrolysis time is 40 minutes.
[0087] The porous hydrogel has a porosity of 75% and an average pore size of 80 μm.
[0088] Comparative Example 1
[0089] Select a representative Example 1, remove step S3, and keep the rest the same as Example 1, as Comparative Example 1.
[0090] Comparative Example 2
[0091] Example 1, a representative example, was selected. Step S3 was omitted, and 15% of the monomer mass of a porogen (20 μm sodium chloride particles) was added to step S1, resulting in a porosity of 78%. All other steps were the same as in Example 1. This example served as Comparative Example 2.
[0092] Note: The hydrogels prepared in Comparative Examples 1-2 were also washed with water after being rolled up and peeled off.
[0093] The performance of the porous hydrogels prepared in Examples 1-3 and the hydrogels prepared in Comparative Examples 1-2 was tested, and the results are shown in Table 1.
[0094] Table 1
[0095] Testing items Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Tensile strength (MPa) 2.52 2.41 2.35 1.3 1.5 Compression resilience (%) 80 77 75 54 61 Relative cell proliferation rate (%) 92.7 91.5 90.8 56 62
[0096] Unless otherwise specified, all proportions and percentages mentioned in this invention are mass proportions and mass percentages; all raw materials are commercially available.
[0097] Finally, it should be noted that the above descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.
Claims
1. A method for preparing a medical-grade highly biocompatible porous hydrogel, characterized in that, The method for preparing the porous hydrogel includes the preparation, coating, and Faraday reaction of the hydrogel photocuring system. The hydrogel photocuring system is prepared by adding hydrogel monomer, initiator, crosslinking agent, catalyst and solubilizer into deionized water and stirring for 20-30 min, then adding ion source and stirring for another 5-10 min to obtain the hydrogel photocuring system solution. The hydrogel monomer is one or more of acrylic acid, N-vinylpyrrolidone, N,N-dimethylacrylamide, acrylamide, and acrylamide. The ion source is sodium chloride or potassium chloride, with a concentration of 0.5–2 wt% of the hydrogel photocuring system solution. The coating process involves producing hydrogel sheets using a continuous UV curing hydrogel production line. A 365nm wavelength mercury lamp or LED ultraviolet lamp is used as the light source, with the light intensity controlled between 5 and 50 mW / cm². The hydrogel curing system solution is uniformly coated onto a continuously moving PET film using a coating device. After UV curing, heat dissipation, and winding steps, the hydrogel sheet is obtained. The Faraday reaction involves removing the PET film from the hydrogel sheet, then tightly attaching the electrodes to both sides of the hydrogel and connecting them to a power source to ensure full contact between the electrodes and the hydrogel surface. The current is continuously applied until a porous structure is formed inside the hydrogel. After the reaction is complete, the hydrogel is washed with water 2-3 times to successfully prepare a porous hydrogel. In the electrode, a titanium sheet is used as the cathode and is attached to the front side of the hydrogel sheet; graphite is used as the anode and is attached to the back side of the hydrogel sheet; the front side of the hydrogel sheet refers to the side that comes into contact with the wound.
2. The method for preparing a medical-grade highly biocompatible porous hydrogel according to claim 1, characterized in that, The initiator is 2-hydroxy-2-methyl-1-phenyl-1-propanone or 1-hydroxy-cyclohexyl-phenyl ketone; the crosslinking agent is N,N-methylenebisacrylamide; The catalyst is tripropylene glycol diacrylate.
3. The method for preparing a medical-grade highly biocompatible porous hydrogel according to claim 1, characterized in that, The solubilizer is glycerol.
4. The method for preparing a medical-grade highly biocompatible porous hydrogel according to claim 1, characterized in that, The amount of the initiator added is 1-3% of the mass of the hydrogel monomer, the amount of the crosslinking agent added is 0.5-2% of the mass of the hydrogel monomer, and the amount of the catalyst added is 0.1-1% of the mass of the hydrogel monomer. The mass ratio of the hydrogel monomer, solubilizer, and deionized water is 1–1.5:0.8–1.2:9–12.
5. The method for preparing a medical-grade highly biocompatible porous hydrogel according to claim 1, characterized in that, The coating rate is 0.5 to 11 m / min.
6. The method for preparing a medical-grade highly biocompatible porous hydrogel according to claim 1, characterized in that, The power supply is set to a potential range of -1V to 1V, the current density is controlled between 1 and 20 mA / cm², and the electrolysis time is between 20 and 40 min.