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CN-121971717-A - Anti-hemolysis hydrogel coating and preparation method and application thereof

CN121971717ACN 121971717 ACN121971717 ACN 121971717ACN-121971717-A

Abstract

The invention discloses an anti-hemolytic hydrogel coating, a preparation method and application thereof, wherein a micron-sized porous structure and a hydrophilic silane bonding layer are constructed on the surfaces of various base materials, the adhesion of the hydrogel coating to the substrate is significantly enhanced by physical topowinding and covalent bonding. The method can be suitable for blood contact medical instruments with different shapes and materials by spraying, dipping, coating, mold forming and other methods, can meet the special requirements of different medical instruments by adjusting the formula and the preparation process parameters of the hydrogel, and has wide applicability and good expandability. The anti-hemolysis hydrogel coating has remarkable technical advantages in the aspects of reducing the risk of hemolysis, improving the biocompatibility, simplifying the structure of medical equipment and the like through optimized materials and designs.

Inventors

  • LI YONGJIAN
  • CHEN HAOSHENG
  • LIU QIWEI
  • MENG KUILIN

Assignees

  • 清华大学

Dates

Publication Date
20260505
Application Date
20251231

Claims (11)

  1. 1. A method of preparing an anti-hemolytic hydrogel coating comprising the steps of: (1) Preparing a porous structure on the surface of a substrate, performing activation treatment, and introducing hydroxyl functional groups; (2) Soaking the substrate in an amino silane-containing coupling agent solution; (3) Immersing the substrate in a first reagent to crosslink; (4) Immersing the substrate in an acidic solution, cleaning and drying, immersing the substrate in an alkaline solution, cleaning and drying; (5) Dissolving hydrogel monomer, cross-linking agent and ultraviolet initiator in water to obtain hydrogel precursor solution, coating the hydrogel precursor solution on the surface of a substrate, performing ultraviolet light-initiated polymerization to form a coating, and soaking the coating in physiological saline to obtain an anti-hemolysis hydrogel coating; Wherein the solute of the first reagent comprises one or more than two of poly (ethylene-alt-maleic anhydride), polymethyl vinyl ether-alt-maleic anhydride, polyallylamine and polyethylene glycol diamine; The mass fraction of hydrogel monomer is 10-30wt%, the mass fraction of cross-linking agent is 0.05-0.2wt% and the mass fraction of ultraviolet initiator is 0.05-0.2wt% based on 100% of hydrogel precursor solution.
  2. 2. The production method according to claim 1, wherein the production method further comprises: Immersing the coating formed by ultraviolet light initiated polymerization in copper salt solution.
  3. 3. The method of manufacturing according to claim 1, wherein the substrate comprises a metal, a ceramic, or a polymer; preferably, the porous structure is prepared by a sintering method, plasma spraying, sol-gel method or electrochemical deposition technology; Preferably, the pore size of the porous structure is 10 μm to 50 μm.
  4. 4. The preparation method according to claim 1, wherein the aminosilane-containing coupling agent comprises one or a combination of two or more of 3-aminopropyl triethoxysilane, N- β - (aminoethyl) - γ -aminopropyl trimethoxysilane, N- (2-aminoethyl) -3-aminopropyl trimethoxysilane; preferably, in the amino silane-containing coupling agent solution, the mass fraction of the amino silane-containing coupling agent is 2-5wt%.
  5. 5. The production method according to claim 1, wherein the mass fraction of the solute in the first reagent is 0.1 to 0.5wt%.
  6. 6. The production method according to claim 1, wherein, in the production method: in the step (2), the soaking time is 1-3h; In the step (3), the time for immersing the substrate in the first reagent is 8-12h; In the step (4), the time for immersing the substrate in the acidic solution is 1-2h, and the time for immersing the substrate in the alkaline solution is 1-2h.
  7. 7. The method of claim 1, wherein the hydrogel monomer comprises one or a combination of two or more of acrylamide, acrylic acid, vinyl alcohol, poly N-isopropyl acrylamide, [ (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide.
  8. 8. The production method according to claim 1, wherein the crosslinking agent comprises a bifunctional unsaturated bond crosslinking agent; Preferably, the difunctional unsaturated bond cross-linking agent comprises one or more than two of N, N '-methylenebisacrylamide, N' -phenylenediacrylamide, polyethylene glycol diacrylate and 1, 4-bisacrylamide butane.
  9. 9. The preparation method of claim 1, wherein the ultraviolet initiator comprises one or a combination of more than two of 2-hydroxy-4- (2-hydroxyethoxy) -2-methyl propiophenone, 2,4, 6-trimethylbenzoyl diphenyl phosphine oxide, 1-hydroxycyclohexyl phenyl ketone and benzophenone; preferably, the means for applying the hydrogel precursor solution to the surface of the substrate comprises one or a combination of two or more of spraying, dipping, coating and die forming.
  10. 10. An anti-hemolytic hydrogel coating prepared by the preparation method of any one of claims 1to 9; preferably, the hydrogel coating has a thickness of 10 μm to 200 μm.
  11. 11. Use of an anti-hemolytic hydrogel coating of claim 10 in the preparation of a blood contacting medical device; preferably, the blood contacting medical device comprises one or a combination of more than two of a prosthetic heart pump, a prosthetic heart valve, a vascular stent, a heart occluder.

Description

Anti-hemolysis hydrogel coating and preparation method and application thereof Technical Field The invention relates to an anti-hemolysis hydrogel coating, a preparation method and application thereof, and belongs to the technical field of biological material surface modification. Background With advances in medical technology, blood contacting medical devices, particularly prosthetic heart valves and prosthetic heart pumps, have been widely used in clinical therapy. However, blood exposure to the device, particularly under high shear stress and high flow conditions, can cause red blood cell damage, leading to hemolysis and its associated complications such as anemia, renal failure, and the like. Currently, reducing hemolysis caused by blood contacting the surface of the device is achieved primarily by structure optimization and surface modification techniques. However, the structure optimization method has no universality and is difficult to be applied to different blood contact medical instruments in an expanding way. The sliding property and the softness property of the hydrogel material are beneficial to reducing wall shear stress and red blood cell collision damage, and have great potential in solving the problem of hemolysis of blood contacting medical equipment. However, the existing hydrogel coating technology mainly focuses on functions of anticoagulation, antibiosis, anti-infection and the like, and is not applied to the aspect of anti-hemolysis. And the hydrogel coating has weak adhesion with the surface of the blood contacting medical instrument and poor stability, and is difficult to play a role in the in-vivo environment for a long time. There is therefore a need to develop an anti-hemolytic hydrogel coating with strong adhesion and high stability. To sum up, in order to better realize the functions of the wearable device, a new high-precision patterned hydrogel system with good biocompatibility, loose pore channel structure capable of allowing drug molecules and ions to pass through and miniaturization requirement as low as below 5 μm needs to be designed. CN114887217a discloses a heart pump with a superhydrophobic surface, wherein a superhydrophobic coating is coated on the surface of an overcurrent component of the heart pump, and the superhydrophobic coating is composed of a superhydrophobic material. When the super-hydrophobic coating is coated, the super-hydrophobic material is arranged on the surface of the flow-through part of the heart pump by a vapor deposition method, a thermal spraying method, a template method or electrostatic spinning to form the super-hydrophobic coating, and the hemolysis rate and the thrombus rate of the artificial heart pump can be effectively reduced by forming the super-hydrophobic coating on the wall surface of the flow-through part of the heart pump. However, superhydrophobic coatings are difficult to stably exist and function in high-speed shear flow fields. First, superhydrophobic coatings have long-term stability problems. The durability of the superhydrophobic coating may be poor, and particularly in the case of long-term contact with blood, medicines, mechanical friction, etc., the coating may fall off or fail, resulting in a decrease in superhydrophobic performance thereof. Superhydrophobic coatings typically rely on nanostructures or chemical modifications to achieve their specific hydrophobic properties. However, these nanostructures may wear or age during prolonged blood contact, mechanical abrasion (e.g., blood flow and instrument movement), and cleaning. As the coating ages, the superhydrophobic effect weakens and the surface of the device may become more hydrophilic, rather increasing the likelihood of bacterial attachment and thus increasing the risk of infection. Second, superhydrophobic coatings can interfere with other functions of certain instruments. Certain medical devices, such as vascular stents or artificial organs, require specific hydrophilicities on the surface of the device to promote the attachment and growth of vascular cells and to avoid the formation of blood clots. The superhydrophobic coating may have adverse effects on cell adhesion due to its water droplet repellent effect, impeding normal growth and function of cells, and further affecting therapeutic effects. In these cases, the application of the superhydrophobic coating may not be compatible with the biofunctional requirements of the instrument. CN116350931a discloses a lubricating coating for the pumping components of a catheter pump. At least a portion of the inner and/or outer surfaces of the pumping assembly has a roughness structure, a lubricating liquid is introduced at the roughness structure and forms a film layer, and the lubricating liquid comprises one or more of medical polytetrafluoroethylene, perfluoro tri-n-pentylamine, perfluoropolyether, oil, liquid paraffin, and vegetable oil. The smooth surface constructed by the lubricating coating is beneficial to