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CN-122005935-A - Biological valve coating and method of forming a coating on a biological valve

CN122005935ACN 122005935 ACN122005935 ACN 122005935ACN-122005935-A

Abstract

The embodiment of the application relates to the technical field of medical coating materials, in particular to a biological valve coating and a method for forming the coating on the biological valve. The biological valve coating provided by the embodiment of the application comprises polylactic acid-glycolic acid copolymer loaded with curcumin @ curcumin nano-particles, platelet inhibitors, piezoelectric nanofiber membranes and hydrogels of methacryloyl gelatin-methacryloyl heparin (GelMA-HepMA). The biological valve coating provided by the embodiment of the application can ensure that the biological valve has the comprehensive performances of early antithrombotic, mid-term anti-inflammatory and antioxidant implantation and long-term delay of calcification degeneration of the valve leaflet, and is beneficial to promoting endothelialization of the biological valve and improving long-term functional stability and biocompatibility of the biological valve.

Inventors

  • PAN XIANGBIN
  • LI ZEFU

Assignees

  • 中国医学科学院阜外医院

Dates

Publication Date
20260512
Application Date
20260224

Claims (10)

  1. 1. A biological valve coating comprising a curcumin loaded polylactic acid-glycolic acid copolymer @ curcumin nanoparticle, a platelet inhibitor, a piezoelectric nanofiber membrane, and a hydrogel of methacryloyl gelatin-methacryloyl heparin (GelMA-HepMA).
  2. 2. The biological valve coating of claim 1, wherein the biological valve coating is a polymeric material, The mass content ratio of the polylactic acid-glycolic acid copolymer @ curcumin nano-particles, the platelet inhibitor, the piezoelectric nanofiber membrane and the methacryloyl gelatin-methacryloyl heparin (GelMA-HepMA) hydrogel is 20:1:20:225.
  3. 3. A method of forming a coating on a biological valve, comprising the steps of: s10, preparing a polylactic acid-glycolic acid copolymer @ curcumin nanoparticle loaded with curcumin; S20, adding the polylactic acid-glycolic acid copolymer@curcumin nano particles prepared in the step S10 into a degradable high polymer material L-polylactic acid (PLLA) and adding the polylactic acid-glycolic acid copolymer@curcumin nano particles into an electrostatic spinning machine to prepare a piezoelectric nanofiber membrane in directional arrangement; S30, preparing a hydrogel solution of methacryloylated gelatin-methacryloylated heparin; S40, adding a platelet inhibitor to the hydrogel solution of the methacryloylated gelatin-methacryloylated heparin prepared in the step S30; S50, arranging the piezoelectric nanofiber membrane prepared in the step S20 on the blood contact surface of the biological valve, and coating the mixture obtained in the step S40 on the piezoelectric nanofiber membrane; and S60, carrying out photo-crosslinking treatment on the mixture so as to form a coating on the blood contact surface of the biological valve.
  4. 4. The method of claim 3, wherein the step of, In step S10, the method further comprises the steps of: S11, placing a preset amount of polylactic acid-glycolic acid copolymer (PLGA) into a preset amount of chloroform, and stirring in an ice water bath to dissolve the polylactic acid-glycolic acid copolymer; S12, dispersing a predetermined amount of curcumin (Cur) in the mixed solution obtained in the step S11; S13, preparing a carrier solution, dissolving the carrier solution in the mixed solution obtained in the step S12, and performing membrane emulsification treatment on the mixed solution to generate emulsified water suspension; S14, stirring the emulsified aqueous suspension in a vacuum environment to remove chloroform and generate a polylactic acid-glycolic acid copolymer@curcumin nanoparticle aqueous dispersion; and S15, removing redundant ions of the polylactic acid-glycolic acid copolymer@curcumin nanoparticle aqueous dispersion and re-suspending in deionized water to obtain the polylactic acid-glycolic acid copolymer@curcumin nanoparticles.
  5. 5. The method of claim 4, wherein the step of determining the position of the first electrode is performed, In step S13, the method further includes the steps of: A polyvinyl alcohol (PVA) solution having a mass to volume ratio of 1% was prepared, and sodium chloride was added to the polyvinyl alcohol (PVA) solution to a molar concentration of 0.05, to obtain a carrier solution.
  6. 6. The method of claim 4, wherein the step of determining the position of the first electrode is performed, In step S13, a film-passing emulsification treatment was performed using an SPG film-passing emulsification apparatus, the SPG pipe temperature was set at 35℃and the film-passing pressure was set at 0.1MPa, and nitrogen gas was used as a pressure gas to pass through the film 2 times at a film-passing speed of 0.5 mL/S.
  7. 7. The method of claim 3, wherein the step of, In step S20, the method further comprises the steps of: s21, dissolving L-polylactic acid (PLLA) with a preset molecular weight in Hexafluoroisopropanol (HFIP) to generate an electrostatic spinning solution with a preset concentration; S22, adding the polylactic acid-glycolic acid copolymer@curcumin nano particles prepared in the step S10 into the electrostatic spinning solution, and adding the nano particles into an electrostatic spinning machine to generate a directional arrangement fiber film; And S23, maintaining the oriented fiber membrane at a preset temperature for a preset time, and naturally cooling to generate the oriented piezoelectric nanofiber membrane.
  8. 8. The method of claim 4, wherein the step of determining the position of the first electrode is performed, In step S20, the method further comprises the steps of: S21', dissolving L-polylactic acid (PLLA) with a preset molecular weight in Hexafluoroisopropanol (HFIP) to generate an electrostatic spinning solution with a preset concentration; S22', taking the polylactic acid-glycolic acid copolymer@curcumin nanoparticle aqueous dispersion prepared in the step S14 as an electrostatic spraying solution; S23', adding the electrostatic spinning solution and the electrostatic spraying solution into an electrostatic spinning machine, and simultaneously carrying out electrostatic spinning and electrostatic spraying under the conditions of a preset temperature and a preset humidity to generate a directional arrangement fiber film; and S24', maintaining the oriented fiber membrane at a preset temperature for a preset time, and naturally cooling to generate the oriented piezoelectric nanofiber membrane.
  9. 9. The method of claim 3, wherein the step of, In step S30, the method further comprises the steps of: S31, dissolving a predetermined amount of methacryloyl gelatin (GelMA) in a predetermined amount of buffer solution at a predetermined temperature to obtain a methacryloyl gelatin solution; S32, dissolving a predetermined amount of methacryloyl heparin (HepMA) in the methacryloyl gelatin solution; And S33, adding a preset amount of photoinitiator into the mixed solution prepared in the step S32, and stirring in a dark place until the solution is clear to obtain the hydrogel solution of the methacryloylated gelatin-methacryloylated heparin.
  10. 10. The method of claim 3, wherein the step of, In step S50, the method further comprises the steps of: s51, determining a blood flushing area in a blood contact surface of the biological valve; s52, arranging the piezoelectric nanofiber membrane prepared in the step S20 on the blood contact surface of the biological valve, so that the piezoelectric nanofiber membrane covers the blood flushing area; s53, fixing the piezoelectric nanofiber membrane; and S54, coating the mixture obtained in the step S40 on the piezoelectric nanofiber membrane.

Description

Biological valve coating and method of forming a coating on a biological valve Technical Field The embodiment of the application relates to the technical field of medical coating materials, in particular to a biological valve coating and a method for forming the coating on the biological valve. Background The statements herein merely provide background information related to the present disclosure and may not necessarily constitute prior art. For patients with severe valve stenosis or insufficiency, in clinical treatment, surgical valve replacement, transcatheter aortic valve/mitral valve replacement and other treatment strategies are mainly adopted, and biological valves are widely used in terms of replacement material selection due to the characteristics of good hemodynamic performance, relatively low thrombus risk, small dependence on long-term strong anticoagulation in theory and the like. However, after implantation of a biological valve into the heart, three major problems remain, namely the early stage of implantation is susceptible to thrombosis, the recent inflammatory response and oxidative stress persist, and the risk of calcification degeneration of the leaflets at long term implantation, with the potential for valve regurgitation or recurrence of stenosis and the need for re-surgical intervention. Specifically, from the viewpoint of blood compatibility mechanism, after the biological valve is implanted, the blood contact surface of the biological valve is easy to generate protein adsorption and conformation change, then platelet adhesion, aggregation and activation are triggered, and further the coagulation cascade reaction is activated, especially in application scenes such as catheter valve replacement or valve in valve, the valve is in a complex blood flow shearing and vortex environment, and the local stagnation area and the low shearing area are more easy to promote thrombosis. From the standpoint of inflammation and immune response, biological valve tissue is typically subjected to fixation, cross-linking or other chemical treatments to reduce immunogenicity and increase mechanical stability, but such treatments may introduce residual reactive groups or alter tissue microstructure, resulting in sustained local inflammatory response, and in addition, residual cellular components, phospholipids and microdamages introduced during processing may induce macrophage infiltration, inflammatory factor release and oxidative stress accumulation, and inflammatory and oxidative stress not only exacerbate thrombotic tendencies, but also promote transformation of leaflet mesenchymal and surrounding cells to osteogenic phenotype, promoting calcification deposition. Disclosure of Invention The following presents a simplified summary of the application in order to provide a basic understanding of some aspects of the application. It should be understood that this summary is not an exhaustive overview of the application. It is not intended to identify key or critical elements of the application or to delineate the scope of the application. Its purpose is to present some concepts in a simplified form as a prelude to the more detailed description that is discussed later. In a first aspect, embodiments of the present application provide a biological valve coating comprising a curcumin loaded polylactic acid-glycolic acid copolymer @ curcumin nanoparticle, a platelet inhibitor, a piezoelectric nanofiber membrane, and a hydrogel of methacryloyl gelatin-methacryloyl heparin (GelMA-HepMA). The biological valve coating provided by the embodiment of the application provides stable anticoagulation and bionic extracellular matrix microenvironment through the hydrogel of the methacryloyl gelatin-methacryloyl heparin, and is combined with a platelet inhibitor, so that the platelet adhesion activation and coagulation cascade reaction caused by protein adsorption can be reduced at the early stage of biological valve implantation, the rapid antithrombotic effect is achieved, the extracellular matrix microenvironment provided by the polylactic acid-glycolic acid copolymer@curcumin nanoparticles loaded with curcumin is protected and slowly released by utilizing the polylactic acid-glycolic acid copolymer to resist inflammatory and antioxidant active ingredient curcumin, the accumulation of local Reactive Oxygen (ROS) is reduced, the inflammatory cascade reaction is regulated, driving factors of the valve She Gaihua are weakened from the source, the valve She Gaihua is delayed, the thickening and structural degeneration are delayed, meanwhile, a piezoelectric nanofiber membrane is introduced, and the piezoelectric nanofiber membrane can generate micro-electrical signals favorable for endothelialization under the non-invasive stimulation of periodic mechanical load or external ultrasound and the like generated by the valve implantation, so that the extracellular matrix microenvironment provided by the endothelial cell is cooper