WO2022134858A1 - Procédé de traitement de tissu prothétique biologique, et valvule cardiaque prothétique biologique - Google Patents
Procédé de traitement de tissu prothétique biologique, et valvule cardiaque prothétique biologique Download PDFInfo
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- WO2022134858A1 WO2022134858A1 PCT/CN2021/127694 CN2021127694W WO2022134858A1 WO 2022134858 A1 WO2022134858 A1 WO 2022134858A1 CN 2021127694 W CN2021127694 W CN 2021127694W WO 2022134858 A1 WO2022134858 A1 WO 2022134858A1
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- Prior art keywords
- solution
- capping
- tissue
- bioprosthetic tissue
- reducing
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3641—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
- A61L27/3687—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/20—Materials or treatment for tissue regeneration for reconstruction of the heart, e.g. heart valves
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/40—Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
Definitions
- the invention relates to the technical field of medicine, in particular to a biological prosthetic tissue processing method and a biological prosthetic heart valve.
- the reported methods of anti-calcification of bioprosthetic tissue include: decellularization treatment, alcohol treatment, surfactant treatment, metal ion competitive adsorption, etc.
- decellularization treatment can remove most of the antigens and DNA, but it will make biological tissues loose, and its mechanical properties will be reduced;
- the risk of calcification is still high in the early stage;
- surfactant treatment can remove phospholipids in bioprosthetic tissues, but aldehyde groups still exist as calcification-inducing factors;
- competitive adsorption of metal ions can bind to the existing binding sites of bioprosthetic tissues and play a role in It has a certain anti-calcification effect, but cannot completely solve the long-term calcification induction of aldehyde groups. That is, although the above method has a certain anti-calcification effect, the anti-calcification effect is not good in practical application, and it is also accompanied by the risk of reducing the mechanical properties of the bioprosthetic tissue.
- the object of the present invention is to provide a biological prosthetic tissue processing method and a biological prosthetic heart valve, so as to solve the problem that the biological prosthetic tissue processing method and the biological prosthetic heart valve in the prior art have poor anti-calcification effect, and Technical issues with the risk of mechanical degradation.
- the present invention provides a method for processing bioprosthetic tissue, including:
- Step S10 providing a bioprosthetic tissue, wherein the bioprosthetic tissue is at least partially cross-linked;
- Step S20 using an end-capping agent to perform end-capping treatment on the bioprosthesis tissue
- Step S30 use a reducing agent to perform reduction treatment on the bioprosthesis tissue after the end-capping treatment.
- the step S30 includes: placing the bioprosthesis tissue after the end-capping treatment in a reducing solution composed of the reducing agent and a phosphate buffer solution, and under a first predetermined condition, make the bioprosthesis tissue
- the reducing agent performs reducing treatment on the bioprosthesis tissue after the end-capping treatment.
- the pH value of the reducing solution is 6.8-8.6, the concentration of the reducing agent in the reducing solution is 0.02%-2.0% W/V, and the concentration of the phosphate buffer solution in the reducing solution is 0.02%-2.0% W/V. Concentrations greater than 0.05M.
- the first predetermined condition includes: a first predetermined temperature, a first predetermined rotational speed, and a first predetermined oscillation time, wherein the first predetermined temperature is 15°C to 50°C, and the first predetermined rotational speed is 50rpm ⁇ 200rpm, the first predetermined shaking time is 2h ⁇ 96h.
- the method further includes: replacing the reduction solution after the reduction treatment with the reduction solution at least once , and under the first preset condition, the reducing agent in the replaced reducing solution is allowed to continue reducing the bioprosthesis tissue.
- the number of times of replacing the reducing solution is 1 to 5 times.
- the reducing agent is a hydride or a sulfide.
- the reducing agent is selected from sodium borohydride, potassium borohydride, sodium cyanoborohydride, sodium triacetoxyborohydride, diisobutylaluminum hydride, diisobutylpotassium hydride, sodium bisulfite , at least one of sodium thiosulfate.
- the method for capping the bioprosthesis tissue includes: placing the bioprosthesis tissue in a capping solution consisting of a capping agent and a phosphate buffer solution, under a second predetermined condition , allowing the capping solution to treat the bioprosthetic tissue.
- the pH value of the end-capping solution is 6.8-8.6, the concentration of the end-capping agent in the end-capping solution is 0.02%-2.0% W/V, and the The concentration of the phosphate buffer solution is greater than 0.05M.
- the second predetermined condition includes: a second predetermined temperature, a second predetermined rotational speed, and a second predetermined oscillation time, wherein the second predetermined temperature is 15°C to 50°C, and the second predetermined rotational speed is 50rpm ⁇ 200rpm, the second shaking time is 2h ⁇ 96h.
- the end-capping agent is selected from at least one of amino acids, saturated alkyl amines, unsaturated alkyl amines, amino alcohols, polyether amines, amino alkyl acids, amino alkyl diacids, and amino surfactants. kind.
- the method further includes: using a second cleaning solution to perform a second cleaning on the bioprosthesis tissue, wherein the second cleaning solution is selected from ethanol solution, physiological saline Or one of the phosphate buffer solutions, the times of the second cleaning are 3 to 5 times, and each cleaning is 3 minutes to 5 minutes.
- the second cleaning solution is selected from ethanol solution, physiological saline Or one of the phosphate buffer solutions, the times of the second cleaning are 3 to 5 times, and each cleaning is 3 minutes to 5 minutes.
- the present invention also provides a bioprosthetic heart valve, comprising bioprosthetic tissue processed according to the above-mentioned method for processing a bioprosthetic component.
- the calcification degree of the bioprosthetic tissue can be significantly reduced. And does not affect the mechanical properties of bioprosthetic tissue.
- FIG. 1 is a schematic flow chart of the method for processing bioprosthetic tissue of the present invention.
- FIG. 2 is a comparison chart of calcium content after implanting bovine pericardium tissue treated by the bioprosthetic tissue processing method of the present invention under different experimental conditions into a rat for 8 weeks.
- FIG. 1 is a schematic flow chart of the method for processing bioprosthetic tissue of the present invention.
- FIG. 2 is a comparison chart of calcium content after implanting bovine pericardium tissue treated by the bioprosthetic tissue processing method of the present invention under different experimental conditions into a rat for 8 weeks. A method for reducing tissue calcification of a bioprosthesis of the present invention will be described in detail below with reference to FIG. 1 and FIG. 2 .
- a method for processing bioprosthetic tissue includes:
- Step S10 is performed: providing bioprosthetic tissue, wherein the bioprosthetic tissue is at least partially cross-linked.
- the groups generated during the cross-linking process of the bioprosthetic tissue are related to the toxicity, calcification and immunogenicity in the bioprosthetic tissue.
- the group is at least one of an aldehyde group and a carboxylic acid group.
- the bioprosthetic tissue includes, but is not limited to, selected from the group consisting of pericardium, heart valve, membrane, pleura, submucosa of small intestine, dura mater, dura mater, ligament, tendon, blood vessel, bladder endothelium or skin, the center of which may be selected from bovine pericardium or porcine pericardium, preferably bovine pericardium.
- the bioprosthetic tissue may be cross-linked using glutaraldehyde or formaldehyde.
- the crosslinking treatment can be performed using a 0.625% w/v glutaraldehyde solution.
- the method further includes: first cleaning the bioprosthesis tissue with a first cleaning solution, wherein the first cleaning solution is selected from One of physiological saline, phosphate buffer solution or ethanol solution, the number of times of the first cleaning is 3 to 5 times, and each cleaning is 3 minutes to 5 minutes.
- the unreacted glutaraldehyde or formaldehyde can be washed away sufficiently to avoid interfering with the treatment effect when the bioprosthetic tissue is subsequently treated.
- the pH value of the phosphate buffer solution used for the first cleaning is 6.8-8.6, and the concentration is 0.05M-0.2M. If an ethanol solution is used for the first cleaning, the concentration of the ethanol solution used for the first cleaning is 20% to 80%.
- Step S20 is performed, and the bioprosthesis tissue is capped with the capping solution.
- end-capping refers to blocking, removing, or altering functional groups that would have an adverse effect on the bioprosthetic tissue performance.
- ethanolamine is added to cap incompletely reacted aldehyde groups on bioprosthetic tissue.
- This "capping” may also be referred to as capping, grafting, or the like.
- the capping agent is selected from amino acids, saturated alkyl amines, unsaturated alkyl amines, amino alcohols, polyether amines, amino alkyl acids, amino alkyl diacids, amino surfactants at least one of the agents.
- it can be selected from amino alcohols, 2-amino alkyl acids, and amino alkyl diacids. More preferably, the capping agent is selected from ethanolamine, 2-aminooleic acid.
- the method for capping the bioprosthetic tissue includes: placing the bioprosthetic tissue in a capping solution composed of the capping agent and a phosphate buffer solution to Under a second predetermined condition, the capping agent is caused to treat the bioprosthetic tissue.
- the pH value of the end-capping solution is 6.8-8.6
- the concentration of the end-capping agent in the end-capping agent solution is 0.02%-2.0% W/V
- the phosphate buffer in the end-capping solution The concentration of the solution is greater than 0.05M, preferably, the concentration of the phosphate buffer solution in the capping solution is 0.05M-0.2M.
- the second predetermined condition includes: a second predetermined temperature, a second predetermined rotational speed, and a second predetermined oscillation time, wherein the second predetermined temperature is 15°C to 50°C, the The second predetermined rotational speed is 50 rpm to 200 rpm, and the second oscillation time is 2 h to 96 h.
- the bioprosthetic tissue can be sufficiently capped.
- the method further includes: performing a second cleaning on the bioprosthesis tissue with a second cleaning solution, wherein the second cleaning solution is selected from ethanol One of the solution, physiological saline or phosphate buffer solution, the number of times of the second cleaning is 3 to 5 times, and each cleaning is 3 min to 5 min.
- the free end-capping agent can be sufficiently removed to reduce the influence of the end-capping agent on subsequent processing steps.
- the second cleaning solution is an ethanol solution
- the concentration of the ethanol solution used for the second cleaning is 10%-50% V/V.
- the second cleaning solution is a phosphate buffer solution
- the pH value of the phosphate buffer solution used for the second cleaning is 6.8-8.6, and the concentration thereof is 0.05M-0.2M.
- Step S30 using a reducing solution to perform reduction processing on the bioprosthesis tissue after the end-capping treatment.
- using a reducing solution to treat the bioprosthesis tissue refers to reacting the bioprosthesis tissue after the end-capping treatment in the above step S20 with a reducing agent, so as to reduce the end-capping treatment of the bioprosthesis tissue. body components are restored.
- the reducing agent mainly reacts with the Schiff base generated in the above-mentioned cross-linking and end-capping treatment steps to reduce the Schiff base, thereby stabilizing the chemical bonds in the bioprosthesis tissue.
- the reducing agent is a hydride or a sulfide, wherein the hydride is preferably a borohydride, and the borohydride is selected from sodium borohydride, potassium borohydride, sodium cyanoborohydride, At least one of sodium triacetoxyborohydride, diisobutylaluminum hydride and diisobutylpotassium hydride.
- the sulfide may include sodium bisulfite or sodium thiosulfate, and the like.
- the step S30 includes: placing the bioprosthesis tissue in a reducing solution composed of a reducing agent and a phosphate buffer solution, so that under a first predetermined condition, the reducing agent is The bioprosthetic tissue after the capping treatment is subjected to reduction treatment.
- the pH value of the reducing solution is 6.8-8.6, the concentration of the reducing agent in the reducing solution is 0.02%-2.0% W/V, and the concentration of the reducing agent may preferably be 0.05% ⁇ 0.5% W/V.
- the concentration of the phosphate buffer solution in the reducing solution is greater than 0.05M, and preferably, the concentration of the phosphate buffer in the reducing solution is 0.05M-0.2M.
- the first predetermined condition includes: a first predetermined temperature, a first predetermined rotational speed, and a first predetermined oscillation time, wherein the first predetermined temperature is 15°C to 50°C, and the first predetermined temperature is 15°C to 50°C.
- a predetermined rotation speed is 50rpm-200rpm, and the first predetermined oscillation time is 2h-96h.
- the method further includes: storing, drying or sterilizing the bioprosthetic tissue treated with the reducing agent.
- the bioprosthetic tissue treated with the reducing agent may be placed in a liquid for liquid storage.
- the liquid may be a glutaraldehyde storage solution.
- placing the bioprosthetic tissue in the liquid for storage can also sterilize the bioprosthetic tissue.
- the drying treatment method may include: immersing the bioprosthesis tissue in a saccharide solution with an increasing concentration gradient at room temperature for dehydration; the saccharide solution is a monosaccharide and a disaccharide with water absorption and moisturizing properties. , trisaccharide, polysaccharide or sugar alcohol sugar solution; preferably, the sugar solution is fructose, sucrose, trehalose, amorphous raffinose, chitosan and chitosan-modified polysaccharide, sorbose alcohol or mannitol solution.
- the bioprosthetic tissue is sequentially immersed in an aqueous solution of sucrose with concentrations of 30%, 40%, 50%, 55%, 60%, and 65% (w/v) at room temperature. , each immersion time is 30min, and then the pericardium is taken out and dried on the fiber desiccant.
- the sterilization treatment can be sterilized by EO (ethylene oxide).
- the subsequent processing methods of the bioprosthetic tissue after the end-capping treatment and the reduction treatment are not specifically limited here, and the actual situation prevails.
- Experiments 1 to 6 are carried out below to process the bioprosthetic tissue, and further illustrate the beneficial effects of the method for processing the bioprosthetic tissue in this embodiment, wherein the bioprosthetic tissue is bovine pericardium tissue .
- the bioprosthesis tissue was not subjected to end-capping and reduction treatment; in experiment 2, only end-capping treatment was performed on the bioprosthesis tissue without reduction treatment; in experiment 3, the The end-capping treatment and the reduction treatment of the bioprosthesis tissue were performed simultaneously in the same step; in Experiment 4, Experiment 5 and Experiment 6, the end-capping treatment and reduction treatment in the bioprosthetic tissue were performed step by step, wherein the above-mentioned The reduction conditions of Experiment 4, Experiment 5 and Experiment 6 are different.
- the bovine pericardium tissue was cross-linked under the same conditions before the experiment, that is, the uncross-linked bovine pericardium tissue was placed in a 0.625% glutaraldehyde solution for cross-linking treatment.
- the bovine pericardial tissue was placed in 20% ethanol for 3 times of washing, 5 min each time.
- the dehydration and drying process was performed, that is, the bovine pericardium was immersed in the 30%, 40%, 50%, 55%, 60%, 65% (w/v) sucrose aqueous solution at room temperature in turn, and the immersion time was For 30 min, the pericardium was removed and dried on a fiber desiccant.
- the bovine pericardial tissue was placed in 20% ethanol for 3 times of washing, 5 min each time.
- end-capping treatment was performed, that is, 1 L of end-capping solution was prepared, and the cleaned bovine pericardium tissue was placed in the end-capping solution, and placed on a constant temperature shaker at a speed of 60 rpm and a temperature of 25°C for 24 hours. After completion, use 0.1M sterile phosphate buffer solution to wash 5 times, each wash 5min.
- the capping solution is a phosphate buffer solution of 8 mM ethanolamine, the concentration of the phosphate buffer solution is 0.1M, and the pH value of the capping solution is between 7.40 ⁇ 0.1.
- the dehydration and drying process is carried out, that is, the bovine pericardium is immersed in an aqueous solution of 30%, 40%, 50%, 55%, 60% and 65% (w/v) of sucrose at room temperature in turn, for each immersion time. For 30 min, the pericardium was removed and dried on a fiber desiccant.
- the bovine pericardial tissue was placed in 20% ethanol for 3 times of washing, 5 min each time.
- end-capping reduction treatment is performed, that is, 1 L of end-capping reduction solution is prepared, and the cleaned bovine pericardium tissue is placed in the end-capping reduction solution, and placed on a constant temperature shaker at a rotating speed of 60 rpm and a temperature of 25° C. After shaking for 4 hours, wash with 0.1M sterile phosphate buffer solution for 5 times, each wash for 5 min, and then wash with 20% ethanol for 5 times, each wash for 5 min.
- the end-capping reducing solution is a phosphate buffer solution of 8mM ethanolamine and 0.4% sodium borohydride (W/V), and the concentration of the phosphate buffer solution is 0.1M.
- the dehydration and drying process is carried out, that is, the bovine pericardium is immersed in an aqueous solution of 30%, 40%, 50%, 55%, 60% and 65% (w/v) of sucrose at room temperature in turn, for each immersion time. For 30 min, the pericardium was removed and dried on a fiber desiccant.
- the bovine pericardial tissue was placed in 20% ethanol for 3 times of washing, 5 min each time.
- end-capping treatment was performed, that is, 1 L of end-capping solution was prepared, and the cleaned bovine pericardium tissue was placed in the end-capping solution, and placed on a constant temperature shaker at a speed of 60 rpm and a temperature of 25°C for 24 hours. After completion, use 0.1M sterile phosphate buffer solution to wash 5 times, each wash 5min.
- the capping solution is a phosphate buffer solution of 8 mM ethanolamine, the concentration of the phosphate buffer solution is 0.1M, and the pH value of the capping solution is between 7.40 ⁇ 0.1.
- the reduction treatment was performed, that is, the end-capped bovine pericardium was assembled into a reduction solution, and then shaken at a constant temperature of 60 rpm and a temperature of 25 °C for 4 h, and then washed with 20% ethanol for 5 times, each cleaning for 5 min.
- the reducing solution is a phosphate buffer solution of 0.4% sodium triacetoxyborohydride (W/V), and the concentration of the phosphate buffer solution is 0.1M.
- the dehydration and drying process is carried out, that is, the bovine pericardium is immersed in an aqueous solution of 30%, 40%, 50%, 55%, 60% and 65% (w/v) of sucrose at room temperature in turn, for each immersion time. For 30 min, the pericardium was removed and dried on a fiber desiccant.
- the bovine pericardial tissue was placed in 20% ethanol for 3 times of washing, 5 min each time.
- end-capping treatment was performed, that is, 1 L of end-capping solution was prepared, and the cleaned bovine pericardium tissue was placed in the end-capping solution, and placed on a constant temperature shaker at a speed of 60 rpm and a temperature of 25°C for 24 hours. After completion, use 0.1M sterile phosphate buffer solution to wash 5 times, each wash 5min.
- the capping solution is a phosphate buffer solution of 8 mM ethanolamine, the concentration of the phosphate buffer solution is 0.1M, and the pH value of the capping solution is between 7.40 ⁇ 0.1.
- the reduction treatment was performed, that is, the end-capped bovine pericardium was assembled into the reduction solution, and the temperature was 25° C. for 2 hours under constant temperature shaking at a rotational speed of 60 rpm. Then wash with 20% ethanol for 5 times, each wash for 5 min.
- the reducing solution is a phosphate buffer solution of 0.05% sodium borohydride (W/V), and the concentration of the phosphate buffer solution is 0.1M.
- the dehydration and drying process is carried out, that is, the bovine pericardium is immersed in an aqueous solution of 30%, 40%, 50%, 55%, 60% and 65% (w/v) of sucrose at room temperature in turn, for each immersion time. For 30 min, the pericardium was removed and dried on a fiber desiccant.
- the bovine pericardial tissue was placed in 20% ethanol for 3 times of washing, 5 min each time.
- end-capping treatment was performed, that is, 1 L of end-capping solution was prepared, and the cleaned bovine pericardium tissue was placed in the end-capping solution, and placed on a constant temperature shaker at a speed of 60 rpm and a temperature of 25°C for 24 hours. After completion, use 0.1M sterile phosphate buffer solution to wash 5 times, each wash 5min.
- the capping solution is a phosphate buffer solution of 8 mM ethanolamine, the concentration of the phosphate buffer solution is 0.1M, and the pH value of the capping solution is between 7.40 ⁇ 0.1.
- the reducing solution is a phosphate buffer solution of 0.4% sodium cyanoborohydride (W/V), and the concentration of the phosphate buffer solution is 0.1M.
- the dehydration and drying process is carried out, that is, the bovine pericardium is immersed in an aqueous solution of 30%, 40%, 50%, 55%, 60% and 65% (w/v) of sucrose at room temperature in turn, for each immersion time. For 30 min, the pericardium was removed and dried on a fiber desiccant.
- the last step does not affect the experimental effect.
- it is a drying treatment.
- a liquid storage treatment can also be performed.
- the dehydrated and dried bovine pericardium tissue was rehydrated, and then subjected to a mechanical tensile test in a solution environment.
- the length of bovine pericardial tissue in each experiment is 50mm and the width is 5mm.
- the length of the test gauge is set to 25mm, and the tensile rate is 100mm/min, and the tensile test is carried out until the test sample fracture.
- the breaking strength and elongation at break of the test sample are obtained, wherein the breaking strength refers to the ratio of the tensile force when the test sample breaks to the fracture cross-sectional area during the mechanical tensile test; the elongation at break refers to the mechanical tensile test , the ratio of the elongation length of the test sample after stretching to the length before stretching.
- the breaking strength refers to the ratio of the tensile force when the test sample breaks to the fracture cross-sectional area during the mechanical tensile test
- the elongation at break refers to the mechanical tensile test , the ratio of the elongation length of the test sample after stretching to the length before stretching.
- the fracture strengths of the bovine pericardial tissue treated in the above experiments 1, 2, 4, 5 and 6 are generally the same.
- the bovine pericardium tissue treated in Experiment 3 that is, the bovine pericardial tissue obtained by end-capping treatment and reduction treatment simultaneously in the same step, has a significantly lower breaking strength than the above-mentioned Experiment 1, Experiment 2, Experiment 4, Experiment 5 and Experiment 5.
- the bovine pericardial tissue after the above experimental treatment was also implanted into 3-week-old rats just after weaning, and the samples were taken out 8 weeks after implantation, and dried in a constant temperature oven at 80°C for 48 hours. to constant weight. After that, the calcium content of the removed bovine pericardial tissue was measured with a flame-atomic absorption spectrophotometer, and the test results are shown in Figure 2.
- the calcification degree of the bioprosthesis tissue can be improved by subjecting the at least partially cross-linked bioprosthesis tissue to end-capping treatment and reduction treatment respectively in two steps. Relatively obvious reducing effect, and does not affect the mechanical properties of bioprosthetic tissue.
- the method further includes: using the reducing solution that has not treated the bioprosthesis tissue at least once to replace the treatment
- the reducing solution after the bioprosthesis tissue, and under the first preset condition, the reducing agent in the replaced reducing solution is allowed to continue the reducing process on the bioprosthesis tissue.
- the number of times of replacing the reducing solution is 1 to 5 times.
- the dosage of the reducing agent used for each reduction treatment is smaller than the dosage of the reducing agent used for only one reduction. In this way, the reduction environment of each reduction is made milder, so as to reduce the influence of the reduction process on the bioprosthetic tissue.
- the reducing solution that has not been treated with the bioprosthetic tissue can be replaced with the reducing solution that has not treated the bioprosthetic tissue in the same container.
- the reduction-treated bioprosthetic tissue may also be removed from the reduction solution in which the bioprosthetic tissue has been treated, and then placed in another reduction solution having the bioprosthetic tissue untreated for further processing. There is no specific limitation here, and the actual situation shall prevail.
- this embodiment also discloses a bioprosthetic heart valve, wherein the bioprosthetic heart valve includes bioprosthetic tissue processed by the above-mentioned method for processing bioprosthetic tissue.
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- Public Health (AREA)
- Epidemiology (AREA)
- Transplantation (AREA)
- Oral & Maxillofacial Surgery (AREA)
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