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Kit and method for permanently keeping artificial blood vessel smooth

An artificial blood vessel and kit technology, used in prosthesis, tissue regeneration, medical science and other directions, can solve the problems of weak mechanical properties, complex preparation process, intimal hyperplasia, etc., and achieve improved mechanical properties and patency rate, mild structure and Long-lasting effect of mechanical properties and anti-clogging properties

Active Publication Date: 2017-12-22
海迈医疗科技(苏州)有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the two small-caliber blood vessels of acellular matrix pipelines approved by the U.S. Food and Drug Administration (FDA) for clinical trials are: 1) the acellular matrix tissue engineering blood vessels used by Nicolas L'Heureux et al. The 6-week patency rate of the abdominal aorta transplantation experiment in large animal rhesus monkeys was 100% (n=3), the 1-month patency rate of the arteriovenous fistula phase I clinical trial was 78% (7 / 9), and the 6-month patency rate was 60% (5 / 8), but the preparation process is complicated. It takes 7-9 months to prepare a pipeline and costs 15,000 US dollars. The long-term patency rate is not ideal, and it is difficult to promote clinical application; 2) Tissues prepared by Laura Niklason et al. For engineering blood vessels, human cadaver vascular smooth muscle cells are planted and cultured on degradable lactic acid (PGA) tubes. After PGA is degraded, a tubular tissue rich in cells and extracellular matrix (collagen fibers) is formed, and the collagen fibers are obtained by decellularization. Tissue-engineered blood vessels (containing a small amount of residual PGA), the 6-month patency rate of the arteriovenous fistula transplantation experiment in the large animal baboon was 100% (3 / 3), and the 6-month patency rate of the FDA-approved Phase II clinical trial was 63%, 12, 18, 24 The monthly patency rates are 28%, 18%, and 15% respectively
Because allografts have transplantation immune reactions, and the preparation process is complicated, the preparation time is at least 2 months, which can easily lead to thrombosis, intimal hyperplasia, poor patency rate, and the use of cadaveric vascular smooth muscle cells has spread such as AIDS, B Risk of diseases such as hepatitis virus
[0003] In addition, due to the dense wall structure of the above-mentioned two kinds of acellular matrix tubes, the surrounding cells cannot enter the tube wall to participate in the reconstruction, and the components of the extracellular matrix of the tube wall cannot be effectively renewed, especially the elastic fibers that maintain the elasticity of the arterial tube wall cannot be synthesized, which seriously affects its function. Mechanical properties and patency
[0004] Non-decellularized autologous vascular grafts prepared by other researchers have weak mechanical properties, thrombus formation, and hyperplasia of vessel wall cells, resulting in low vascular patency. Achieving clinical translation
[0005] The inventors of the present invention have used Teflone ​​tubes to be implanted under the skin of humans or animals to obtain tissue tubes, decellularized the obtained tissue tubes, and modified the surface with heparin to obtain artificial blood vessels with better biocompatibility. However, this The artificial blood vessel obtained by this method has not been able to achieve the best in maintaining the patency rate for a long time

Method used

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  • Kit and method for permanently keeping artificial blood vessel smooth
  • Kit and method for permanently keeping artificial blood vessel smooth
  • Kit and method for permanently keeping artificial blood vessel smooth

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] 1) Preparation of artificial tubular tissue

[0035] Cut the Teflon tube (outer diameter 1 / 16 inch, about 1.59mm) that matches the inner diameter of the blood vessel to be replaced to an appropriate length, sterilize it with 75% alcohol for 30 minutes, place it in the human subcutaneous tissue, and take it out after 4 weeks. The tube and surrounding neonatal tissue were taken out, and the Teflon tube was extracted to obtain an artificial tubular tissue with a thickness of 324.1±57.4 microns (n=6, n is the number of test samples, n has the same meaning below).

[0036] 2) Decellularization treatment

[0037] Configure the decellularization reagent as shown in Table 1

[0038] Table 1 Components of decellularization reagents

[0039]

[0040] Add the precisely weighed reagent into a clean wide-mouthed glass bottle and shake it on a shaker for 2-3 hours to fully dissolve the reagent. At this time, the solution becomes clear. Prepare a decellularization reagent and sto...

Embodiment 2

[0051] 1) Preparation of artificial tubular tissue

[0052] Cut the Teflon tube (outer diameter 1 / 16 inch, about 1.59mm) whose diameter matches the inner diameter of the blood vessel to be replaced to an appropriate length, sterilize with 75% alcohol for 30 minutes, place it in the subcutaneous tissue of the pig, take it out after 2 weeks and put the subcutaneous Teflon tube The tube was taken out together with surrounding neonatal tissue, and the Teflon tube was extracted to obtain artificial tubular tissue with a thickness of 154.3±56.4 μm (n=6).

[0053] 2) Decellularization treatment

[0054] Configure the decellularization reagent as shown in Table 3

[0055] Table 3 Components of Decellularization Reagent

[0056]

[0057] Add the precisely weighed reagent into a clean wide-mouthed glass bottle and shake it on a shaker for 2-3 hours to fully dissolve the reagent. At this time, the solution becomes clear. Prepare a decellularization reagent and store it at 4°C for la...

Embodiment 3

[0068] 1) Preparation of artificial tubular tissue

[0069] Cut the Teflon tube (outer diameter 1.59mm) that matches the inner diameter of the blood vessel to be replaced to an appropriate length, sterilize it with 75% alcohol for 30 minutes, and place it under the human skin (it can also be implanted in other mammals such as mice, pigs, etc. Subcutaneous) tissue was taken out after 5 weeks. The subcutaneous Teflon tube was taken out together with the surrounding new tissue, and the Teflon tube was removed to obtain artificial tubular tissue with a thickness of 352.1±43.2 microns (n=6).

[0070] 2) Decellularization treatment

[0071] Configure the decellularization reagent as shown in Table 5

[0072] Table 5 Components of Decellularization Reagent

[0073]

[0074] Add the precisely weighed reagent into a clean wide-mouthed glass bottle and shake it on a shaker for 2-3 hours to fully dissolve the reagent. At this time, the solution becomes clear. Prepare a decellulariza...

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Abstract

The invention relates to a kit for permanently keeping an artificial blood vessel smooth. The kit consists of an acellular reagent and an anti-blocking reagent group; the acellular reagent is a water solution which contains 6-10mmol / L of CHAPS, 20-30mmol / L of EDTA disodium salt, 0.10-0.15mmol / L of NaCl and 0.8-1.2mol / L of NaOH; and the anti-blocking reagent group comprises a solution A, a solution B and a solution C, wherein the solution A is an MES buffer solution which contains 30-50mg / ml of EDC and 10-30mg / mL of Sulfo-NHS; the solution B is an MES buffer solution containing 75-90mg / ml of heparin; and the solution C is an MES buffer solution containing 10-20[mu]g / ml of S-SDF-1.

Description

technical field [0001] The present invention relates to the field of tissue materials, more particularly, to a kit and method for improving the biocompatibility of artificial blood vessels. Background technique [0002] The most important grafting vessels clinically used in coronary artery bypass surgery and other small-caliber vessel bypass surgery are generally autologous vessels such as great saphenous vein and internal mammary artery. At present, the US Food and Drug Administration (FDA) has approved two small-caliber blood vessels of acellular matrix pipelines for clinical trials: 1) the acellular matrix tissue engineering blood vessels used by Nicolas L'Heureux et al. The 6-week patency rate of the abdominal aorta transplantation experiment in large animal rhesus monkeys was 100% (n=3), the 1-month patency rate of the arteriovenous fistula phase I clinical trial was 78% (7 / 9), and the 6-month patency rate was 60% (5 / 8), but the preparation process is complicated. It t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/50A61L27/36A61L27/54A61L27/20A61L27/22
CPCA61L27/20A61L27/227A61L27/3604A61L27/3687A61L27/50A61L27/507A61L27/54A61L2300/236A61L2300/42A61L2430/40C08L5/10C08L89/00
Inventor 邱雪峰
Owner 海迈医疗科技(苏州)有限公司
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