A kit and method for durable patency of artificial blood vessels

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, and more particularly, to a kit and method for improving the biocompatibility of artificial blood vessels. Background technique [0002] Clinically, the main graft vessels used in coronary artery bypass surgery and other small-caliber vessel bypass surgery are generally autologous blood vessels such as the great saphenous vein and internal mammary artery. At present, the two small-caliber acellular matrix tubes approved by the U.S. Food and Drug Administration (FDA) for clinical trials are: 1) The acellular matrix tissue engineered blood vessels used by Nicolas L'Heureux and others that do not contain synthetic materials. The 6-week patency rate of the large animal rhesus monkey abdominal aorta transplantation experiment 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 pro...

AI Technical Summary

Problems solved by technology

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 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) The tissue 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, tubular tissues rich in cells and extracellular matrix (collagen fibers) are formed, and collagen fibers are obtained by decellularization. Tissue engineered blood vessels (containing a small amount of residual PGA), the 6-month patency rate of the large animal baboon arteriovenous fistula transplantation experiment 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

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