Department of Anatomy, Engineering Research Center for Organ Intelligent Biological Manufacturing of Chongqing, key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing, 400038, P. R. China.
Engineering Research Center of Tissue and Organ Regeneration and Manufacturing, Ministry of Education, Chongqing, 400038, P. R. China.
Adv Healthc Mater. 2023 Sep;12(23):e2300340. doi: 10.1002/adhm.202300340. Epub 2023 Jun 23.
Small-diameter tissue-engineered vascular grafts (sdTEVGs) are essential materials used in bypass or replacement surgery for cardiovascular diseases; however, their application efficacy is limited because of patency rates, especially under hyperlipidemia, which is also clinically observed in patients with cardiovascular diseases. In such cases, improving sdTEVG patency is challenging because cholesterol crystals easily cause thrombosis and impede endothelialization. Herein, the development of a biomimetic antithrombotic sdTEVG incorporating cholesterol oxidase and arginine into biomineralized collagen-gold hydrogels on a sdTEVG surface is described. Biomimetic antithrombotic sdTEVGs represent a multifunctional substrate for the green utilization of hazardous substances and can convert cholesterol into hydrogen peroxide, which can react with arginine to generate nitric oxide (NO). NO is a vasodilator that can simulate the antithrombotic action of endothelial cells under hyperlipidemic conditions. In vivo studies show that sdTEVGs can rapidly produce large amounts of NO via a cholesterol catalytic cascade to inhibit platelet aggregation, thereby improving the blood flow velocity and patency rates 60 days after sdTEVG transplantation. A practical and reliable strategy for transforming "harmful" substances into "beneficial" factors at early transplantation stages is presented, which can also promote vascular transplantation in patients with hyperlipidemia.
小直径组织工程血管移植物（sdTEVGs）是用于心血管疾病旁路或替代手术的重要材料；然而，由于通畅率，尤其是在高血脂症下，其应用效果受到限制，这也是心血管疾病患者临床观察到的情况。在这种情况下，由于胆固醇晶体容易引起血栓形成和阻碍内皮化，因此提高 sdTEVG 的通畅率具有挑战性。在此，描述了一种仿生抗血栓形成的 sdTEVG，即在 sdTEVG 表面的生物矿化胶原-金水凝胶中纳入胆固醇氧化酶和精氨酸。仿生抗血栓形成的 sdTEVGs 代表了一种对有害物质进行绿色利用的多功能基底，可将胆固醇转化为过氧化氢，然后与精氨酸反应生成一氧化氮（NO）。NO 是一种血管扩张剂，可模拟内皮细胞在高血脂条件下的抗血栓作用。体内研究表明，sdTEVGs 可通过胆固醇催化级联反应迅速产生大量的 NO，抑制血小板聚集，从而提高 sdTEVG 移植后 60 天的血流速度和通畅率。提出了一种在早期移植阶段将“有害物质”转化为“有益因素”的实用可靠策略，也可促进高血脂患者的血管移植。
