Navarro Renato S, Jiang Longtan, Ouyang Yang, Luo Jiawen, Liu Zhiyong, Yang Ying, Qiu Ping, Kuroda Kenichi, Chen Y Eugene, Ma Peter X, Yang Bo
Macromolecular Science and Engineering Center, The University of Michigan, Ann Arbor, MI, 48109, USA; Department of Biologic and Materials Sciences & Prosthodontics, The University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Cardiac Surgery, The University of Michigan, Ann Arbor, MI, 48109, USA; Department of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People's Republic of China.
Biomaterials. 2021 Jul;274:120874. doi: 10.1016/j.biomaterials.2021.120874. Epub 2021 May 12.
To address the clinical need for readily available small diameter vascular grafts, biomimetic tubular scaffolds were developed for rapid in situ blood vessel regeneration. The tubular scaffolds were designed to have an inner layer that is porous, interconnected, and with a nanofibrous architecture, which provided an excellent microenvironment for host cell invasion and proliferation. Through the synthesis of poly(spirolactic-co-lactic acid) (PSLA), a highly functional polymer with a norbornene substituting a methyl group in poly(l-lactic acid) (PLLA), we were able to covalently attach biomolecules onto the polymer backbone via thiol-ene click chemistry to impart desirable functionalities to the tubular scaffolds. Specifically, heparin was conjugated on the scaffolds in order to prevent thrombosis when implanted in situ. By controlling the amount of covalently attached heparin we were able to modulate the physical properties of the tubular scaffold, resulting in tunable wettability and degradation rate while retaining the porous and nanofibrous morphology. The scaffolds were successfully tested as rat abdominal aortic replacements. Patency and viability were confirmed through dynamic ultrasound and histological analysis of the regenerated tissue. The harvested tissue showed excellent vascular cellular infiltration, proliferation, and migration with laminar cellular arrangement. Furthermore, we achieved both complete reendothelialization of the vessel lumen and native-like media extracellular matrix. No signs of aneurysm or hyperplasia were observed after 3 months of vessel replacement. Taken together, we have developed an effective vascular graft able to generate small diameter blood vessels that can function in a rat model.
为满足临床对易于获得的小直径血管移植物的需求，开发了仿生管状支架用于快速原位血管再生。管状支架设计为具有内层，该内层多孔、相互连通且具有纳米纤维结构，为宿主细胞的侵入和增殖提供了良好的微环境。通过合成聚（螺乳酸 - 共 - 乳酸）（PSLA），一种在聚（L - 乳酸）（PLLA）中用降冰片烯取代甲基的高功能聚合物，我们能够通过硫醇 - 烯点击化学将生物分子共价连接到聚合物主链上，从而赋予管状支架所需的功能。具体而言，将肝素偶联到支架上以防止原位植入时形成血栓。通过控制共价连接的肝素量，我们能够调节管状支架的物理性质，从而在保持多孔和纳米纤维形态的同时实现可调节的润湿性和降解速率。这些支架作为大鼠腹主动脉替代物进行了成功测试。通过动态超声和再生组织的组织学分析证实了通畅性和活力。收获的组织显示出良好的血管细胞浸润、增殖和迁移，细胞呈层状排列。此外，我们实现了血管腔的完全再内皮化和类似天然的中膜细胞外基质。血管置换3个月后未观察到动脉瘤或增生迹象。综上所述，我们开发了一种有效的血管移植物，能够在大鼠模型中生成具有功能的小直径血管。
