Electrospun vascular scaffold for cellularized small diameter blood vessels: A preclinical large animal study
Electrospun vascular scaffold for cellularized small diameter blood vessels: A preclinical large animal study
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DOI：
10.1016/j.actbio.2017.06.027
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发表时间：
2017-09-01
影响因子：
9.7
通讯作者：
Lee, Sang Jin
中科院分区：
文献类型：
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作者：
Ju, Young Min;Ahn, Hyunhee;Lee, Sang Jin
血管组织工程的策略是通过将自体血管细胞与管状可生物降解支架相结合来创建血管替代品。我们之前已经开发了一种新型的电纺双层血管支架，它具有合适的生物和生物力学性能以及结构配置。在这项研究中，我们在一个临床前的大动物模型中研究了细胞化血管支架的临床可行性。我们利用自体内皮祖细胞(EPC)来源的内皮细胞(ECs)和平滑肌细胞(SMC)构建了细胞化的血管结构，随后进行了脉动生物反应器的预适应。这种完全细胞化的血管结构在绵羊颈动脉间置模型中进行了测试。经预处理后，支架内的EC层和SMC层融合成熟。在绵羊的6个月期间，细胞化的结构保持了结构的完整性，移植物高度通畅，没有引起炎症反应。移植后6个月，管腔内已形成成熟的EC覆盖层，并形成较厚的平滑肌层。我们证明了电纺双层血管支架结合自体血管细胞可能是一种临床适用的替代传统人工血管移植的替代品。意义陈述本研究证明了组织工程学的实用性，为严重、破坏性心血管疾病的康复患者提供了平台技术。长期目标是提供血管移植的替代方案，使用来自自体细胞来源的生物工程血管和功能化的血管支架。这种用于工程血管的新型双层血管结构旨在为临床翻译提供“现成”的可用性。(C)2017 Acta Materialia Inc.由Elsevier Ltd.出版。保留所有权利。
The strategy of vascular tissue engineering is to create a vascular substitute by combining autologous vascular cells with a tubular-shaped biodegradable scaffold. We have previously developed a novel electrospun bilayered vascular scaffold that provides proper biological and biomechanical properties as well as structural configuration. In this study, we investigated the clinical feasibility of a cellularized vascular scaffold in a preclinical large animal model. We fabricated the cellularized vascular construct with autologous endothelial progenitor cell (EPC)-derived endothelial cells (ECs) and smooth muscle cells (SMCs) followed by a pulsatile bioreactor preconditioning. This fully cellularized vascular construct was tested in a sheep carotid arterial interposition model. After preconditioning, confluent and mature EC and SMC layers in the scaffold were achieved. The cellularized constructs sustained the structural integrity with a high degree of graft patency without eliciting an inflammatory response over the course of the 6-month period in sheep. Moreover, the matured EC coverage on the lumen and a thick smooth muscle layer were formed at 6 months after transplantation. We demonstrated that electrospun bilayered vascular scaffolds in conjunction with autologous vascular cells may be a clinically applicable alternative to traditional prosthetic vascular graft substitutes.Statement of SignificanceThis study demonstrates the utility of tissue engineering to provide platform technologies for rehabilitation of patients recovering from severe, devastating cardiovascular diseases. The long-term goal is to provide alternatives to vascular grafting using bioengineered blood vessels derived from an autologous cell source with a functionalized vascular scaffold. This novel bilayered vascular construct for engineering blood vessels is designed to offer "off-the-shelf" availability for clinical translation. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.