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在静电纺聚(乳酸-共-乙醇酸)微管阵列膜上平滑肌细胞与人内皮静脉细胞共培养的组织工程血管移植物

Tissue-Engineered Vascular Graft with Co-Culture of Smooth Muscle Cells and Human Endothelial Vein Cells on an Electrospun Poly(lactic-co-glycolic acid) Microtube Array Membrane.

作者信息

Chew Chee Ho, Sheu Bo-Long, Chen Amanda, Huang Wan-Ting, Cheng Tsai-Mu, Shih Chun-Ming, Chang Austin, Chen Chien-Chung

机构信息

Graduate Institute of Biomedical Materials & Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11052, Taiwan.

Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.

出版信息

Membranes (Basel). 2021 Sep 27;11(10):732. doi: 10.3390/membranes11100732.

Abstract

Coronary artery disease is one of the major diseases that plagues today's modern society. Conventional treatments utilize synthetic vascular grafts such as Dacron and Teflon in bypass graft surgery. Despite the wide adaptation, these synthetic grafts are often plagued with weaknesses such as low hemocompatibility, thrombosis, intimal hyperplasia, and risks of graft infection. More importantly, these synthetic grafts are not available at diameters of less than 6 mm. In view of these challenges, we strived to develop and adapt the electrospun Poly Lactic-co-Glycolic Acid (PLGA) Microtube Array Membrane (MTAM) vascular graft for applications smaller than 6 mm in diameter. Homogenously porous PLGA MTAMs were successfully electrospun at 5.5-8.5 kV under ambient conditions. Mechanically, the PLGA MTAMs registered a maximum tensile strength of 5.57 ± 0.85 MPa and Young's modulus value of 1.134 ± 0.01 MPa; while MTT assay revealed that seven-day Smooth Muscle Cells (SMCs) and Human Umbilical Vein Endothelial Cells (HUVECs) registered a 6 times and 2.4 times higher cell viability when cultured in a co-culture setting in medium containing α-1 haptaglobulin. When rolled into a vascular graft, the PLGA MTAMs registered an overall degradation of 82% after 60 days of cell co-culture. After eight weeks of culturing, immunohistochemistry staining revealed the formation of a monolayer of HUVECs with tight junctions on the surface of the PLGA MTAM, and as for the SMCs housed within the lumens of the PLGA MTAMs, a monolayer with high degree of orientation was observed. The PLGA MTAM registered a burst pressure of 1092.2 ± 175.3 mmHg, which was sufficient for applications such as small diameter blood vessels. Potentially, the PLGA MTAM could be used as a suitable substrate for vascular engineering.

摘要

冠状动脉疾病是困扰当今现代社会的主要疾病之一。传统治疗方法在搭桥手术中使用合成血管移植物,如涤纶和特氟龙。尽管这些合成移植物应用广泛,但它们常常存在一些缺点,如血液相容性低、血栓形成、内膜增生以及移植物感染风险。更重要的是,这些合成移植物的直径小于6毫米时无法使用。鉴于这些挑战,我们努力开发并改造了静电纺聚乳酸-乙醇酸共聚物(PLGA)微管阵列膜(MTAM)血管移植物,用于直径小于6毫米的应用。在环境条件下,于5.5 - 8.5 kV成功静电纺制出均匀多孔的PLGA MTAM。在力学性能方面,PLGA MTAM的最大拉伸强度为5.57±0.85 MPa,杨氏模量值为1.134±0.01 MPa;而MTT分析显示,在含有α-1触珠蛋白的培养基中进行共培养时,七天的平滑肌细胞(SMC)和人脐静脉内皮细胞(HUVEC)的细胞活力分别提高了6倍和2.4倍。当卷成血管移植物时,在细胞共培养60天后,PLGA MTAM的总体降解率为82%。培养八周后,免疫组织化学染色显示在PLGA MTAM表面形成了具有紧密连接的单层HUVEC,至于PLGA MTAM管腔内的SMC,则观察到高度取向的单层。PLGA MTAM的爆破压力为1092.2±175.3 mmHg,足以用于小直径血管等应用。PLGA MTAM有可能用作血管工程的合适基质。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4df0/8539722/20e649e02283/membranes-11-00732-g001.jpg

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