Biofabrication of Small Vascular Graft with Acellular Human Amniotic Membrane: A Proof-of-Concept Study in Pig

O Aung, Peter Rossi, Mitchell Dyer, Austin Stellpflug, Yingnan Zhai, Allen Kenneth, Xiaolong Wang, Jackie Chang, Yiliang Chen, Brandon James Tefft, Rongxue Wu, Lingxia Gu, Bo Wang
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Abstract

Synthetic vascular grafts, such as expanded polytetrafluoroethylene (ePTFE), are commonly used for large vessel surgeries [internal diameter (ID) ≥ 10 mm] but present significant challenges in medium to small vessels (ID < 10 mm) due to increased risks of thrombosis, stenosis, and infection. In this study, we developed a small-diameter vascular graft using decellularized human amniotic membrane (DAM graft) (ID = 6 mm) and transplanted it into porcine carotid arteries, comparing it with ePTFE grafts to assess inflammation, biocompatibility, patency, and overall function. One-week post-implantation, ultrasound imaging confirmed blood patency in both graft types. However, after one-month, gross examination revealed pronounced neointimal hyperplasia in ePTFE grafts, while DAM grafts maintained open lumens without signs of stenosis or thrombosis. Histological analysis showed extensive fibrous tissue formation in ePTFE grafts, resulting in luminal narrowing, whereas DAM grafts displayed sustained lumen patency and vascular integration. Immunofluorescence confirmed reduced inflammation and improved tissue organization in DAM grafts, characterized by lower macrophage infiltration and better cellular architecture. These findings suggest that DAM grafts offer superior biocompatibility and significantly lower risks of neointimal hyperplasia, making them a promising alternative for small-diameter vascular surgeries compared to ePTFE grafts.
用细胞人羊膜生物制造小血管移植:猪的概念验证研究
合成血管移植物,如膨体聚四氟乙烯(ePTFE),常用于大血管手术[内径(ID)≥ 10 mm],但由于血栓形成、狭窄和感染的风险增加,在中小口径血管(ID < 10 mm)中面临巨大挑战。在这项研究中,我们利用脱细胞人羊膜开发了一种小直径血管移植物(DAM 移植物)(内径 = 6 毫米),并将其移植到猪颈动脉中,将其与 ePTFE 移植物进行比较,以评估炎症、生物相容性、通畅性和整体功能。移植一周后,超声波成像证实两种移植物都具有血液通畅性。然而,一个月后,大体检查发现 ePTFE 移植物有明显的新血管增生,而 DAM 移植物则保持着开放的管腔,没有狭窄或血栓形成的迹象。组织学分析表明,ePTFE移植物中有大量纤维组织形成,导致管腔狭窄,而DAM移植物则显示出持续的管腔通畅和血管整合。免疫荧光证实,DAM 移植物的炎症减少,组织结构改善,巨噬细胞浸润减少,细胞结构改善。这些研究结果表明,DAM移植物具有良好的生物相容性,新内膜增生的风险明显降低,因此与ePTFE移植物相比,DAM移植物有望成为小直径血管手术的替代品。
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