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从体外到围手术期血管组织工程:通过可追溯的纺织增强缩短生产时间。

From In Vitro to Perioperative Vascular Tissue Engineering: Shortening Production Time by Traceable Textile-Reinforcement.

机构信息

Department of Biohybrid and Medical Textiles (BioTex), Center for Biohybrid Medical Systems (CBMS), Institute for Applied Medical Engineering, RWTH Aachen University, Forckenbeckstr. 55, 52074, Aachen, Germany.

Institute for Experimental Molecular Imaging, RWTH Aachen University, Forckenbeckstr. 55, 52074, Aachen, Germany.

出版信息

Tissue Eng Regen Med. 2022 Dec;19(6):1169-1184. doi: 10.1007/s13770-022-00482-0. Epub 2022 Oct 6.

Abstract

BACKGROUND

The production of tissue-engineered vascular graft (TEVG) usually involves a prolonged bioreactor cultivation period of up to several weeks to achieve maturation of extracellular matrix and sufficient mechanical strength. Therefore, we aimed to substantially shorten this conditioning time by combining a TEVG textile scaffold with a recently developed copolymer reinforced fibrin gel as a cell carrier. We further implemented our grafts with magnetic resonance imaging (MRI) contrast agents to allow the in-vitro monitoring of the TEVG's remodeling process.

METHODS

Biodegradable polylactic-co-glycolic acid (PLGA) was electrospun onto a non-degradable polyvinylidene fluoride scaffold and molded along with copolymer-reinforced fibrin hydrogel and human arterial cells. Mechanical tests on the TEVGs were performed both instantly after molding and 4 days of bioreactor conditioning. The non-invasive in vitro monitoring of the PLGA degradation and the novel imaging of fluorinated thermoplastic polyurethane (F-TPU) were performed using 7T MRI.

RESULTS

After 4 days of close loop bioreactor conditioning, 617 ± 85 mmHg of burst pressure was achieved, and advanced maturation of extracellular matrix (ECM) was observed by immunohistology, especially in regards to collagen and smooth muscle actin. The suture retention strength (2.24 ± 0.3 N) and axial tensile strength (2.45 ± 0.58 MPa) of the TEVGs achieved higher values than the native arteries used as control. The contrast agents labeling of the TEVGs allowed the monitorability of the PLGA degradation and enabled the visibility of the non-degradable textile component.

CONCLUSION

Here, we present a concept for a novel textile-reinforced TEVG, which is successfully produced in 4 days of bioreactor conditioning, characterized by increased ECM maturation and sufficient mechanical strength. Additionally, the combination of our approach with non-invasive imaging provides further insights into TEVG's clinical application.

摘要

背景

组织工程血管移植物(TEVG)的生产通常需要长达数周的延长生物反应器培养期,以实现细胞外基质的成熟和足够的机械强度。因此,我们旨在通过将 TEVG 纺织支架与最近开发的共聚物增强纤维蛋白凝胶作为细胞载体相结合,大幅缩短这种调理时间。我们进一步将我们的移植物与磁共振成像(MRI)造影剂结合,以允许体外监测 TEVG 的重塑过程。

方法

将可生物降解的聚丙交酯-乙交酯(PLGA)电纺到不可降解的聚偏二氟乙烯支架上,并与共聚物增强纤维蛋白水凝胶和人动脉细胞一起成型。在成型后即刻和生物反应器调理 4 天后对 TEVGs 进行机械测试。使用 7T MRI 对 PLGA 降解的非侵入性体外监测和新型氟化热塑性聚氨酯(F-TPU)成像进行了研究。

结果

经过 4 天的闭环生物反应器调理,TEVG 的爆破压力达到了 617±85mmHg,通过免疫组织化学观察到细胞外基质(ECM)的成熟度得到了显著提高,尤其是在胶原和平滑肌肌动蛋白方面。TEVGs 的缝线保持力(2.24±0.3N)和轴向拉伸强度(2.45±0.58MPa)值高于用作对照的天然动脉。TEVGs 的造影剂标记允许监测 PLGA 降解,并使不可降解的纺织组件具有可见性。

结论

在这里,我们提出了一种新型纺织增强 TEVG 的概念,该概念在 4 天的生物反应器调理中成功生产,其特点是 ECM 成熟度增加和足够的机械强度。此外,我们的方法与非侵入性成像相结合,为 TEVG 的临床应用提供了进一步的见解。

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