Novel Bioreactor Design for Non-invasive Longitudinal Monitoring of Tissue-Engineered Heart Valves in 7T MRI and Ultrasound.

IF 3 2区 医学 Q3 ENGINEERING, BIOMEDICAL Annals of Biomedical Engineering Pub Date : 2024-10-22 DOI:10.1007/s10439-024-03632-8
Saurav Ranjan Mohapatra, Elena Rama, Maximillian P Werner, Tobias Call, Tanja Loewenberg, Alexander Loewen, Christian Apel, Fabian Kiessling, Stefan Jockenhoevel
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Abstract

The development of cardiovascular implants is abundant, yet their clinical adoption remains a significant challenge in the treatment of valvular diseases. Tissue-engineered heart valves (TEHV) have emerged as a promising solution due to their remodeling capabilities, which have been extensively studied in recent years. However, ensuring reproducible production and clinical translation of TEHV requires robust longitudinal monitoring methods.Cardiovascular magnetic resonance imaging (MRI) is a non-invasive, radiation-free technique providing detailed valvular imaging and functional assessment. To facilitate this, we designed a state-of-the-art metal-free bioreactor enabling dynamic MRI and ultrasound imaging. Our compact bioreactor, tailored to fit a 72 mm bore 7 T MRI coil, features an integrated backflow design ensuring MRI compatibility. A pneumatic drive system operates the bioreactor, minimizing potential MRI interference. The bioreactor was digitally designed and constructed using polymethyl methacrylate, utilizing only polyether ether ketone screws for secure fastening. Our biohybrid TEHV incorporates a non-degradable polyethylene terephthalate textile scaffold with fibrin matrix hydrogel and human arterial smooth muscle cells.As a result, the bioreactor was successfully proven to be MRI compatible, with no blooming artifacts detected. The dynamic movement of the TEHVs was observed using gated MRI motion artifact compensation and ultrasound imaging techniques. In addition, the conditioning of TEHVs in the bioreactor enhanced ECM production. Immunohistology demonstrated abundant collagen, α-smooth muscle actin, and a monolayer of endothelial cells throughout the valve cusp. Our innovative methodology provides a physiologically relevant environment for TEHV conditioning and development, enabling accurate monitoring and assessment of functionality, thus accelerating clinical acceptance.

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用于 7T 磁共振成像和超声波无创纵向监测组织工程心脏瓣膜的新型生物反应器设计
心血管植入物的发展十分迅速,但在临床应用中,瓣膜疾病的治疗仍面临巨大挑战。组织工程心脏瓣膜(TEHV)因其重塑能力而成为一种前景广阔的解决方案,近年来已被广泛研究。心血管磁共振成像(MRI)是一种无创、无辐射的技术,可提供详细的瓣膜成像和功能评估。为此,我们设计了一种最先进的无金属生物反应器,可进行动态核磁共振成像和超声成像。我们的生物反应器结构紧凑,适合 72 毫米孔径的 7 T 磁共振线圈,采用集成回流设计,确保与磁共振成像兼容。生物反应器由气动驱动系统控制,最大程度地减少了核磁共振成像的潜在干扰。生物反应器采用聚甲基丙烯酸甲酯进行数字化设计和制造,仅使用聚醚醚酮螺钉进行安全紧固。我们的生物混合 TEHV 将不可降解的聚对苯二甲酸乙二醇酯织物支架与纤维蛋白基质水凝胶和人类动脉平滑肌细胞结合在一起。利用选通磁共振成像运动伪影补偿和超声成像技术,观察了 TEHV 的动态运动。此外,在生物反应器中对 TEHV 进行调理可增强 ECM 的生成。免疫组织学显示,整个瓣膜尖部有大量胶原蛋白、α-平滑肌肌动蛋白和单层内皮细胞。我们的创新方法为 TEHV 的调理和开发提供了一个生理相关的环境,能够对功能进行准确的监测和评估,从而加快临床应用。
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来源期刊
Annals of Biomedical Engineering
Annals of Biomedical Engineering 工程技术-工程:生物医学
CiteScore
7.50
自引率
15.80%
发文量
212
审稿时长
3 months
期刊介绍: Annals of Biomedical Engineering is an official journal of the Biomedical Engineering Society, publishing original articles in the major fields of bioengineering and biomedical engineering. The Annals is an interdisciplinary and international journal with the aim to highlight integrated approaches to the solutions of biological and biomedical problems.
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