Sphingosine-1-Phosphate (S1P) in Whole Liver Recellularization Improves Endothelization of Acellular Liver Scaffold.

IF 5.4 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS
Usha Yadav, Chandra J Yadav, Sadia Afrin, Jun-Yeong Lee, Jihad Kamel, Kyung-Mee Park
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引用次数: 0

Abstract

Endothelialization is crucial for tissue bioengineering, particularly in developing functional blood vessel linings to ensure proper vascularization. Effective re-endothelialization of the vasculature in bioengineered organs is challenging, often leading to blood coagulation and hindering successful engraftment. Endothelial cell proliferation, migration, and angiogenesis are essential processes for constructing functional and vascularized bioengineered organs. Sphingosine-1-phosphate (S1P), a low-molecular-weight phospholipid mediator, regulates various biological activities in endothelial cells including survival, proliferation, and cell barrier integrity. In this study, we present a novel approach to enhance the re-endothelialization of decellularized rat liver scaffolds by seeding human umbilical vein endothelial cells (HUVECs) in the presence of S1P, aiming to bioengineer a fully endothelialized liver. Initially, we validated the effects of S1P on HUVECs in a 2D cell culture system, confirming that S1P significantly promotes endothelial functions. Following this validation, we seeded HUVECs in the presence of S1P into decellularized rat liver scaffolds via the portal vein. The seeded liver was maintained in the bioreactor and perfused with medium supplemented with S1P for 7 days. The efficacy of S1P on liver scaffolds was evaluated through the longitudinal monitoring of cell proliferation using the resazurin reduction assay, indicating higher cell proliferation in the constructs. Further characterization through histological and molecular analyses demonstrated efficient coverage of vessels of re-endothelialized scaffolds maintaining their function. The antithrombotic effect of the fully endothelialized scaffold was assessed via ex vivo whole-blood perfusion. Our results indicate that S1P is a key regulator of endothelialization processes, promoting HUVECs proliferation and survival and facilitating the formation of a functional endothelial layer on the vascular structure of re-endothelialized liver scaffold.

鞘氨醇-1-磷酸(S1P)在全肝细胞再化中促进脱细胞肝支架内皮化。
内皮化对于组织生物工程至关重要,特别是在开发功能性血管内膜以确保适当的血管化方面。在生物工程器官中有效的血管再内皮化是具有挑战性的,经常导致血液凝固并阻碍成功的植入。内皮细胞的增殖、迁移和血管生成是构建功能性和血管化生物工程器官的基本过程。鞘氨醇-1-磷酸(S1P)是一种低分子量磷脂介质,调节内皮细胞的多种生物活性,包括存活、增殖和细胞屏障完整性。在这项研究中,我们提出了一种新的方法,通过在S1P存在下播种人脐静脉内皮细胞(HUVECs)来增强脱细胞大鼠肝脏支架的再内皮化,旨在生物工程构建完全内皮化的肝脏。首先,我们在2D细胞培养系统中验证了S1P对HUVECs的作用,证实了S1P显著促进内皮功能。在此验证之后,我们在S1P存在的情况下,通过门静脉将HUVECs植入去细胞化的大鼠肝脏支架。将种子肝置于生物反应器中,用添加S1P的培养基灌注7天。通过瑞祖脲还原法对细胞增殖的纵向监测来评估S1P对肝支架的作用,表明构建物中细胞增殖更高。通过组织学和分子分析进一步表征表明,再内皮支架有效覆盖血管,维持其功能。通过体外全血灌注评估完全内皮支架的抗血栓作用。我们的研究结果表明,S1P是内皮化过程的关键调节因子,促进HUVECs增殖和存活,并促进再内皮化肝支架血管结构上功能内皮层的形成。
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来源期刊
ACS Biomaterials Science & Engineering
ACS Biomaterials Science & Engineering Materials Science-Biomaterials
CiteScore
10.30
自引率
3.40%
发文量
413
期刊介绍: ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics: Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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