Tissue Engineering & Additive Manufacturing Lab, Center for Nanotechnology & Advanced Biomaterials, SASTRA Deemed-to-be University, Thanjavur, Tamil Nadu, India.
Cells Tissues Organs. 2022;211(3):335-347. doi: 10.1159/000514986. Epub 2021 May 31.
Modeling of the human vascular microphysiological system (MPS) has gained attention due to precise prediction of drug response and toxicity during drug screening process. Developing a physiologically equivalent vascular MPS still remains complex as it demands the recapitulation of dynamic structural and biological microenvironment similar to native vasculature. Hence, an ideal MPS would involve developing perfusable 3D in vitro models with multilayered human vascular cells encapsulated in a matrix to regulate the vascular tone resembling the native. Several attempts to model such anatomically accurate physiological and pathological blood vessels often fail to harmonize the essential vascular microenvironment. For instance, conventional microfluidic-based approaches employed for vascular MPS, though offering creation of perfusable channel, do not replicate the vascular hierarchical cellular arrangement due to planar geometry and confluent monolayered cell seeding. Also, recent advances with 3D biofabrication strategies are still limited by fabrication of small-diameter constructs and scalability besides post-processing techniques that indirectly distort the structural integrity of the hydrogel tubular constructs. These existing limitations toward fabricating a relevant vascular MPS demand a facile and mechanically stable construct. Hence, the present study is aimed toward developing a stable viable self-standing perfusable hydrogel construct by a rapid and scalable strategy toward vascular MPS application. The fabricated tubular constructs were found to be structurally stable with end-to-end perfusability exhibiting their potential as self-standing perfusable structures. Also, the construct exhibited nonhemolytic behavior with perfusion of red blood cells inside the luminal channel. The present study evidences creation of a dual-crosslinked stable, viable self-standing hydrogel construct with multilayered homogenous distribution of viable smooth muscle cells throughout the construct, thereby demonstrating its applicability as a promising 3D in vitro vascular microphysiological system.
由于在药物筛选过程中能够精确预测药物反应和毒性，因此人类血管微血管生理系统（MPS）的建模受到了关注。开发与生理等效的血管 MPS 仍然很复杂，因为它需要再现类似于天然血管的动态结构和生物微观环境。因此，理想的 MPS 将涉及开发可灌注的 3D 体外模型，其中多层人类血管细胞封装在基质中，以调节类似于天然的血管张力。为了模拟这种解剖学上精确的生理和病理血管，人们进行了多次尝试，但往往无法协调重要的血管微观环境。例如，血管 MPS 中使用的传统基于微流控的方法虽然可以创建可灌注的通道，但由于平面几何形状和融合的单层细胞接种，无法复制血管层次结构的细胞排列。此外，3D 生物制造策略的最新进展仍然受到小直径构建体的制造和可扩展性的限制，以及间接破坏水凝胶管状构建体结构完整性的后处理技术的限制。这些制造相关血管 MPS 的现有局限性需要一种简单且机械稳定的构建体。因此，本研究旨在通过一种快速且可扩展的策略开发一种稳定的、有活力的、独立的可灌注水凝胶构建体，用于血管 MPS 应用。所制造的管状构建体被发现具有结构稳定性，并且具有端到端的可灌注性，表明它们具有作为独立可灌注结构的潜力。此外，该构建体在管腔内部灌注红细胞时表现出非溶血行为。本研究证明了具有双层交联的稳定、有活力的独立水凝胶构建体的创建，其中有活力的平滑肌细胞在整个构建体中均匀分布，从而证明了其作为有前途的 3D 体外血管微血管生理系统的适用性。
