Di Gravina Giulia M, Loi Giada, Auricchio Ferdinando, Conti Michele
Department of Civil Engineering and Architecture, University of Pavia, Via Ferrata 3, 27100 Pavia, Italy.
Biophys Rev (Melville). 2023 Aug 21;4(3):031303. doi: 10.1063/5.0156704. eCollection 2023 Sep.
Two main challenges are currently present in the healthcare world, i.e., the limitations given by transplantation and the need to have available 3D models. In this context, bioreactors are devices that have been introduced in tissue engineering as a support for facing the mentioned challenges by mimicking the cellular native microenvironment through the application of physical stimuli. Bioreactors can be divided into two groups based on their final application: macro- and micro-bioreactors, which address the first and second challenge, respectively. The bioreactor design is a crucial step as it determines the way in which physical stimuli are provided to cells. It strongly depends on the manufacturing techniques chosen for the realization. In particular, in bioreactor prototyping, additive manufacturing techniques are widely used nowadays as they allow the fabrication of customized shapes, guaranteeing more degrees of freedom. To support the bioreactor design, a powerful tool is represented by computational simulations that allow to avoid useless approaches of trial-and-error. In the present review, we aim to discuss the general workflow that must be carried out to develop an optimal macro- and micro-bioreactor. Accordingly, we organize the discussion by addressing the following topics: general and stimulus-specific (i.e., perfusion, mechanical, and electrical) requirements that must be considered during the design phase based on the tissue target; computational models as support in designing bioreactors based on the provided stimulus; manufacturing techniques, with a special focus on additive manufacturing techniques; and finally, current applications and new trends in which bioreactors are involved.
当前，医疗保健领域存在两个主要挑战，即移植带来的限制以及对可用3D模型的需求。在这种背景下，生物反应器作为一种设备已被引入组织工程领域，通过施加物理刺激来模拟细胞天然微环境，以应对上述挑战。根据其最终应用，生物反应器可分为两类：宏观生物反应器和微观生物反应器，它们分别应对第一个和第二个挑战。生物反应器的设计是关键步骤，因为它决定了向细胞提供物理刺激的方式。这在很大程度上取决于为实现该设计所选择的制造技术。特别是在生物反应器原型制作中，增材制造技术如今被广泛使用，因为它们能够制造定制形状，从而保证更多的自由度。为了辅助生物反应器设计，计算模拟是一种强大的工具，它可以避免无用的试错方法。在本综述中，我们旨在讨论开发最佳宏观和微观生物反应器必须执行的一般工作流程。因此，我们通过讨论以下主题来组织论述：基于组织目标，在设计阶段必须考虑的一般要求和特定刺激要求（即灌注、机械和电刺激）；基于所提供刺激设计生物反应器时作为支持的计算模型；制造技术，特别关注增材制造技术；最后是生物反应器所涉及的当前应用和新趋势。
