1 Department of Biomedical Engineering, Eindhoven University of Technology , Eindhoven, The Netherlands .
2 Institute for Complex Molecular Systems, Eindhoven University of Technology , Eindhoven, The Netherlands .
Tissue Eng Part C Methods. 2017 Jun;23(6):377-387. doi: 10.1089/ten.TEC.2017.0141. Epub 2017 May 29.
Tissue growth and remodeling are essential processes that should ensure long-term functionality of tissue-engineered (TE) constructs. Even though it is widely recognized that these processes strongly depend on mechanical stimuli, the underlying mechanisms of mechanically induced growth and remodeling are only partially understood. It is generally accepted that cells sense mechanical changes and respond by altering their surroundings, by means of extracellular matrix growth and remodeling, in an attempt to return to a certain preferred mechanical homeostatic state. However, the exact mechanical cues that trigger cells to synthesize and remodel their environment remain unclear. To identify the driving mechanical stimuli of these processes, it is critical to be able to temporarily follow the mechanical state of developing tissues under physiological loading conditions. Therefore, a novel "versatile tissue growth and remodeling" (Vertigro) bioreactor was developed that is capable of tissue culture and mechanical stimulation for a prolonged time period, while simultaneously performing mechanical testing. The Vertigro's unique two-chamber design allows easy, sterile handling of circular 3D TE constructs in a dedicated culture chamber, while a separate pressure chamber facilitates a pressure-driven dynamic loading regime during culture. As a proof-of-concept, temporal changes in the mechanical state of cultured tissues were quantified using nondestructive mechanical testing by means of a classical bulge test, in which the tissue displacement was tracked using ultrasound imaging. To demonstrate the successful development of the bioreactor system, compositional, structural, and geometrical changes were qualitatively and quantitatively assessed using a series of standard analysis techniques. With this bioreactor and associated mechanical analysis technique, a powerful toolbox has been developed to quantitatively study and identify the driving mechanical stimuli of engineered tissue growth and remodeling.
组织生长和重塑是确保组织工程（TE）构建体长期功能的必要过程。尽管广泛认为这些过程强烈依赖于机械刺激，但机械诱导生长和重塑的潜在机制仅部分理解。人们普遍认为，细胞感知机械变化，并通过细胞外基质的生长和重塑来改变其周围环境，试图恢复到某种特定的机械平衡状态。然而，确切的机械线索，触发细胞合成和重塑其环境仍然不清楚。为了确定这些过程的驱动机械刺激，能够暂时跟踪生理负荷条件下发育组织的机械状态是至关重要的。因此，开发了一种新型的“通用组织生长和重塑”（Vertigro）生物反应器，该生物反应器能够在延长的时间内进行组织培养和机械刺激，同时进行机械测试。Vertigro 的独特的双室设计允许在专用培养室中轻松、无菌地处理圆形 3D TE 构建体，而单独的压力室则在培养过程中方便压力驱动的动态加载模式。作为概念验证，通过经典的凸起测试，使用无损机械测试来量化培养组织的机械状态的时间变化，其中使用超声成像跟踪组织位移。为了证明生物反应器系统的成功开发，使用一系列标准分析技术定性和定量评估了组成、结构和几何形状的变化。通过该生物反应器和相关的机械分析技术，已经开发出了一个强大的工具包，用于定量研究和确定工程组织生长和重塑的驱动机械刺激。
