Abstract
Mechanical stimuli play important roles on the growth, development, and behavior of tissue. A simple and novel paper-based in vitro tissue chip was developed that can deliver two types of mechanical stimuli—local compression and shear flow—in a programmed manner. Rat vascular endothelial cells (RVECs) were patterned on collagen-coated nitrocellulose paper to create a tissue chip. Localized compression and shear flow were introduced by simply tapping and bending the paper chip in a programmed manner, utilizing an inexpensive servo motor controlled by an Arduino microcontroller and powered by batteries. All electrical compartments and a paper-based tissue chip were enclosed in a single 3D-printed enclosure, allowing the whole device to be independently placed within an incubator. This simple device effectively simulated in vivo conditions and induced successful RVEC migration in as early as 5 h. The developed device provides an inexpensive and flexible alternative for delivering mechanical stimuli to other in vitro tissue models.Graphical abstract
Highlights
Mechanical stimuli are key parameters for reproducing cellular microenvironment in vitro [1]
We propose a novel, simple, small, and cost-effective device, where both compression and shear flow can be applied to a tissue model in a programmed manner (Fig. 1)
On the other hand, was much more successful in accommodating endothelial cell adhesion, presumably due to its rigorous coating over paper fibers compared to GRGD SPK (Fig. 2c) as well as collagen’s better representation of natural extracellular matrix (ECM) [27]
Summary
Mechanical stimuli are key parameters for reproducing cellular microenvironment in vitro [1]. The most common mechanical stimuli found in the human body are shear flow, compression, and stretch/strain [2]. The most popular and simplest method is external pumping, typically utilizing a syringe pump or a peristaltic pump Such external pumping has frequently been demonstrated in various silicone-based microfluidic tissue models to evaluate the effects of shear flow within the model [4,5,6]. Those pumps are still bulky in size, expensive, and typically require a separate AC power. While passive flow controls are gaining popularity in recent years, the precise control of flow rate can potentially be challenging, and the platform may fail (typically by leaking) in long-term experiments [12]
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