Abstract
In this paper, we report on a novel biocompatible micromechanical bioreactor (actuator and sensor) designed for the in situ manipulation and characterization of live microtissues. The purpose of this study was to develop and validate an application-targeted sterile bioreactor that is accessible, inexpensive, adjustable, and easily fabricated. Our method relies on a simple polydimethylsiloxane (PDMS) molding technique for fabrication and is compatible with commonly-used laboratory equipment and materials. Our unique design includes a flexible thin membrane that allows for the transfer of an external actuation into the PDMS beam-based actuator and sensor placed inside a conventional 35 mm cell culture Petri dish. Through computational analysis followed by experimental testing, we demonstrated its functionality, accuracy, sensitivity, and tunable operating range. Through time-course testing, the actuator delivered strains of over 20% to biodegradable electrospun poly (D, L-lactide-co-glycolide) (PLGA) 85:15 non-aligned nanofibers (~91 µm thick). At the same time, the sensor was able to characterize time-course changes in Young’s modulus (down to 10–150 kPa), induced by an application of isopropyl alcohol (IPA). Furthermore, the actuator delivered strains of up to 4% to PDMS monolayers (~30 µm thick), simultaneously characterizing their elastic modulus up to ~2.2 MPa. The platform repeatedly applied dynamic (0.23 Hz) tensile stimuli to live Human Dermal Fibroblast (HDF) cells for 12 hours (h) and recorded the cellular reorientation towards two angle regimes, with averages of −58.85° and +56.02°. The device biocompatibility with live cells was demonstrated for one week, with no signs of cytotoxicity. We can conclude that our PDMS bioreactor is advantageous for low-cost tissue/cell culture micromanipulation studies involving mechanical actuation and characterization. Our device eliminates the need for an expensive experimental setup for cell micromanipulation, increasing the ease of live-cell manipulation studies by providing an affordable way of conducting high-throughput experiments without the need to open the Petri dish, reducing manual handling, cross-contamination, supplies, and costs. The device design, material, and methods allow the user to define the operational range based on their targeted samples/application.
Highlights
Micromanipulation is an essential part of the study of cell and microtissue mechanical characteristics [1]
This paper demonstrates the design and validation of a uniaxial tensile actuator/sensor made of polydimethylsiloxane (PDMS) with a predictable and tunable operating range based on the targeted specimens/applications
Examples of cells’ reorientation before and after 12 h are shown in Figure 17, for all groups. These results demonstrate the ability of the PDMS bioreactor to apply micro-cellular manipulations with a predicted performance based on the application or purpose of the test
Summary
Micromanipulation is an essential part of the study of cell and microtissue mechanical characteristics [1]. It is known that the mechanical properties are correlated with healthy or diseased statuses of cells and tissues [2,3,4,5]. The mechanical properties of substrates can influence the growth of cells cultured for regenerative tissue bioengineering applications [6,7,8]. For the study of bioengineered tissue reconstruction, the mimicry of an in vivo environment that provides relevant physiological stimuli to cells is vital [7]. The application of mechanical stimuli to microtissues on a cellular level is one fundamental approach. Cells rearrange their cytoskeleton anchorage to the substrate based on its mechanical cues [12]
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