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UBC Theses and Dissertations

Mechanical strain bioreactor design and assessment for culture of human airway smooth muscle Cavers, Andrew


Bioreactors capable of subjecting cells and tissues to time-varying mechanical strain are one aspect of simulating in vivo conditions. A bioreactor to impart arbitrary strain waveforms on cells or tissue scaffolds for loading conditions found in the airway was designed and developed and, in the process, it was determined that there are sources of experimental error which could invalidate bioreactor experiments if not properly mitigated. Without effective design and validation, bioreactors can impart significantly different stimuli than the assumed experimental conditions. Cyclic strain is thought to play a role in airway remodeling by mediating cytoskeletal contraction of the airway smooth muscle. In vitro experiments have demonstrated varying changes to the cytoskeleton depending on experimental conditions. Based on literature review, the strain waveform, magnitude, mechanical properties of the substrate, and anisotropy of the strain stimulus may all affect airway smooth muscle (ASM) differentiation. A bioreactor capable of imparting a broad range of strain stimulus was developed using stepper motors as actuators to allow open-loop control. Any changes in the cells subjected to cyclic strain in these bioreactors would be assumed to correlate with cyclic strain, but a poorly designed bioreactor could introduce confounding experimental stimuli which could easily invalidate the experiment. Heat generated by the actuators can overheat the cell cultures. Vibration might alter the cytoskeletal response. Strain response across the substrate can drastically vary from modeling predictions depending on the loading conditions and how the substrate has been constrained. Methods of mitigating heat generation and transfer were developed. The vibrations emitted by the two stepper motor options were evaluated. A method of mapping the substrate was developed such that nonplanar strains across the substrate surface could be characterized to validate the experimental conditions prior to testing. Finally, ASM cells were subjected to cyclic and static strain on PDMS substrates and cell realignment evaluated. Cells were noted to realign in the cyclic strain tests, as has been reported in several earlier publications, but also realigned under static strain conditions. The bioreactor design objectives were met.

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