Journal
BIOMATERIALS
Volume 172, Issue -, Pages 30-40Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.04.041
Keywords
Microdevice; Mechanical stimulation; On-chip strain sensing; Tissue stiffness monitoring; Hydrogel; Mesenchymal stromal cell
Funding
- Canadian Institute of Health Research (CIHR) [MOP-130481]
- Canada Research Chair in Mechanobiology
- Canada Research Chair in Micro and Nanoengineering Systems
- NSERC CREATE Program in Microfluidic Applications and Training in Cardiovascular Health (MATCH) scholarship
- Heart and Stroke Richard Lewar Centre of Excellence (HSRLCE) studentship
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Native and engineered tissue development are regulated by the integrative effects of multiple micro environmental stimuli. Microfabricated bioreactor array platforms can efficiently dissect cue-response networks, and have recently integrated critical 2D and 3D mechanical stimulation for greater physiological relevance. However, a limitation of these approaches is that assessment of tissue functional properties is typically limited to end-point analyses. Here we report a new deformable membrane platform with integrated strain sensors that enables mechanical stretching or compression of 3D cell-hydrogel arrays and simultaneous measurement of hydrogel construct stiffness in situ. We tested the ability of the integrated strain sensors to measure the evolution of the stiffness of cell-hydrogel constructs for two cases. First, we demonstrated in situ stiffness monitoring of degradable poly (ethylene glycol)-norbornene (PEG-NB) hydrogels embedded with mesenchymal stromal cells (MSCs) and cultured with or without cyclic tensile stimulation for up to 15 days. Whereas statically-cultured hydrogels degraded and softened throughout the culture period, mechanically-stimulated gels initially softened and then recovered their stiffness corresponding to extensive cell network and collagen production. Second, we demonstrated in situ measurement of compressive stiffening of MSC-seeded PEG-NB gels cultured statically under osteogenic conditions, corresponding to increased mineralization and cellularization. This measurement technique can be generalized to other relevant bioreactor and organ-on-a-chip platforms to facilitate online, non-invasive, and high-throughput functional analysis, and to provide insights into the dynamics of engineered tissue development that are otherwise not available. (C) 2018 Elsevier Ltd. All rights reserved.
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