Development and Characterization of a low intensity vibrational system for microgravity studies.

The advent of extended-duration human spaceflight demands a better comprehension of the physiological impacts of microgravity. One primary concern is the adverse impact on the musculoskeletal system, including muscle atrophy and bone density reduction. Ground-based microgravity simulations have provided insights, with vibrational bioreactors emerging as potential mitigators of these negative effects. Despite the potential they have, the adaptation of vibrational bioreactors for space remains unfulfilled, resulting in a significant gap in microgravity research. This paper introduces the first automated low-intensity vibrational (LIV) bioreactor designed specifically for the International Space Station (ISS) environment. Our research covers the bioreactor's design and characterization, the selection of an optimal linear guide for consistent 1-axis acceleration, a thorough analysis of its thermal and diffusion dynamics, and the pioneering use of BioMed Clear resin for enhanced scaffold design. This advancement sets the stage for more authentic space-based biological studies, vital for ensuring the safety of future space explorations.

Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields.

Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using biological or chemical strategies, harnessing cell mechanosensitivity represents a promising - albeit less studied - physical pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive. We tested the hypothesis that mechanical signals, delivered non-invasively using low-intensity vibration (LIV; <1g, 10-500Hz), will enhance cell expansion, and determined that any unique signal configuration was not equally influential across a range of cell types. Varying frequency, intensity, duration, refractory period, and daily doses of LIV increased proliferation in CHO-adherent cells (+79% in 96h) using a particular set of LIV parameters (0.2g, 500Hz, 3x30 min/d, 2h refractory period), yet this same mechanical input suppressed proliferation in CHO-suspension cells (-13%). Exposing these same CHO-suspension cells to distinct LIV parameters (30Hz, 0.7g, 2x60 min/d, 2h refractory period) increased proliferation by 210%. Particle image velocimetry combined with finite element modeling showed high transmissibility of these signals across fluids (>90%), and LIV effectively scaled up to T75 flasks. Ultimately, when LIV is tailored to the target cell population, its highly efficient transmission across media represents a means to non-invasively augment biomanufacturing endpoints for both adherent and suspended cells, and holds immediate applications, ranging from small-scale, patient-specific personalized medicine to large-scale commercial bio-centric production challenges.