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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; 90%), and LIV effectively scaled up to T75 flasks. Ultimately, when LIV is tailored to the target cell population, it's 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.

Aged individuals and astronauts experience bone loss despite rigorous physical activity. Bone mechanoresponse is in-part regulated by mesenchymal stem cells (MSCs) that respond to mechanical stimuli. Direct delivery of low intensity vibration (LIV) recovers MSC proliferation in senescence and simulated microgravity models, indicating that age-related reductions in mechanical signal delivery within bone marrow may contribute to declining bone mechanoresponse. To answer this question, we developed a 3D bone marrow analog that controls trabecular geometry, marrow mechanics and external stimuli. Validated finite element (FE) models were developed to quantify strain environment within hydrogels during LIV. Bone marrow analogs with gyroid-based trabeculae of scaffold volume fractions (SV/TV) corresponding to adult (25 ​%) and aged (13 ​%) mice were printed using polylactic acid (PLA). MSCs encapsulated in migration-permissive hydrogels within printed trabeculae showed robust cell populations on both PLA surface and hydrogel within a week. Following 14 days of LIV treatment (1 ​g, 100 ​Hz, 1 ​h/day), cell proliferation, type-I collagen (Collagen-I) and filamentous actin (F-actin) were quantified for the cells in the hydrogel fraction. While LIV increased all measured outcomes, FE models predicted higher von Mises strains for the 13 ​% SV/TV groups (0.2 ​%) when compared to the 25 ​% SV/TV group (0.1 ​%). While LIV increased collagen-I volume 34 ​% more in 13 ​% SV/TV groups when compared to 25 ​% SV/TV groups, collagen-I and F-actin measures remained lower in the 13 ​% SV/TV groups when compared to 25 ​% SV/TV counterparts, indicating that both LIV-induced strains and scaffold volume fraction (i.e. available scaffold surface) affect cell behavior in the hydrogel phase. Overall, bone marrow analogs offer a robust and repeatable platform to study bone mechanobiology.

To clarify the place of time direction of change in nature (time arrow), the present article shows why Evolution and Irreversibility are two distinct phenomena. Their distinct laws of nature are the Constructal Law and the Second Law, respectively. The demonstration is based on the simplest setting imaginable: a solid body moving in a pool of water. The view is holistic: the system selected for analysis is the body and the pool, not the body alone, and the phenomenon is the evolution of the image (configuration) of the whole. New is also the answer to the question of what flows in this evolving flow configuration. Along the way, important terms are defined: phenomenon, law, irreversibility, nature, design, freedom, theory versus empiricism, information, knowledge, selection, purpose, engine, refrigeration, and wheel. More complex natural settings for the demonstration are in the second part of the article: engines, refrigeration, heating and cooling, the wheel, and a pushed boat sliding on water., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Adrian Bejan reports financial support was provided by Captive Aire Systems. Adrian Bejan reports financial support was provided by U.S.Air Force Office of Scientific Research. Pezhman Mardanpour reports financial support was provided by U.S. Air Force Office of Scientific Research. Adrian Bejan reports a relationship with U.S. Air Force Office of Scientific Research that includes: funding grants. Adrian Bejan reports a relationship with Captive Aire Systems that includes: funding grants. Pezhman Mardanpour reports a relationship with U.S. Air Force Office of Scientific Research that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)