MicroAge Mission: Experimental Design, Hardware Development and Operational Considerations for a Bespoke Culture System to Support Tissue-Engineered Skeletal Muscle Constructs.

Abstract

Microgravity provides a unique model for understanding accelerated skeletal muscle loss, and potentially a model of muscle ageing, offering insights into the molecular mechanisms underlying reductions in muscle mass and function. During spaceflight, astronauts experience pronounced skeletal muscle atrophy. These effects appear similar to age-related muscle decline on Earth but on a significantly shorter timescale. Despite the incorporation of daily aerobic and resistance exercise on the International Space Station (ISS), countermeasures remain suboptimal, reflecting analogous challenges in exercise efficacy observed in ageing populations. The MicroAge Mission aimed to exploit microgravity conditions aboard the ISS to determine whether the molecular mechanisms underpinning reduced adaptive responses to contractile activity during ageing are analogous to those induced by spaceflight. The mission also explored proof-of-concept genetic interventions, including overexpression of Heat Shock Protein 10 (HSP10), a mitochondrial chaperone, to mitigate muscle atrophy and functional loss. To conduct these investigations, a tissue-engineering approach was employed to fabricate human skeletal muscle constructs, which were secured to custom-designed, 3D-printed scaffolds. The scaffolds featured integrated microfluidic channels designed to interface with the fluid handling system within the flight hardware. The hardware, developed by Kayser Space Ltd, was specifically designed to interface with the European Space Agency (ESA) Kubik incubator located within the Columbus module of the ISS. This research addresses critical methodological constraints in low Earth orbit (LEO) experimentation, providing a detailed account of pre-flight protocol development, muscle construct biofabrication techniques, and operational considerations. The findings establish a translational framework for future investigations into musculoskeletal degeneration, with implications for therapeutic strategies targeting both terrestrial ageing and astronaut musculoskeletal health.