Abstract

Applying Analytics to Muscle Tissue Chip Real-Time Biomechanics for In-Space Biomonitoring of Tissue Degradation

Siobhan Malany, Associate Professor, University of Florida, Founder of Micro-gRx

Tissue-on-chip (TOC) platforms are microscale, perusable devices mimicking native human biology that are revolutionizing drug discovery and development. Space-based TOCs offer an approach to advance our understanding of the value microgravity can have in more accurately modeling diseases, particularly those related to aging as the space environment is a novel stressor. Through repeated access to the International Space Station, we have advanced the development of an autonomous human muscle-on-chip drug development platform that incorporates real-time muscle biomechanics monitoring. Our interest lies in using space to monitor the effects of microgravity on the muscle TOC which may mimic the salient features of age-related muscle atrophy in a faster timescale. Advancing this technology from fundamental research to commercial viability requires more robust validation of translational and predictive in vivo-like biology.  The unmet medical need is a standardized platform that can provide a solid reference and evaluate patient-specific tissue pathophysiological responses to potential therapeutics in real-time. In this presentation, we describe the collaborative approach by the University of Florida, Microg-Rx, and G-SPACE to develop computer vision-based analytics to extract microstructural information related to intrinsic tissue properties that will facilitate understanding of tissue degradation over time as a further indication of accelerated aging in space. The application of machine learning will serve to increase the technology maturation of TOC platforms and eventually validate the tech platform as a commercial product. Muscles of aged individuals considered sarcopenic, undergo significant muscle loss and a decrease in strength due to a period of inactivity, injury, or illness, which is associated with increased tissue degradation and metabolic changes. With an increasingly aging population, sarcopenia is an enormous healthcare burden and there are currently no FDA-approved therapeutics to treat this clinical disease progression. We have incorporated human 3D skeletal myobundles derived from biopsies from younger and older adult volunteers into the Space Tango CubeLabTM designed to autonomously control fluid exchange, electrical pulse generation, imaging, and video recording. On SpaceX CRS-25, these muscle TOCs were electrically stimulated with 3V, 2Hz, 2msec pulse every 12hr to demonstrate real-time functional skeletal muscle biomechanics in microgravity. On SpaceX CRS-26, these electrically stimulated muscle TOCs were delivered an atrophy natural product. An important feature of our payload is the real-time monitoring and image collection of the contractile function.  The data downlinked from the ISS was analyzed by digital image correlation to determine the fold-displacement prior to and during electrical stimulation as a measure of contractile function. A preliminary comparative analysis of image series collected on TOC samples in microgravity versus ground controls was performed. The ability to decipher intrinsic muscle properties from muscle contractile function will facilitate validation of the TOC technology real-time analytics platform for decision-making of drug testing.