Characterization and Mechanism Study of an Articular Cartilage Repair Material for Space Medicine: Influence by Microgravity and Cosmic Radiation

Description

Advances in human spaceflight leads to an increasing demand for repairing articular cartilage in space as microgravity and cosmic radiation during long-duration space missions pose threat to joint health of space travellers. This project aims to investigate the impact of microgravity and cosmic radiation on the repair efficiency of a tissueengineered cartilaginous graft (dLhCG) in traumatic and articular cartilage defects (ACDs) for space medicine. Preliminary data has indicated that dLhCG engraftment facilitated successful traumatic ACD regeneration in ongoing clinical trials and excellent osteoarthritic ACD regeneration in rat knees. dLhCG was found to promote rejuvenation of hyaline cartilaginous phenotype through inhibition of Wnt/β-catenin signaling pathway via dLhCG-integrin α5 ligation. These superior outcomes endow dLhCG with promising prospects for space medicine in ACD regeneration. Motivated by this, dLhCG scaffolds were delivered to the China Tiangong Space Station for an over 6-month exposure test inside (In-dLhCG) and outside (Out-dLhCG) the spacecraft in May 2023, with corresponding dLhCG scaffolds remained on the ground (G-dLhCG) as a control. The ACD regeneration potential of returned dLhCGs will be subsequently assessed on Earth. Accordingly, the Specific Objectives are listed as follows. The Objective 1 is to investigate whether exposure to microgravity and cosmic radiation in space alters the physical, chemical, and biological characteristics of dLhCG. For this sake, mechanical properties, structural properties, chemical composition, quantitative proteomics, and in vitro cytotoxicity will be evaluated for three groups of dLhCG. Alterations in these properties of dLhCGs are expected to influence their regeneration capacity. The Objective 2 is to investigate the repair efficiency among G-dLhCG, In-dLhCG, and OutdLhCG for traumatic and osteoarthritic ACDs in vivo. The three groups of dLhCG will be implanted into traumatic and osteoarthritis critical-sized ACDs followed by the examination of histological structure, subchondral bone morphology, biochemical composition, and biomechanical properties of regenerated and surrounding native tissue. The Objective 3 is to explore mechanisms of three groups of dLhCG for ACD regeneration and identify whether differences exist in mechanisms among three groups of dLhCG. To achieve this, an integrative multi-omics approach will be exploited, including RNA sequencing, 4D-DIA proteomics, and single-cell sequencing. Importantly, the pivotal genes and proteins in involved signaling pathways will be verified using quantitative polymerase chain reaction and western blotting. Overall, the contribution of this study lies in conducting the first space experiment on cartilage repair scaffolds and laying the foundation for fulfilling future requirement of repairing articular cartilage in space.