Space missions expose astronauts to multiple physiological stressors, including microgravity, radiation, confinement, and circadian disruption, which collectively contribute to immune dysfunction, musculoskeletal loss, cardiovascular alterations, impaired wound healing, neurocognitive changes, and increased susceptibility to infection. Current countermeasures, primarily exercise protocols, pharmacological treatments, and pre-flight conditioning, provide only partial protection and remain limited in their ability to actively guide tissue adaptation during long-duration missions. Advanced biomaterials are emerging as promising platforms to address these challenges by enabling controlled therapeutic delivery, modulation of cellular responses, and regeneration of damaged tissues under spaceflight conditions. In this review, we summarize recent progress in biomaterials research conducted in real and simulated microgravity environments. We cover advances in nanomaterials, hydrogels, surface-engineered materials, bioprinting technologies, and organ-on-chip systems, and discuss how these platforms can mitigate oxidative stress, modulate immune responses, support musculoskeletal and cardiovascular health, and promote tissue repair. We also examine how biomaterials originally developed for terrestrial regenerative medicine can be adapted for space applications, as well as the role of emerging space-based biomanufacturing approaches. Finally, we discuss key challenges and future directions for translating biomaterial technologies into practical medical countermeasures for long-duration missions. Together, these developments position biomaterials as central components of next-generation space medicine strategies.
