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Near-future objectives of human spaceflight expose a wide spectrum of challenges. This research explores the value Design Thinking through a human-centered lens can offer, especially when applied from the early stages of problem-solving. While extensive research and development through a systems engineering approach is being done for the EVA and IVA/ flight suits, much less has been developed for astronaut’s intravehicular daily wear. And, especially from a Design Thinking approach, considering a range of aspects of the human physiology and psychology at every stage of the development process. Prototyping the Antagonist Exomuscle bodysuit, an individual-specific countermeasure for the microgravity-induced bone loss and muscle atrophy during >6 months long missions, started during my MA studies. The purpose of the suit is to keep postural muscles engaged throughout the day so that the weight-bearing bone loading would occur more as it does on Earth. Human spaceflight research suggests the need for greater adaptability and comfort levels of countermeasures for microgravity-induced musculoskeletal deconditioning. Traditional and novel methodologies from tailoring and textiles, such as physical/bespoke/virtual 3D fitting and prototyping as well as advanced garment manufacturing techniques can be used to integrate the smart musculoskeletal conditioning system into a bodysuit, which is made with the neutral body posture and task-specific movements in mind. Research through design has the potential to offer a valuable contribution to the current paradigm in human spaceflight, especially regarding user experience and feasibility.