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This efficacy research study investigated the impact and experience of high school students participating in a ten week, biodesign makerspace program focused on teaching a life science curriculum through an art and design pedagogy. Situated in a classroom specifically designed on principles of biophilia, the curriculum focused on topics of biomimicry in form, biomaterials and biosystems weaving together Next Generation Science Standard topics with object design based on deep observation of organisms design strategies. Qualitative and quantitative data were collected around interrelated dimensions of engagement: affect, behavior, and cognition. This study suggests that novel, biodesign learning spaces coupled with transdisciplinary curricula may be an effective model for helping students internalize nature-based life science content and broaden interest in STEM topics.