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With the aim of developing a comprehensive framework to enhance self-directed learning (SDL) in adolescents via maker tools (e.g., 3D printing), a systematic review of studies that targeted SDL was conducted. Three main theories (self-regulated, inquiry-based, and problem-based learning) and six key characteristics of SDL environments were identified (guiding supports, SRL components, inquiry and choice, collaboration, differentiation, and hypothesis testing and inquiry). Based on the results, a new framework for using making-activities in high school classrooms is proposed that integrates all of the key characteristics for SDL and organizes them according to the design process and SRL phases. The proposed Design-Centered -SDL Model provides a framework for integrating process-oriented, maker-based activities in classrooms that support learners’ agency and autonomy.