Traditionally, the design of exoskeletons (from choice of configuration to selection of parameters) as well as the process of fitting this exoskeleton (to the individual user/patient) has largely depended on intuition and/or practical experience of a designer/physiotherapist. However, improper exoskeleton design and/or incorrect fitting can cause buildup of significant residual forces/torques (both at joint and fixation site). Performance can be further compromised by the innate complexity of human motions and need to accommodate the immense individual variability (in terms of patient–geometries, motion–envelopes and musculoskeletal–strength). In this paper, we propose a systematic and quantitative methodology to evaluate various alternate exoskeleton designs using twist- and wrench-based modeling and analysis. This process is applied in the context of a case-study for developing optimal configuration and fixation of a knee brace/exoskeleton. An optimized knee brace is then prototyped using 3D printing and instrumented with 6–DOF force-torque transducer. Knee brace is then physically tested together with a saw-bones knee model in a scaled knee bracing test. Preliminary results of the physical testing of the knee brace show promise and are discussed.

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