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In particular, this paper presents a novel Series Elastic Transmission (SET) used as power transmission on a Hand Exoskeleton System (HES) based on a Series Elastic Actuator (SEA). The elastic element of the transmission has been designed through the innovative topology optimization approach which has led to manufacture a component whose mechanical features strictly replicate the desired ones. The authors have validated the proposed approach by testing a real elastic component. Suitable mechanical tests, whose results are reported in the paper, were executed in order to evaluate the goodness of the design procedure.