The last decades have been marked by a growing concern over scarcity of resources caused by the rapid industrialization of emerging economies as well as by the high material consumption at a global scale. These changing environmental conditions have inevitably created new challenges and demands for mediation of the interaction between the natural and the human-made environments. In response to these challenges, designers are currently moving away from conventional top-down design, towards a nature-inspired approach in search of the underlying principles of morphogenesis and materialization inherent to biological entities. Inscribed in this approach, this paper proposes an innovative design-to-fabrication workflow for the conception of nature-inspired load-responsive skin systems which integrates the use of computational tools, Additive Manufacturing, and material experiments with full-scale prototypes. The design phase employs custom algorithms to determine an optimal material distribution for free-form architectural shapes, given a specific loading condition. Through fabrication tests at different scales, the viability of a production system based on Fused Deposition Modelling is demonstrated. Subsequently, the realization of a final prototype of a load-responsive cellular envelope cladded with Fiber-Glass Reinforced Plastic is presented. Opportunities and current limitations of the approach and the emerging architectural system are critically discussed towards future developments.