Currently, CyberPhysical Systems (CPS) represents a great challenge for automatic control and smart systems engineering on both theoretical and practical levels. Designing CPS requires approaches involving multidisciplinary competences. However they are designed to be autonomous, the CPS present a part of uncertainty, which requires interaction with human for engineering, monitoring, controlling, performing operational maintenance, etc. This human-CPS interaction led naturally to the human in-the-loop (HITL) concept. Nevertheless, this HITL concept , which stems from a reductionist point of view, exhibits limitations due to the different natures of the systems involved. As opposed to this classical approach, we propose, in this paper, a model of Bio-CPS (i.e. systems based on an integration of computational elements within biological systems) grounded on theoretical biology, physics and computer sciences and based on the key concept of human systems integration.