New generations of devices for tissue engineering (TE) should rationalize better the physical and biochemical cues operating in tandem during native regeneration, at the scale/organizational-level of the stem cell niches. The understanding and the deconstruction of these factors (e.g. multiple cell types exchanging both paracrine and direct signals, structural and chemical arrangement of the extra-cellular matrix, mechanical signals) should be then incorporated into the design of truly biomimetic biomaterials. ATLAS proposes rather unique toolboxes combining smart biomaterials and cells for the ground-breaking advances of engineering fully time-self-regulated complex 2D and 3D devices, able to adjust the cascade of processes leading to faster high quality new tissue formation with minimum pre-processing of cells. Biomaterials based on marine-origin macromolecules were used, namely in the supramolecular assembly of instructive multilayers as nanostratified building-blocks for engineer such structures. The backbone of these biopolymers are equipped with a variety of (bio)chemical elements permitting: post-processing chemistry and micro-patterning, specific/nonspecific cell attachment, and cell-controlled degradation. ATLAS integrates cells from different units of tissue physiology, namely bone and hematopoietic basic elements and consider the interactions between the immune and skeletal systems. These ingredients permit to architect innovative films with high-level dialogue control with cells, in sophisticated quasi-closed 3D capsules able to compartmentalize such components in a “globe-like” organization. Bone is used as the model system, but it is expected that the developed methodologies can be used for an all range of other tissues. Besides the potential in regenerative medicine, we envisage to apply the developed capsules in two other important areas: bioengineered cell niches for basic biological research and in vitro platforms for modelling disease and drug screening. We believe that ATLAS, with its integrated multidisciplinary approach and the unique research environment found at our research group and the expertise of the PI, will for sure allow for a major step further in the development of radically new bone TE strategies. We trust that under this ERC grant framework, knowledge will be created, but simultaneously we will be able to optimize procedures and devices that might be exploited clinically. This is really applied research, with a very strong basic and fundamental support, that can create value and in the long-term an impact in the economy and quality of life of patients.