2 D , 3 D and 4 D active compound delivery in tissue engineering and 1 regenerative medicine

9 Recent advances in tissue engineering and regenerative medicine have shown that controlling cells 10 micro-environment during growth is a key element to the development of successful therapeutic 11 system. To achieve such control, researchers have first proposed the use of polymeric scaffolds that 12 were able to support cellular growth and, to a certain extent, favor cell organization and tissue 13 structure. With nowadays availability of a large pool of stem cell lines, such approach has appeared to 14 be rather limited since it does not offer the fine control of the cell micro-environment in space and time 15 (4D). Therefore, researchers are currently focusing their efforts in developing strategies that include 16 active compound delivery systems in order to add a fourth dimension to the design of 3D scaffolds. This 17 review will focus on recent concepts and applications of 2D and 3D techniques that have been used to 18 control the load and release of active compounds used to promote cell differentiation and proliferation 19 in or out of a scaffold. We will first present recent advances in the design of 2D polymeric scaffolds and 20 the different techniques that have been used to deposit molecular cues and cells in a controlled fashion. 21 We will continue by presenting the recent advances made in the design of 3D scaffolds based on 22 hydrogels as well as polymeric fibers and we will finish by presenting some of the research avenues that 23 are still to be explored. 24 25 26