A major question in regenerative medicine is how far in vitro or in vivo models can approach the complexity of the human in vivo situation. This presentation will look critically at both theoretical and practical aspects of this theme and give examples from the author’s own research. Two fields will be examined : bone regeneration, with emphasis on vascularization, and respiratory tract regeneration. We have shown that coculture models can be established, involving two or at maximum three cell types, the gold standard of which are the organotypic primary cell types in the human. It will be discussed how human permanent cell lines can be used to replace the primary system, and how the various models can be designed to help unravel mechanisms of cellular crosstalk, this being an essential basis for the development of novel regenerative strategies. The important role of biomaterials, especially polymers, in such approaches will be emphasized.