Developing cellular systems in vitro to simulate regeneration.

In the past two decades, cellular systems in vitro have progressed from predominantly monocellular testing models to study the toxic effects of new biomaterials for replacement to relevant human coculture systems for regeneration, often a combination of progenitor cells with novel biomaterials. Considerable progress has been made in understanding cellular cross talk and its contribution to the vascularization of bone. Future challenges include using the established physiological, that is, nonactivated, stem cell niches as a platform to develop coculture models, which will enable the true in situ regenerative niche to be investigated. Hypoxia and a changing inflammatory status are factors that need to be incorporated. Major advances in polymer synthesis permitting the incorporation of specific biologically relevant signals in hydrogels will help make this a reality.