Osteogenic differentiation influence stem cell migration out of scaffold free microspheres.

Complete bone regeneration of critical size defects (CSDs) frequently fail due to the use of acellular bone substitutes and due to partially negative influences of artificial scaffolds. However, the supply of cells to CSDs is essential for the regeneration. Therefore, engineered scaffold free tissues, with outgrowing cells that fill up spaces in the bony defect, are promising candidates for bone regeneration approaches. Here we demonstrate such a scaffold free tissue construct (microspheres) that, if osteogenic differentiated, mineralizes while maintaining the capability to let cells grow out of the united cell structure. A superior outgrowth capability of microspheres composed of human cord-blood derived USSCs (unrestricted somatic stem cells) compared to murine ESCs (embryonic stem cells) was found and a time dependent reduction in outgrowth was evident, in vitro. Even after five days of osteoinduction and strong mineralization cells migrate out of the microsphere. Since migration of cells out of USSC-microspheres was also found in extracellular matrix gel, we suggest that cells would migrate also in vivo. Thus microspheres could serve as the scaffold and the source of osteogenic cells in future bone regeneration approaches. Furthermore microspheres permit the precise administration of large amount of cells into an area of interest.