Scaffold-free microtissues: differences from monolayer cultures and their potential in bone tissue engineering

Cell-based therapies for bone augmentation after tooth loss and for the treatment of periodontal defects improve healing defects. Usually, osteogenic cells or stem cells are cultivated in 2D primary cultures, before they are combined with scaffold materials, even though this means a loss of the endogenous 3D microenvironment for the cells. Moreover, the use of single-cell suspensions for the inoculation of scaffolds or for the direct application into an area of interest has the disadvantages of low initial cell numbers and susceptibility to unwanted cellular distribution, respectively. We addressed the question whether an alternative to monolayer cultures, namely 3D microtissues, has the potential to improve osteogenic tissue engineering and its clinical outcome. By contrast, to monolayer cultures, osteogenic differentiation of 3D microtissues is enhanced by mimicking in vivo conditions. It seems that the osteogenic differentiation in microtissues is enhanced by strong integrin-extracellular matrix interaction and by stronger autocrine BMP2 signaling. Moreover, microtissues are less prone to wash out by body fluids and allow the precise administration of large cell numbers. Microtissue cultures have closer characteristics with cells in vivo and their enhanced osteogenic differentiation makes scaffold-free microtissues a promising concept in osteogenic tissue engineering. Microtissues are particularly suitable for tissue engineering because they improve seeding efficiency of biomaterials by increasing the cell load of a scaffold. This results in accelerated osteogenic tissue formation and could contribute to earlier implant stability in mandibular bone augmentation.