Search

The majority of fractures heal through the process of endochondral ossification, in which a cartilage intermediate forms between the fractured bone ends and is gradually replaced with bone. Recent studies have provided genetic evidence demonstrating that a significant portion of callus chondrocytes transform into osteoblasts that derive the new bone. This evidence has opened a new field of research aimed at identifying the regulatory mechanisms that govern chondrocyte transformation in the hope of developing improved fracture therapies. In this article, we review known and candidate molecular pathways that may stimulate chondrocyte-to-osteoblast transformation during endochondral fracture repair. We also examine additional extrinsic factors that may play a role in modulating chondrocyte and osteoblast fate during fracture healing such as angiogenesis and mineralization of the extracellular matrix. Taken together the mechanisms reviewed here demonstrate the promising potential of using developmental engineering to design therapeutic approaches that activate endogenous healing pathways to stimulate fracture repair.

Developmental engineering is a potential option for neo-organogenesis of complex organs such as the kidney. The application of this principle requires the ability to construct a tubular structure from dispersed renal progenitor cells with defined size and geometry. In this present study we report the generation of tubular structures from dispersed ureteric bud cells in vitro by using a micropatterned gel. Dispersed CMUB-1 cells, a mouse ureteric bud-derived cell line, or mIMCD cells, a mouse collecting duct-derived cell line, were suspended in collagen I and seeded into an agarose-based micropatterned gel. We found that within 24-36 h of incubation, the cells developed a tubular structure that conformed to the geometry of the micropattern of the gel. The lumen formation of the tubular structure was confirmed by immunohistochemical staining and observed by confocal microscopy. We found that higher concentrations of collagen I negatively influenced the efficiency of tubular formation. Tubule formation in CMUB-1, but not mIMCD, cells was positively influenced by the addition of aldosterone (10, 50 and 200 µg/ml), FGF (50 and 100 µg/ml) and fibronectin (10 and 50 µg/ml) to the growth medium. We further demonstrated the functionality of the generated tubes by in vitro budding, which was induced by growth factors, such as glial cell-derived neurotrophic factor (GDNF) or fibroblast growth factor 7 (FGF7), in the presence of beads soaked with the activin A inhibitor follistatin. Our current study thus demonstrates the possibility of constructing a functional tubular structure from dispersed ureteric bud cells in vitro in a controlled manner. Copyright © 2014 John Wiley & Sons, Ltd.