Achieving and maintaining safe and reliable lineage specific differentiation of stem cells is important for clinical translation of tissue engineering strategies. In an effort to circumvent the multitude of problems arising from the usage of growth factors and growth factor delivery systems, we have explored the use of exosomes as biomimetic tools to induce stem cell differentiation. Working on the hypothesis that cell-type specific exosomes can trigger lineage-specific differentiation of stem cells, we have evaluated the potential of exosomes derived from dental pulp cells cultured on under growth and odontogenic differentiation conditions to induce odontogenic differentiation of naïve human dental pulp stem cells (DPSCs) and human bone marrow derived stromal cells (HMSCs) in vitro and in vivo. Results indicate that the exosomes can bind to matrix proteins such as type I collagen and fibronectin enabling them to be tethered to biomaterials. The exosomes are endocytosed by both DPSCs and HMSCs in a dose-dependent and saturable manner via the caveolar endocytic mechanism and trigger the P38 mitogen activated protein kinase (MAPK) pathway. In addition, the exosomes also trigger the increased expression of genes required for odontogenic differentiation. When tested in vivo in a tooth root slice model with DPSCs, the exosomes triggered regeneration of dental pulp-like tissue. However, our results indicate that exosomes isolated under odontogenic conditions are better inducers of stem cell differentiation and tissue regeneration. Overall, our results highlight the potential exosomes as biomimetic tools to induce lineage specific differentiation of stem cells. Our results also show the importance of considering the source and state of exosome donor cells before a choice is made for therapeutic applications.

Numerous discarded ProFile GT, ProFile, and ProTaper nickel-titanium rotary instruments obtained from two graduate endodontic clinics were examined by scanning electron microscopy. These instruments had an unknown history of clinical use and had fractured or experienced considerable permanent torsional deformation without complete separation. The failure processes generally exhibited substantial ductile character, evidenced by a dimpled rupture fracture surface. Crack propagation at grain boundaries and cleavage surfaces indicative of transgranular fracture were observed for some specimens. It appeared that oxide particles from the manufacturing process served as nucleating sites for the microvoids, leading to dimpled rupture. A previously unreported fracture mode also was observed, in which crack propagation, approximately parallel to the local flute orientation, connected pitted regions on the surface. Combining present and previous scanning electron microscopy observations of clinically failed instruments, suggestions are offered for improving their fracture resistance.

No abstract

The appearances of the tip sections of ProFile 0.04 taper and Lightspeed 25-mm long, ISO size 25, nickel-titanium rotary instruments were compared with a scanning electron microscope in the as-received condition and after one, three, and six simulated clinical uses to prepare mesial canals of extracted mandibular molars. For the used ProFile instruments, there was some flattening of the characteristic material rollover and minor apparent wear at the edges of the flutes, but there was little change in the tip regions of the used Lightspeed instruments. Deposits on the surfaces of the instruments were attributed to the manufacturing processes and the in vitro preparation of root canals in the extracted teeth. The simulated clinical use did not cause substantial changes in the regions of these two brands of rotary instruments that are involved in the clinical preparation of root canals.