The Force at the Tip--Modelling Tension and Proliferation in Sprouting Angiogenesis.

Sprouting angiogenesis, where new blood vessels grow from pre-existing ones, is a complex process where biochemical and mechanical signals regulate endothelial cell proliferation and movement. Therefore, a mathematical description of sprouting angiogenesis has to take into consideration biological signals as well as relevant physical processes, in particular the mechanical interplay between adjacent endothelial cells and the extracellular microenvironment. In this work, we introduce the first phase-field continuous model of sprouting angiogenesis capable of predicting sprout morphology as a function of the elastic properties of the tissues and the traction forces exerted by the cells. The model is very compact, only consisting of three coupled partial differential equations, and has the clear advantage of a reduced number of parameters. This model allows us to describe sprout growth as a function of the cell-cell adhesion forces and the traction force exerted by the sprout tip cell. In the absence of proliferation, we observe that the sprout either achieves a maximum length or, when the traction and adhesion are very large, it breaks. Endothelial cell proliferation alters significantly sprout morphology, and we explore how different types of endothelial cell proliferation regulation are able to determine the shape of the growing sprout. The largest region in parameter space with well formed long and straight sprouts is obtained always when the proliferation is triggered by endothelial cell strain and its rate grows with angiogenic factor concentration. We conclude that in this scenario the tip cell has the role of creating a tension in the cells that follow its lead. On those first stalk cells, this tension produces strain and/or empty spaces, inevitably triggering cell proliferation. The new cells occupy the space behind the tip, the tension decreases, and the process restarts. Our results highlight the ability of mathematical models to suggest relevant hypotheses with respect to the role of forces in sprouting, hence underlining the necessary collaboration between modelling and molecular biology techniques to improve the current state-of-the-art.

Micro Push-out Bond Strength and Bioactivity Analysis of a Bioceramic Root Canal Sealer.

INTRODUCTION: Bioactive endodontic sealers have been developed to improve the quality of root canal obturation. EndoSequence Bioceramic (BC) Sealer is amongst calcium silicate-based materials recently developed for permanent root canal filling. The objective of this study was to evaluate the bioactivity of BC Sealer and its micro push-out bond strength to dentin compared to AH-Plus (AH) sealer. METHODS AND MATERIALS: To perform the micro push-out test, 24 root canals of mandibular premolars were instrumented and divided into two groups (n=12). Each root was cut into 4 slices and lumens of the canals were filled with the sealers and submitted to micro push-out test. Failure mode was assessed using scanning electron microscopy (SEM). Bioactivity of BC sealer was investigated with scanning electron microscopy/energy-dispersive X-ray (SEM/EDS) and X-ray diffraction (XRD). Bioactivity assessments were reported descriptively. Bond strength data were analyzed by parametric t-test (α=5%). RESULTS: In micro push-out test AH had higher bond strength mean values (16.29 MPa) than BC sealer (9.48 MPa) (P<0.05). Both groups had low amount of adhesive failure. SEM showed the presence of a mineral precipitate after 30 days and EDS analysis showed that those precipitates have high proportion of Ca. XRD showed peaks of crystalline phases of calcium carbonate compatible with the bioactivity. CONCLUSION: BC sealer showed indications of bioactivity and lower bond strength to dentine compared to AH.