Effect of mechanical boundary conditions on orientation of angiogenic microvessels

Aim Mechanical forces are important regulators of cell and tissue phenotype. We hypothesized that mechanical loading and boundary conditions would influence neovessel activity during angiogenesis. Methods and resuts Using an in vitro model of angiogenesis sprouting and a mechanical loading system, we evaluated the effects of boundary conditions and applied loading. The model consisted of rat micro-vessel fragments cultured in a 3D collagen gel, previously shown to recapitulate angiogenic sprouting observed in vivo. We examined changes in neovascular growth in response to four different mechanical conditions. Neovessel density, diameter, length and orientation were measured from volumetric confo-cal images of cultures exposed to no external load (free-floating shape control), intrinsic loads (fixed ends, no stretch), static external load (static stretch), or cyclic external load (cyclic stretch). Neoves-sels sprouted and grew by the third day of culture and continued to do so during the next 3 days of loading. The numbers of neovessels and branch points were significantly increased in the static stretch group when compared with the free-floating shape control group. In all mechanically loaded cultures, neovessel diameter and length distributions were heterogeneous, whereas they were homo-geneous in shape control cultures. Neovessels were significantly more oriented along the directio