Figure Legends:
Figure 1: In vitro multi-modal loading system with 3D bone mimetic scaffolds. (a) In future experiments, breast cancer cells will be seeded in bone-mimicking scaffolds fabricated from poly(lactide-co-glycolide) and bone mineral (hydroxyapatite). (b) Scaffolds will be loaded in a multi-modal bioreactor system under nine configurations of dynamic compression and direct perfusion.
Figure 2: 3D reconstruction of scaffold from microCT image and solid-fluid assembly model. (a) The bone-mimicking scaffold is highly porous with mean macropore size 432 μm and mean wall thickness 58 μm (Pathi et al., 2010). (b) A scaffold was scanned using high-resolution microCT images with voxel size 5.4 μm (Liu et al., 2018). (c) The 3D voxel model of the scaffold (shown in ivory) as well as the fluid domain (shown in cyan) was generated using ScanIP. The solid-fluid assembly was a sub-domain of the whole model, with final dimensions 1.2 mm thick and 2 mm wide.
Figure 3: Multiphysics simulation model. (a) Volumetric meshes of the fluid and solid domains were directly generated in ScanIP from 3D voxel models. (b) Fluid and solid surface meshes formed a watertight assembly along with shared nodes one the interior fluid-solid interfaces. (c) Boundary conditions were assigned to match the experimental setup. Interior fluid-solid interface was linked together in order to transfer coupled data (i.e., solid displacements and fluid forces).
Figure 4: Heat maps and distributions of surface principle strain of low and high compression. (a) Surface strain contours of 5% compression were distributed evenly in the scaffold with 70% values located in 5,000-20,000 με range. (b) Strains of 10% compression shifted towards higher range (10,000-40,000 με).
Figure 5: Median WSS versus time during the 1 Hz loading cycle.WSSs induced by compression alone revealed symmetrical waveforms. However, when scaffolds were loaded with both compression and perfusion, the waveforms became asymmetric. Peak WSS values occurred at 0.25 sec of each cycle and increased with higher magnitude loading. WSS = wall shear stress.
Figure 6: Cyclic compression caused dynamic interstitial fluid flow. (a) In the C+P- simulation, velocity vectors showed fluid flow changed direction during scaffold loading (fluid perfused out) and unloading (fluid resorbed in). (b) In contrast, during combination loading (shown C+P+), fluid velocity vectors at 0.25 sec showed greater fluid flow going upward, the same as the direction of applied perfusion. Fluid flow was much lower at 0.75 sec with some reversed velocity vectors seen.