The supply of oxygen and nutrients from capillaries as well as the mechanical stimuli transmitted to cells are critical factors that influence tissue differentiation. The effect of these two factors can be investigated using mechanobiological computational models.
In the study Simulation of angiogenesis and cell differentiation in a CaP scaffold subjected to compressive strains using a lattice modeling approach in Biomaterials, Clara Sandino and Damien Lacroix from the Institute for Bioengineering of Catalonia (IBEC), and researchers from the Trinity College Dublin (Ireland) have simulated angiogenesis and tissue differentiation in a scaffold to be used for bone tissue engineering.
Briefly, a calcium phosphate cement scaffold with heterogeneous porosity was studied. Vessels growth and cell differentiation within the pores of the scaffold were determined according to the local mechanical stimuli, and mechanical properties were updated based on a mechanoregulation concept. It was found that at the beginning of the simulation, vessels grow in the external pores of the scaffold. However they were blocked by the scaffold walls and did not reach the center of the sample.
At the end of the simulation different types of cells were predicted across the scaffold according to the stimuli and the oxygen supply. Osteoblasts were predicted in pores at the periphery of the sample, near the vessels, chondrocytes in the pores at the center of the scaffold and fibroblasts in narrow regions of the porous structure, where the stimuli were higher.
Comparing this heterogeneous construct with regular morphology scaffolds, that can be obtained using rapid prototyping for example, it is possible to understand how the interconnectivity of the pores influences tissue formation within a scaffold. The irregular morphology can cause both blockage of the vessel growth and peaks of mechanical stimuli having an important effect on the performance of the scaffold. These results are relevant to understand the performance of the scaffolds when implanted in vivo. One of the key results was the sensitivity of tissue differentiation to mechanical loading. The results of this study therefore can explain part of the variability encountered in in vitro bioreactors and in vivo studies.