Microrods control cellular proliferation and organization in three-dimensional tissue scaffolds

Cell culture substrates photolithographically patterned with microposts have been shown to alter primary cardiac fibroblast proliferation rates. When cells encounter a micropost on the culture surface, they attach to it and change from a proliferative to a quiescent state. For tissue engineering applications it would be desirable to move from a two-dimensional culture to a three-dimensional one. To create a three-dimensional analogue to the micropost surface, photolithographically produced microrods of SU-8 are embedded into a three-dimensional Matrigel matrix along with cells. The proliferation of both neonatal rat ventricular fibroblast and IMR-90 cell-line fibroblasts was retarded in gels containing microrods at concentrations as low as 1% of the cell concentration. Both fibroblast types attach and bridge microrods in the matrix and neonatal rat ventricular myocytes appear to cluster around the microrods. Bulk rheological properties of the matrix are unaffected by incorporation of the microrods.{09}The F-actin cytoskeleton appears to span attachment points to microrods and cell nuclei deform to contours of the microrods suggesting the alteration in proliferative state occurs on a cell-to-microrod basis and not as a population level phenomenon.; Ultimately, computational modeling of cell behavior with microfeatures can allow for testing a large number of feature variations before fabrication begins and may shed light onto the mechanisms behind cell-microfeature interactions. Here stochastic model of fibroblast migration and proliferation on 2D micropost substrates is presented. This model is able predict population level attachment rates and proliferation but not individual cell-microfeature interaction frequencies suggesting an underlying mechanism of cell-microfeature interactions that is not completely random.