Cancer cell migration within 3D layer-by-layer microfabricated photocrosslinked PEG scaffolds with tunable stiffness.

Our current understanding of 3-dimensional (3D) cell migration is primarily based on results from fibrous scaffolds with randomly organized internal architecture. Manipulations that change the stiffness of these 3D scaffolds often alter other matrix parameters that can modulate cell motility independently or synergistically, making observations less predictive of how cells behave when migrating in 3D. In order to decouple microstructural influences and stiffness effects, we have designed and fabricated 3D polyethylene glycol (PEG) scaffolds that permit orthogonal tuning of both elastic moduli and microstructure. Scaffolds with log-pile architectures were used to compare the 3D migration properties of normal breast epithelial cells (HMLE) and Twist-transformed cells (HMLET). Our results indicate that the nature of cell migration is significantly impacted by the ability of cells to migrate in the third dimension. 2D ECM-coated PEG substrates revealed no statistically significant difference in cell migration between HMLE and HMLET cells among substrates of different stiffness. However, when cells were allowed to move along the third dimension, substantial differences were observed for cell displacement, velocity and path straightness parameters. Furthermore, these differences were sensitive to both substrate stiffness and the presence of the Twist oncogene. Importantly, these 3D modes of migration provide insight into the potential for oncogene-transformed cells to migrate within and colonize tissues of varying stiffness.

Spatial tuning of negative and positive Poisson's ratio in a multi-layer scaffold.

While elastic modulus is tunable in tissue engineering scaffolds, it is substantially more challenging to tune the Poisson's ratio of scaffolds. In certain biological applications, scaffolds with a tunable Poisson's ratio may be more suitable for emulating the behavior of native tissue mechanics. Here, we design and fabricate a scaffold, which exhibits simultaneous negative and positive Poisson's ratio behavior. Custom-made digital micro-mirror device stereolithography was used to fabricate single- and multiple-layer scaffolds using polyethylene glycol-based biomaterial. These scaffolds are composed of pore structures having special geometries, and deformation mechanisms, which can be tuned to exhibit both negative Poisson's ratio (NPR) and positive Poisson's ratio (PPR) behavior in a side-to-side or top-to-bottom configuration. Strain measurement results demonstrate that analytical deformation models and simulations accurately predict the Poisson's ratios of both the NPR and PPR regions. This hybrid Poisson's ratio property can be imparted to any photocurable material, and potentially be applicable in a variety of biomedical applications.