Towards Cellular Sieving: Exploring the Limits of Scaffold Accessibility for Cell Type Specific Invasion

Coordinating the behavior of multiple cell types provides a challenge for the tissue engineer, since response to structure is highly cell type dependent. Here, human primary fibroblast invasion is compared with that of the MC3T3 and HT1080 cell lines to demonstrate proof-of-concept that controlled changes in 3D collagen scaffold architecture can modi the invasion response of one cell type, while keeping that of other cells constant. While complete invasion is seen for all three cell types where pore size and percolation diameter are sufficiently high, both primary fibroblasts and MC3T3 require a percolation diameter above roughly 40 mu m to permit efficient invasion by day 3. Conversely, substantial HT1080 invasion is observed in all scaffold conditions. By day 7, MC3T3 and fibroblast invasion responses to structure are also distinct, with only MC3T3 inhibited by low percolation diameters. Collagen scaffolds can therefore act as cellular sieves, using structural control to promote the invasion of some cell types, while restricting the movement of others. As well as holding promise for the design of tissue engineering scaffolds for complex applications, this result is highly relevant for the development of in vitro systems for studying in vivo phenomena such as cancer cell invasion and metastasis.