Nanostructured designs of biomedical materials: applications of cell sheet engineering to functional regenerative tissues and organs

Biomaterials surface design is critical for control of cell-materials interactions. Materials surface characteristics important to cell-materials interactions are the following: (a) nonfouling surfaces where cells cannot interact; (b) surfaces that interact with cells but do not alter cell morphology or metabolism (passive adhesion processes); and (c) surfaces that strongly interact with cells and cell-surface receptors to alter cell shape after metabolic interactions (active adhesion). In this paper, we briefly discuss the relationship between materials surface characteristics and cells for biomaterials designs in these categories. We have extensively investigated the thermoresponsive polymer, poly(N-isopropylacrylamide) (PIPAAm), as grafted surfaces allowing recovery of confluent cell monolayers as contiguous living cell sheets for tissue engineering applications. Cellular interactions with PIPAAm-grafted surfaces can be regulated vertically using the thickness of the PIPAAm-grafted layers in nanometer-scale levels, as well as laterally (spatially) using nano-patterned PIPAAm chemistry on various other surface chemistries. PIPAAm-grafted surfaces with 15-20-nm thick layers exhibit temperature-dependent cell adhesion/detachment control, while surfaces with PIPAAm layer thicknesses of more than 30 nm do not support cell adhesion. These changes in cell adhesion are explained by the limited mobility of the surface grafted polymer chains as a function of grafting, hydration, and temperature.