Dynamic cell behavior on shape memory polymer substrates Kevin A. Davis a, b , Kelly A. Burke b, c , Patrick T. Mather a, b , James H. Henderson a, b, * a Department of Biomedical and Chemical Engineering,121 Link Hall, Syracuse University, Syracuse, NY 13244, USA b Syracuse Biomaterials Institute, 318 Bowne Hall, Syracuse University, Syracuse, NY 13244, USA c Department of Macromolecular Science and Engineering, 2100 Adelbert Road, Case Western Reserve University, Cleveland, OH 44106, USA article info Article history: Received 15 November 2010 Accepted 1 December 2010 Available online xxx Keywords: Cell culture Shape memory Thermally responsive material Surface topography abstract Cell culture substrates of defined topography have emerged as powerful tools with which to investigate cell mechanobiology, but current technologies only allow passive control of substrate properties. Here we present a thermo-responsive cell culture system that uses shape memory polymer (SMP) substrates that are programmed to change surface topography during cell culture. Our hypothesis was that a shape- memory-activated change in substrate topography could be used to control cell behavior. To test this hypothesis, we embossed an initially flat SMP substrate to produce a temporary topography of parallel micron-scale grooves. After plating cells on the substrate, we triggered shape memory activation using a change in temperature tailored to be compatible with mammalian cell culture, thereby causing topographic transformation back to the original flat surface. We found that the programmed erasure of substrate topography caused a decrease in cell alignment as evidenced by an increase in angular dispersion with corresponding remodeling of the actin cytoskeleton. Cell viability remained greater than 95% before and after topography change and temperature increase. These results demonstrate control of cell behavior through shape-memory-activated topographic changes and introduce the use of active cell culture SMP substrates for investigation of mechanotransduction, cell biomechanical function, and cell soft-matter physics. Ó 2010 Elsevier Ltd. All rights reserved. 1. Introduction Cells are capable of surveying the mechanical properties of their surrounding environment [1]. This capacity is critical to events of embryogenesis, postnatal tissue development and maintenance, and the onset of certain pathological conditions [2e4]. In the synthetic realm, substrates of defined topography or elastic modulus have emerged as powerful tools in the investigation of the underlying cellular mechanisms. In particular, mesoscale, micro- scale, and nanoscale patterns of substrate topography have been shown to direct cell alignment, cell adhesion, and cell traction forces [5e12], while isotropic and anisotropic substrate elasticity have been used to direct cell lineage specification, growth, and migration [1,13,14]. Defined topographies have also found applica- tion in biomedical device design, for example to enhance implant cell adhesion and tissue ingrowth [15]. These findings have underscored the potential for substrates to control and assay the mechanical interactions between cells and their physical environment during cell culture; however, the substrates used to date have generally been passive, with substrate properties that could not be programmed to change significantly during culture. This physical stasis has limited the potential of substrates to control cells in culture and, therefore, to advance both fundamental understanding of cell biology and cell-based bioengineering applications. To overcome the limitations of physically static systems, there has been growing interest in the development of stimuli-respon- sive biomaterials for cell culture, with several notable areas of progress. Poly(N-isopropylacrylamide) (PIPAAm) has been used to release cell layers [16] that can be used in laminar tissue engi- neering [17] by taking advantage of the material’s lower critical solution temperature (LCST) at 32  C and a change in hydropho- bicity around this temperature. PIPAAm’s thermo-responsive behavior has also been exploited in copolymer hydrogels designed to apply equibiaxial stretching to encapsulated cells when the temperature is lowered to 25  C [18]. Elastin-like polypeptides (ELPs) are stimuli-responsive biomaterials that can exhibit an LCST in a physiologically relevant range [19] and have been used to capture and release proteins at surfaces [20], which can be used to control cell adhesion. Thermo-responsive ELP hydrogels for cell culture or tissue engineering applications have also been * Corresponding author. Syracuse Biomaterials Institute, 318 Bowne Hall, Syracuse University, Syracuse, NY 13244, USA. Tel.: þ1 315 443 9739; fax: þ1 315 443 7724. E-mail address: jhhender@syr.edu (J.H. Henderson). Contents lists available at ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials 0142-9612/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2010.12.006 Biomaterials xxx (2010) 1e9 Please cite this article in press as: Davis KA, et al., Dynamic cell behavior on shape memory polymer substrates, Biomaterials (2010), doi:10.1016/ j.biomaterials.2010.12.006