Dynamic Scaffolds for Stem Cell Differentiation

We have designed and fabricated a nanocomposite substrate that can provide seeded cells with spatially and temporally defined mechanical force. This new nanocomposite substrate comprises a 1.5 mm thick bottom near infrared NIR mechanoresponse layer of few-walled carbon nanotubes (FWCNTs) that are uniformly distributed and covalently connected to thermally responsive poly(N-isopropylacrylamide), and an approximately 0.15 mm thick top cell-seeding layer of collagen functionalized poly(acrylic acid)-co-poly(N-isopropylacrylamide) that interpenetrates into the bottom layer. Covalent-coupling of all the components and uniform distribution of FWCNTs leads to large and fast mechanoresponse, e.g. 50 % change in strain at the point of irradiation on the order of 1 Hz, can be produced reversibly under near infrared (NIR) stimulationwith 0.02 wt % FWCNTs. We have further demonstrated that the mechanical strain imposed by NIR stimulation can be transmitted onto cells.  Human fetal hepatocytes change shape with no sign of detrimental effect on cell viability. To the best of our knowledge, this is the first demonstration of a platform enabled by nanotechnology that can generate fast and controlled mechanical force to actuate cells. 

Biophysical forces are position-specific and time-dependent, evolving from relatively simple traction/compression forces to a complex set of forces that cells experience as they mature. We are developing a platform that can recapitulate the dynamic force aspects of embryogenesis for controlled differentiation and investigating mechanotransduction. This is accomplished by using porous polymer/carbon nanotube scaffolds that undergo reversible volume shrinkage at 36 °C.  Employing a spatial light modulator to sculpt the light intensity, diverse mechanical stimulation forces can be produced. Moreover, the same substrate can generate different types of forces at different locations on the same substrate to allow side by side investigation of the effect of different force types on cells.

 

 

Representative publications:
ACS Nano, 2014, 8(11),  11695-11706
Advanced Materials, 2010, 3342-3347