Microgel-modified surfaces enhance short-term osteoblast response

Modulations of surface structure or chemistry over various length scales are able to control the interactions of cells with biomaterials surfaces. This effect has been extensively studied using a number of top-down lithographic patterning processes. We create a modulated surface using a simple, bottom-up, self-assembly method involving the electrostatic deposition of microgels onto surfaces. We copolymerize acrylic acid (AA) with poly(ethylene glycol) (PEG) by suspension polymerization to form negatively charged, submicron-sized PEG-AA microgels and electrostatically deposit these onto cationic poly- l-lysine (PLL) primed substrates. The PEG-AA microgels resist fibronectin adsorption while the exposed PLL between adjacent microgels adsorbs fibronectin, thus producing a disordered array of submicron sized non-adhesive features separated from each other by microscale distances on an otherwise cell-adhesive surface. Relative to continuously adhesive surfaces, microgel-modulated adhesiveness increases both short-term cell spreading and cell proliferation (MTS) while maintaining the same differentiation behavior (ALP). Scanning electron microscopy indicates that osteoblasts grow over the microgels while adhering to the exposed adhesive surface between the microgels. Time-resolved optical microscopy shows that microgel-modified surfaces induce higher cell motility than the unmodified controls. These findings are consistent with the idea that cell-surface interactions are regulated by the spatial distribution of cell-adhesive sites on a surface, and they furthermore suggest a simple method by which to influence cellular processes associated with healing after the implantation of a tissue-contacting biomedical device.