GROWTH-FACTOR RELEASE FROM THERMALLY REVERSIBLE TISSUE-CULTURE SUBSTRATES

Thermally reversible poly(N-isopropylacrylamide) (PIPAAm) was covalent ly grafted onto tissue culture dishes to allow detachment of cultured cells upon temperature change from physiological to room temperature. In addition the grafted polymer matrix was used to entrap biomolecules such as growth factors either to be released by diffusion early in ce ll cultures, or remain entrapped and be reversibly exposed to cell rec eptors. Experiments with model proteins trypsin and insulin show that amount loaded and released depends upon the PIPAAm grafting density. D ishes grafted with 2.5 mu g/cm(2) PIPAAm released approximately four t imes more model protein over 4 h than dishes grafted with 1.8 mu g/cm( 2). This in vitro drug delivery system can be used to deliver factors to the basal side of cells early in cell culture by providing high loc al concentrations without high bulk concentration. Cultures of human r etinal pigmented epithelium showed higher growth rate on insulin loade d dishes than on controls containing a similar bulk solution concentra tion. These cultures retained the ability to detach singly or as confl uent sheets from the loaded surfaces. (C) 1998 Elsevier Science B.V. A ll rights reserved.