An important unsolved problem in bioengineering is learning to control polymer-cell interactions. Achieving this control can allow engineering of artificial tissues as an alternative to organ transplantation, the development of materials for targeted drug delivery, and surfaces that detect diseased cells or even biological warfare agents. We describe the development of “combinatorial biosurface chip” (CBC) technology for high-throughput assays of the effects of polymer surface chemistry and structure on cell function. Combinatorial measurements allow the rapid screening of thousands of surfaces in order to design novel biomaterials prior to detailed culturing experiments. A range of polymer blends has been developed for use with the CBC. AFM and optical microscope image analysis indicates a diverse surface microstructure formed as a result of crystallization of poly(ε-caprolactone) (PCL) and phase separation of PCL and poly(D,L-lactide-co-glycolide) (PLGA). The temperature-composition libraries provide rich variation in microstructure that allows rapid and efficient investigation of these effects on cell proliferation and differentiation. We present the results of culturing different cell types on various surface chemistries and microstructures. After seeding of primary cultured mouse aortic smooth muscle cells (MASMC) on PLGA-PCL libraries, the cell population was higher in high PCL, high annealing temperature areas after 7d. BrdU incorporation assays showed that surface structures in these areas enhanced cell proliferation over two-fold from 1 to 7d in culture. MC3T3-E1 osteoblasts cultured on PDLA-PCL libraries after 5d and stained for alkaline phosphatase (AlP) showed dramatically enhanced AlP expression near the center of the library. Combinatorial libraries distinguish between the response of different cell types to surface features. Features generated on libraries are reproducible in 3D scaffolds, providing a connection between high-throughput screening and biomaterial development.

We are currently trying to prove that this technology can also be used to develop patterned blends of conductive polythiophene and nonconductive polystyrene as substrates for regulating cell functions such as attachment and proliferation in MC3T3-E1 osteoblasts. We intend to incorporate the ability of conducting polymers to regulate cell functions with patterned surfaces that may induce specific interactions in cells. The combinatorial approach will allow us to quickly identify osteoblast response to surface pattern and conductivity.