SPATIALLY CONTROLLED CELL ENGINEERING ON BIODEGRADABLE POLYMER SURFACES

Controlling receptor-mediated interactions between cells and template surfaces is a central principle in many tissue engineering procedures (1-3). Biomaterial surfaces engineered to present cell adhesion ligand s undergo integrin-mediated molecular interactions with cells (1, 4, 5 ), stimulating cell spreading, and differentiation (6-8). This provide s a mechanism for mimicking natural cell-to-matrix interactions. Furth er sophistication in the control of cell interactions can be achieved by fabricating surfaces on which the spatial distribution of ligands i s restricted to micron-scale pattern features (9-14). Patterning techn ology promises to facilitate spatially controlled tissue engineering w ith applications in the regeneration of highly organized tissues. Thes e new applications require the formation of ligand patterns on biocomp atible and biodegradable templates, which control tissue regeneration processes, before removal by metabolism. We have developed a method of generating micron-scale patterns of any biotinylated ligand on the su rface of a biodegradable block copolymer, polylactide-poly(ethylene gl ycol). The technique achieves control of biomolecule deposition with n anometer precision. Spatial control over cell development has been obs erved when using these templates to culture bovine aortic endothelial cells and PC12 nerve cells. Furthermore, neurite extension on the biod egradable polymer surface is: directed by pattern features composed of peptides containing the IKVAV sequence (15, 16), suggesting that dire ctional control over nerve regeneration on biodegradable biomaterials can be achieved.