Integration of surface modification and 3D fabrication techniques to prepare patterned poly(L-lactide) substrates allowing regionally selective cell adhesion

Regeneration of organizationally complex tissue requires regulation of spatial distributions of particular cell types in three dimensions. Ln this paper we demonstrate an integration of polymer processing and selective polymer surface modification using methods suitable for construction of three-dimensional polymer scaffolds which may aid such cell organization. Specifically, the surfaces of degradable polyesters were modified with poly(ethylene-oxide) (PEO)-poly(propylene-oxide) (PPO) copolymers using a process compatible with a solid free-form fabrication technique, the 3Dp(TM) printing process. We demonstrate inhibition of cell (hepatocyte and fibroblast) adhesion to regions of two-dimensional poly(lactide) (PLA) substrates modified with PEO-PPO-PEO copolymers. We further show that PEO-PPO-PEO-modified surfaces which are not adhesive for hepatocytes or fibroblasts can be made selectively adhesive for hepatocytes by covalent linkage of a carbohydrate ligand specific for the hepatocyte asialoglycoprotein receptor to the PEO chain ends. Our approach may be generally useful for creating regionally selective, microarchitectured scaffolds fabricated from biodegradable polymers, for spatial organization of diverse cell types.