Cell transplantation therapy, in which isolated cells are attached to a scaffold for implantation into a host, is attractive for organ replacement and tissue repair for numerous medical disorders including diabetes, liver failure and skin damage. The recent development of poly(lactic acid-co-lysine) (PLAL) by Barrera et al. (1993) represents a potentially enormous step toward attaining the ideal matrix for cell transplantation. PLAL is a biodegradable copolymer containing lysine residues that can be modified with desired ligands. Thus, the conjugation of PLAL to various biological factors opens the door for precision engineering of materials to elicit specific medical responses. In the current proposal, research is directed toward characterizing cell interactions with peptide-coupled PLAL. Peptides corresponding to attachment factors found in fibronectin and laminin will be assayed for their ability to promote cell adhesion, migration, differentiation and/or proliferation of several diverse cell types, including fibroblasts and hepatocytes. Image analysis approaches will be used to monitor migration of cells, and cell biological and biochemical techniques will be invoked to measure proliferation, adhesion and differentiation. In addition, peptide coupling to PLAL will be explored in detail to determine ideal peptide concentrations, cross-linking chemistry, and optimal length between the peptide and polymer. This work should shed insights into ways by which effects of natural biological matrix proteins can be reproduced. From this work, supports can be designed to serve as a temporary extracellular matrix to guide cells toward synthesizing their own matrix and restructuring a desired tissue.
