This application is part of a package of four individual R01 applications. The long-term goal of this application is to develop a new paradigm for the optimization of the design of porous polymeric scaffolds based on combinatorial approaches to both polymer design and the exploration of cell-scaffold interactions. The work plan is built around the hypothesis that the interaction of cells with a polymeric scaffold is influenced by both materials-related and architecture-related design parameters. To explore the multifaceted interactions between cells and surfaces, four distinct research aspects have been defined that will be addressed concomitantly by a team of collaborators consisting of a polymer scientist, a biomedical engineer, and a cell/molecular biologist. Initially, a unique, combinatorial library of new polymers will be created such that specific material properties can be varied in a predictable and incremental fashion. Next, microscopically smooth, flat surfaces will be used as a simple model architecture. Mouse L929 fibroblasts, human dermal fibroblasts, osteoblasts, and endothelial cells will be used to examine the cellular responses in terms of attachment, migration, growth, and differentiation. These observations will be correlated to specific surface properties and the adsorption of extracellular matrix (ECM) proteins. Employing poly(DTE adipate) as a representative material, polymeric scaffolds will be fabricated using a series of specific architectural designs. Finally, in an efficient combinatorial scheme, both materials-and architecture-related design parameters will be varied in specific scaffold configurations to examine the cellular responses in 3-D culture conditions. The outcomes of this research plan are threefold: (1) predictive, quantitative models will be developed describing the correlations between material chemical composition, protein adsorption, and cellular responses in 2- and 3-D culture conditions, (2) the design of polymeric scaffolds with optimal properties will be facilitated, and (3) the possible applications in tissue engineering of the first combinatorial library of degradable polymers will be evaluated. The associated research projects of Professor Parsons (using the same library of polymers in hard tissue) and Professor Edelman (using the same library of polymers in cardiovascular applications) will provide the necessary extension of this work to in vivo systems.
