published_or_final_version / abstract / toc / Orthopaedics and Traumatology / Master / Master of Philosophy

Combinatorial techniques have changed the paradigm of materials research by allowing a faster data acquisition in complex problems with multidimensional parameter space. The focus of this thesis is to demonstrate biomaterials design and characterization via preparation of two dimensional combinatorial libraries with chemically-distinct structured patterns. These are prepared from blends of biodegradable polymers using thickness and temperature gradient techniques. The desired pattern in the library is chemically-distinct cell adhesive versus non-adhesive micro domains that improve library performance compared to previous implementations that had modest chemical differences. Improving adhesive contrast should minimize the competing effects of chemistry versus physical structure. To accomplish this, a method of blending and crosslinking cell adhesive poly(季aprolactone) (PCL) with cell non-adhesive poly(ethylene glycol) (PEG) was developed. We examine the interaction between MC3T3-E1 osteoblast cells and PCL-PEG libraries of thousands of distinct chemistries, microstructures, and roughnesses. These results show that cells grown on such patterned biomaterial are sensitive to the physical distribution and phases of the PCL and PEG domains. We conclude that the cells adhered and spread on PCL regions mixed with PEG-crosslinked non-crystalline phases. Tentatively, we attribute this behavior to enhanced physical, as well as chemical, contrast between crystalline PCL and non-crystalline PEG.

Combinatorial techniques, which overcome limitations of actual models of material research permitting to effectively address this large amount of variables, are utilized in this work to prepare combinatorial libraries of the blend of the biodegradable polymers Poly(e-caprolactone) and Poly(lactic acid). These libraries present continuous composition and temperature gradients in an orthogonal fashion that permit to obtain multiple surface morphologies with controllable microstructures due to the blends low critical solution phase behavior (LCST). The goal of this study is to investigate the effect of surface morphology (surface chemical patterning and surface topography) on cell behavior. The varied surface topography of the libraries is used as a valuable tool that permits to assay the interaction between MC3T3-E1 cells and hundreds of different values of critical surface properties, namely, surface roughness and microstructure size. The outcome of this tool is a rapid screening of the effect of surface topography on cell behavior that is orders of magnitude faster than the standard 1-sample for 1 measurement techniques. The results obtained show that cells are very sensitive to surface topography, and that the final effect of surface properties on cell function is intimately related with the stage of the cell developmental process. Meaning that, for example, areas with optimal characteristics to elicit enhancement of cell attachment is not necessarily the same that promotes cell proliferation. This study imparts an improved understanding of an often neglected factor in biomaterials performance: surface morphology (particularly surface topography). The results provide a new insight into the importance of taking into consideration both chemistry and physical surface features for superior biomaterial design.