(8g) High-Throughput and Combinatorial Technologies in Biomaterial Development and Characterization

As the field of tissue engineering progresses, new technology is essential to accelerate the identification of potentially translatable approaches for the repair of tissues damaged due to disease or trauma. The development of high-throughput and combinatorial technologies is helping to speed up research that is applicable to all aspects of the tissue engineering paradigm. This diverse technology can be used for both the rapid synthesis of polymers and their characterization with respect to local and bulk properties in a high-throughput fashion. The interactions of cells with many diverse materials in both 2- and 3-dimensions can be assessed rapidly through the use of microarrays and rapid outcome measures and with microfluidic devices for investigation of soluble factor and material combinations. Finally, small molecule screening of large libraries is being used to identify molecules that exhibit control over cell behavior, including stem cell differentiation. All of these approaches are aimed to move beyond traditional iterative methods to identify unique materials and molecules that would not have been identified otherwise. Our laboratory is particularly interested in the use of these approaches for the synthesis of libraries of biodegradable and radically polymerizable networks, for the identification of optimal material/cell interactions, and for the isolation of small molecules that can be delivered from biodegradable polymers to control stem cell differentiation. With regards to polymer development, we recently synthesized the first combinatorial library of degradable photocrosslinked biomaterials, namely a library of 120 acrylate-terminated poly(β-amino ester) (PBAE) macromers that could be formed into networks using a photoinitiated polymerization. The synthesis is rapid, does not involve any purification steps, and uses commercially available reagents, components that are important in this type of an approach. This library contains polymers that vary greatly in their property characteristics, including degradation behavior (e.g. mass loss) and mechanical properties (e.g. elastic modulus). We have further developed the library by showing that parameters such as molecular weight and macromer branching significantly influence the resulting PBAE network and bulk properties. We are now using this library to identify optimal polymers to meet design criteria, including optimal degradation profiles and mechanical properties for specific engineered tissue functions. Towards small molecule mediators of stem cell differentiation, we have been screening large libraries of molecules towards their ability to induce or inhibit the osteogenic differentiation of mesenchymal stem cells. We have identified a range of ?hits? that meet statistical criteria with respect to changes in cell behavior (e.g., alkaline phosphatase activity). Currently, we are delivering the identified molecules from biodegradable scaffolds (from the PBAE library) to alter stem cell interactions. Overall, these approaches are accelerating the field of tissue engineering, yet much work needs to be performed for optimal standardization of techniques and data analysis and modeling to take full advantage for material characterization and development applications.