(624a) Structurally Controlled Bio-Hybrid Materials Based On Unidirectional Association of Anisotropic Microparticles with Human Endothelial Cells

Authors: 
Lahann, J., University of Michigan
Yoshida, M., University of Michigan, Ann Arbor
Roh, K., University of Michigan
Mandal, S., University of Michigan, Ann Arbor


In recent decades, biomedical researchers have increasingly realized the importance of local interactions between synthetic materials and cells for their macroscopic functionality. To date, a range of different approaches towards custom-tailored biomaterials exist, such as hydrogels, microfabricated biomaterials, or electrospun fiber scaffolds. In addition, so-called bio-hybrid materials have been proposed, where cells and synthetic building blocks form structurally and functionally integrated architectures. While bio-hybrid materials have so far been mostly realized as two-dimensional cell sheets, a next generation of integrated biomaterials may be contemplated, where both synthetic building blocks, such as micro- or nanoparticles, and cells become integral, structural elements that ultimately form the actual biomaterial through directional self-assembly in all three dimensions.

We will present initial work towards a novel type of microstructured bio-hybrid material comprised of anisotropic polymer particles with spatially-controlled affinity towards human endothelial cells. These anisotropic particles consist of two distinct compartments that can exhibit vastly different functions. Here, functional bipolarity was realized by selective surface modification to create polymer particles with two biologically distinguishable hemispheres: one exhibiting high binding affinity for human endothelial cells and the other being essentially resistant towards cell binding. Bicompartmental particles are synthesized by simultaneous electrohydrodynamic co-jetting of two different solutions of polyacrylamide/ polyacrylic acid co-polymers. While the base polymers were generally the same for both hemispheres, different functional groups were selectively incorporated into compartments to enable subsequent surface modifications. For this purpose, acetylene-modified PAAm-co-AA was prepared using a method similar to the one used for biotin modification of PAAm-co-AA. Free acid groups were activated in the presence of EDC/sulfo-NHS and were reacted with propargyl amine at room temperature for 4 hrs and confirmed by proton NMR. Moreover, fluorescein isothiocyanate (FITC)- or rhodamine-conjugated dextran were selectively added to the jetting solutions to confirm particle anisotropy or to monitor unidirectional association between particles and cells using fluorescence imaging. When self-assembled with human endothelial cells, these particles exhibit a strongly bipolar behavior, where one compartment exhibits binding affinity towards human endothelial cells, while the other compartment was essentially non-binding. In this design, particles not only bound to the top of the human endothelial cells, but associated all around the perimeter of cells forming a single particle lining and effectively isolating cells.