Current applications of poly- cations are limited by their low biocompatibility.

1. Making positively charged polymer biocompatibleYadongWang, University of Pittsburgh, DMR 1005766 Self assembly between cations (positively charged ions) and anions (negarively charged ions) is ubiquitous throughout nature. Important biological structures such as chromatin (DNA assembly) are assembled by a poly-cation and a poly-aninon.Biomedical importance ofsyntheticpolycations arises from their affinity to polyanions such as DNA. However, the toxicity of synthetic poly-cations hampers the realization of their immense potential. We reason that to make a poly-cation biocompatible, our body has to be able to break it down and it should be made from parts naturally found in our body. This design philosophy guided us to a biocompatible poly-cation based on arginine (a positively charged natural amino acid). The poly-cation is orders of magnitude more compatible than conventional polycations. This biocompatibility diminishes when L-arginine is substituted with the un-natural D-arginine or when cells can’t break down the polymer. This design can lead to many biocompatible polycations that will significantly advance a wide range of applications including controlled release, tissue engineering, biosensing, and medical devices. * BJ Zern, H Chu, AO Osunkoya, J Gao, and Y Wang: A Biocompatible Arginine-based Polycation, in press at Advanced Functional Materials

2. Making positively charged polymer biocompatibleYadong Wang, University of Pittsburgh, DMR 1005766 • Current applications of poly-cations are limited by their low biocompatibility. • Our work on philosophy of polycation design would lead to next generations of biocompatible poly-cations. • The hugely improved biocompatibility will enable translation of polycation research in delivery of biological therapeutics, tissue engineering, biosensors, and many other fields. • AO Osunkoya is an African American collaborator. The polymer will be compatible with our body even when highly positively charged if1: our body can break it down and 2: the polymer is made from parts naturally found in our body. The top panel is a polymer made following this design philosophy. The green cells are alive, very few dead cells (red) are visible. Bottom panel: deviation from either rules, the polymer is toxic. Far more dead (red) cells than alive (green). This is validated in animals.