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Amino Acid – Based Zwitterionic Antifouling Polymers: Development, Biofouling Properties and Applications Wenchen Li, Qingsheng Liu, Lingyun Liu*. Department of Chemical and Biomolecular Engineering, The University of Akron, Akron, OH 44325. Statement of Purpose: Surfaces with antifouling properties are critical to many applications, such as biomedical implants, biosensors, drug delivery, and ship hulls. Due to unique zwitterionic and biomimetic nature of amino acids, we developed a group of amino acidbased zwitterionic (AAZ) antifouling monomers, derived from natural amino acids – serine (Ser), ornithine (Orn), lysine (Lys), aspartic acid (Asp), and glutamic acid (Glu), respectively. The structures of five amino acid-based zwitterionic monomers together with their precursors are summarized in Fig. 1. The antifouling properties of the surface-grafted pAAZ to resist protein adsorption, cell adhesion, and long-term bacterial attachment were explored. The cytotoxicity of monomers and nanogels Figure 1. Structures of five amino acid-based zwitterionic made from pAAZ were also investigated. (AAZ) antifouling monomers. The amino acid portion in the vinyl monomers is shaded. Methods: The SerMA, OrnAA, and LysAA were synthesized by reacting the terminal group of the side chain of the corresponding amino acid (-OH or -NH2) with methacryloyl chloride. To obtain AspAA and GluAA, aspartic aid and glutamic acid, with both -amine and -carboxylic acid protected, were first coupled with a vinyl monomer; the intermediate product was then treated with trifluoroacetic acid to remove the protected groups to generate the zwitterionic structure. The corresponding polymer brushes were then prepared on gold via the Figure 2. Adsorption from 100% human blood serum and surface-initiated photoiniferter-mediated polymerization. plasma onto the bare and pAAZ-modified surfaces. The nonspecific adsorption from undiluted human blood serum and plasma was studied by surface plasmon resonance (SPR). Cell adhesion on pAAZ grafted surfaces was evaluated against bovine aortic endothelial cells. P. aeruginosa (Gram-negative) and S. epidermidis (Grampositive), as two model bacterial species, were used to Figure 3. Attachment of P. aeruginosa (a and b) and S. evaluate biofilm formation (14 days) on the pAAZEpidermidis (c and d) after 14-day culture. Bar = 10 μm. grafted surfaces. Considering multiple potential The bacterial accumulation on the pAAZ surfaces after 9 applications (e.g. medical devices and drug delivery) of or 14 days was even lower than on the surfaces grafted the antifouling materials, we further systematically with poly[poly(ethyl glycol) methyl ether methacrylate, evaluated the cytotoxicity of both monomers and polymer one of the most common antifouling materials known to nanogels made from AAZ at various concentrations. date. Very low cytotoxicity was observed for all tested Results: We developed a group of amino acid-based amino acid-based monomers and polymer nanogels using zwitterionic polymers which are ultralow fouling, cytotoxicity assay. biomimetic, and possess multiple reactive groups for Conclusions: The pAAZ-grafted surfaces effectively further conjugation. These materials are highly resistant to resist protein adsorption from undiluted human blood serum/plasma adsorption, cell attachment, and long-term serum and plasma. Moreover, the polymers can highly bacterial adhesion. All five polymers can significantly resist adhesion from endothelial cells, and prevent long reduce protein adsorption by more than 90% compared to term biofilm formation from P. aeruginosa and S. the bare gold surface (Fig. 2). The adsorption variance epidermidis. Not only such materials can be coated on the among 5 polymers are related to their structural biomedical device surfaces to prevent biofouling, they can differences. No cell attachment was observed on pAAZalso be utilized to create or coat nanoparticles (e.g., grafted surfaces. The biofilm formation assay nanogels, gold nanoparticles) for a variety of applications demonstrates that compared to the unmodified gold, the such as targeted drug delivery for cancer treatment. pAAZ surfaces were highly resistant to bacterial adhesion References: after culturing for 1, 5, 9, or even 14 days, representing at Liu QS. Acta Biomaterialia. 2014; 10: 2956-2964. least 95% reduction at all time points compared to the Li WC. Langmuir. 2014; 30: 12619-12626. control unmodified surfaces (Fig. 3). Liu QS. Langmuir. 2016; 32: 7866-7874.