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Our group has performed extensive simulation and experimental studies on the interactions of zwitterionic materials with themselves, ions, water molecules, and biomolecules. From these studies we have worked out molecular-level nonfouling mechanisms and designed new materials using three approaches - rational design, combinatorial discovery and biomimetics.
* S. Chen, J. Zheng, L. Li, and S. Jiang, Strong Resistance of Phosphorylcholine Self-Assembled Monolayers to Protein Adsorption: Insights into Nonfouling Properties of Zwitterionic Materials, Journal of the American Chemical Society, 127, 14473 (2005).
Our group demonstrated that polysulfobetaine (pSB) and polycarboxybetaine (pCB) are ultra low fouling (less than 0.3 ng/cm2 adsorbed proteins). Various "graft-to" and "graft-from" approaches for attaching these zwitterionic groups onto surfaces and controlling their packing densities and film thicknesses have been explored. These materials are evaluated against proteins, cells, bacteria, biofilms, spores, undiluted blood plasma and serum, whole blood, and tissues.
* S. Jiang and Z. Q. Cao, Ultralow-Fouling, Functionalizable, and Hydrolyzable Zwitterionic Materials and Their Derivatives for Biological Applications, Advanced Materials, 22, 920 (2010).
Our group also demonstrated that ultra low fouling materials can be prepared from a large number of polymers with positively and negatively charged groups if they are mixed uniformly. The advantages of these mixed charge nonfouling materials include the simplicity of synthesis, abundance of raw materials, and availability of functional groups. One system of particular interests is the all-natural charge-alternating peptides, such as glutamic acid (E) and lysine (K).
* S. Chen and S. Jiang, A New Avenue to Nonfouling Materials, Advanced Materials, 20, 335 (2008).
Capsule formation has been a major obstacle for the development of implantable medical devices in tissue. No materials have been shown to be free from capsule formation to date. Zwitterionic hydrogels are shown not to stimulate capsule formation upon implantation for 3 months. This finding has strong impacts on implantable medical devices and tissue scaffolds. In addition, zwitterionic-hydrogel-coated glucose sensors are stable in whole blood for >42 days, and cells have high viability in zwitterionic hydrogels.
* L. Zhang, Z. Cao, L. Carr, T. Bai, J.R. Ella-Menye, C. Irvin, B.D. Ratner and S. Jiang, Zwitterionic hydrogels implanted in mice resist the foreign body reaction, Nature Biotechnology, 31, 553-556 (2013).
For cancer diagnostics, blood samples are often diluted to 1 or 10%, further reducing already low biomarker concentrations. Zwitterionic pCB has not only excellent nonfouling properties, but also abundant functional groups for ligand immobilization. Zwitterionic surface platforms enable one to detect cancer biomarkers directly in undiluted blood plasma or serum for the first time. Furthermore, the high stability of pCB-coated glucose sensors (>42 days) well exceeds the performance of commercial sensors.
* H. Vaisocherova, W. Yang, Z. Zhang, Z. Cao, G. Cheng, M. Piliarik, J. Homola, and S. Jiang, Ultralow Fouling and Functionalizable Surface Chemistry Based on a Zwitterionic Polymer Enabling Sensitive and Specific Protein Detection in Undiluted Blood Plasma, Analytical Chemistry, 80, 7894 (2008).
PEGylation is used to increase protein stability, but significantly reduces bioactivity due to its amphiphilicity. Zwitterionic-modified proteins are shown to retain both stability and bioactivity due to its superhydrophilic nature. Zwitterionic amphiphilic copolymers and conjugates are used to form much more stable micelles and liposomes than PEG counterparts. Zwitterionic materials have been used to modify iron oxides, silica, gold, and quantum dots, and zwitterionic nanogels have also been developed. Cationic and hydrolyzable pCB esters are used for gene delivery with high efficacy and low toxicity. For drug delivery and diagnostics, PEGylated nanoparticles have a short blood circulation half-life with a severe immunological response; zwitterionic-modified NPs have a much longer blood circulation time without an immunological response.
* A. Keefe and S. Jiang, Poly(zwitterionic) protein conjugates offer increased
stability without sacrificing binding affinity or bioactivity, Nature Chemistry,
4, 59 (2012).
Conventional cationic antimicrobial coatings have problems with toxicity and losing activity due to attachment of killed microbes onto the coatings. A switchable polymer surface integrating antimicrobial and non-fouling properties has been developed. This integration demonstrates a new concept of “Catching, Killing, Releasing and Resisting”. Furthermore, antimicrobial agents can be integrated into the cationic polymer as its counter ions or hydrolyzed groups. Recently, one smart zwitterionic structure has been demonstrated to switch reversibly between ring (antimicrobial) and linear (nonfouling) forms.
* L. Mi and S. Jiang, Integrated Antimicrobial and Nonfouling Properties of Zwitterionic Polymers and Their Derivatives, Angew. Chem. Int. Ed., accepted (2013).
Biofouling on ship hulls and other marine surfaces has become a global environmental and economic issue. Currently, the majority of marine coating products are based on the release of TBT, Cu or biocides. Our group has successfully developed the first environmentally benign, durable, effective, and low-cost zwitterionic nonfouling coatings. Field tests have been performed in Florida, California, Hawaii and Singapore. This work is highlighted by an ONR press release.