Poly(ethylene glycol) (PEG) is widely used for nonfouling materials, but is unstable for long-term applications. Our group has performed extensive simulation and experimental studies of protein interactions with PEG and zwitterionic groups. From these studies we have worked out molecular-level nonfouling mechanisms. A set of new zwitterionic and mixed charge materials with unique properties have been designed and developed based on the principles learned.
Our group demonstrated for the first time that polysulfobetaine (pSB) and polycarboxybetaine (pCB) are ultra low fouling (< 0.3ng / cm2 adsorbed proteins). various approaches for attaching these zwitterionic groups onto surfaces and controlling their packing densities/film thicknesses have been explored. these materials are evaluated against proteins, cells, bacteria, biofilms, undiluted blood plasma and serum, whole blood, and tissues in vivo.
Our group demonstrated for the first time that a wide spectrum of ultra low fouling materials can be prepared from a large number of polymers with positively and negatively charged groups. The advantages of mixed charge nonfouling materials include the simplicity of synthesis, abundance of raw materials, and availability of functional groups. This work opens a new avenue to design new biomaterials. One system of particular interests is ultra low fouling peptides composed of certain positively and negatively charged residuals (e.g., glutamic acid and lysine), which are the first all natural and biologically stealthy materials. New peptide-based nonfouling materials are discovered via combinatorial synthesis and modeling.
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 environmentally benign, durable, effective, and low-cost zwitterionic nonfouling coatings. This work is highlighted by an ONR press release.
Our group demonstrated that zwitterionic materials are highly resistant to nonspecific protein adsorption from undiluted blood and have excellent biocompatibility in vivo. Zwitterionic hydrogel coated glucose sensors are stable in whole blood for >42 days with high and linear response and cells have high viability in zwitterionic hydrogels.
Zwitterionic pCB has not only excellent nonfouling properties, but also abundant functional groups for ligand immobilization. This enables one to perform cancer biomarker diagnostics in undiluted blood plasma and serum for the first time. pCB materials integrated with various sensor platforms are being applied to biomarker discovery and food safety monitoring.
Our group is developing highly stable and functionalizable zwitterionic nanoparticles (NPs) for targeted drug/gene delivery and diagnostics. Zwitterionic materials have been used to modify proteins, iron oxides, silica, gold, and quantum dots. Zwitterionic amphiphilic copolymers and conjugates are used to form micelles and liposomes, respectively. Degradable zwitterionic nanogels have also been developed. These NPs are shown to have superior performance over their PEG counterparts due to the superhydrophilic and functionalizable properties of pCB polymers. Cationic and hydrolysable pCB esters are being used to deliver genes with high efficacy and low toxicity.
A fully switchable polymer surface integrating antimicrobial and non-fouling properties has been developed. The cationic surface can effectively kill bacterial cells and switch to a non-fouling zwitterionic surface, which releases killed microorganisms upon its hydrolysis. The cationic surfaces can also be regenerated. This work was highlighted by Science and Nature Biomaterials.