Professor Anja Mueller Develops Polymers for Medical and Environmental Applications

CAMP Professor Anja Mueller, from the Department of Chemistry at Clarkson University, is developing green syntheses for a variety of polymers. These polymers are being prepared for medical and environmental applications. In all of these applications, the interactions between the polymer surface and their environment are crucial. These interactions are another focus of Professor Mueller's research. Highlights of her work include projects about the development of: enzymatic syntheses for aliphatic polyethers and polysaccharides, an anti-thrombogenic coating for artificial heart valves, a layered skin scaffold with the ability of drug delivery built in, and of more efficient flocculants and filters for wastewater treatment.

Enzymatic Polymer Synthesis

Horseradish peroxidase (HRP) is a redox enzyme that has been widely used for the synthesis of aromatic and vinyl polyethers. In Professor Mueller's laboratory, HRP is used for a variety of other monomers, therefore expanding the utility and the understanding of this enzyme. In all her studied cases, the polymerization proceeds in water or buffer so no toxic organic solvents or high temperatures are needed. The structure and solubility can be controlled by the exact reaction conditions and the polymer can often be isolated by filtration. Enzymes also increase the control of monomer region selectivity, reducing the cost of separation and purification of the synthesized polymers. HRP is used for phenols, aliphatic alcohols, and sugars in Professor Mueller's laboratory. The simple synthesis developed for poly(glucuronic acid) is particularly exciting, since organic syntheses of polysaccharides have been difficult and always included several protection-deprotection steps that reduce the yield. So far enzymatic polysaccharide synthesis has only been done with specialized, expensive enzymes that are not generally commercially available. Lipase is the other enzyme widely used for polymer synthesis, specifically for synthesizing polyesters. In Professor Mueller's laboratory, lipase is used in water for biodegradable polymers such as poly(lactic acid) (PLA) and poly(glycolic acid) (PGA). These polymers are commonly used for drug delivery. Enzymatic block copolymer synthesis from a variety of monomer mixtures is also studied in Professor Mueller's laboratory. Adhesion to thin films of these polymers is being investigated by common adhesion tests and also by Atomic Force Microscopy (AFM). AFM is important, since protein adhesion might be regulated by nanoscale surface variations missed by bulk scale testing. Mechanical properties and surface structure are also being measured by AFM.

Anti-Thrombogenic Heart Valve Coating

Artificial materials placed into the blood always cause blood coagulation. Blood coagulation on artificial surfaces starts with the adhesion of platelets via specific glycoproteins of the membrane. When platelets adhere to a surface they start the signaling cascade that eventually leads the crosslinking of fibrin and subsequently to blood clot formation. Therefore, a surface that prevents platelet adhesion also prevents blood coagulation.

Cardiovascular implants such as artificial heart valves and vascular stents, are made out of a variety of materials. These diverse materials are needed to allow for the appropriate mechanical properties. All of these materials have different adhesion properties towards blood proteins, but all of them eventually induce blood clotting.

Professor Mueller's group is developing a coating that adheres to the different materials used to make heart valves and prevents adhesion of proteins to the surface. Since the surface properties of the mentioned materials are very different, it will not be possible to make one coating that can be used for all of the materials. Therefore, two thin films will be covalently connected: one that provides strong adhesion to the surface in question and another that prevents adhesion of blood proteins. The anti-thrombogenic thin film will be used for all coatings (Figure 4).

The adhesion layer of the coating will consist of branched polyresorcinol made by enzymatic polymerization by HRP. The anti-thrombogenic layer of the coating will consist of either poly(ethylene glycol) (PEG) or a polysaccharide. Polyethylene glycol has been shown to prevent the adhesion of proteins to surfaces in drug delivery applications. Polysaccharides have also been investigated as non-adhesive surfaces for the body. No organic solvent or toxic chemical will be used in the syntheses, which helps to obtain the Food and Drug Administration's ( FDA) approval for these materials.

Figure 4. Design of an anti-thrombogenic heart valve coating. An adhesive thin film and an anti-thrombogenic thin film will be covalently linked to form the coating. Both thin films consist of branched polymers to increase the flexibility of the coating and reduce the destructive forces resulting from the constant pressure changes in the heart.