Anja Mueller Develops Polymers for Medical and Environmental Applications
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.
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.
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.
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.
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).
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.
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.