Bioengineering - Research Interest
Dr. Siedlecki’s research interests are centered on elucidating the molecular-level processes involved in the interactions of proteins with biomaterial surfaces. These research activities include determining how the physical and chemical properties of synthetic and natural surfaces (e.g. chemical composition, hydrophilic/hydrophobic balance, surface charge, topography) influence protein structure/function relationships, and the development of novel strategies for synthesis and modification of biomaterials at the submolecular level (nanoscale engineering). One area of particular interest is the role of the biomaterial interface on the initial events that promote the formation of surface-induced thrombus on implanted cardiovascular devices. Thrombogenesis is influenced by a series of poorly understood interactions occurring at the blood/biomaterial interface, primarily involving adsorbed and circulating proteins, platelets, and the biomaterial itself.
When a biomaterial is placed into contact with blood, a layer of proteins is rapidly adsorbed on the surface. This protein layer may trigger thrombosis through either of 2 pathways. The first of these involves adhesive proteins such as fibrinogen and von Willebrand Factor. These proteins mediate the adhesion and activation of circulating platelets. The second pathway involves Hageman Factor (human coagulation factor XII) and initiates the contact activation pathway of the coagulation cascade.
It has been demonstrated that surface properties of the underlying biomaterial substrate are important in both the nature and extent of thrombogenesis. However, little is known about the underlying mechanisms behind this phenomena. We utilize a variety of surface techniques and in-vivo and in-vitro biological measurements in order to more clearly define what are the roles of surface chemistry, surface functionality, and surface energy in thrombogenesis in order to provide rationale for further development of blood-contacting materials.
Our research group works very closely with faculty in the Department of Materials Science and Engineering. Together with Dr. Erwin Vogler, we have helped to establish the Hematology at Biomaterial Interfaces Research Group. The goals of this group are to understand the unique biology that occurs at the blood/biomaterials interface. We also work with the laboratory of Dr. Jim Runt to understand polyurethane biomaterials. An AFM image showing the distribution of the separated microphases in a biomedically relevant polyurethane material is shown below. The purple areas represent the H-bonded hard segments dispersed in a soft segment background matrix. The image is 500 nm on each side.
Our research is currently funded by research grants from the National Institutes of Health and the American Heart Association. We also have previously received funding from The Whitaker Foundation. We also receive funding from The Penn State University in the form of a Tobacco Formula Funded Health Research Grant. This funding allows us to investigate nanofabrication techniques for altering the thrombogenic response to implanted materials.