Univ. of Uppsala, Sweden. Development of Separations Methodology for Biomaterials Characterization; Interfacial Protein Chemistry; Protein-Implant Interaction.

Biomaterials Design: Engineering At The Interface Between Synthetic Matter And Living Tissues

SURFACE MODIFICATION OF BIOMATERIALS

1. Suppression of Surface Fouling by Protein and Bacteria: The effects of chain length and mobility as well as close-packing, on the ability of certain synthetic hydrophilic polymers to protect surfaces from protein adsorption and bacterial colonization are being studied. Analogous behavior is found among natural hydrophilic polymers of proteoglycan type, which appear to protect epithelial surfaces from bacterial adsorption. The findings are relevant for analytical uses of surfaces, e.g. in immunosensing, as well as for surfaces in clinical use, e.g. as catheters or contact lenses.

2. Immobilization of Macromolecules with Optimal Biological Activity: Although simple adsorption is a commonly used technique for protein immobilization, a large number of proteins are shown to undergo severe structural changes when in direct contact with polymeric materials. By contrast, immobilization via polymeric tethers is proving to protect even delicate structures, as seen by microcalorimetry as well as in assays of enzymatic and other activites. The effects of tether length on structural integrity, as well as on transport of substrate/ligand to the immobilized biomolecule are subjects of investigation.

3. Surface Modification for Cell Growth and Tissue Engineering: By treating polymeric surfaces with anchors for cell adhesion peptides or larger integrin molecules in a manner such that their surface concentration is under strict control, it is possible to examine the relationship between the density of attachment sites and the metabolic activity of cells in culture.

4. Colloid Separation Methods and their Uses in Surface Characterization: Field-Flow Fractionation (FFF) is a family of separation techniques which provide physical characteristics of samples through the separation process. This process takes place in thin fluid-filled channels and results from the coupled interaction of an externally applied field with the laminar flow of fluid through the separator. Centrifugal, electric, and hydraulic fields are being applied to effect the separation and provide data on mass, charge characteristics and size of the colloidal samples under investigation. By using polymeric colloids as model biomaterial surfaces, the FFF techniques provide desired information on the nature of adsorbed surface layers.

5. Cell Separations: Using the FFF methodology viable cells are rapidly separated based on differnces in size, charge, density and deformability. Methods are investigated for allowing the cells to attach differentially to particles with different surface ligands, and thereby facilitate selective retrieval of cells from contaminants with comparable physical characteristics.

Dr. Caldwell is the Chairman of the Department of Bioengineering..

Selected References:

S.-C. Huang, H. Swerdlow, and K.D. Caldwell, "Binding of Biotinylated DNA to Streptavidin-Coated Polystyrene Latex," Anal. Biochem., accepted.

G.-Y. Tan, J.-T. Li, S.-C. Huang, and K.D. Caldwell, "Calorimetric Observations of Protein Conformation at Solid/Liquid Interfaces," Advances in Chemistry: Proteins at Interfaces 1994, accepted.

J.S. Tan, D.E. Butterfield, C.L. Voycheck, K.D. Caldwell, and J.T. Li, "Surface Modification of Nanoparticles by PEO-PPO Block Copolymers to Minimize Interactions with Blood Components and Prolong Blood Circulation in Rats," Biomaterials 14, 823-833 (1993).