Electrospun nanofibers at University of Helsinki Dr. Antti Laukkanen 8.2.2007 DDTC Drug Discovery and Development Technology Center Antti.laukkanen@helsinki.fi

Cell Culture Models On filter, for example Toropainen et al.: Culture model of human corneal epithelium for prediction of ocular drug absorption More difficult with other cell types which need truly 3D environment Toropainen E, Ranta VP, Talvitie A, Suhonen P, Urtti A: Invest Ophthalmol Vis Sci., 2001, 42, 2942-2948.

Extra Cellular Matrix – Should we try to mimic it? Griffith L. and Swartz M., Nature Reviews, 216 (7), 2006

Advanced matrices Schematic drawing of an artificial mimic of an extracellular matrix. The fibrillar skeleton is composed of electrospun biodegradable polymer fibers. The matrix is modified by incorporating cell adhesion ligands on the surface of nanofibers to improve the cell attachment. Hydrophilicity is increased with grafted polymer chains and the cell culturing is controlled with a controlled release of growth factors.

Advanced matrices Electrospinning of functional polymers Post-modification with peptides or direct solid phase synthesis

Functional polymers and functional fibers What is the needed functionality? Fiber should be cross-linkable or water insoluble g, UV, or plasma treatment What other solvents should be tolerated?

Fibers for solid phase synthesis Need for highly stable amino functionalized polymer Should tolerate DMF and NMP Synthesis route of amino-functional poly(styrene). The amino-modification could be conducted before or after the electrospinning. The role 1,4 diaminobutane is twofold: first it will provide the needed amino-functionality on the fibers and secondly it will slightly cross-link the nanofibers. The degree of cross-linking is dependent on the relative amounts of diamine and chloromethyl functionality in the modification reaction.

Electrospinning Instrumentation V Polymer solution Needle High voltage power supply Collector + Taylor cone Simplified set-up

The Electrospinning device

PVP Nanofibers Pore size 20-30 mm

PEVA Nanofibers Water insoluble – stable in physiological conditions Fiber diameter 1 -2 mm, pore size 20-40 mm Easily modified via hydroxyl group Possibility to graft other chains by redox polymerization