(5bd) Engineering Novel Surfaces for Tissue Engineering and Drug Delivery Applications

Over the past decades, the development of new methods for fabricating thin films that provide precise control of the three-dimensional topography and cell adhesion has generated lots of interest. These films could lead to significant advances in the fields of tissue engineering, drug delivery and biosensors which have become increasingly germane areas of research in the field of chemical engineering. The ionic layer-by-layer (LbL) assembly technique called “Polyelectrolyte Multilayers (PEMs)”, introduced by Decher in 1991, has emerged as a versatile and inexpensive method of constructing polymeric thin films, with nanometer-scale control of ionized species. PEMs have long been utilized in such applications as sensors, eletrochromics, and nanomechanical thin films but recently they have also been shown to be excellent candidates for biomaterial applications. During my doctoral research, I engineered these highly customizable PEM thin films to engineer in vitro cellular microenvironments to control cell adhesion and for drug delivery applications.

PEM films were engineered to control the adhesion of primary hepatocytes and primary neurons without the aid of adhesive proteins/ligands. We capitalized upon the differential cell attachment and spreading of primary hepatocytes and neurons on sulfonated polystyrene (SPS) and poly diallyldimethylammoniumchloride) (PDAC)surfaces to make patterned co-cultures of primary hepatocytes/ fibroblasts^1,2 and primary neurons /astrocytes³ on the PEM surfaces. We further demonstrated that PEM-coated PDMS surfaces with different topographies affect the attachment, spreading and even proliferation of three types of mammalian cell, transformed 3T3 fibroblasts (3T3s), HeLa (transformed epithelial) cells and primary hepatocytes.⁴ In addition, we developed self-assembled monolayer (SAM) patterns of m-d-poly(ethylene glycol) (m-dPEG) acid molecules onto PEMs.⁵ The created m-dPEG acid monolayer patterns on PEMs acted as resistive templates, and thus prevented further deposits of consecutive poly(anion)/poly(cation) pairs of charged particles and resulted in the formation of three-dimensional (3-D) patterned PEM films or selective particle depositions atop the original multilayer thin films.⁶ These new patterned and structured surfaces have potential applications in microelectronic devices and electro-optical and biochemical sensors. The PEG patterns developed are tunable at certain salt conditions and be removed from the PEM surface without affecting the PEM layers underneath the patterns. These removable surfaces provide an alternative method to form patterns of multiple particles, proteins and cells. This new approach provides an environmentally friendly and biocompatible route to designing versatile salt tunable surfaces. Finally, we illustrate the use of PEM films to engineer aptamer and siRNA based drug delivery systems.⁷

References:

1.“Controlling Primary Hepatocyte Adhesion and Spreading on Protein Free Polyelectrolyte Multilayer Films” Srivatsan Kidambi, Ilsoon Lee, Christina Chan. J. Am. Chem. Soc., 126 (50), 16286 -16287, 2004.

2.“Selective Adhesion of Primary Hepatocytes on Polyelectrolyte Multilayers: Template for Patterned Cell Co-culture” Srivatsan Kidambi, Lufang Sheng, Mehmet Toner, Martin Yarmush, Ilsoon Lee, Christina Chan. Macromol Biosci, 7(3), 344-53, 2007.

3.“Patterned Co-culture of Neurons and Astrocytes on Polyelectrolyte Multilayer Films for Studying Astrocyte Mediated Oxidative Stress in Neurons” Srivatsan Kidambi, Ilsoon Lee, Christina Chan. Advanced Functional Materials, 18, 294-301, 2008.

4.“Cell Adhesion on Polyelectrolyte Multilayer coated PDMS Surfaces with Varying Topographies” Srivatsan Kidambi, Natasha Udpa, Stacey Schroeder, Ilsoon Lee, Christina Chan. Tissue Engineering, 13 (8), 2105-2117, 2007.

5. “Selective Depositions on Polyelectrolyte Multilayers: Self-Assembled Monolayers of m-dPEG Acid as Molecular Templates” Srivatsan Kidambi, Christina Chan, Ilsoon Lee. J. Am. Chem. Soc., 126, 4697-4703, 2004.

6.“pH and Salt Responsive m-dPEG Acid Self Assembled Monolayers on Polyelectrolyte Multilayers” Srivatsan Kidambi, Christina Chan, Ilsoon Lee., Langmuir,24(1),224-30, 2008.

7. “Aptamer Incorporated Polyelectrolyte Multilayer Films Targeting Influenza Virus's Hemagglutinin Bnding Region” Srivatsan Kidambi, Ilsoon Lee, Christina Chan., submitted ChemBioChem.

8. “Effect of propofol on neuronal gene expression” Srivatsan Kidambi, Joel Yarmush, Wayne Fong, Sangeetha Kamath, Joseph SchianodiCola, Yaakov Nahmias, submitted Neuroscience Letters

9. “Effect of FMRP KO on the pluripotent genes in embryonic stem cells” Monica Casali, Srivatsan Kidambi, John Levine, Martin Yarmush, submitted Stem Cells