Tissue engineering, an emerging field in the area of human health care,
combines biology and materials science and engineering to generate products with
suitable biochemical and physiochemical performance to repair or replace
portions of or whole tissues (i.e., bone, cartilage, blood vessels, bladder,
etc.).1 One of the challenges in tissue engineering
applications is to preserve cells normal physical activities on synthetic
scaffolds and maintain tissue-specific function.
Since cells in tissues adhere to and interact with their extracellular
environment via specialized cell-cell and cell-extracellular matrix (ECM)
contacts,2 maintaining tissue-specific function of
artificial tissues depends on cell/scaffold and cell/cell interactions.3 in vivo growth of tissue formation and maturation
are the viability, proliferation, and spreading of cells.
Extracellular Matrix, also referred
to as ECM, is the extracellular part of animal tissue that usually provides
structural support to the animal cells in addition to performing various other
Cell is the basic structural and functional unit of all
known living organisms. It is the smallest unit of an organism that is
classified as a living thing, and is often called the building block of
To improve each of these parameters, increasing efforts have been made to
develop new coatings to improve the biocompatibility of a given surface. The
layer-by-layer (LBL) molecular-level adsorption of polymers through different
interactions is now a well-established methodology for creating conformal thin
film coatings with precisely tuned physical, biochemical, and chemical
This technique involves sequential adsorption of materials that can form
intermolecular interactions. Intermolecular interactions including opposite
electrostatic interactions, 4 hydrogen
bondings5,6 and acid-base
interactions7,8 have been used in
building LBL self-assembled multilayer systems, or referred as polyelectrolyte
multilayer films. Such technique provides a versatile platform for the assembly
of materials and nanostructures of interest in the contexts of functionalizing
surfaces for tissue engineering applications.
Polyelectrolyte multilayers have been deposited on planar substrates and
polymeric electrospun fibers to explore their capability of manipulating the
cell activities such as proliferation and spreading. The electrospun fibers
functionalized with polyelectrolyte multilayer films can mimic the ECM which is
a highly hydrated network hosting three major components: fibrous elements (e.g.
collagens, elastin and reticulin), space filling molecules (e.g.
glycosaminoglycans covalently linked to proteins in the form of proteoglycans)
and adhesive glycoproteins (e.g. fibronectin, vitronectin and laminin).
Professor Lei Zhai and his colleagues at the Nanoscience Technology
Center have explored the applicability of polyelectrolyte multilayers for
the patterning and manipulation of different mammalian cells using the Young's
modulus of multilayer films. By utilizing such different cellular behavior on
different surfaces, we have generated stable cellular patterns by creating
multilayer patterns using laser ablating through photo masks.
Figure 1. Microscope
Images of Hippocampal cells day 20 of the culture (left panel) and neonatal
cardiac myocytes day 100 of the culture (right panel). Scale bar depicts 100
Figure 1 shows the patterns of cardiac cells on PAA/PAAm-bare glass patterns
and hippocampal cells on PAA/PAH-bare glass patterns. The cell patterns are
stable up to more than a hundred days. In comparison, the most commonly used
cell patterning material-poly(ethylene glycol) (PEG) can achieve the stability
only for a couple of weeks.9 Polyelectrolytes
functionalized polymer nanofibers have also been used to promote the cell
growth, and demonstrated better cell compatibility compared to bare glass
substrates (Figure 2).
Figure 2. (A) a
scanning electron microscope (SEM) image of polymer nanofibers. (B) the skeletal
muscle C2C12 cells on glass substrate. (C) the skeletal muscle C2C12 cells on
Polyelectrolyte films have offered not only a versatile approach to generate
well-controlled environments for tissue engineering applications, but also
provide a ideal platform for investigating cell/material and cell/cell
interactions from a fundamental research point of view.
Future research of polyelectrolyte films require collaboration with materials
scientists, biologist, and clinicians to investigate the films stability, and
the response of the immune systems and phagocytic cells.
1. Langer, R & Vacanti JP, Tissue engineering. Science 260,
2. H. K. Kleinman, D. Philp and M. P. Hoffman,
Curr. Opin. Biotechnol., 2003, 14, 526.
3. Li, M.; Mondrinos,
M. J.; Gandhi, M. R.; Ko, F. K.; Weiss, A. S.; Lelkes, P. Biomaterials 2005, 26,
4. Decher,G. "Fuzzy Nanoassemblies: Toward Layered
Polymeric Multicomposites" Science 1997, 277, 1232.
S.; Rubner, M. F. "Micropatterning of Polymer Thin Films with pH-Sensitive and
Cross-linkable Hydrogen-Bonded Polyelectrolyte Multilayers" J. Am. Chem. Soc.
2002, 124, 2100.
6. Sukhishvili, S. A.; Granick, S. "Layered,
Erasable Polymer Multilayers Formed by Hydrogen-Bonded Sequential Self-Assembly"
Macromolecules 2002, 35, 301.
7. Yam, C.; Kakkar, A. K.
"Molecular Self-Assembly of Dihydroxy-Terminated Molecules via Acid-Base
Hydrolytic Chemistry on Silica Surfaces: Step-by-Step Multilayered Thin Film
Construction" Langmuir 1999, 15, 3807.
8. Li, D.; Jiang, Y.;
Li, C.; Wu, Z.; Chen, X.; Li, Y. "Self-assembly of Polyaniline/polyacrylic Acid
Films via Acid-Base Reaction Induced Deposition" Polymer 1999, 40, 7065.
9. Dhir, V.; Natarajan, A.; Stanceescu, M.; Chunder, A.; Bhargava,
N.; Das, M.; Zhai, L.; Molnar, P. "Patterning of Diverse Mammalian Cell Types in
Serum Free Medium with Photoablation" Biotechnol. Prog. 2009, 25, 594.
Copyright AZoNano.com, Professor Lei Zhai (University of Central