Polyelectrolyte Films - Versatile Approach to Generate Well-Controlled Environments for Tissue Engineering Applications

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.

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 properties.

This technique involves sequential adsorption of materials that can form intermolecular interactions. Intermolecular interactions including opposite electrostatic interactions, ⁴ hydrogen bondings^5,6 and acid-base interactions^7,8 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 µm.

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 polymer nanofibers.

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.

References

1. Langer, R & Vacanti JP, Tissue engineering. Science 260, 920-6; 1993.
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, 5999.
4. Decher,G. "Fuzzy Nanoassemblies: Toward Layered Polymeric Multicomposites" Science 1997, 277, 1232.
5. Yang, 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.

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