Low Biofouling Chitosan-Hyaluronic Acid Multilayers with Ultra-Low Friction Coefficients Jeroen H. H. Bongaerts, †,‡ Justin J. Cooper-White,* ,§ and Jason R. Stokes ‡,⊥ Unilever Corporate Research, Colworth Science Park, Sharnbrook, Bedfordshire, United Kingdom, and Tissue Engineering and Microfluidics Laboratory, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, Brisbane, Australia Received September 24, 2008; Revised Manuscript Received March 13, 2009 Resistance to biofouling is an advantageous material property in a variety of biomedical and biofluid processing applications. Protein-resisting surface coatings must also be resistant to wear and degradation and in certain applications good aqueous lubricating properties are required. We show that cross-linked polyelectrolyte multilayers, consisting of chitosan and hyaluronan on polydimethylsiloxane (PDMS) surfaces, form a highly lubricating film that is resistant to wear and protein adsorption. The multilayer film shows much stronger resistance to protein adsorption from human whole saliva than both hydrophobic and hydrophilic PDMS surfaces; the latter two showed identical adsorbed salivary film thicknesses. The boundary friction coefficient under aqueous conditions was extremely low (μ ∼ 0.01) between multilayer-coated PDMS substrates and the film is robust against dry rubbing and many hours of tribological experiments in a range of aqueous lubricants. The origins of the assembly’s low friction coefficients and robustness are discussed. In addition, we found that the addition of negative phosphate ions to water lowers the boundary lubricating properties of negatively charged hydrophilic PDMS surfaces by 1 order of magnitude to μ ∼ 0.01. We consider this to arise from the large hydration sheaths and resulting “ball- bearing” properties of the hydrated phosphate ions, which form a lubricating barrier against asperity contact. These findings offer new insights toward biolubrication processes and suggest that chitosan-hyaluronan polyelectrolyte multilayer films have the potential to be used in (bio-) applications requiring low friction as well as resistance to biofouling and wear. 1. Introduction Protein resistance is an advantageous property of material surfaces utilized within medical prostheses and implants, such as contact lenses, catheter tubes, and artificial joints. Nonspecific protein adsorption otherwise can initiate a chain of events that ultimately leads to inflammation and rejection of the device or implant. In addition to being protein resistant, some applications require surfaces to be highly lubricating and, most importantly, robust enough to resist both wear in rubbing contacts and degradation upon exposure to biological fluids (for example, artificial joints). Having a nonfouling surface with low surface friction is also useful in many other bioengineering processes that require the prevention of the formation of biofilms via the adhesion of biological components to device surfaces. One example where this is particularly important is in microfluidic devices targeted for diagnostics and biofluid analysis and manipulation. Surface coatings that are biocompatible, resistant to protein adsorption, and lubricating under physiological conditions thus constitute a highly relevant technological challenge. In particular, aqueous bio(mimetic)-lubrication has become an increasingly active area of research. 1,2 It is well-known that hydrophobic surfaces are especially prone to nonspecific protein adsorption due to hydrophobic- hydrophobic interactions. It is for this reason that polydimeth- ylsiloxane (PDMS), a common material in implants and in biomedical devices, is often rendered hydrophilic by plasma treatment. 3 This converts methyl groups to hydroxyl and carboxyl groups at the exposed surface and also dramatically improves the aqueous lubricating properties of PDMS. 4,5 However, the plasma-treated surfaces are unstable and revert back to being hydrophobic with time. 6-8 Alternatively, adsorption and grafting of certain (co)polymers, most notably polyethylene glycol (PEG) or polyethylene oxide (PEO) can be used to hydrophilise surfaces more permanently. 9 Grafting polymer entities such as amphiphilic block copoly- mers 10,11 and mucin 12 onto bare or plasma-treated PDMS substrates provides effective aqueous lubrication through a hydrated polymeric film, that also provides a steric barrier for asperity contact. Lee et al. 10 showed that poly(L-lysine) (PLL)- g-PEG bound to negatively charged oxide surfaces acts as a polymer “brush” and that the boundary friction coefficient between PDMS surfaces was around ∼0.03 under solvent conditions where the polymer was extended and highly solvated. This surface was shown to display some resistance to protein adsorption and wear in rubbing contacts. The creation of such a biocompatible lubricating surface coating that prevents adsorp- tion of biological components may also be a very suitable starting point for designing surfaces that selectively bind particular proteins; selective binding can be essential for mediating cell adherence and integration of an object under physiological conditions. Mucin coatings, for example, have been shown to provide a protective film as well as simulta- neously promoting specific interactions on a range of implant surfaces. 13-15 * To whom correspondence should be addressed. Tel.: +61 7 3346 3858. E-mail: j.cooperwhite@uq.edu.au. † Current address: SKF Engineering and Research Centre, Kelvinbaan 16, 3439 MT, Nieuwegein, The Netherlands. ‡ Unilever Corporate Research. § The University of Queensland. ⊥ Current address: The University of Queensland, Division of Chemical Engineering, St. Lucia, Brisbane, Australia. E-mail: jason.stokes@uq.edu.au. Biomacromolecules 2009, 10, 1287–1294 1287 10.1021/bm801079a CCC: $40.75  2009 American Chemical Society Published on Web 04/07/2009