Poly(l-lysine)-g-Poly(ethylene glycol) Layers on Metal Oxide Surfaces:  Attachment Mechanism and Effects of Polymer Architecture on Resistance to Protein Adsorption

Abstract

The generation of surfaces and interfaces that are able to withstand protein adsorption is a major challenge in the design of blood-contacting materials for both medical implants and bioaffinity sensors. Poly(ethylene glycol)-derived materials are generally considered to be particularly effective candidates for the fabrication of protein-resistant materials. Most metallic biomaterials are covered by a protective, stable oxide film; converting such oxide surfaces, which are known to strongly interact with proteins, into noninteractive surfaces requires a specific design of the surface/interface architecture. A class of copolymers based on poly(L-lysine)g-poly(ethylene glycol) (PLL-g-PEG) was found to spontaneously adsorb from aqueous solutions onto several metal oxide surfaces, such as TiO 2 , Si 0.4 Ti 0.6 O 2 , and Nb 2 O 5 , as measured by the in situ optical waveguide lightmode spectroscopy technique and by ex situ X-ray photoelectron spectroscopy. The resulting adsorbed layers are highly effective in reducing the adsorption both of blood serum and of individual proteins such as fibrinogen, which is known to play a major role in the cascade of events that lead to biomaterial-surfaceinduced blood coagulation and thrombosis. Adsorbed protein levels as low as <5 ng/cm 2 could be achieved for an optimized polymer architecture. The modified surfaces are stable to desorption under flow conditions at 37 °C and pH 7.4 in HEPES [4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid] and PBS (phosphatebuffered saline) buffers. The adsorbed layer of copolymer is thought to form a comblike structure at the surface, with positively charged primary amine groups of the PLL bound to the negatively charged metal oxide surface, while the hydrophilic and uncharged PEG side chains are exposed to the solution phase.Copolymer architecture is an important factor in the resulting protein resistance; it is discussed on the basis of packing-density considerations and the corresponding radii of gyration of the different PEG chain lengths studied. This surface functionalization technology is believed to be of value for use in both the biomaterial and biosensor areas, as the chosen macromolecules are biocompatible and the application is straightforward and cost-effective. † Part of the special issue "Gabor Somorjai Festschrift".

Influence of the molecular architecture on the adsorption onto solid surfaces: comb-like polymers

“…The latter agree with the scenario of irreversible adsorption of grafted polymers reported previously by other authors. 25,26 Fig. 2a also gives qualitative information on the mechanical behavior of the adsorbed polymer layers.…”

Adsorption of a PEO–PPO–PEO triblock copolymer on metal oxide surfaces with a view to reducing protein adsorption and further biofouling

“…A high level of carbon-based contamination was always observed (Kenausis et al 2000) on native Ti and SS surface due to adventitious hydrocarbon from air or XPS chamber, and low concentrations of nitrogen, phosphorus, silicon and sulfur were detected as well. After OPA assembly, an increase in carbon and phosphorus content is observed as was expected from OPA composition.…”

“…where PEG stands for poly(ethylene glycol), a synonym of PEO) is well-known to anchor to negatively charged metal oxide surfaces through the positively charged PLL backbone Kenausis et al 2000), and is efficient to reduce protein adsorption. However, the amount of adsorbed PLL-g-PEG on metal oxide surfaces is pH-and ionic strength-dependent.…”

Aqueous Lubrication of SiC and Si3N4 Ceramics Aided by a Brush-like Copolymer Additive, Poly(l-lysine)-graft-poly(ethylene glycol)

“…Little difference in the adsorption and tribological performance is expected in these two polymers [34]. Complete details of the synthesis of PLL-g-PEG can be found in previous publications [32,36,37]. Briefly, 20 kDa poly(L-lysine) hydrobromide (Fluka, Switzerland) was dissolved at a concentration of 100 mM in a 50 mM sodium borate buffer solution adjusted to pH 8.5.…”