Poly(L-lysine)-g-poly(ethylene glycol) layers on metal oxide surfaces: Attachment mechanism and effects of polymer architecture on resistance to protein adsorption
Gl. Kenausis et al., Poly(L-lysine)-g-poly(ethylene glycol) layers on metal oxide surfaces: Attachment mechanism and effects of polymer architecture on resistance to protein adsorption, J PHYS CH B, 104(14), 2000, pp. 3298-3309
The generation of surfaces and interfaces that are able to withstand protei
n adsorption is a major challenge in the design of blood-contacting materia
ls for both medical implants and bioaffinity sensors. Poly(ethylene glycol)
-derived materials are generally considered to be particularly effective ca
ndidates for the fabrication of protein-resistant materials. Most metallic
biomaterials are covered by a protective, stable oxide film; converting suc
h 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 solutio
ns onto several metal oxide surfaces, such as TiO2, Si0.4Ti0.6O2 and Nb2O5,
as measured by the in situ optical waveguide lightmode spectroscopy techni
que 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 ma
jor role in the cascade of events that lead to biomaterial-surface-induced
blood coagulation and thrombosis. Adsorbed protein levels as low as <5 ng/c
m(2) could be achieved for an optimized polymer architecture. The modified
surfaces are stable to desorption under flow conditions at 37 degrees C and
pH 7.4 in HEPES [4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid] and P
BS (phosphate-buffered saline) buffers. The adsorbed layer of copolymer is
thought to form a comblike structure at the surface, with positively charge
d primary amine groups of the PLL bound to the negatively charged metal oxi
de surface, while the hydrophilic and uncharged PEG side chains are exposed
to the solution phase. Copolymer architecture is an important factor in th
e resulting protein resistance; it is discussed on the basis of packing-den
sity considerations and the corresponding radii of gyration of the differen
t PEG chain lengths studied. This surface functionalization technology is b
elieved to be of value for use in both the biomaterial and biosensor areas,
as the chosen macromolecules are biocompatible and the application is stra
ightforward and cost-effective.