Surface Modifications for Reducing Nonspecific Protein Adsorption

There have been many interests in membrane processes for last decade because of they are extremely efficient, have a low energy consumption, and are easy to carry out. Nowadays, membranes are used widely, especially in biomedical applications such as dialysis, plasmapheresis, and oxygenation of blood during cardiac surgery. However, it is well known that the major obstacle to the extensive use of membrane processes in therapeutic treatment is protein fouling of polymeric membrane materials. Protein deposition on the membrane surface can cause unstable transport characteristics, and cellular interactions with artificial surface are also assumed to be mediated through adsorbed proteins (Deppisch et al. 1998). Designing a polymer surface that rejects proteins (i. e., a nonfouling surface) has been a central issue in the field ofbiomedical materials research (Ikada 1994; Klee and Hocker 1999; Ratner et al. 1979). The adsorption of proteins is highly complex. We do understand that these interactions are determined by the

Qian Yang, Zhi-Kang Xu, Zheng-Wei Dai: Institute of Polymer Science, Zhejiang University, Hangzhou 310027, People's Republic of China, E-mail: [email protected]

Principles and Practice Proteins at Solid-Liquid Interfaces Philippe Dejardin (Ed.) © Springer-Verlag Berlin Heidelberg 2006

hydrophobic/hydrophilic, charged/uncharged, and polar/nonpolar parts of the proteins, and by the nature of the membrane surface. The adsorbed protein film shows time-dependent conformational changes, which may cause desorption or protein exchange. Adsorption processes are described by the typical Langmuir isotherms. After a long contact time, a stationary state is reached, which corresponds to an irreversible protein adsorption (Lundstrom and Elwing 1990; Sonderquist and Walton 1980). However, in spite of extensive investigations (Guell et al. 1999; Kuberkar and Davis 2000; Mueller and Davis 1996; Tie et al. 2003), the mechanism of protein adsorption onto the membrane surface remains unsolved.

Nevertheless, The primary method of reducing protein adsorption onto polymeric materials is surface modification. There are many methods of surface modification, as outlined in Table 1 (Ratner 1995). Among them, the covalent method offers a more stable modification surface as compared to other methods (Gupta and Anjum 2003). Graft polymerization is one such method in which polymer chains are tethered to the material surface. Grafting has several advantages over other methods, including easy and controllable introduction of graft chains with a high density and exact

Table 1. Physical and chemical surface modification methods. UV Ultraviolet, RF radio frequency

Covalently attached coatings

Radiation grafting (electron accelerator and gamma)

Photografting (UV and visible sources)

Plasma (gas discharge; RF, microwave, acoustic)

Gas phase deposition

Ion beam sputtering

Chemical vapor deposition

Chemical grafting (e. g., ozone treatment + grafting) Silanization

Biological modification (biomolecule immobilization)

Modification of the original surface

Ion beam implantation (e. g., nitrogen)

Plasma etching (e. g., nitrogen, argon, oxygen, water vapor)

Corona discharge (in air)

Electron beam treatment

Ion exchange

UV irradiation

Chemical reaction

Nonspecific oxidation (e. g., ozone)

Functional group modifications (oxidation, reduction)

Addition reactions (e. g., acetylation, chlorination)

Conversion coatings (phosphating, anodization)

location of graft chains to the surface, with the bulk properties remaining unchanged. This method is also applied in membrane surface modification to reduce protein adsorption and there are many research groups making efforts to develop membrane surface biocompatibility using this method. Hydrophilic polymers are often used for this purpose because of their wettability and biocompatibility. However, derivatives of native substances existing in the biological systems (such as phospholipid, carbohydrate, and polypeptide), which have excellent biocompatibility, are thought to be efficient for the reduction of protein deposition. Herein, the discussion will focus on these biomimetic polymer modifiers used by our group, although other polymers will also be mentioned.

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