New Frontiers in Polymer Surface ModificationNew Frontiers in Polymer Surface Modification

Today's sophisticated polymer-based medical devices are more likely to be successful if they are engineered with optimal bulk properties and precisely controlled surface chemistries. For plastics and elastomers, the bulk properties provide structural integrity and determine properties such as tensile strength, flex life, and permeability. It is mostly surface chemistry that determines biological interactions such as biostability, blood compatibility, and the level of inflammation in the human body associated with foreign-body response. To satisfy both sets of requirements, material selection is critical—but materials with optimal bulk properties rarely have optimal surface properties.

Generally, to obtain the desired surface chemistry, a material is chosen primarily for its bulk properties and then surface coatings are applied. Unfortunately, surface coatings may come with drawbacks such as added expense, a limited range of chemistries, lack of durability, and increased potential for bulk-polymer degradation. As a result, there is growing demand for technologies that can offer seamless surface modification during the manufacturing process.

Self-Assembling Monolayer End Groups

Self-assembling monolayer end groups (SAMEs) can be used to address this challenge. They are engineered into biomedical polymers during synthesis to provide a robust, built-in surface chemistry that self-assembles after device fabrication (see Figure 1). Medical product components made from SAME polymers can be manufactured by many high-volume methods, including molding, extrusion, dipping, casting, spinning, melt blowing, and spraying. SAME technology also enables biostability, controlled wetting, and minimal protein adsorption. Using more than one SAME on a single polymer allows a manufacturer's desired properties to be combined on the same surface. Bulk-polymer properties are determined by the selection of a polymer backbone chain, while the end groups dominate surface properties.

This versatile architecture offers the potential for a seamless transition from research and development to manufacturing for new polymeric devices optimized for biomedical applications, including antimicrobial catheters, antithrombotic stents, and lubricious contact lenses. In the case of contact lenses, SAME technology can be used to enhance surface lubricity. It can also reduce protein adsorption while maintaining bulk properties such as oxygen and water permeability as well as the lens flexibility necessary to eye comfort.

In the examples presented in this article, a –CH₃ or methyl group is used as the head group, which is the outermost portion of the molecular chain. If desired, other head groups can be used to couple biologically active molecules to the self-assembled surface. These other groups include peptides, proteins, polysaccharides, and biocides. Such surfaces are similar to those formed by self-assembling monolayers (SAMs). SAMs are currently used in research, but they have a limitation; namely, they are too fragile to survive a surgical procedure.

However, even with this limitation, SAMs offer an advantage over counterparts such as secondary coatings or plasma treatments. Because they form well-defined monolayers, SAMs enable optional attachment of biologically active molecules, which allows for a precisely controlled surface chemistry. SAMs are primarily only useful as model systems, however, and their translation into real medical devices is limited. Using advanced surface analytical techniques and in vitro experiments using SAMs, laboratories are gaining a better understanding of the interaction of artificial materials and the body.

SAME versus SAM

Polymers with SAMEs, in contrast to SAMs, are designed to spontaneously form robust surfaces analogous to SAMs but with much stronger chemical bonds holding them to the surface of the base polymer. A reserve of end groups within the bulk polymer is available to selfreplenish the surface if it is damaged. SAMEs are composed of three parts: a chemically reactive group to bond them to the polymer raw material as it is being made; spacer chains (e.g., alkanes in Figure 1), which act as hydrophobic chains that promote self-assembly on the surface of devices made from the polymer; and a head group presenting a specific surface chemistry.

One example of such a molecule is a SAME-modified polycarbonate urethane using an octadecane end group. Figure 2 shows a comparison between an octadecane thiol SAM on gold and the analogous octadecane SAME. The only difference is the reactive tail group that anchors the octadecane. The SAM uses a thiol group to adsorb to the gold substrate whereas the SAME uses an alcohol group to bond to the polymer chain via a covalent urethane linkage.

SAMEs and SAMs share similar driving forces for self-assembly (see Table I). In sulfur-containing (yellow) SAMs, the monomer is usually chemically absorbed on a gold or other noble metal surface from a solution (e.g., ethyl alcohol). As more of the monomers arrive on the surface, they begin to pack more tightly together, lift off the surface, and assume close packing, with the head group forming the outermost layer. In polymers with SAMEs, the end groups assemble on the surface by first diffusing from the bulk. Once they arrive at the surface, the rest of the self-assembly packing process is the same as a SAM monomer on gold.

In other words, SAME is a two-dimensional nanotechnology that overcomes the complexity and expense of coating surfaces after they are formed. Instead, specific end groups are built into a structural polymer so that it will spontaneously modify its own surface both during and after surface formation.

Advances in biomedical material design focused on surface properties are achieved using highly surface-specific analytical techniques. For example, sum frequency generation (SFG) surface vibration spectroscopy (see Figure 3) has been proven to provide surface-specific information at the molecular level for polymeric surfaces.¹ SFG is based on second-order nonlinear optics and is not sensitive to amorphous bulk properties, but only to the outermost surface monolayer.

The SFG spectra for both the SAM on gold and the SAME attached to a biomedical polyurethane chain are dominated by the terminal methyl groups of the respective C₁₈ chains at 2875 and 2940 cm^–1 (see Figure 4). This demonstrates that both the SAM and SAME are well ordered because the methylene (-CH₂-) peaks in the spacer groups are not observed.

SAME surfaces self-assemble on extruded components. Figure 5 shows the self-assembly of an octadecanol SAME on polyurethane tubing relative to a control without SAME groups. The control spectrum shows only soft-segment methylene groups from the polymer backbone, while the spectrum with SAME technology is dominated by the terminal methyl groups of the octadecane. Further, the waxy octadecane SAME also improves processability, consistency, and surface smoothness of extruded tubing by acting as a permanent processing aid. Table II shows the melt-flow rate of the polymer increased when C₁₈ SAMEs were added, while tensile properties remained good. Traditionally, processing has been assisted by adding low-molecular-weight stearate waxes. These waxes improve processibility; however, they may leach from tubing after implantation. Because SAMEs are a permanent part of the base polymer, they are nonleachable.

Once assembled on the surface of a device, SAME groups resist degradation when immersed in water in contrast to SAMs on gold. If a SAM is placed in water, the surface monolayer will degrade within several hours owing to oxidation. Figure 6 shows that even after 72 hours of exposure to water, SAME groups are unaffected. Hydrophobic interactions among the spacer chain, as well as the stable covalent bond connecting the end group to the polymer, prevent degradation in water while resisting disassembly of the surface. This resistance is a critical property of SAME technology when it is used to create devices that will be exposed to the water-rich environment of the human body.

Conclusion

Until now, SAMs have been made with silanes or by adsorbing thiol-terminated molecules onto gold or other noble metals. The sulfur-containing thiols create well-controlled surfaces for research, but they fall apart within a few days and, therefore, are too fragile for long-term applications. Self-assembly of SAMs is inherent to metal substrates and not to polymeric materials. Furthermore, metal thiol bonds are prone to rapid oxidation and this instability leads to a limited life for SAM surfaces. Similar monomers (without sulfur) may be chemically bonded to high-strength polymers when the polymers are being made using SAME technology. Although permanently attached to the polymer, these SAMEs can still form well-ordered surfaces on any component made from the modified polymer.

Optimal bulk properties and precisely controlled surface chemistries are key to developing sophisticated polymer-based medical devices. Bulk properties provide structural integrity and determine properties such as tensile strength, flex life, and permeability. However, it is surface chemistry that determines biological interactions. SAME technology offers seamless surface modification during the manufacturing process, providing a robust, built-in surface chemistry.

SAME technology can be applied to virtually any polymer, making it useful for many applications. For this reason, it is a candidate technology for use in many biomedical disposables and implantable devices. It is useful in any application in which tailoring of surface properties can improve performance or reliability.

Disclosure

All data in this article are based on laboratory work performed at the Polymer Technology Group.

Robert Ward is president and CEO of The Polymer Technology Group (Berkeley, CA). He can be contacted at [email protected].

References

1. Zhan Chen et al., “Detection of Hydrophobic End Groups on Polymer Surfaces by Sum-Frequency Generation Vibrational Spectroscopy,” Journal of the American Chemical Society 122, no. 43 (2000): 10615–10620.

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