First, biologically active surfaces. Then, targeted functions.
Hydrophilic coatings have come a long way in the medical field. They originated in other industries and now are used as advanced functional components to catheters, guidewires, and other devices. For a number of designs on the market, hydrophilic coatings are the difference between functional and nonfunctional devices.
However, for all of the current advancements over the last 40 years, hydrophilic coatings are still in their infancy and are just now moving toward biologically active surfaces that perform tasks other than imparting lubricity. To appreciate this evolution, it is useful to review the history of hydrophilic coatings for medical devices.
Origins of hydrophilic coatings
Soon after the medical industry began using plastics for its mechanical properties about 50 years ago, it realized that surface interactions with biological systems were equally important. Most of the materials, then, that met mechanical design needs had poor biological interactions.
Coatings were offered as solutions to this problem by imparting consistent surface properties to devices. The oldest patent on a hydrophilic coating obtained for this article was filed by DuPont in 1956, and although it did not describe usage in medical devices, it revealed some basic polymeric-coating modalities that would be mimicked in one form or another by hydrophilic-coating patents in subsequent years. The DuPont patent described a two-layer system, where a bonding layer is first placed over the substrate to provide for consistent binding for a top coat. Later, patents differentiated the technology into heat-cured versus photo-cured coatings, as well as coating systems with a single layer versus systems with a two-layer structure comprised of a bonding layer and a top coat. Common polymeric components in hydrophilic coatings patented in the 1960s, 70s, and 80s included polyvinylpyrolidone (PVP), polyurethanes, polyacrylic acid (PAA), polyethylene oxide (PEO), and polysaccharides. Variations of these materials continue to be studied today.
In the first generation of hydrophilic coatings, lubricity and anti-fouling properties were seen as key needs. These needs arise from surface associations with water, which inhibit protein adsorption generally through steric (i.e., forces due to molecular shape and arrangement), van der Waals (i.e., dipole-dipole interactions, both permanent and induced), and electrostatic interactions. If net attractive forces between proteins and surfaces are low, adsorption is reduced or inhibited. For blood-contacting materials, protein adsorption is a precursor to thrombosis, and reducing the propensity for proteins to stick to a surface is a key approach to making a non-thrombogenic material. Some hydrophilic coatings employ heparin, which is anti-thrombogenic in that it actively catalyzes a reaction between antithrombin and thrombin, which ultimately affects clotting by reducing fibrin formation.
Devices with these forms of coatings are still widely used. Some of the earliest devices approved in the United States were a heparin coated catheter by Cook in 1983, and a hydrophilic guidewire and angiographic catheter system launched by Terumo in 1986. Other hydrophilic catheters followed in the fields of cardiology and urology (1988). By and large, the overarching characteristics of these first generation hydrophilic coatings are that they impart lubricity, biocompatibility, and durability for their applications.
Meeting needs of today'smedical-device market
A large number of medical devices today in the peripheral vascular, urological, cardiological, and ophthalmic fields use first-generation hydrophilic coatings, and other devices in other fields will likely use these coatings in the future. Currently, the market for hydrophilic coatings in medical devices is expanding by 25% annually. For years, such coatings have been used to coat vascular access devices, such as guide wires. Today, the coatings are also used on disposable delivery devices, such as catheters or introducers. Areas for expansion include fertility, contraception, endoscopy, and respiratory care.
Upgraded second-generation hydrophilic technologies allow for expanded function as medical devices progress. These hydrophilic coatings not only provide lubricity and biocompatibility, they also have characteristics common to other types of coatings, such as drug-delivery capabilities.
Hydrophilic coatings are also being called upon to battle infection, a pervasive problem in most medical fields. For example, central venous catheters (CVCs) and peripherally inserted central catheters (PICCs) have serious potential to cause life-threatening sepsis, and catheter infection rates are 5.3 per 1,000 catheter days. Consequently, there's a large push to incorporate antimicrobial materials into hydrophilic coatings, which can present special challenges depending on the coating system.
Each antimicrobial-coating pair or system has different requirements dependent on the relative chemical relationship between the compounds. Thus each system must thoroughly be tested and verified. In general, antimicrobial agents used in today's devices are silver, silver sulfadiazine, chlorhexidine, and an assortment of antibiotics including minocycline and rifampin in combination.
Antimicrobial impregnated catheters have been shown to reduce catheter infection rates. However, as technology for releasing antimicrobial agents from hydrophilic surfaces matures, it becomes evident that other approaches may be equally or more effective. When releasing an antimicrobial agent from a coating, the local concentration of the agent reaches levels toxic to targeted bacteria species, but for devices with long implantation times (>21 days), the release drops off and the local concentration of antimicrobial agent dips below inhibitory levels. For substances such as antibiotics, this can initiate drug resistance if some bacteria are residing in the area.
Additionally, in cases where large numbers of bacteria are able to attach to the surface of the device early after implantation and create a biofilm, they are shielded from the effects of the antimicrobial agent while encased in their polysaccharide-based biofilm and are free to reproduce. In this situation, bacterial colonies are tough to kill. Thus, another current approach in hydrophilic coating technology is to have surfaces that inhibit biofilm formation and bacterial attachment. By modifying the surface with specific chemical species and charges, protein adsorption can be delayed, which can directly or indirectly affect attachment of bacteria to the surface protein layer. Doing this cuts off the process of colonization, and if the numbers of bacteria in the local area can be kept low, biofilm formation can be reduced or delayed.
Coatings of the future
Future hydrophilic coatings promise more targeted functions with regard to tissue interaction. Whereas a current, “second-generation” coating might release a drug or provide a surface that inhibits attachment of a specific cell type, the next generation coatings will likely do this, and more, while retaining all previous hydrophilic features. The driver for this advancement is that current coatings do not completely meet all needs for drug delivery, antimicrobial activity, and specific biocompatibility.
Another driver in the area of antimicrobial coatings is the new Medicare rule requiring hospitals to cover the cost of nosocomial infections arising from catheters. The rule gives incentive to hospitals to create and use more methods to reduce infections.
This suggests that future iterations of hydrophilic coatings will be multifunctional and tailored more specifically to applications. For example, short-term implants will prevent clotting and integration while simultaneously releasing pharmaceutical agents or growth factors at timed intervals. At this time, long-term implants will provide specific tissue integration or lack thereof, such as allowing for different cell types to cover the device surface in different locations (or no locations at all).