Surface Modification of Plastics for MEDICAL DEVICE APPLICATIONS -
By: June-Jim Schepple,Jeff Dykhouse
Plastics, polymers, and resins have become widely accepted for in vivo and in vitro medical applications. Many of these materials have properties that lend themselves well to the manufacture of medical appliances or devices; they are relatively inexpensive and easily molded or formed into complex shapes, and bulk physical properties may be selected from a wide range of parameters such as rigidity and temperature stability. Unfortunately, fabrication procedures that require bonding are difficult to achieve, and biological interface reactions within the body or in the laboratory can limit their in vivo and in vitro performance.
Gas plasma technology offers a technique for easing these limitations by modifying the surfaces of these polymers. By altering just the first few atomic layers, the surfaces of most medical polymers can be rendered wettable so that adhesive bonding can be achieved to troublesome materials such as polyolefins, silicones, and fluoropolymers. In a similar fashion, more exotic processes such as plasma grafting and polymerization can produce totally new custom surfaces without loss of the desirable characteristics of the bulk material.
Plasma is a low pressure, gaseous “glow discharge” process that has been used in the aerospace, semiconductor, and electronics industries for more than 30 years for cleaning, etching, and surface treatment of various materials. Plasma treatment does not affect the bulk of the materials and plasma treated parts are generally visually and physically indistinguishable from untreated parts.
Plasma is now routinely used for controlling the wettability of test tubes and lab vessels, for pre-bonding preparation of angioplasty balloons and catheters, for treating blood filtration membranes, and to manipulate surface conditions of in vitro structures to enhance or prohibit culture cell growth.
Given enough energy, any gas can be excited into a “plasma,” which is a mixture of ions, electronics, excited species, and free radicals. There are many temperature and pressure conditions where this phenomenon will occur, but for practical considerations, radio frequency or microwave energy is commonly used, enabling these processes to take place at low temperatures (25-100¡C) and low pressure (0.1-1 torr), where surface reactions with polymers are feasible without bulk interactions.(1,2)
Plasma “treatment” usually refers to a plasma reaction that either results in modification of the molecular structure of the surface or atomic substitution. Even with be-nign gases such as oxygen or nitrogen, plasma treatment can create highly reactive species at low temperatures. High energy ultraviolet light is emitted in the process, which along with the high energy ions and electrons provide the energy necessary to fracture polymer bonds and initiate chemical reactions at the surface. Only a few atomic layers on the surface are involved in the process, so the bulk properties of the polymer remain unaltered by the chemistry, while the low process temperature eliminates concerns about thermal modification or distortion of the bulk. Unique reactions can be promoted by appropriate choice of reactant gases, and unusual polymer byproducts and structures can be formed.
In many instances, plasma cleaning with benign gases such as oxygen or nitrogen provides adequate surface activation for enhanced wetting and adhesive bonding. With other targeted end results or substrate materials, it may be necessary to utilize reactants which result in “grafting” or surface chemistry modification to achieve the desired results.
It is frequently possible to select reactants that form volatile byproducts upon reaction of the plasma with the substrate material. These, upon desorbtion from the surface of the treated material, are removed by the vacuum pump, resulting in etching of the surface without the necessity for further scrubbing or neutralizing.
Oxidizing species such as air, oxygen, water vapor, or nitrous oxide are often used to remove organics, leaving functional oxygen-containing groups on the surface. These groups greatly enhance wetting, improve adhesive bonding, and, in some instances, create acidic surfaces.(3,4) In at least one instance, sterilization of components has been reported with the use of strong oxidizers such as ozone or hydrogen peroxide vapors.
Reducing gas species such as hydrogen or methane-often diluted with argon, helium, or nitrogen-may be used to remove organics from surfaces sensitive to oxidation. This chemistry may also be used to partially substitute hydrogen atoms for fluorine or oxygen in polymer surfaces. The noble gas species, such as argon or helium, are chemically inert, so they do not combine or become part of the surface chemistry. Instead, they transport energy to break chemical bonds in polymer chains. Broken polymer chains result in “dangling bonds,” which recombine with other reactive sites, resulting in significant molecular restructuring and cross-linking. The creation of dangling bonds allows for chemical “grafting” reactions to occur. This process is involved in several of the biomedical applications.(5)
Active gases, such as ammonia, are used to create amino groups on the surface. This type of functionality has an influence on important surface properties such as pH and Lewis basicity.
Fluorinated species such as Tetrofluoromethane (CF4), Sulfur Hexafluourine (SF6), and perfluorohydrocarbons may be used to induce substitution of fluorine atoms for hydrogen atoms in the surface structure. Teflon-like structures may be created, resulting in a very hydrophobic, chemically inert surface with significant chemical stability.
Polymerization, or deposition, processes may include reactions utilizing a wide variety of gases, including some of the organic or organo-metallic compounds, which deposit nonvolatile polymer films.6 In many instances these reactant gases maybe toxic, corrosive, or otherwise hazardous and require special handling such as heated gas transfer plumbing and measurement instrumentation, reactor exhaust scrubbing, and trapping of reaction byproducts. Polymerization processes will generally necessitate frequent cleaning of the reaction chamber, since all surfaces ex-posed to the plasma will be coated.
BIOMEDICAL DEVICE APPLICATIONS
Surface Wetting. Plasma treatment of polyethylene or polypropylene disposable Petri or Assay dishes greatly enhances wetting. Contact angles as low as 22û have been demonstrated on these materials after only a few minutes of oxygen plasma exposure (see Table 1). When these parts are properly packaged after treatment, the contact angle has been seen to be stable for several years.
Conversely, many medical polymers can be made extremely hydrophobic. Teflon-like films and other similar surface treatments can be easily accomplished on most polymers using fluorinated gases. For example, small diameter tubes can be treated so that when immersed in aqueous solutions they do not draw fluid by capillary action.
One of the simplest techniques used to evaluate plasma surface treatment is a wetting angle test using a contact goniometer. Surface roughness and substrate cleanliness need to be tightly controlled to obtain quantitative data. Standard wetting solutions are often used to obtain accurate surface energy values.
Most untreated polymers are only poorly wettable. Initial contact angles may vary from 60-100û. Table 1 shows a sample of some typical contact angle measurements:
Typical wetting angles,
before and after
Oxygen plasma treatment.(7)
After 5 min. of oxygen plasma treatment, the contact angle decreases significantly.
Adhesive Bonding. Many intravascular devices, such as balloon catheters, are assembled by adhesive bonding of polyethylene components. Chemical surface activation or mechanical surface roughening techniques provide only modest bonding performance, with bond failures noted after as few as eight repetitive inflations. With plasma treatment, up to 40 repetitions are achievable. Typical bond strength data are shown in Table 2.(7)
Typical lap-shear bond
strengths (psi), without and
with plasma treatment.
An oxygen plasma not only removes organic residues but also chemically reacts with the surface to form strong covalent carbon-oxygen bonds, which are much more polar and more reactive than the initial carbon-hydrogen bonds. The increased polarity of the surface accounts for the substantial increases in wettability and adds a degree of covalent bonding to the surface-adhesive interface. (Note that other gases may be used to attain similar results in instances where oxidizing species may be harmful to components of the assembly.)
The bond strength ultimately realized will certainly be affected by:
1. Initial cleanliness of the surface(s).
2. Wetting of the surface by the adhesive.
3. Cross-linking effects.
4. Chemical interaction of the adhesive with the surface.
Any mold release compounds, unpolymerized monomers, plasticizers, or additives that may have migrated to the surface must be removed either by plasma cleaning or washing before surface modification is attempted. Immediate assembly is usually advised after the surface has been prepared. Once the surface has been optimized and bonded, the bond is permanent and does not degrade over time.
In-vivo and in-vitro applications. To increase biocompatibility in vivo, the issue of thrombogenesis (the propensity of a surface to form or initiate clotting) must be addressed. Many unmodified materials encourage protein binding and thus initiate the process of clot formation. To combat this process, antithrombonin (anticlotting) coatings are often applied to the surface, but when dealing with polymers these antithrombonin coatings often fail to effectively bond to the target surface.
Using an active gas plasma, surfaces may be modified by heparinizing or by grafting of antithrombotic functional groups, which achieve effective chemical bonding to previously inert material surfaces. Process variables are dependent upon a range of factors including selection of the base materials, composition of the antithrombotic, and the expected product lifetime.
Animal test results of the procedure on surface modified and heparin coated polyure-thane catheters revealed no protein attachment after a 30-day indwelling. Simultaneous testing on surface modified but uncoated polyurethane catheters disclosed only slight protein attachment, while unmodified and uncoated catheters show severe thrombus formation.
In tests performed on plasma modified blood filters, results showed substantial reduction in platelet retention compared to untreated materials.
Attachment of in vitro cultures. It is sometimes necessary to manipulate surface conditions of in vitro structures so as to encourage or enhance culture cell growth. In specific cases where cell attachment is necessary to ensure proliferation, plasma modified in vitro culture cell containers yielded dramatic improvement over untreated containers. Testing has confirmed that, by using gas plasma surface modification procedures, materials such as PET, polyethylene and K-Resin can yield substantially higher performance than in the untreated state.
1 J.R. Hollohan and A.T. Bell, Techniques and Applications of Plasma Chemistry, John Wiley & Sons, New York, NY, 1974
2 Chapman, Glow Discharge Processes, John Wiley & Sons, New York, NY, 1980
3 T.J. Hook, J.A. Gardella, and L. Salvati, Journal of Materials Research, 2, 132, 1987
4 D.S. Everhart and C.N. Reilly, Annals of Chemistry, 53, 665, 1981
5 M. Szycher and W.J. Robinson, Editors, Synthetic Biomedical Polymers, Technomic, Westport, CT, 1980
6 R. d’Agostino, Editor, Plasma Deposition, Treatment, and Etching of Polymers, Academic Press Inc., San Diego, CA, 1990
7 E.M. Liston, Journal of Adhesion, 30, 198, 1989