With so many options, manufacturers should arm themselves with enough information to make a smart choice.
|Selecting the right polymer, or blend of polymers, is essential for catheter design.|
Today’s minimally invasive surgical techniques involve incisions that are small enough for a surgeon to insert a catheter into a blood vessel. These small incisions are a conduit through which instruments and devices can be inserted to treat diseased blood vessels, clean out blocked vessels, or deliver clot-dissolving medications directly at the problem area.
Vascular catheters used in minimally invasive surgery face a number of design challenges. While they must be fairly stiff at their proximal end to allow the pushing and maneuvering of the catheter as it progresses through the body, they must also be sufficiently flexible at the distal end to allow passage of the catheter tip through smaller blood vessels without causing significant trauma to the vessels themselves or to the surrounding tissue. This combination of flexibility, high tensile strength, and compression resistance is what makes designing a vascular catheter challenging.
Selecting the appropriate polymer for an optimal catheter design requires an understanding of the biological, physical, and chemical characteristics needed as well as a thorough knowledge of the polymers that are commercially available. This article provides an overview of these elements so that OEMs can select a polymer that meets their particular needs.
Biological Properties. Vascular catheters come in contact with blood as well as the inner walls of the veins and arteries of the circulatory system. As a result, biocompatibility is a must. These catheters must also avoid producing an inflammatory response when in contact with the blood vessels. Such ability is even more critical in catheters that will stay in the blood vessel for an extended period of time.
Vascular catheters must also avoid causing thrombus or clots when in contact with blood. Although most polymers will show some thrombogenic characteristics, this issue can be overcome by coating the surface with a nonthrombogenic material. An example of this is a coating containing heparin. Before the catheterization procedure, a patient may also be injected with heparin, which is an anticoagulant drug. Another anticoagulant drug, warfarin (Coumadin), may be taken orally.
Vascular catheters must be nonmutagenic. They must also be nontoxic and resist biofilm formation and microbial adhesion, because vascular catheters have sometimes been a pathway for infections to enter the body. This is especially true for catheters that stay in the body for an extended period of time.
Let’s Talk Tensile Strength
Like the catheter, the wall between lumens is also thin. The lumen serves specific purpose. For example, in a balloon catheter, one lumen is used for inflating the balloon and another will be used to deflate it. On inflation, high pressure is used. A high tensile strength prevents the lumen from bursting, which could tear the blood vessel and cause severe bleeding or death.
A vacuum is used for deflation. The high tensile strength prevents the lumen from collapsing. If the lumen collapses, the balloon will not deflate, which would make balloon and catheter removal much more difficult. Such a situation requires invasive surgery to remove the catheter and balloon.
Physical Properties. Vascular catheters have thin walls, so selecting a material with high tensile strength is essential (see the sidebar "Let's Talk Tensile Strength"). The catheter is pushed through the blood vessel system and must be able to withstand the twisting and applied torque while being maneuvered through the body’s blood vessels to the blockage or damaged area.
The material selected for the vascular catheter must resist collapsing. Resistance to compression allows the catheter to maintain its shape, which is also important in preventing damage to the blood vessel. Such resistance can be achieved by selecting a material with an appropriate high modulus and good kink resistance. A change in shape of the catheter can make it difficult to remove and may negatively affect its functionality.
Vascular catheters require optimal flexibility for moving through the blood vessel system. The human vascular system is a weaving, nonlinear pathway. In order to travel through it, the catheter must have appropriate flexibility. Selection of a polymer with the appropriate modulus can provide the desired flexibility. There are no specific numbers that define the flexibility for a catheter. Typically the proximal end is stiff, and the distal end is more flexible. The stiffness can and usually does vary along the length of the shaft. The flexibility that is designed in will be dependent on the type and function of the catheter. It is also influenced by the feel the surgeon desires. As an example, the proximal end may range from 110,000 to 300,000 psi, and the distal end may range from 2000 to 10,000 psi. It all depends on the function needed to perform the desired procedure.
A low coefficient of friction is another desired trait. Because catheters are threaded through vascular pathways, they must have an outer surface that can easily slide through the blood vessels. Use of lubricious coatings on the inner or outer surface may also be used to accomplish this.
|Polymers must be made radiopaque to achieve a proper x-ray response.|
Because catheters are basically tubing, extrusion is a critical part of the production process. The polymers must be easily shaped and formed. For example, the distal end of the catheter must be tipped. Catheters usually vary in flexibility from the proximal end to the distal end. Such variation is achieved by bonding sections of differing moduli together. The proximal end is usually stiff while the distal end, or tip, is usually lower in modulus with a soft tip. Ease of fabrication is necessary to accomplish the assembly of variable moduli along the catheter shaft.
The polymers must be capable of being made radiopaque, which is usually accomplished by compounding in radiopaque filler. The filler and the amount of it used should not negatively affect the physical and mechanical characteristics of the polymer. The percentage of radiopaque filler should be sufficient to show up on x-ray and on fluoroscope. For example, thermoplastic polyurethanes, discussed later in more detail, can be loaded with up to 40% by weight of radiopaque filler.
The amount and type of radiopaque filler influence both the effect on physical properties and x-ray response. For example, barium sulfate has a lower x-ray response than bismuth subcarbonate. It takes more barium sulfate to get the same x-ray response as bismuth subcarbonate. Because the density of barium sulfate is about half that of bismuth subcarbonate, it takes up more volume in the polymer mix. The greater the volume that the radiopaque filler takes up in the polymer mix, the greater the reduction in physical properties. So the OEM needs to select the radiopaque filler that will have the best x-ray response and least reduction in physical properties for the specific catheter application.
|Resins need to be stabilized before being made into pellets.|
There is also an economic factor in the selection process. Bismuth subcarbonate is seven to 10 times the cost of barium sulfate. The selection will have an effect on physical properties. The choice needs to be balanced between physical property needs and x-ray visibility.
Another factor to consider is that catheters must be sterilized before being used in the body. Irradiation is a physical method of sterilization. The two most common irradiation methods are gamma sterilization and electron beam sterilization. OEMs must consider the effects on the properties and functionality of the catheter after sterilization because this sterilization method can have detrimental effects on mechanical properties of many polymers.
Chemical Properties. The polymer selected for vascular catheters should not contain leachable additives that could cause failure in biocompatibility testing. Leachable additives could be cytotoxic or have systemic toxicity characteristics. Most commercially available polymers typically have stabilizers or process aides. In addition, the polymer may be acceptable as a material for catheter tubing if it meets USP Class VI classifications. Polymers meeting FDA’s 21 CFR requirements for plastics in contact with food applications are another source for selection, but they still must be tested for biocompatibility—the food requirements do not guarantee compatibility with living tissue.
Fast Facts on Ethylene Oxide
Ethylene oxide (EtO) is a sterilant in the form of a gas. This method of sterilization is used for heat- and irradiation-sensitive medical devices. It is not used in office-based practice due to the long sterilization and aeration times required. EtO is very toxic and irritating to skin and mucous membranes and is considered a hazardous chemical. It must be used with great care.
Microorganism destruction is caused by a chemical reaction. Effective sterilization is dependent on the concentration of gas, exposure time, temperature, and relative humidity. Typical cycle times are 16–24 hours at a temperature of 50˚–60˚C. The product must be aerated after exposure to ensure that no residual EtO is left in the product.
The polymers must remain stable during storage and while in the body. The loss of properties during storage could cause failure when used. In storage, materials could be exposed to moisture (humidity), heat, or light. Some polymers will degrade when exposed to these conditions. For example, moisture and heat can cause reduction in molecular weight. Light can cause loss in molecular weight leading to embrittlement and color change. Polymers and finished products should be stored in temperature- and humidity-controlled warehouses. They should be stored in light-blocked containers or packaging.
As mentioned previously, catheters must be sterilized before they can be used in the body. Chemical sterilization methods are sometimes used, including ethylene oxide (EtO), Sterrad, Steris System 1, and Cidex OPA processes. EtO is typically the method chosen for the sterilization of catheters (see the sidebar “Fast Facts on Ethylene Oxide”).
Most vascular catheters are an assembly of several components. Some components may be different materials that are members of the same family of polymers. Other components may be tubes with different moduli that are assembled so that the softer tip goes into the body first and the stiffer end stays outside to manipulate the device. The ability of the components to adhere to each other is critical to the functionality of the catheter. Whether through thermal bonding or the use of adhesives, the ability to form a strong bond is critical.
The polymer selected should be able to accept coatings. Vascular catheters are often coated for lubricity to protect against microbial growth or to prevent thrombus. The polymer surface is usually treated so that the coatings will adhere. The coatings typically consist of a moisture-sensitive polymer that becomes lubricious when wetted by blood.
They may contain an antimicrobial additive or an antithrombic additive as well. To achieve good adhesion, the surface of the catheter may have to be treated. Examples of treatments are chemical etchants, plasma treatments, and corona surface treatments.
Catheters are exposed to a wide range of chemicals. For example, they are exposed to cleaning solvents for various assembly operations, certain chemicals for sterilization, and possibly pharmaceutical drugs as well. Selection of the polymer should take into account the possible exposure to the types of chemicals that will be used.
Polymers most likely to be chosen for vascular catheters include the following.
Polyurethanes. Thermoplastic polyurethanes are one of the key polymers used in the vascular catheter market, and they dominate the central venous catheter sector. They also are used in some diagnostic and guiding catheter designs. There are many types of thermoplastic polyurethanes available, including polyester-based polyurethanes, polyether-based polyurethanes, and polycarbonate-based polyurethanes. They are available in aromatic and aliphatic grades as well as in a wide range of durometers—from about 75 Shore A to 75 Shore D. Such variety enables the design of catheters with a wide range of characteristics.
|Wax is often used to prevent degradation and sticking of the resin pellets.|
Polycarbonate-based polyurethanes exhibit excellent oxidative stability, which leads to long-term biostability. This is what makes them appropriate choices for long-term central venous catheter applications. There is growing controversy about polycarbonate releasing bisphenol A (BPA), a component of its manufacture. BPA has been banned in Europe and Canada and is currently under review by FDA.
Polyether-based polyurethanes are either aliphatic or aromatic polyurethanes. They soften considerably within minutes of insertion in the body. This promotes patient comfort and reduces risk of vascular trauma. The softening effect is more pronounced with the aliphatic grades than with the aromatic grades. The aromatic grades exhibit better solvent resistance and better biostability when compared with the aliphatic grades.
Thermoplastic polyurethanes do not use plasticizers to obtain softness and flexibility like polyvinyl chloride (PVC). They consist of a hard segment and a soft segment to control softness and flexibility. The ratio of the hard segment to soft segment determines the softness and flexibility. Thermoplastic polyurethanes can be loaded with up to 40% by weight of radiopaque filler, which makes the material detectable by x-ray or fluoroscope.
This polymer contains antioxidants and process aides. To pelletize the resin, the manufacturer needs to stabilize the resin and use a wax to prevent degradation and sticking of the pellets. The additives used are biocompatible.
Polyamides. Polyamides and polyamide block copolymers are another family of polymers used to produce vascular catheters. They dominate the percutaneous transluminal coronary angioplasty area of the catheter market, in addition to being the polymer of choice for balloon catheters and for stent delivery catheters. The polyamides most often used are the nylon 11 and nylon 12 and its other block copolymers. The block copolymers offer a wide range of durometers and flexibility so that the catheter can be designed with variable flexibility along the shaft.
Fluoropolymers. The most commonly used fluoropolymer in the manufacture of vascular catheters is polytetrafluoroethylene (PTFE). PTFE is primarily used as a liner for the inner lumen of a catheter. PTFE allows various devices to slide through the inner lumen easily because it has the lowest coefficient of friction of all polymers.
However, PTFE is difficult to bond to and must be etched to achieve bonding of the outer jacket. The etching can be performed using chemical etchants or plasma etching. A tie layer is then typically used to bond the PTFE inner layer to the outer jacket. Catheters using PTFE cannot be sterilized by irradiation because the irradiation process degrades PTFE.
Polyolefins. High-density polyethylene is also used as a liner for the inner lumen of vascular catheter designs. It does not have as low a coefficient of friction as PTFE, but still offers a coefficient that is better than polyamides and polyurethanes, especially the low-durometer resins. It is generally extruded with a tie layer to bond to the outer jacket.
PVC. This was one of the first materials used for vascular catheters but has mostly been replaced by thermoplastic polyurethanes and polyamides. It is slowly being phased out of most medical devices due to the health concerns of using phthalate plasticizers in PVC. Phthalates are known to be endocrine disrupters, which have been proven to be dangerous to humans—especially young children and unborn fetuses. Due to these concerns, most device manufacturers avoid the use of PVC in new medical device designs.
Polyimides. Polyimides are used in vascular catheter applications in which thin walls, stiffness, and strength are critical. These polymers enable manufacturers to produce small thin-walled catheters with exceptional physical properties such as high tensile strength and modulus. They are used as the proximal shaft portion of the catheter because they are too stiff to be used on the distal end. Polyimide catheters are not made by extrusion. Rather, they are produced by dip coating a solid copper wire in a multiple-pass coating process. Each coating pass is heat cured.
The polyimide layers are built up until the desired wall thickness is achieved. The coated wire is then cut into desired lengths. The ends are stripped of the polyimide coating, and then the stripped ends are clamped into a stretching device. The copper wire is then stretched to reduce its diameter so that the polyimide tube can be slipped off.
PEEK. Polyetheretherketone (PEEK) vascular catheters can be used in the same applications as the polyimide catheters. However, because they are extruded, they cannot achieve as small a size and as thin a wall as the polyimides. The big disadvantage is cost, because PEEK is a relatively expensive material for medical devices. This limits its use to specialty devices.
Polymer selection is the keystone of a successful vascular catheter design. The unique requirements of each application must be matched to the biological, physical, and chemical properties of thousands of available medical-grade polymers. The impact of polymer selection on each fabrication step must also be considered to ensure manufacturability. Achieving a safe catheter design that is both functional and manufacturable requires extensive polymer knowledge and experience.
Charles O’Neil is senior project manager for PolyMedex Discovery Group (Putnam, CT).