Since the first pacemaker was implanted in a patient almost a half-century ago, implantable devices have become a way of life for many people suffering from heart disease and a range of other illnesses. However, the rapid proliferation of such devices as defibrillators, catheters, and orthopedic implants comes with a price: the body's resistance to foreign objects and the increased risk of infection. By exploiting and manipulating polymers' physical and structural properties, however, medical device professionals are working overtime to overcome these risks in order to optimize implants for short- and long-term use.

Now You See It, Now You Don't
Founded by two plastics engineers, PolyMedex Discovery Group (Putnam, CT) develops biocompatible polymer formulations with a range of properties, including bioresorbable and osseointegrative capabilities. "For long-term implantable applications, we work with resorbable polymers such as polycaprolactone, polylactide (PLA), polyglycolide (PGA), and copolymers combining PLA/PGA," comments Tony Listro, PolyMedex's managing director. "These are examples of bioresorbable polymers that can be tailored to meet the mechanical performance and resorption rates required for applications ranging from nonstructural drug delivery to resorbable screws or anchors."

As a polymer-engineering contract developer and manufacturer, PolyMedex combines different ingredients to create new polymer products that medical device manufacturers can use to produce resorbable devices with unique shapes. One of its materials, beta tricalcium phosphate (ß-TCP), is a very pure grade of tricalcium phosphate with bioresorbable properties. Standard TCP is not an osteoinductive material, which means that it does not stimulate primitive, undifferentiated, and pluripotent cells to develop into a bone-forming cell lineage. ß-TCP, on the other hand, is osteoconductive--it permits bone growth on its surface or down into its pores. As a bicomposite material, ß-TCP/PLA can be used in bone screws and maxillofacial and spinal implants. "The ability to combine ß-TCP and resorbable polymers results in a unique material for demanding orthopedic applications," Listro says.

"The key design parameter required for engineering bioresorbable polymers is how long it takes for them to degrade in the body," Listro notes. "That rate, in turn, depends on the molecular weight and chemical structure of the polymer. A PLA, for example, degrades much quicker than a PGA."

A polymer's degradation time is also influenced by the biochemistry of the host tissue and by how it is designed and extruded. In particular, the shear, heat, and moisture to which the polymer is exposed affect the material's longevity. Luckily, PolyMedex can control these particular factors. "We design processes for maintaining the molecular and chemical structure of the polymer by controlling how long the material is subjected to heat," Listro explains. "Our twin-screw extrusion process is modular, enabling us to design the screw and barrel profile for balancing the amount of thermal and mechanical energy required versus simple conveying of the materials."

Living Stress-Free
In addition to exhibiting osseointegrative and resorbable characteristics, biocompatible polymers are increasingly expected to satisfy another basic physical requirement: crack resistance. Preventing environmental stress cracking (ESC) or in vivo microfissures is a focus of AdvanSource Biomaterials (ASB; Wilmington, MA), a materials science company that specializes in polymer technologies for a variety of applications, including stents, artificial heart components, catheters, and orthopedic devices.

Formulated to enhance biodurability, the company's polycarbonate-based materials allow for the elimination of ESC, remarks Khristine Carroll, senior vice president, commercial operations. Among its polycarbonate-based materials for combating this problem is the ChronoFlex line of medical-grade biodurable polyurethanes, which includes both aliphatic and aromatic diisocyanate polymers.

"Polycarbonate-based polyurethanes were developed to overcome a very public, widely known problem in the field with the use of a polyether-based polyurethane material," Carroll says. A main cause of ESC is the unwanted action of macrophagic enzymes, which attack the ether linkages in the polyether-based polyurethane structure. This attack can cause surface fissures and polymer degradation, which can lead to catastrophic device failure.

While they are suitable for disposable or short-term applications, polyether materials are prone to breaking down during longer-term use. Polycarbonates, in contrast, do not exhibit the ether linkage that causes this deterioration, Carroll says. They are also resistant to oxidation, which is a potential cause of ESC and such surface-degradation phenomena as stress-induced microfissures.

"ASB's biomaterials--including polycarbonate and polyether-based thermoplastic polyurethanes, thermoplastic silicone polycarbonate urethanes, and extrudable and solution-based hydrophilic materials--feature a wide range of chemical and mechanical properties that result in the materials' dimensional stability and ease of manufacturability," Carroll says. Because they are tailored for focused application areas, the company's different materials used for different applications can have the exact same durometer and simultaneously be formulated to achieve greater or lesser elongation or greater tensile strength to optimize customers' end products."

Scaling PEEK's Peaks
Invibio Biomaterial Solutions (West Conshohocken, PA) is investigating other physical characteristics that influence the biological response to polymers: topography and surface chemistry. Specializing in implantable PEEK-based products, the company is learning that there's more to a biomaterial than how it's used or what's in it. As PEEK materials begin to be employed in trauma devices, Invibio is investigating how manufacturing influences the material's surface texture, which affects its ability to prevent bacterial adhesion and decrease the risk of infection.

To determine PEEK's susceptibility to infection, Invibio commissioned the AO Research Institute (Davos, Switzerland), in collaboration with Aberystwyth University (Penglais, UK) and Cardiff University (UK), to compare PEEK's resistance to bacterial adhesion to that of titanium. "This study revealed that bacterial adhesion depends on both the adherent organism and the material surface," explains John Devine, Invibio's strategic development director.

Injection-molded PEEK, for example, is less susceptible to both S. epidermidis 138 and S. aureus V8189-94 colonization than machined PEEK, Devine says. In the case of S. epidermidis 138, the decreased bacterial adhesion to injection-molded PEEK is attributable to its smoother surface, while the adhesion of S. aureus to PEEK appears to be linked to the material's oxygen content, or surface chemistry. "S. epidermidis 138 adhesion to injection-molded PEEK is comparable to the 'gold standard' of orthopedics--titanium," Devine notes. "While less bacterial adhesion on a smoother surface has also been demonstrated in metals, polymeric materials offer greater scope to reduce bacterial adhesion through additives, surface modifications, and slow-release agents."

Over the years, PEEK's biocompatible properties have enabled surgeons to use it in spinal applications such as interbody devices, semirigid posterior dynamic stabilization rods, and--most recently--vertebroplasty devices. "In addition, the material exhibits critical mechanical properties, including high strength, radiolucency, and a modulus comparable to that of native bone," Devine says. "Hence, it can be used as a mechanical spacer in cervical and lumbar fusion devices, offers wear resistance in self-mating applications such as cervical disks, and enables clear monitoring of the surgical site."

However, PEEK's use in other application fields presents new challenges. "The results of the tests performed to determine our material's resistance to bacterial growth illustrate that the biological response to PEEK can be tailored by the choice of manufacturing method," Devine concludes. "Different manufacturing methods result in different surface topographies, and different surface topographies can affect bacterial adhesion."