By RONALD TRAHAN
BB&T Contributing Writer
And JEFFREY BERG, PhD,
BB&T Contributing Editor
BOSTON — Polymers. These are materials so ubiquitous that they are almost invisible. They come in both natural and synthesized forms, the synthesized forms providing the basis for toothpaste, antiperspirants, vitamins, hair gel, granola bars, disposable diapers, condoms, wound dressings and an indescribable array of other medical products or materials linked to medical products. Polymer is prodigous and prodigal in its many uses.
So, what is a polymer anyway?
"Any material produced by chemical — synthesized or biological — processes that contains a covalently linked, repeating unit," according to Randy Mrsny, PhD, of Welsh School of Pharmacy at Cardiff Unviersity (Cardiff, Wales).
Mrsny's definition was provided at a session of last month's national meeting of the American Chemical Society (ACS; Washington) at the Boston Convention Center, attended by some 14,000 chemical scientists from around the world. One focus of the meeting was a series of four sessions called "Polymer Science of Everyday Things," which included 24 presentations about "how medical devices that people encounter and use every day depend on polymer science."
"Think of a desired application, and/or a desired property, and it is highly likely that a polymer exists or can be designed to perform that task," said Mrsny. "Polymers come in a multitude of forms that can allow for selection of properties based not only on function but also compatibility."
Polymers improve permeability
A presentation on "The Polymer Chemistry of Contact Lenses: Improving Comfort with Bulk and Surface Modification" by Robert Ward, president/CEO of Polymer Technology Group (Berkeley, California), focused on the bulk and surface properties required in polymers made from silicone hydrogel and the innovative processing method that PTG uses, enabling rapid scale-up from small R&D formulation to automated manufacturing for producing silicone-hydrogel polymers in bulk quantities —and the resulting positive effect on the market for contact lenses.
"Silicone-hydrogels make possible a new generation of super-permeable contact lenses that can transmit unprecedented amounts of oxygen to the cornea and, in some cases, enable 30 consecutive days of extended wear without removal," said Ward. "Silicone-hydrogel contact lenses represent a breakthrough over traditional hydrogel soft contact lenses because silicone permits so much more oxygen to pass through the lens, which is essential for a healthy cornea."
In fact, he said, "These next-generation lenses allow as much as seven times more oxygen to permeate than previous contact lenses, which is why they are becoming very popular with both wearers and eye care professionals. Most people find silicone-hydrogel lenses much more comfortable to wear than traditional hydrogel lenses, and this is dramatically growing the market for silicone-hydrogels."
In addition to increased oxygen permeability, comfort is improved through control of surface chemistry, without which high-silicone lenses might actually adhere to the eye, Ward said. Thus, the success of silicone-hydrogel lenses comes from well-known bulk modifications of the lens material (i.e., the inclusion of silicone), combined with sophisticated surface modifications that convert the normally hydrophobic surface of silicone to a very wettable, hydrophilic surface that discourages protein accumulations and supports a normal "tear film" on the outer surface of the lens.
State-of-the-art contact lenses made from silicone-hydrogel polymers that allow for extended wear are expected to represent more than two-thirds of U.S. soft contact lens sales by 2009, according to an equity research report by Robert W. Baird & Co.
Must-use for spinal applications
Alastair Clemow, PhD, president/CEO of Nexgen Spine (Whippany, New Jersey), gave a presentation titled "The Challenge of Spinal Disc Replacement," focused on how biomaterials for disc replacement to treat lumbar spinal stenosis and other spinal maladies must be capable of enduring high loads, acidic environments and have a long service life. "Polymers are flexible," said Clemow, a past president of the Society for Biomaterials (Mt. Laurel, New Jersey). "And they are compliant, which makes a polymer solution more attractive than metals, ceramics and composites."
The "gold standard" for treating lumbar spinal stenosis today is spinal fusion, with a clinical success rate of 75% over 30 years. However, spinal fusion surgery typically requires a long recuperation period of nine to 15 months, according to Clemow, and an incidence of 10% to 30% for adjacent-level disc degeneration over a period of five to 10 years post-fusion.
Nexgen Spine has designed a total-disc prosthesis constructed of elastomeric polycarbonate polyurethanes (another form of polymer) of differing hardness that the company believes provides "near-physiologic motion patterns."
"First-generation artificial discs have demonstrated a lack of resistance to motion, which overloads adjacent structures, because the remaining segments of the spine are required to move more in order to provide the necessary mobility," Clemow said. "Such hyper-mobility can cause further degeneration of the spine, leading to the need for further spinal surgery."
Nexgen has said it believes there will be about 302,000 lumbar fusions by 2010, and that some 65% of these patients will be candidates for artificial discs. "For good reason, there is a lot of interest in generation-2 implants for total disc replacement," Clemow said. "No doubt, disc replacement represents a difficult materials challenge. With a soft inner nucleus, a stiffer encapsulating nucleus and a rigid outer endplate, we believe our materials are optimized to closely match the intact physiologic disc."
Polymer combined with aspirin
A third presentation, "From Willow Bark to PolyAspirin: Discovery and Innovations," by Kathryn Uhrich, PhD, professor of chemistry and chemical biology at Rutgers University (Piscataway, New Jersey), discussed applications for PolyAspirin (a novel polymer form of aspirin, or salicylic acid) used in medical device coatings for cardiac stents, as standalone stents and other products.
"Salicylic acid (SA)-derived polymers inhibit biofilm (bacteria) formation," said Uhrich. "Initial PolyAspirin uses include a drug-eluting coronary stent coating and carrier for antiproliferative agents developed by Polymerix (also Piscataway). In this application, a stent is combined with a pharmaceutical agent and then placed into a human coronary artery to help prevent restenosis (when scar tissue reblocks arteries).
"In more recent studies sponsored by Bioabsorbable Therapeutics (Menlo Park, California), the same pharmaceutical agents are released from a completely resorbable stent. The stent's delivery of drug to the wounded artery is controlled by the PolyAspirin coating that gradually releases a drug into the vessel lining to prevent scar tissue growth, a frequent reaction that leads to restenosis. These biodegradable coatings are unique in that they are non-inflammatory and targeted to disappear in six to nine months after providing their therapeutic effects and delivering other agents," Uhrich said.
According to BCC Research (Norwalk, Connecticut), the value of worldwide sales for all categories of coatings and surface treatment processes used in manufacturing medical devices reached $2.96 billion in 2005 and is expected to grow to $5.31 billion by 2010. The greatest demand for coated medical devices will come from cardiovascular medicine, dentistry, general and plastic surgery, general hospital settings, neurology, ophthalmology, orthopedics and radiology.
Following is a review of other applications of polymer materials, presented at a biomaterials conference earlier this year.
Scaffolds via tissue engineering
Tissue engineering generally requires the use of biocompatible and biodegradable 3D scaffolds for cell attachment and tissue regeneration. A variety of polymeric and nanocomposite materials were presented for use in fabricating biocompatible and biodegradable 3D scaffolds necessary for cell attachment and tissue regeneration. These scaffolds provide the backbone in engineering both hard (bone) and soft (cardiac and bladder) tissue.
Concordia Manuafacturing (Coventry, Rhode Island) is a developer of engineered yarns and fibers. It has developed Biofelt for use as a tissue engineering scaffold. Biofelt is a porous non-woven material with the ability to rapidly grow cells and form organized 3D tissue structures. Biofelt scaffolds are absorbable and can be produced from polyglycolic acid (PGA) and poly-L lactic acid (PLLA) fibers that can be formed into sheets, discs and tubes. Concordia has collaborations with companies seeking to use Biofelt for regenerating the bladder and heart valves by rapidly growing autologous cells and forming organized tissue structures.
NovaMatrix (Oslo), a subsidiary of FMC BioPolymer (Philadelphia), is focusing on the use of medical grade alginates, chitosan and hyaluronic acid in regenerative medicine and for tissue engineering applications. It has developed and patented foams from these materials for use as biofactories in growing cells and islets which are available for licensing. The engineering of alginate foam was the subject of a poster. A dispersion of calcium alginate particles in a solution of sodium alginate has been developed which forms a gel in situ after injection. This self-gelling system is also available for licensing for drug delivery applications.
Polymers for antimicrobial applications
CardioTech International (Plymouth, Massachusetts) is developing a line of proprietary antimicrobial polyurethane polymers from which the antimicrobial agent does not leach out. The active agent is the subject of a pending patent. Its identity has not been disclosed. Studies have shown that these polymers can prevent bioslime formation. The polymers are intended for use in long-term implantable cardiovascular devices and currently are being evaluated by both large and small companies.
The polymers will be marketed under CardioTech's established brand names of Hydromed, ChronoFlex and ChronoThane.
In a separate effort, CardioTech is in early clinical trials on its CardioPass vascular graft for use in cardiac bypass surgery. CardioPass is fabricated from ChronoFlex polyurethane and has a proprietary construction that matches the natural compliance of arteries.
Invibio (West Conshohocken, Pennsylvania), a subsidiary of Victrex (Lancashire, UK), has added barium sulfate to impart radio-opacity to its polyetheretherketone- (PEEK-) Optima polymers which it offers in a range of image contrast grades. The company had a poster presentation on carbon fiber reinforced PEEK-Optima which reported comparable strength to titanium in endosteal dental implants. Also, the presence of mineralization suggests that PEEK may contribute to osseointegration of dental implants. Carbon fiber reinforced cages of PEEK-Optima are being used in spinal fusion surgery.
Polymer Technology Group (Berkeley, California) supplies a line of extrusion, compression and injection molded polyurethanes and polycarbonates for use in medical devices. Its heparin-bonded silicone-polycarbonate-polyurethanes is used in a lumbar spinal disc sold by AxioMed Spine Corporation (Garfield Heights, Ohio).
The company is seeking to become an end product manufacturer, rather than a supplier of individual components and coatings used in medical devices. The company made two presentations on polymer surface modification with self-assembling monolayer end groups.
Other innovative applications
Nerites (Madison, Wisconsin) is developing protein-based adhesive materials that are modeled after materials secreted by mussels. It combines these adhesive proteins with polymers to create novel materials for potential use as a tissue adhesive and as anti-bacterial and anti-clotting coatings on medical devices. It has a co-development program with the Midwest Orthopaedic Research Foundation (Minneapolis). The company's technology is based on the research of professor Phil Messersmith at Northwestern University (Evanston, Illinois).
Biomec (Cleveland), which was recently acquired by Greatbach (Clarence, New York), is developing a polymer coating that mimics the surface of endothelial cells of blood vessels. It has potential use on medical devices including indwelling central venous catheters, cardiac pacing leads and extracorporeal blood pump circuits in bypass surgery.
Artificial Cell Technologies (New Haven) is studying the application polypeptides assembled into multilayer nanofilms for use as extracellular matrices. The adjacent layers adhere to each other by electrical charge interactions. When the film is formed on a flat surface, the result is a coating and when it is formed on a spherical surface, the result is a non-immunogenic artificial cell.
Boehringer-Ingelheim (Ridgefield, Connecticut /Ingelheim, Germany) is in the process of determining the market's interest in its line of Resormer di- and triblock copolymers of polyethylene glycol (PEG) and polylactide/glycolide (PLGA) as matrices for controlled drug release. The pegylated PLGA was found to have comparable strength to untreated PLGA but exhibited faster degradation. The addition of PEG overcomes the limitation of the strongly hydrophobic PLGA. This material has been patented for use in medical devices, such as orthopedic implants.
Inamed (Fremont, California), a subsidiary of Allergan (Irvine, California), is developing an extracellular matrix product for use in immobilizing cells. It is comprised of type I collagen, fibronectin, elastin and heparin sulfate. It is based on bovine and human bioengineered fibroblasts that lay down their own extracellular matrix. It would compete against Matrigel, sold by BD Biosciences (San Jose), a basement membrane containing laminin, type IV collagen heparan sulfate, and entactin that is extracted from mouse sarcoma, a tumor rich in extracellular matrix proteins.
At room temperature, BD Matrigel polymerizes to produce biologically active matrix material resembling the mammalian cellular basement membrane. Cells behave as they do in vivo when they are cultured on BD Matrigel. It provides a physiologically relevant environment for studies of cell morphology, biochemical function, migration or invasion, and gene expression.
Proxy Biomedical (Galway, Ireland) is collaborating with researchers at Case Western Reserve University (Cleveland, Ohio) on the use of its MotifMesh machined 3D tissue porous scaffold made by an electrospinning process. It is used in hernia repair and for correcting facial defects.
MotifMESH is a macroporous, non-woven implant made of condensed PTFE (cPTFE). It is designed to combine the favorable ingrowth and healed strength characteristics of large pore traditional polypropylene mesh, with the biocompatibility and reduced adhesions of PTFE mesh. The product contains polypropylene, which is one of the six commodity polymers in use.