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Vertical LSR Molder Eliminates Flash Trimming

Originally Published January/February 2001

EQUIPMENT NEWS: Molding Equipment

Vertical LSR Molder Eliminates Flash Trimming

Machine to debut at MD&M West

As the market for medical disposables continues to grow, so does demand for molding equipment and tooling suited for the efficient, cost-effective production of compliant parts. In this section, equipment manufacturers describe recent additions to their product lines, such as a molding machine designed for the manufacture of intraocular lenses that is being introduced for other device applications. A briefcase-sized system for tipping and welding thermoplastics into finished catheters, a rotary table injection press suited for the assembly of IV components, and highly precise core pins used in the manufacture of syringes and related products are also featured.

A liquid-silicone injection molding machine originally developed for the manufacture of intraocular lenses will be introduced to industry for other applications at the MD&M West 2001 show in Anaheim, CA. Created by Kuntz Mfg. Co., Inc., the LSR 2010 meets the unique requirements of liquid silicone rubber (LSR) micromolding applications by accomodating mold materials of varied viscosity levels. "Having manufactured liquid injection molding equipment for more than 10 years and listening closely to our clients, we feel the LSR 2010 taps into the best concepts for a very versatile machine," says Axel Kuntz, vice president of operations. The molding machine offers dependable shot size, repeatability and accuracy, and flash-limited molding when using precision molds.

Designed by Kuntz Mfg. Co., Inc., a vertical molding machine is suited for the production of miniature to medium-sized products in clean environments.

The LSR 2010 features microinjection technology that was developed for intraocular lens manufacturing, which does not allow flash trimming. Using precision molds, each part is formed accurately, with no spillover or other irregularities, removing the need for operators to touch the finished product. Because there is no barrel screw, the injection design minimizes the amount of material waste. The machine is nonhydraulic and thus is less unlikely to cause contamination in cleanrooms.

Other enhancements to the LSR 2010 include a vertical layout with a 47 x 48-in. footprint and compatibility with standard molds measuring up to 8 x 8 in. The model also offers standard platen mounting hole patterns, adjustable daylight settings in 1-in. increments, and up to a 10-tn clamp force.

The machine was designed for miniature to medium-sized, single- or multicavity parts, and for insert molding applications. Automatic door opening provides easy part removal. Material can be fed from cooled, prefilled disposable cartridges or from in-line mix and metering equipment.

The LSR 2010 is suited for the production of implantables and other medical applications, as well as insert and overmolding operations. The unit is small enough for R&D setups and durable enough for nonstop 7-day production runs.



Press assembles medical consumables

A rotary table injection press from C. A. Lawton can be automated to load inserts such as needles and lances.

A 10-tn rotary table injection press is available to device OEMs for the assembly of tubes, IV manifolds, and related consumable medical devices. Designed and built by C. A. Lawton Co., the press can also be automated to load inserts such as needles or lances, or to remove finished devices. Presses can be custom built in 10- to 30-tn sizes, or in any size necessary to suit a requested application. Allen Bradley Pro-Set injection controls can be integrated into the presses to provide adaptive tuning and consistent shot sizes regardless of environmental conditions.
 
 
 

Compact molder suited for cleanroom production

A compact injection molding machine with a 2100 x 800-mm footprint incorporates an injection unit that meets the same quality criteria as much larger units. Developed by Arburg Gmbh + Co., the unit is designed for the molding of small technical parts and can be easily adapted to cleanroom use. "The combination of small floor space, low purchase cost, highly flexible production capabilities, and the quality of the molded parts makes this a very interesting machine for manufacturers of medical parts," says director of corporate communications Christoph Schumacher.

An Arburg press combines a small footprint with features typically found in larger units.

To achieve a small footprint while maintaining acceptable performance levels, Arburg placed the control cabinets underneath the injection unit. Likewise, the water manifold has been integrated into the machine base behind the control cabinets. The plasticizing unit has been optimized for the production of very small parts: the screw has a 15-mm diameter and an L/D ratio of approximately 18:1.

The pivotable injection unit is designed as a modular assembly for easy removal, and the plasticizing cylinder incorporates a coupling that snaps into a central socket. The two-stage programmable injection speed profile includes adaptive temperature regulation, and back pressure can be programmed to positive and negative values.



Unit designed for prototyping, small parts

The AB-300-4 from A.B. Machinery comes with a foot-operated hopper.
Also suited for cleanroom production, an ergonomical plastic injector incorporates "no-lube" pneumatic components and a stainless-steel injection chamber and piston. The unit was designed for insert molding, prototyping, and production of small parts. The AB-300-4, available from A.B. Machinery, features a foot air-operated material hopper that frees the operator's hands for faster handling of molds. The mold stop and clamp are adjustable to accommodate various mold thicknesses. The AB-300-4 features a 4000-lb clamp force, 0.25-oz shot capacity, and 6333-psi injection pressure.
 
 


Catheter-forming system in a "briefcase"

A briefcase-sized molding machine is capable of forming and welding thermoplastics such as polyethylene, fluoropolymers, polyvinyl chloride, polypropylene, and polyurethane. The PIRF system from SEBRA measures 3 x 7 x 10 in. and molds at up to 400°C. It can be used to produce 0.5–13 mm diameters for single- or multilumen catheters measuring 1–19 mm. The molding machine includes a solid-state RF generator, a flexible computer controller, and a compact power supply. Now CE marked, the PIRF system provides fast, precise, and repeatable control of heat time, cool time, and insertion pressure.



Company offers core-pin expertise

Core pins that feature multiple complex steps, counterbore-style heads, end detailing, and flat work can be custom manufactured for medical molding operations. Available from Ross Tool Corp., the core pins are precision ground from M-2 and 300- or 400-series stainless steel. They can be made as small as 0.01-in. diam and in lengths ranging from 0.5 to 8 in. Used for manufacturing syringes, tapered luer components, catheters, and related medical products, core pins provide 0.0001-in. tolerances for diameter and 0.001-in. tolerances for length. Styles include shoulder-type, bottom, and beveled, or a combination with 0.005-in. steps.



Stainless-steel molds

High-tolerance molds are designed and built by Mold Craft Inc. using state-of-the-art CNC coordinate-measuring equipment and machining centers.
 
High-volume, multicavity, and multimold projects are a specialty of Mold Craft Inc., which designs and builds injection molds. Using a CNC coordinate-measuring machine, Mold Craft can provide dimensional certification of the mold steel and first-article inspection of the plastic parts. Leader pin and bushing holes are precision bored, and parting-line locator technology provides exact pocket sizing and location. The company can process 24 x 48-in. molds that weigh up to 8000 lb; they can be fabricated from full and prehardened 420 stainless steels, precipitation hardening stainless steel, H-13, and standard P-20 mold base steels. —Katherine Sweeny


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Copyright ©2001 Medical Product Manufacturing News

Microscope accessory improves operatory comfort and productivity

Originally Published January/February 2001

HOTLINE

Microscope accessory improves operatory comfort and productivity

Norbert Sparrow

Designed to replace traditional eyepieces on mono, routine, research, and stereo microscopes, a device significantly improves the performance of conventional binocular microscopes. The ISIS eyepiece, developed by Vision Engineering, uses the company's multienticular and expanded pupil technologies to enhance operator comfort and increase productivity.

The ISIS eyepiece permits greater freedom of head movement, thus reducing operator fatigue.

"Compared to the conventional binocular setup, you can move your head back and forth and find your optimal working distance," says UK-based sales and marketing director Mark Curtis. In fact, the distance between the user's eyes and the eyepiece is increased by a factor of four compared to conventional instruments, allowing workers who wear eyeglasses to avoid physical contact with the microscope without sacrificing a loss in the field or quality of vision. Expanded pupil technology dispenses with the requirement to precisely align the eye with the center of each eyepiece, adds Curtis. "You can move your eye around and look at the outer parts of the optical field without losing the full image area."

Another advantage of the ISIS system, according to Curtis, is the elimination of mouches volantes or "floaters" in the eye, tiny tissue fragments that float within the eyeball and hinder microscope viewing operations. The expanded pupil principle prevents these elements from cluttering the image. "This eye defect is accentuated as you get older," notes Curtis, "and it affects a lot of highly qualified personnel in labs that need to constantly pull back from the microscope and blink their eyes to rid themselves of these clouds."

ISIS can be installed in seconds on microscope systems produced by Leica, Nikon, Olympus, Zeiss, and a host of other companies. "It's a low-cost alternative to our Lynx and Mantis machines, suited for companies that aren't ready to invest in a whole new system," explains Curtis, but who are looking for ways to increase productivity and operator comfort."

For more information, contact Vision Engineering at 570 Danbury Rd., New Milford, 06776 CT; phone: 860/355-3776; fax: 860/355-0712; e-mail: [email protected].


High-Frequency Ultrasound Provides Nondestructive Seal Testing Technology can be used on interface bonds and packaging seals

Katherine Sweeny

A C-Mode scanning acoustic microscope (C-SAM) allows the nondestructive inspection of bond sites and seal areas for medical devices and pharmaceutical packaging. Acoustic microimaging (AMI), developed by Sonoscan Inc. (Elk Grove Village, IL), uses high frequency ultrasound to detect microscopic air gaps that occur in the form of voids, cracks, delaminations, and disbonds. The microscope generates images by mechanically scanning a transducer in a raster pattern over the sample. A focused spot of ultrasound is generated by an acoustic lens assembly at 10-230 MHz frequencies and is brought to the sample by a coupling medium, usually deionized water or an inert fluid. The transducer alternately acts as a sender and receiver, being electronically switched between transmitting and receiving modes. A very short acoustic pulse enters the sample and the return echoes are used as a basis for investigating anomalies at specific intervals within a part or seal.

An acoustic microimaging station can detect microscopic air gaps in bonds and seals.

The technology can be applied to a variety of materials and package types including laminate films and foils, formed and molded cassettes, and cartridges. AMI can assist in R&D and process control to help support product validation in ISO 9000 and CGMP production environments. For more information, contact Sonoscan Inc. at 2149 E. Pratt Blvd., Elk Grove Village, IL 60007; phone: 847/437-6400; fax: 847/437-1550; e-mail: [email protected].


Integrated System Molds, Handles, and Tests Miniature Components

Suited for molding components weighing as little as 0.8 mg, an integrated system for the production of microcomponents incorporates an electric molder and parts handling, testing, and packaging modules. Cleanroom conditions are maintained inside the system housing to prevent contamination of the injection molded parts. Battenfeld of America Inc. launched the electric machine in North America at the NPE show in Chicago.

The Microsystem's integrated modular design enables redued cycle times in the production of low-weight miniature components.

Developing a system that would enable the cost-efficient production of miniature components was one of the key challenges faced by Battenfeld when the company embarked on the Microsystem project at its facility in Austria. By combining a stable injection unit with a rotary table design that allows parallel movements, the firm was able to achieve a 50% reduction in cycle time. The rotary table requires only two-axis handling, and the parts are transported via suction cups to the quality control and packaging stations.

At its world premiere in Europe, the Microsystem was shown molding a hearing-aid housing weighing 2.2 mg. Since that time, additional testing on parts and materials for use in devices has been conducted, according to project manager Martin Ganz. "We have tested two other medical parts recently," says Ganz. "One is a hearing aid and the other is a product that involves the use of biodegradable materials." Other materials slated for testing on the Microsystem include PEEK, PPS, and liquid crystal polymers. "Metal injection molding applications are also on the schedule," adds Ganz. "So you see, there are many potential medical device applications using this system." One application for which Ganz sees a bright future is the production of lenses used in diagnostic equipment. "Manufacturers require extremely small and highly accurate lenses," says Ganz, adding that Battenfeld's product is well suited for the molding of these components.

Other potential applications include the production of miniature parts used in sensors, pumps, implants, diagnostic equipment, and microsurgical instruments.

The company also offers a gas-assisted injection molding process called Airmould (in which nitrogen is introduced into the interior of the mold cavity) or Airmould Contour (the gas flows between the rear of the molding and the part wall). This technique enables a reduction in cycle times and tonnage requirements while enhancing the molded part's surface finish by eliminating sink marks. Dimensional stability is also improved and part weight is reduced, thereby lessening the amount of material used.

For more information, contact Battenfeld of America Inc., 31 James P. Murphy Hwy., West Warwick, RI 02893; phone: 401/823-0700; fax: 401/823-5641.



MPMN January/February 2001 table of contents | MPMN home page

Copyright ©2001 Medical Product Manufacturing News

INDUSTRY NEWS

Originally Published January/February 2001

INDUSTRY NEWS

Welch Allyn Launches OEM Business Unit

Welch Allyn Inc. (Skaneateles Falls, NY) has established a business unit dedicated to the development and sales of subsystems and modules for patient-monitoring OEM applications. The formation of Welch Allyn OEM Technologies (Beaverton, OR), which was announced at the recent Medica trade show in Düsseldorf, Germany, was spurred by the company's acquisition of Protocol Systems Inc. and its Pryon OEM subsidiary in August. "Pryon is a leading supplier of CO2 monitoring equipment, and this expertise has provided us with an avenue to offer a broad range of vital signs technology to OEMs," says marketing and communications director Grant Gibson, who fielded questions about the launch from the company's stand at Medica.

One-piece blood pressure cuffs developed for OEM applications have been shown to last more than 100,000 inflation cycles.

The convergence of Pryon's noninvasive blood pressure, ECG, and capnography subsystems with Welch Allyn's thermometry and blood pressure cuffs has created an "opportunity to shrink costs as well as product size for our customers," says Gibson. The POEM noninvasive blood pressure module that was introduced at the show is an illustration of how device manufacturers will benefit from the pooling of resources, he says.

"The POEM module is smaller, lighter, and draws less power than competing products," says Gibson. It incorporates a pneumatic design that is unique in products of this type, he adds. The palm-sized module consumes 4 W maximum power—17 mW in sleep mode—while providing a 6-second inflation rate. Weighing only 124 g, the product is available in two versions: the robust POEM Basic and an advanced module with Smartcuf motion artifact rejection algorithms. Smartcuf's capability to furnish accurate noninvasive blood pressure readings despite patient shivering, vehicle vibration, and other sources of motion artifact has been documented in an independent study.

A palm-sized noninvasive blood pressure module that consumes 4-W maximum power was introduced by Welch Allyn OEM Technologies at the Medica trade show.

One-piece blood pressure cuffs were also introduced for the OEM market by Welch Allyn at Medica. The one-piece design provides an alternative to traditional cuff-with-bladder combination systems, thus eliminating the need to remove, clean, or replace the bladder, according to the company. The latex-free cuffs are constructed of 200 denier nylon, and have been engineered to meet clinical standards for cuff sizing and fit as set forth by the Association of Medical Instrumentation and the American Heart Association. During tests, the cuffs lasted more than 100,000 inflation cycles; the one-piece construction and flat port tubing connectors that protect against leakage are among the features designed to prolong the product's life cycle.

"These products are only the first splash for Welch Allyn OEM Technologies," says Gibson, who notes that the development of smart modules is a particular area of focus. —Norbert Sparrow

Sensor with Syringe Packaging Applications Featured at Assembly West Show


Sensor with Syringe Packaging Applications Featured at Assembly West Show

A collision sensor that ensures the correct placement of syringes in trays and robotic systems suited for the assembly of small parts were among the products featured at Assembly West in Long Beach, CA, a smaller regional version of Assembly Technology Expo.

This collision sensor from Applied Robotics can be used with pick-and-place and other machines.

The collision sensor was one of the products on display at the Applied Robotics (Scotia, NY) booth. The dynamically variable QuickStop sensor can be used in welding and cutting applications or on packaging machines. Regional sales manager Stephen Quirini demonstrated an application in which the sensor was incorporated into a machine that placed syringes in a tray. When the machine accidentally slammed a syringe into the side of the tray, QuickStop immediately shut it down and sounded an alarm to alert the operator.

QuickStop operates on an air-pressure system. A regulated air supply provides positive, variable pressure to hold the sensor rigid during normal operation. If there is an impact, the air-chamber seal is opened, and a shutdown signal is immediately sent to the system controller. Features include dynamically variable trip points, permanent repeatability, and easy programming and resetting. The sensor is suited for use with robots, linear actuators, and pick-and-place machines.

Small robots like this one from Denso alleviate tedious assembly tasks.

Robots designed for the assembly of small parts and electronic components were featured at the stand of Denso (Long Beach, CA). According to Brian Jones, senior product manager, these robots alleviate the tedious, repetitive tasks that can lead to worker injuries. Several different robot models were demonstrated, including Models VS and TETRAM. The VS features a flexible, compact body, 652-mm reach, and high payload capacity, while the TETRAM has a 460-mm reach, pressing force up to 300 lb, and multiple-angle mounting. Jones told us an interesting fact: Denso is itself the world's largest user of small assembly robots, employing thousands of them in its manufacturing facilities to assemble the robots it sells.

Quickdraw Conveyor Systems Inc. (Burnsville, MN) showed off its belt-edge conveyors, which are designed for the accurate conveyance of PCBs, BGA flex arrays, MCMs, and ceramic substrates within electronic assembly, test, and inspection equipment. John Fresonke, a company sales rep, said that features especially beneficial to medical device manufacturers include the system's clean and quiet operation, which makes it suitable for cleanroom use. The belt-edge conveyors offer customer-specified or adjustable widths, many standard or custom rail lengths, standard or low-profile extruded rails, zone-control or product-metering options, and a variety of motors. Quickdraw offers a range of other types of conveyor systems, and, Fresonke explained, the company can not only customize its standard units but can also build them from the ground up for unique applications.

Readers may be familiar with >sortimat (Torrance, CA), a company that has been featured in this magazine and that is heavily involved with the medical device and pharmaceutical industries. Sortimat manufactures high-performance assembly machines and feeders for complex assembly processes. Being a systems supplier, the company offers a variety of solutions from simple stand-alone units to complex production lines.

Sortimat sales engineer Morrie Rice explained that, in addition to the need for an integrally hygienic product, medical applications typically require a modular design concept to allow for flexible manufacturing processes.

Examples of medical products routinely processed by sortimat machines include two- and three-part disposable syringes, drip chambers, infusion catheters, infusion and transfusion sets, two- and three-way stopcocks, aerosol valves, atomizer pumps, puncture pieces for aeration caps, and safety syringes and catheters. —Karim Marouf

Smart Products Inaugurates Cleanroom


Smart Products Inaugurates Cleanroom

Although Smart Products specializes in components for low-pressure and low-flow applications, the company's business strategy is anything but low profile. After almost doubling in capacity in 1999, the supplier of check valves, fittings, and pumps has announced the addition of a cleanroom to its facility in San Jose, CA. According to owner Doris H. Patterson, it's all a matter of keeping the customer satisfied.

A supplier of valves has installed a Class 10,000 cleanroom suited for molding and assembly operations.
"More and more of our business is geared to the device industry," says Patterson, "and we were missing out on opportunities by not having an on-site cleanroom. Our clients are making increasingly stringent demands," she adds, "and we are committed to responding to their needs." Suited for molding and assembly operations, the Class 10,000 facility is currently equipped with a 55-tn Milacron Roboshot electric molder. "We are forever adding capabilities and services," stresses Patterson, noting that the company has engineers on staff who can assist in product design and mold building. Offering more than 16,000 variations on check valve configurations, Smart Products can design a custom valve from stock parts, specifying all materials and fittings as well as the cracking pressure. A line of plastic fittings, and diaphragm and air pumps are also available.—Norbert Sparrow

Mapping the Future of Gene Research

Originally Published January/February 2001

Erik C. Dellith

Just 10 years ago, students in college-level genetics classes speculated about how advances in gene research would open the doors to new types of therapy and eventually produce a panacea for all of humanity's ills. What seemed like only a dream a decade ago became reality in the late 1990s when scientists revolutionized the biological world by cloning sheep and pigs. More huge news came last summer when the heads of Celera Genomics (Rockville, MD) and the U.S. Human Genome Project (a 15-year endeavor coordinated by the U.S. Department of Energy and the National Institutes of Health) jointly announced completion of a working copy of the human genome—essentially a map of the basic molecules that make humans what they are.

Big Growth

Interview by Greg Freiherr

Bigger is better. It provides the market share and technology base needed to achieve what would otherwise be impossible. There are few examples that illustrate this principle better than the 1997 megamerger between Beckman Instruments Inc. (Fullerton, CA) and Coulter Corp. (Miami).

The union between these two companies laid the groundwork for integrating technologies to address the needs of clinical laboratories. With other acquisitions, including Hybritech Inc. (San Diego) in January 1996 and the rights to the Access immunoassay system from Sanofi Diagnostics Pasteur (Chaska, MN) in April 1997, Beckman Coulter has forged one of the broadest product lines in the in vitro diagnostics (IVD) industry. Together, these acquisitions have transformed the company into the market leader in clinical chemistry and hematology as well as a major provider of immunoassay systems.

Adapting Packaging Technology to Meet Device Industry Needs

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

Originally Published January 2001

PACKAGING

William Leventon

Most medical device manufacturers appear to require two things from the packaging industry. First, they need more: more capability, more efficiency, more options, and more guidance. Second, they need less: less weight, less trouble, less regulatory hassling—and, of course, less-expensive products.

Makers of packaging-related products must offer a variety of capabilities while responding to cost-cutting pressures.

This seems to be a tall order, and some of it appears contradictory, but the packaging industry is trying to deliver. Professional organizations are striving to make standards more uniform and less troublesome. And companies that make packaging-related products are working on new offerings with a variety of capabilities while keeping in mind the tremendous cost-cutting pressures their customers face.

STANDARD PROCEDURES

Much of the recent work on packaging standards has been based on ISO document 11607, "Packaging for Terminally Sterilized Medical Devices." Since FDA recognized ISO 11607 as a consensus standard, the ASTM F02.60 subcommittee on medical device packaging is submitting versions of the test methods cited in the ISO document for recognition as consensus standards.

The reasoning behind these efforts appears to be clear. "Manufacturers are starting to see more FDA questioning of test methods," says Neil Lorimer, senior quality engineer for Rexam Medical Packaging (Mundelein, IL). By persuading FDA to recognize the ASTM test procedures as consensus standards, the packaging subcommittee hopes to reduce the burden on manufacturers to validate test methods.

FDA recognition would mean that "if you follow these test methods, [the agency] for the most part won't challenge your use of them," explains Hal Miller, director of packaging technology for Johnson & Johnson (New Brunswick, NJ) and chairman of the packaging subcommittee. On occasion, however, FDA may still review manufacturers' test data during field Inspections, Miller adds.

Before ASTM submits test methods to FDA, industry professionals vote on the proposed versions. So far, six test methods have been approved in this manner. Miller expects an FDA decision to be rendered on these test methods soon.

Last year, the industry approved a burst-testing standard that required the use of restraining plates. The plates limit package deformation to help ensure that air pressure is distributed evenly in the seal area.

More recently, the committee has been working on package-integrity testing. Standards are being developed for an internal pressurization test and a pressure-decay test for flexible packaging. Both of these test methods will be voted on soon, according to Miller.

This year, Miller expects the committee to consider procedures for several more integrity tests. These include a force-decay test, a pressure-decay procedure, and a test to sense carbon dioxide.

As the ASTM work was under way, another effort to standardize test methods was undertaken by the Flexible Packaging Association (FPA). The FPA's Sterilization Packaging Manufacturers Council issued its "Guide for Design and Evaluation of Primary Packaging for Medical Products," a compendium of package-testing methods used in the medical device industry. The guide distinguishes between R&D test methods and process/quality control methods.

New leak-test standards recommend use of restraining plates such as this system, which is used with a leaktight pressurizing path and pressure sensor.

Technical people throughout the industry participated in developing the guide, according to Andrea Haferkamp, Rexam's director of regulatory affairs. "It's a very good document," Haferkamp says.

Efforts are also being made to harmonize U.S. and European standards. As a first step in this direction, European standard EN 868-1 may soon be incorporated into ISO 11607. A final vote on this proposal is taking place now, according to Miller.

Miller believes the change will have minimal impact on U.S. medical device manufacturers. "We're trying to eliminate the confusion in Europe about what standards they need to maintain," he says.

MATERIAL PROGRESS

Perhaps more than ever before, medical device manufacturers are feeling the need to reduce costs. As a result, they are reassessing packaging materials and procedures for potential cost savings. "OEMs have had overengineered packages for a long time," says Bill Wetzel, director of North American marketing for Perfecseal Inc. (Oshkosh, WI). He adds that, "The packages have been performing well, but price pressures in the marketplace don't allow the luxury of an overengineered package anymore. So we're all trying to find more cost-effective packaging solutions."

Wetzel believes that these solutions will include downgauging of existing packaging materials. "Instead of using an 8-mil forming film, maybe you only need a 6-mil forming film," he says. "You want to maintain package integrity, but in a more cost-effective fashion. That's the name of the game."

In addition to downgauging existing materials, manufacturers can expect to begin using new packaging materials that are less expensive than the more familiar types. A much-touted example of the trend toward lower-cost materials is DuPont's Tyvek 2FS. Although this lightweight version of Tyvek (1.6 oz of polymer per square yard) costs less than previous grades, there is a trade-off. The newer version is limited in its ability to handle the most demanding packaging applications. "It's for soft products that can't poke holes in the package, products that don't have sharp edges or abrasive corners," says Earl Hackett, research associate for DuPont Nonwovens (Wilmington, DE).

Tolas's TPF-0563 autoclavable film is a polyester-based lamination that can be heat sealed to 1073B Tyvek to form a peelable pouch.

Opinion is somewhat divided on the appropriate use of Tyvek 2FS. "It narrows the price gap between Tyvek and paper or even plastic films," according to Carl Marotta, president of Tolas Health Care Packaging Inc. (Feasterville, PA). "It provides most of the quality features that you expect from Tyvek but at a lower cost," he adds.

On the other hand, some users claim that Tyvek 2FS has a tendency to sometimes tear unexpectly when stressed. Miller maintains that "It was touted as [a material] you could use in an uncoated state, but it really doesn't work very well when uncoated."

Because Tyvek 2FS costs less than heavier grades of Tyvek—even when coated—many are switching to the new grade. But not everyone. Donald Barcan, president of Donbar Industries Inc. (Long Valley, NJ), a package-engineering consulting firm, noting differences with 2FS used with some form-fill-seal machines, says that most of my clients are happy to use the other [Tyvek] grades."

To address the shortcomings of the new grade of Tyvek, materials are being developed that will give users the same peel performance they would get from heavier grades. With assistance from DuPont, Perfecseal is developing film and adhesive technology that will work more effectively with Tyvek 2FS. "It's pretty impressive," explains Hackett. "When you peel [the film] open, it's got a real nice feel to it. It's getting to the point where it almost feels like the old coated Tyvek–type peels."

Hackett expects DuPont to introduce other low-cost alternatives to its current offerings in the next two or three years. "Right now, everything is high-density polyethylene," he says. "We might explore different polymers." These include use of polyester and polypropylene, which could accommodate steam sterilization.

At some point, "we'd like to compete head-to-head with paper," Hackett says. "[Tyvek] 2FS was one of our initial approaches to that goal."

METALLOCENE AND COEXTRUSIONS

While Tyvek 2FS has generated a certain amount of controversy, there seems to be little debate about the merits of metallocenes, polyethylene materials that offer the properties of polyester and nylon—but at a lower cost. "They have really come on strong," says John Ozcomert, Rexam's technical manager. "The first generation of metallocene polymers was very difficult to work with, but the second and third generations are much more amenable to processing."

Most major medical packaging film manufacturers now offer downgauged films that incorporate metallocene technology. These films offer excellent formability, toughness, and clarity, Ozcomert says. Barcan explains that these films also provide a wider temperature range for sealing.

In addition to driving the need for new technologies, the current cost-cutting drive is forcing medical device manufacturers to reevaluate an existing technology that has not generated much enthusiasm until now. Instead of buying adhesive-coated paper, manufacturers using so-called direct-seal processes buy plain paper and seal it directly to the rest of the package. Direct seal processes are used widely in Europe, but U.S. manufacturers have been concerned about the possibility of fiber contamination.

"When you peel that [direct seal] package apart, you're going to liberate some paper fibers," Ozcomert notes. "In Europe, [manufacturers] are pretty tolerant of that, but here [in the United States] they tend to be more conservative and opt for adhesive-coated paper."

Economic considerations, however, have recently prompted some U.S. manufacturers to take a second look at direct seal. "If you use a material that doesn't have to be coated with adhesive, you're going to drive down costs," according to Ozcomert.

For manufacturers with concerns about fiber lift, a packaging material from Rexam offers a clever solution to the problem. Now under evaluation at a number of sites, Core Peel is a coextruded multilayer film with separate seal and peel layers. "We don't ask the layer that does the sealing to do the peeling," Ozcomert explains. "The surfaces that come together never come apart again, so fiber lift is a nonissue."

Core Peel is not the only coextruded material that is demonstrating promise in medical device packaging. "Coextrusion is really taking off," Ozcomert says, adding that the process allows researchers to incorporate toughness and barrier properties into new materials.

This coextruded pliable film is designed to combine the strength and formability of Surlyn with the latest single-site metallocene resin technology.

In the past, Ozcomert notes, a coextruded film might contain a single thick layer of nylon. Now, some films are elaborate structures containing several nylon layers, in addition to other layers of thin barrier materials.

ACTIVE BARRIERS

A new group of barrier materials are being studied currently by Rexam, Perfecseal, and other companies. Cyclic olefin copolymers, or COCs, could someday provide excellent oxygen and water-vapor barriers at a reasonable price, according to some observers. "They compete with very expensive materials or materials that would have to be very thick to provide the barrier you want," Ozcomert says.

In addition to their barrier attributes, COCs are proving to be highly formable. They may also offer stiffness that will help in form-fill-seal processing, according to Perfecseal's Wetzel.

Wetzel adds that barrier materials are also in use that provide product visibility. Polyesters and nylons vacuum coated with aluminum oxide are clear yet offer high moisture and oxygen barrier capabilities.

Some medical devices manufacturers want more than an oxygen barrier. They would prefer a package that actively "scrubs" the air around the product. "You can make a package in which the film itself will trap the oxygen inside," Ozcomert says. Although Rexam has yet to roll out an "active barrier" package, the concept remains under consideration.

Also under consideration are packages that absorb interior odors. For example, products that are irradiated sometimes give off odors that can be trapped in impermeable packages. To eliminate these odors or make them less offensive, Perfecseal is working on odor-scavenging additives that can be incorporated into the packaging material.

NEW TECHNOLOGIES

While materials change, so do other packaging technologies, such as package testing. Most current test methods damage packages, rendering them unusable; however, manufacturers seem to be gravitating toward nondestructive testing methods, according to Stephen Franks, executive vice president of T.M. Electronics Inc. (Worcester, MA), which makes package-testing equipment. "I think more nondestructive tests will be evolving over the next year or two," Franks predicts.

Package design is expected to evolve as well. Tolas president Carl Marotta believes that medical device manufacturers are showing more interest in package design than they have in the past. In response, Tolas has been looking at ways to make products less mobile in the package. One way to accomplish this is with compartmented packaging that locks devices tightly in place, making it less likely that they will puncture the package.

Of course, packages can be adversely affected from the outside as well as from within. Chemical and radiation sterilization, for instance, can damage packages and cause toxic effects. Thus, Marotta believes there will be increased demand for packages sterilized by steam autoclave or dry heat. "When devices can tolerate fairly high temperatures, we find that more are being sterilized this way," he says, adding that these methods are less costly than chemical and radiation sterilization.

Marotta also sees more device manufacturers moving to in-line packaging processes. To meet in-line packaging demand, Tolas supplies pouches attached together on continuous rolls. On the packaging line, the pouches are separated, filled, sealed, and sometimes printed.

Pouches are supplied on continuous rolls to customers for in-house printing.

One of the firm's largest customers desired pouches on a roll. Says Marotta, "We used to supply them with millions of individual pouches. But they found that they could reduce inventories by going to continuous pouches on a roll." In addition, pouch rolls were found to reduce the risk of packaging mix-ups. In-line printing on rolls eliminated the possibility that preprinted pouches would be matched with the wrong products.

PRINTING IN-LINE

Use of digital in-line printing qualifies as an important trend all by itself. For one thing, it enables manufacturers to dispose of traditional print-related inventory. In addition, it can help them adapt more effectively to European requirements that medical device packages display information in multiple languages. "On-line, you can print English one minute, then press a button and print any other language the next minute," says DuPont's Hackett.

Although digital printing is not new, it has only recently been able to keep up with production lines. "In the last year, some systems [have appeared] that will run at the line speeds of a form-fill-seal machine," Hackett reports. He adds that three- and four-color digital printing he has seen recently "looked darn good."

Digital printing technology can also help manufacturers carry out "labeling on demand" to reduce the amount of print on European packages. "There are many packages that just aren't big enough to carry 12 or 15 languages," Johnson & Johnson's Miller notes. In these cases, he explains, manufacturers could first print information on the package in a few languages that cover the product's main market areas. Later, as distribution to a country with another language is initiated, a label specific to that country can be printed and placed on the package.

As packages get smaller, and requirements for printed external information increase, Miller expects manufacturers to make increased use of 2-D data-matrix technology. This technology "lets you take a lot of data and put it on an area about the size of a quarter of a postage stamp," he says. The tiny data matrix would be printed on packages instead of much larger types of print—yet would convey the same information.

VALIDATING THE PROCESS

Looking at a packaging operation as a whole, how does a device manufacturer —or FDA, for that matter—evaluate the process? Process validation is mentioned in ISO 11607, which FDA has accepted as a consensus standard. According to Barcan, this means that FDA supports process validation for all medical device packaging. "FDA and the world recognize that if your process isn't under control and hasn't been validated, you run a risk of producing bad packages," Barcan explains.

To reduce this risk, some firms are offering data acquisition and logging systems as options on packaging equipment. The systems measure and record forming and sealing data so that manufacturers can produce an accurate history of their equipment's performance.

Some packaging equipment makers now offer data acquisition systems at extra cost to people who purchase their machines. At some point, Barcan believes that data acquisition systems may simply be included in the base price of packaging systems.

CONCLUSION

Although the changes may not be as dramatic as the light-speed transformations that are taking place in the electronics industry, medical device packaging is hardly a static field. Work is proceeding on a number of innovative materials and technologies that seem certain to improve packaging performance. Industry professionals are also working on standards that, ideally, will make testing and validation functions less burdensome. These developments should make it easier for medical device manufacturers to satisfy customers and survive tough competition.

William Leventon is a freelance writer living in Somers Point, NJ.



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Copyright ©2001 Medical Device & Diagnostic Industry

Clinical Trials: What Executives Need to Know

Originally Published January/February 2001

Jeffrey N. Gibbs

Innovation is the lifeblood of the medical device industry. Medical device manufacturers must constantly develop new products and upgrade existing ones. However, while other industries can develop new products—such as computers and software—that can swiftly enter the marketplace unimpeded, new medical devices must pass through a narrow gate presided over by FDA. Getting by that gatekeeper often requires conducting clinical trials.

Not all new device marketing applications need to be supported by clinical data. Although many premarket notifications (510(k)s) do contain such data—particularly for newer types of products—most are not supported by human testing. Similarly, supplements to many premarket approval (PMA) applications do not require clinical data.

Developments in Medical Polymers for Biomaterials Applications

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

Originally Published January 2001

BIOMATERIALS

by Jon Katz

Like other important scientific concepts that change over time, the notion of biocompatibility has evolved in conjunction with the continuing development of materials used in medical devices. Until recently, a biocompatible material was essentially thought of as one that would "do no harm." The operative principle was that of inertness—as reflected, for example, in the definition of biocompatibility as "the quality of not having toxic or injurious effects on biological systems."1

A cartilage repair unit injection molded from biodegradable polylactide (PLA).

When more-recent devices began to be designed with materials that were more responsive to local biological conditions, the salient principle became one of interactivity, with biocompatibility regarded as "the ability of a material to perform with an appropriate host response in a specific application."1 Of course, this conceptual shift was predicated on the ability to determine just what constituted "an appropriate host response"—the result of insights gained through tremendous advances in molecular biology and biological surface sciences. Such progress also lies behind the current definition of biomaterial as "a material intended to interface with biological systems to evaluate, treat, augment, or replace any tissue, organ, or function of the body."2 In particular, the design approach regarding implantable devices—and especially long-term implants—has moved away from attempts to develop inert biomaterials in favor of biomaterials that interact with and in time are integrated into the biological environment.

The biocompatibility of a medical implant will be influenced by a number of factors, including the toxicity of the materials employed, the form and design of the implant, the skill of the surgeon inserting the device, the dynamics or movement of the device in situ, the resistance of the device to chemical or structural degradation (biostability), and the nature of the reactions that occur at the biological interface. These factors vary significantly depending on whether the implant is deployed, for example, in soft tissue, hard tissue, or the cardiovascular system—to the extent that "biocompatibility may have to be uniquely defined for each application."3 Among the prominent applications for biomaterials are:

  • Orthopedics—joint replacements (hip, knee), bone cements, bone defect fillers, fracture fixation plates, and artificial tendons and ligaments.
  • Cardiovascular—vascular grafts, heart valves, pacemakers, artificial heart and ventricular assist device components, stents, balloons, and blood substitutes.
  • Ophthalmics—contact lenses, corneal implants and artificial corneas, and intraocular lenses.
  • Other applications—dental implants, cochlear implants, tissue screws and tacks, burn and wound dressings and artificial skin, tissue adhesives and sealants, drug-delivery systems, matrices for cell encapsulation and tissue engineering, and sutures.

The types of materials featured in the above uses include metals (stainless steel, titanium, cobalt chrome, nitinol), ceramics and glasses (alumina, calcium phosphate, hydroxyapatite), and a wide range of synthetic and natural polymers. This article focuses on polymers, and presents a brief overview of some of the more exciting recent developments that are radically expanding the capabilities of polymeric biomaterials. These include:

  • New approaches to biodegradable polymers.
  • "Combinatorial" and "supramolecular" chemistry.
  • So-called intelligent materials.
  • Other new formulations, including phospholipids, polymers for gene therapy, enhanced polyurethanes, and protein-based polymers.

It should be kept in mind that the examples presented run the gamut from newly reported research to products in clinical trials or awaiting regulatory approval to devices that are commercially available.

NOVEL BIODEGRADABLE POLYMERS

As for other biomaterials, the basic design criteria for polymers used in the body call for compounds that are biocompatible (new definition), processable, sterilizable, and capable of controlled stability or degradation in response to biological conditions. The reasons for designing an implant that degrades over time often go beyond the obvious desire to eliminate the need for retrieval. For example, the very strength of a rigid metallic implant used in bone fixation can lead to problems with "stress shielding," whereas a bioabsorbable implant can increase ultimate bone strength by slowly transferring load to the bone as it heals. For drug delivery, the specific properties of various degradable systems can be precisely tailored to achieve optimal release kinetics of the drug or active agent.

An ideal biodegradable polymer for medical applications would have adequate mechanical properties to match the application (strong enough but not too strong), would not induce inflammation or other toxic response, would be fully metabolized once it degrades, and would be sterilizable and easily processed into a final end product with an acceptable shelf life. In general, polymer degradation is accelerated by greater hydrophilicity in the backbone or end groups, greater reactivity among hydrolytic groups in the backbone, less crystallinity, greater porosity, and smaller finished device size.

Beginning in the 1960s, a range of synthetic biodegradable polymers have been developed, including polylactide (PLA), polyglycolide (PGA), poly(lactide-co-glycolide) (PLGA), poly(e-caprolactone), polydioxanone, polyanhydride, trimethylene carbonate, poly(ß-hydroxybutyrate), poly(g-ethyl glutamate), poly(DTH iminocarbonate), poly(bisphenol A iminocarbonate), poly(ortho ester), polycyanoacrylate, and polyphosphazene. There are also a number of biodegradable polymers derived from natural sources such as modified polysaccharides (cellulose, chitin, dextran) or modified proteins (fibrin, casein).

To date, the compounds that have been employed most widely in commercial applications are PGA and PLA, followed by PLGA, poly(e-caprolactone), polydioxanone, trimethylene carbonate, and polyanhydride. Some of the common PLA products include tissue screws, tacks, and suture anchors, as well as systems for meniscus and cartilage repair. The first FDA-cleared PLGA product was the Lupron Depot drug-delivery system (TAP Pharmaceutical Products Inc.; Lake Forest, IL), a controlled release device for the treatment of advanced prostate cancer that used biodegradable microspheres of 75:25 lactide/glycolide to administer leuprolide acetate over periods as long as 4 months (replacing daily injections). Another drug-delivery device, the Gliadel Wafer (Guilford Pharmaceuticals Inc.; Baltimore, MD), is used to prolong the life of patients suffering from a particularly deadly form of brain cancer, glioblastoma multiforme. In this case, dime-sized wafers of a biodegradable polyanhydride copolymer—poly[bis(p-carboxyphenoxy) propane:sebacic acid] in a 20:80 molar ratio—are implanted directly into the brain to deliver a powerful chemotherapeutic agent (BCNU) that has deleterious side effects when administered systemically.

BIODEGRADABLE POLYMERS FOR TISSUE ENGINEERING

One area of intense research activity is the use of biodegradable polymers for tissue engineering, which can be defined as "the application of engineering principles to create devices for the study, restoration, modification, and assembly of functional tissues from native or synthetic sources."4 Candidate materials include natural polymers (fibrin, collagen, gelatin, hyaluronan), synthetic polymers (e.g., PLA, PGA, PLGA, ethylene oxide block copolymers), and inorganic materials (tricalcium phosphate, calcium carbonate, nonsintered hydroxyapatite).

A recent project investigated the possibility of manufacturing biodegradable composites for use as bioactive matrices to guide and support tissue ingrowth.5 Composites were prepared using polyhydroxybutyrate (PHB), a naturally occurring ß-hydroxyacid linear polyester, and as much as 30% by volume of either hydroxyapatite (HA) or tricalcium phosphate (TCP) (Figure 1). One of the goals was to achieve a reasonably homogeneous distribution of the HA/TCP particles in the PHB matrix, as this uniformity would provide an anchoring mechanism when the materials would be employed as part of an implant. The composites were successfully manufactured through a compounding and compression molding process. It was observed that microhardness increased with an increase in bioceramic content for both the HA ad TCP compounds.

Figure 1. Polyhydroxybutyrate (PHB) typically requires the presence of enzymes for biodegradation. It is often copolymerized with polyhydroxyvalerate (PHV).

Another team of researchers has addressed the problem of fabricating open-pore, biodegradable polymer scaffolds for cell seeding or other tissue engineering applications.6 The material selected was the tyrosine-derived polycarbonate poly(DTE-co-DT carbonate), in which the pendant group via the tyrosine—an amino acid—is either an ethyl ester (DTE) or free carboxylate (DT). Through alteration of the ratio of DTE to DT, the material's hydrophobic/hydrophilic balance and rate of in vivo degradation can be manipulated. It was shown that, as DT content increases, pore size decreases, the polymers become more hydrophilic and anionic, and cells attach more readily. Previously encountered problems with maintaining sufficient interconnectivity between pores in the structure were avoided through a novel phase-separation technique. Tyrosine-derived polyarylates under study as resorbable coatings for other biomaterials have been reported to significantly decrease blood-coagulation activation and bacterial adhesion without modifying the structure of the substrate.7

Multiblock copolymers of poly(ethylene oxide) (PEO) and poly(butylene terephthalate) (PBT) are also under development as prosthetic devices and artificial skin and as scaffolds for tissue engineering.8 These materials are subject to both hydrolysis (via ester bonds) and oxidation (via ether bonds). Degradation rate is influenced by PEO molecular weight and content, and the copolymer with the highest water uptake degrades most rapidly.

Among the important series of physiological reactions or "cascades" is the fibrinolytic sequence, in which blood clots are removed from the circulation in part through the breakdown of the protein fibrin by the enzyme plasmin. Neurite-associated plasmin activity has also been shown to play a role in nerve growth, and a recent study describes the creation of a new biosynthetic material that imitates fibrin as a vehicle for promoting peripheral nerve regeneration.9 The material incorporates a recombinantly expressed fragment of human fibrin within a photo-cross-linked, polyethylene glycol (PEG)–based hydrogel matrix. According to the study, the resulting system degrades completely upon exposure to plasmin but is otherwise stable, demonstrating that it is possible to design biosynthetic materials with specific enzymatic degradability.

COMBINATORIAL AND SUPRAMOLECULAR CHEMISTRY

A product of revolutionary advances in molecular biology, microfabrication, and information technology, combinatorial chemistry is an emerging discipline of tremendous potential for pharmacological design, biomaterials development, and the entire realm of polymer science. This new approach to the synthesis of materials and characterization of their properties uses multicomponent screening, high-throughput chemical synthesis, and advanced computational techniques to produce and analyze a large number of novel monomeric and polymeric entities.

In a combinatorial synthesis, automated methods are used to process a relatively small number of "ingredients" in a parallel fashion so as to generate a large "library" of elemental combinations on a microscopic scale. Such incrementally controllable, permutationally designed systems hold out the promise of precise structure/property correlations to determine which specific materials will fulfill specific performance needs. One of the first reported examples of a combinatorially prepared library of biomaterials involved A-B type copolymers in which one monomer was a diphenol and the second a diacid.10,11 A total of 14 different diphenols were copolymerized in all combinations with eight different diacids to produce 112 (14 x 8) structurally related polyarylate copolymers. The characteristics of this series of new materials—properties such as wettability, glass-transition temperature, and cellular response—were then analyzed in a systematic manner to identify the relationship between polymer structure, properties, and performance.

Another intriguing new field of great promise is supramolecular chemistry, which is concerned with developing molecular assemblies for biological applications based on macromolecular architectures that mimic nanoscale systems or mechanisms in nature. Novel synthesis methods based on supramolecular chemistry have been used to create branched or graft, cyclic, cross-linked, star, and dendritic polymer structures.

An excellent example of the ability of supramolecular polymer systems to meet complex performance requirements and function like natural chemomechanical materials can be seen in two recent studies using polyrotaxanes—polymers comprising cyclic compounds that are threaded onto linear polymeric chains capped with bulky end groups (Figure 2).12 The first study prepared a series of biodegradable polyrotaxanes in which a-cyclodextrins (a-CDs) were threaded onto a PEG chain capped with amino acids. The resulting structure could be adapted to accomplish a two-stage, controlled release of drugs bonded to the a-CDs: hydrolytic enzymes could first attack the peptide bonds of the macrostructure, degrading the terminal moieties and releasing the drug-immobilized a-CDs, and a second enzyme could then attack the a-CDs and release the drugs. The very rapid and complete degradation of the polyrotaxane prevents problems like that posed by residual crystalline oligomers that can result from the incomplete hydrolysis of highly crystalline materials like PLA.

Figure 2. Polyrotaxanes and other supramolecular polymer structures can be designed to mimic nanoscale systems in nature.

Polyrotaxanes can also be designed to effect dynamic molecular functions similar to those of natural tissues through movement of the cyclic compounds along the polymer's linear chain. The second study used polyrotaxanes with b-cyclodextrins (b-CDs) threaded onto a triblock copolymer of PEG and poly(propylene glycol) (PPG) bounded by fluorescein-4-isothiocyanate end groups. It was observed that the majority of the b-CDs migrated toward the PPG segment with increasing temperature—a phenomenon that, with controlled temperature variation, could suggest the action of a molecular-scale piston. This stimulus response was seen to resemble the action of myosin molecules sliding along actin filaments in the muscle-contraction process.

INTELLIGENT MATERIALS

The polyrotaxane polymers described above can be considered intelligent biomaterials insofar as they can function in a manner similar to molecular structures in the body. Other intelligent materials currently under development include hydrogels exhibiting critical behavior, anionic and cationic hydrogels, controlled porous structures, ultrapure biomaterials, tailored copolymers with desirable functional groups, biomimetic hydrogels, biodegradable polymers responding to specific biological conditions, and polymers precisely replicating selected properties.

One particularly fascinating model of an intelligent material has as its ultimate goal one of the most critical issues in modern medicine—the controlled delivery of insulin for the treatment of diabetes. This hydrogel system features an insulin-containing reservoir within a membrane of poly(methacrylic acid-g-poly[ethylene glycol]) copolymer in which glucose oxidase has been immobilized.13 The surface of the porous membrane contains a series of molecular "gates," which open and release insulin when the hydrogel shrinks at low pH values as a result of the interaction of glucose with glucose oxidase (Figure 3). In addition, the cross-linked polyethylene glycol graft in the decoupled state has the ability to adhere to a specific region in the upper intestine that is a preferred location for the delivery of insulin.

Figure 3. The porous surface of the P(MAA-g-EG) hydrogel system responds to the presence of glucose.

OTHER NEW FORMULATIONS

The tremendous range of current biomaterials research is proposing innovative new polymers for applications ranging from cardiovascular devices to gene therapy. Several of the more interesting formulations are highlighted below.

Phospholipids. Among the materials receiving a great deal of attention for its hemocompatible characteristics is 2-methacryloyloxyethyl phosphorylcholine, or MPC (Figure 4). Created in Japan in the mid-1970s, this polymer has been shown to inhibit to a significant degree the almost-instantaneous protein adsorption and subsequent denaturation that is the initial event affecting practically every material used in the body, and which can lead to thrombus formation. For example, it has been reported that a small-diameter (2-mm) vascular graft prepared from a blend of MPC polymer and segmented polyurethane (SPU) did not occlude for more than 8 months after implantation in a rabbit, whereas an identical SPU graft occluded within 90 minutes.14 The polymer has also been tested as a coating for implantable glucose sensors and hemodialyzer filters and as a rinsing agent to protect contact lenses from protein deposition.15

Figure 4. Molecular structure of the MPC polymer. The material has been shown to inhibit the absorption and denaturation of protein on the surface of an implant.

Polymers for Gene Therapy. Concerns about the potential risks associated with viral gene-delivery systems have led to the development of both degradable and nondegradable, targeted and nontargeted polymeric gene carriers. Examples include PLL-PEG-lactose as a carrier for the transfection of plasmid DNA at hepatocytes16; a biodegradable cationic polymer, poly(a-[4-aminobutyl]-L-glycolic acid), as a carrier for mouse plasmid DNA to prevent insulitis15; and biodegradable gelatin-alginate microspheres as a carrier of adenovirus (Ad5-p53) for intracranial delivery.17

Silicone-Urethane Copolymers. Novel families of silicone-urethane copolymers have been developed that, compared with traditional polyurethane biomaterials, offer advantages in biostability, thromboresistance, abrasion resistance, thermal stability, and surface lubricity, among other properties.18 Copolymer synthesis is performed via two methods: incorporation of silicone into the polymer backbone together with organic soft segments, and the use of surface-modifying end groups to terminate the copolymer chains. The organic soft block can be either polytetramethyleneoxide (PTMO) or an aliphatic polycarbonate used together with polydimethylsiloxane (PSX). Applications for the new materials include balloons, ventricular assist devices, vascular grafts, pacemaker leads, and orthopedic and urologic implants.

Protein-Based Polymers. A series of recently introduced casein- and soy-based biodegradable thermoplastics have recently joined collagen as a source of natural protein-based biomaterials.19 In comparison with collagen, however, these polymers are less susceptible to thermal degradation, can be easily processed via melt-based technologies, and can be reinforced with inert or bioactive ceramics. Temporary replacement implants, scaffolds for tissue engineering, and drug-delivery vehicles are among the potential biomaterials uses under investigation.

CONCLUSION

The discovery of novel polymeric biomaterials—and the refinement of traditional ones—is creating a thoroughly unprecedented excitement in the field as polymer chemists and other materials designers increasingly confront many of the fundamental challenges of medical science. As the biomaterials discipline itself evolves, the startling advances of the last few years in genomics and proteomics, in various high-throughput cell-processing techniques, in supramolecular and permutational chemistry, and in information technology and bioinformatics promise to support the quest for new materials with powerful analytic tools and insights of boundless energy and sophistication.

REFERENCES

1. DF Williams, The Williams Dictionary of Biomaterials (Liverpool, UK: Liverpool University Press, 1999), 40.

2. DF Williams, The Williams Dictionary of Biomaterials (Liverpool, UK: Liverpool University Press, 1999), 42.

3. BD Ratner et al., Biomaterials Science (San Diego: Academic Press, 1996), 6.

4. DF Williams, The Williams Dictionary of Biomaterials (Liverpool, UK: Liverpool University Press, 1999), 318.

5. M Wang et al., Transactions of the Sixth World Biomaterials Congress, I (Minneapolis: Society for Biomaterials, 2000), 81.

6. B Wong et al., Transactions of the Sixth World Biomaterials Congress, I (Minneapolis: Society for Biomaterials, 2000), 363.

7. A Stemberger et al., Transactions of the Sixth World Biomaterials Congress, I (Minneapolis: Society for Biomaterials, 2000), 369.

8. A Deschamps et al., Transactions of the Sixth World Biomaterials Congress, I (Minneapolis: Society for Biomaterials, 2000), 364.

9. S Halstenberg et al., Transactions of the Sixth World Biomaterials Congress, I (Minneapolis: Society for Biomaterials, 2000), 427.

10. S Brocchini et al., Journal of Biomedical Materials Research 42 (1998): 66–75.

11. J Kohn, Transactions of the Sixth World Biomaterials Congress, I (Minneapolis: Society for Biomaterials, 2000), 84.

12. N Yiu, "Design of Polyrotaxanes Aiming at Intelligent Biomaterials," in Supramolecular Approach to Biological Function (Minneapolis: Society for Biomaterials, 2000).

13. N Peppas, Transactions of the Sixth World Biomaterials Congress, I (Minneapolis: Society for Biomaterials, 2000), 554.

14. T Yoneyama et al., Artificial Organs 24 (2000): 23–28.

15. K Ishihara et al., Polymer Journal 31 (1999): 1231–1236.

16. SW Kim, Transactions of the Sixth World Biomaterials Congress, I (Minneapolis: Society for Biomaterials, 2000), 250.

17. HQ Mao et al., Transactions of the Sixth World Biomaterials Congress, I (Minneapolis: Society for Biomaterials, 2000), 252.

18. RS Ward, "Thermoplastic Silicone-Urethane Copolymers: A New Class of Biomedical Elastomers," Medical Device & Diagnostic Industry 22, no. 4 (2000): 68–77.

19. CM Vaz et al., Transactions of the Sixth World Biomaterials Congress, I (Minneapolis: Society for Biomaterials, 2000), 429.

Jon Katz is editor of MD&DI.

Photo courtesy of TESco Associates Inc. and Matrix Biotechnologies Inc.



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