TM

MPMD Materials and Processes for Medical Devices

www.asminternational.org/amp JULY 2008

TECHNICAL AND BUSINESS NEWS FOR THE MEDICAL DEVICE INDUSTRY

Porous High-Density Polyethylene Nanocrystalline Hydroxyapatite Nanocomposites for Bone Regeneration

 Semiconductors  Connectors (including welds)  Sensors  Passive components  RF components  Flex circuits  Precision laser cut or drilled components  Implantables  Minimally invasive surgical tools  Energy storage devices  Coated devices  Bare stents Just a few examples of many areas that require closer examination.

When Microns Matter! The MPC 2000 Micro-Precise Integrated Cross-Sectioning System is specifically designed for cross-sectioning micro-devices and components to remove material within ±1 micron of targeted depth.

Buehler, a manufacturer of laboratory preparation equipment and consumables, has an international reputation for supplying world-class solutions to the medical device and medical electronic industries. Need specific suggestions for your application? Visit the Buehler e-club at http://www.buehler.com for a database of technical publications, educational courses and solutions on a variety of materials or call 1-847-295-6500.

MPC 2000 MicroPrecise Integrated Cross-Sectioning System

Worldwide Headquarters Buehler Ltd • 41 Waukegan Road • Lake Bluff, Illinois 60044 • USA Tel: 1 (800) BUEHLER - 1 (800) 283-4537 • Fax: (847) 295-7979 Email: [email protected] Web Site: http://www.buehler.com/biomedical.htm

P R O V I D I N G S O LU T I O N S F O R O V E R 7 0 Y E A R S

JULY 2008 TM

MPMD Materials and Processes for Medical Devices

Editorial Staff

A publication of ASM International 9639 Kinsman Road Materials Park, OH 44073 Tel: 440/338-5151; Fax: 440/338-4634 www.asminternational.org/amp

Margaret W. Hunt Editor [email protected]

Trisha McKay Contributing Editor

Barbara L. Brody

FEATURES

Art Director

Joanne Miller Production Manager joanne.miller@asminternational. org

Porous High-Density 65 Polyethylene

Joseph M. Zion Publisher [email protected]

Sebastien Henry

Editorial Committee Roger Narayan North Carolina State University and the University of North Carolina, Chair

Ishaq Haider BD Techologies

Harold Pillsbury University of North Carolina

Ray Harshbarger Walter Reed Army Medical Center

Sebastien Henry Porex The MPMD Editorial Committee is strictly an advisory group, and membership on the committee in no way implies endorsement of any of the publication’s content.

Sales Staff National Account Manager

Kelly Thomas, CEM.CMP Materials Park, Ohio. Tel: 440/333-1733 e-mail: kelly.thomas@ asminternational.org

On the Cover Porous silicon discs could deliver drugs on nanoparticles Tiny discs of porous silicon that can deliver two types of nanoparticles simultaneously are under development at University of Texas in Houston. Prof. Mauro Ferrari fabricated porous silicon via previously developed methods, and then used photolithography to carve out tiny structures shaped like red blood cells, but about half the size. Computer models suggest that the structures will tend to stick to the inside of blood vessel walls, a crucial property for targeted delivery. Dr. Ferrari and collaborators then loaded the pores with quantum dots and carbon nanotubes. When administered to cells growing in a dish, the silicon carriers begin to break down, releasing their cargo over the course of several hours. The cells then absorbed the nanoparticles, which accumulated in distinct areas inside the cells. For more information: Mauro Ferrari, University of Texas, Houston, TX 77030; tel: 713/500-2444; Mauro. [email protected] ; www.uth.tmc. edu. Photo credit: Rita Serda/Matthew Landry, University of Texas Health Science Center at Houston.

ADVANCED MATERIALS & PROCESSES/JULY 2008

Nanocomposites 66 for Bone Regeneration Eduardo Saiz, Antoni P. Tomsia, Janice S. Lee, Mahesh H. Mankani, Sally J. Marshall, Grayson W. Marshall, Ulrike G.K. Wegst

Synthesis of 68 Nanocrystalline Hydroxyapatite Samar J. Kalita and Saurabh Verma

Porous NiTi 69 Ampika Bansiddhi and David C. Dunand

DEPARTMENTS Observations Industry News Materials Devices Testing/R&D

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OBSERVATIONS

Opportunities for Next-Generation Implants S

urgeons, clinicians, biomedical engineers, device designers, and materials scientists will gather in Cleveland this August for a unique forum hosted by the Cleveland Clinic and ASM International: Opportunities for Next-Generation Implants.

Engineers are problem solvers; clinicians do whatever they can to extend and improve life. They know that evaluation and selection of biomaterials and medical devices requires dialogue between experts from both groups, as well as input from researchers across a wide range of disciplines. Engineers who are working to develop the medical devices of the future will answer questions based on their knowledge and experience of innovative materials and processes. They will describe the design and manufacturing challenges involved in the selection and applications of materials and coatings, including issues such as manufacturability, reliability, and affordability. By facilitating open discussion, this meeting will identify challenges and solutions that can accelerate the medical adoption of more durable and biocompatible materials into clinical applications. For the medical community, this meeting will proMaterials and Processes vide insight into how recent advances in areas such as nanotechnology for Medical Devices 2008: can transform the roadmap for the future of medicine.

Opportunities for Next-Generation Implants. August 5 – 7, 2008 Intercontinental Hotel Cleveland, Ohio www.asminternational.org/ meddevices

For details of upcoming ASM seminars contact John Cerne. [email protected] or call 800/336-5152, ext. 5637 For a preview, more information or to arrange a site trial of The Materials for Medical Devices Database co-supported by ASM and Granta, contact Raymond Sirochman. raymond.sirochman@ asminternational.org or 800/336-5152, ext. 5576

Technical programming covers the spectrum of materials-related challenges and opportunities in medicine. Experts in their respective fields will cover nearly every topic of interest in the field of implantable biomaterials, including spine biomechanics, minimally invasive surgery, novel bone cements, joint replacement, neurological issues, and cardiovascular stents, valves, and pacemakers. In addition, manufacturers and suppliers will exhibit their materials, test instruments, surface treatments, and process capabilities for medical devices. Prior to the conference, the following courses provide “what you need to know” about materials: • Nitinol for Medical Devices • Stainless Steels, Cobalt-Chromium, and Titanium Alloys for Medical Devices • BioMEMS for Medical Devices • Medical Device Failure Analysis See MPMD p. 23 for more information about the speakers and the program.

Margaret W. Hunt, Editor 52

ADVANCED MATERIALS & PROCESSES/JULY 2008

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INDUSTRY NEWS Invibio and Smith & Nephew to develop bioresorbable polymers Invibio Biomaterial Solutions has entered into a collaboration program with Smith & Nephew for the development of a next generation family of structural bioresorbable polymers. The program goal is to develop advanced structural bioresorbable materials with the performance specifications needed for more rigid, load-bearing applications typically not attainable by today’s resorbable biomaterials. The development collaboration between Invibio and Smith & Nephew is an initial three year project, Bio Nano Centre in London, England, has be- and is co-funded by the Technology Strategy Board's come Bio Nano Consulting, a development Collaborative Research and Development program, consultancy applying nanotechnology tools to following an open competition. The Technology address problems from the biomedical industry. Strategy Board is an executive body established by Established in late 2007, BNC seeks to provide a the Government of the United Kingdom to drive complete concept-to-market route for the bio-nanotechnology sector. innovation. For more information: Invibio Inc., 300 Conshohocken www.bio-nano-consulting.com State Road, West Conshohocken, PA 19428; tel: 866/468 Kyocera Industrial Ceramics Corp. announces 4246 or 484/342-6004; www.invibio.com; www. the availability of components that incorporate a smith-nephew.com. wide range of biocompatible ceramics, including alumina and zirconia; bioactive coatings, such as hydroxyapatite; medical-grade alloys, such as titanium and vanadium-free titanium; and medical-grade ultra-high-molecular-weight polyethylene (UHMWPE) are now available. The company announces that it will be the official North American representative of Japan Medical Materials Corporation for sales of biocompatible ceramic structural components used in orthopedic systems. www.kyocera.com

Norwood Tool Company, a contract manufacturer in Dayton, Ohio, announces that as of May 5, 2008, it will be known as Norwood Medical. The change is due to the company’s focus on medical instruments and implants over the last 30 years. The company will retain the ability to design and build dies, fixtures, gages, automation, and tooling. www.norwoodtool.com Boston Scientific Corp. has received approval from Health Canada’s Therapeutic Products Directorate for the sale of the Taxus Liberte system, which utilizes a paclitaxel-eluting coronary stent. www.bostonscientific.com Creganna Medical Devices, of Galway, Ireland, has opened a new facility in Marlborough, Mass., for the design and manufacturing of components and sub-assemblies for medical device and life science companies. Over the last seven years, Irish companies have increased their presence in the U.S. market fivefold. www.creganna.com Boston Scientific, Natick, Mass., has entered into a definitive agreement to acquire CryoCor, San Diego, Calif. Worth approximately $17.6 million, the agreement involves the development of a console to deliver cryo-energy to Boston Scientific’s proprietary cryo balloon catheter. www.bostonscientific.com; www.cryocor.com

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Knee replacement product line expanded The Sigma Knee group product line has been expanded to include products and solutions designed for a wider range of patients seeking knee replacement, reports DePuy Orthopaedics Inc., Warsaw, Ind. The products offer surgeons the ability to select from many different instruments and implants based on specific patient needs and their own surgical preferences. Sigma CR Porocoat Femur is a cement-less fixation femoral component that contains a porous coating conducive to deep bone ingrowth and better long-term fixation of the implant. The Sigma PS Femur is designed to provide patients with enhanced function from gait to deep flexion activities. For more information: Mindy Tinsley, DePuy Orthopaedics Inc., 700 Orthopaedic Dr., Warsaw, IN 46581; tel: 574/372-7136; www.depuyorthopaedics.com.

Resorbable sutures are stronger and more flexible The first patients have reportedly been treated with an FDA-cleared device derived from a new class of resorbable polymers developed by Tornier Inc., Edina, Minn., and Tepha Inc., Lexington, Mass. The TephaFlex Absorbable Suture, made from polyhydroxyalkanoates (PHA), is said to be up to 30% stronger, as well as more flexible. It also has better retention characteristics with less inflammatory response than currently marketed resorbable sutures. The new polymers are produced with patented recombinant DNA technology that allows the engineering of materials with mechanical and biologic properties that can be matched to specific tissue repair and replacement applications. For more information: Kirsten Harrison, Tornier Inc., Edina, MN 55435; tel: 952/426-7600. www.tornierus.com ADVANCED MATERIALS & PROCESSES/JULY 2008

MATERIALS Two polymer hydrogels build artificial cornea An artificial cornea made from a water-filled polymer that closely resembles the eye's natural cornea is under development at Stanford University, California. Instead of hard plastic, chemical engineer Curtis Frank and former graduate student David Myung have created an artificial cornea based on a soft hydrogel. The water-swollen gel is made of a mesh of two polymer networks. The first network is made of polyethylene glycol, the second of polyacrylic acid. "It's like filling up the holes in the sponge with a second material," says Dr. Frank. "You can't separate one from the other. They become inextricably intertwined." The resulting clear material is mechanically robust, despite being 80% water. The high water content is critical for allowing glucose and other nutrients to diffuse through the cornea and encourage the

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growth of epithelial cells on the implant's surface. For more information: Curtis Frank, Stanford University, Stanford, CA 94305; tel: 650/723-4573; [email protected]; www.stanford.edu.

Titanium Grade 2 introduced to rapidly manufacture implants Titanium Grade 2 (ASTM F67, unalloyed titanium for surgical implant applications) has been introduced to produce orthopedic implants via Free Form Fabrication by Arcam EBM, Gothenburg, Sweden. Electron beam manufacturing (EBM) technology fabricates implants with integrated lattice structures for improved bone ingrowth. Implants produced via EBM technology are built up layer by layer from metal powder melted with a powerful electron beam gun inside a vacuum chamber. The process is fast, and material properties are comparable to those of wrought metal. The technology provides the ability to manufacture implants with integrated lattice surfaces that enhance osseointegration. For more information: Magnus René, Arcam AB, Gothenburg, Sweden; tel: 46 31 710 32 00; magnus. [email protected]; www.arcam.com.

Leap ahead. The Materials for Medical Devices Database Spending too much time searching for materials information?

Shorten Your Time to Market For a preview, more information or to arrange a site trial for the database, contact:

The first and only comprehensive database created specifically to support medical device design; fully relational and modular, featuring both materials properties and biological response data for medical device designers.

ASM International [email protected] 800.336.5152, ext 5576 440.338.5418 www.asminternational.org/meddev/

ADVANCED MATERIALS & PROCESSES/JULY 2008

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MATERIALS Ultrathin polymer films could prevent infections in devices

Silica gel fibers form resorbable wound dressing

Whether bacteria stick to surfaces depends partly on how soft those surfaces are, report engineers at the Massachusetts Institute of Technology, Cambridge. Their study demonstrates that bacteria adhere poorly to soft surfaces and stick to firm surfaces. The researchers have also created soft polymer films that might serve as antibacterial coatings for medical devices and other objects on which harmful bacteria congregate. Called polyelectrolyte multilayers, the films could be designed to prevent accumulation of hazardous bacteria or promote growth of beneficial bacteria. The inexpensive, easy-to-produce films could help to reduce the spread of hospital-acquired infections. For more information: Krystyn Van Vliet, MIT, Cambridge, MA 02139; tel: 617/253-3315; [email protected]; http://web. mit.edu/vvgroup.

Glass implant releases calcium to repair damaged bones

A wound dressing made of silica gel fibers that form a supporting matrix for growing new skin cells and is fully absorbed by the body during the healing process has been developed by scientists at the Fraunhofer Institute for Silicate Research ISC in Würzburg, Germany. The fibers are produced by means of wet-chemical material synthesis, a sol-gel process in which a transparent, honey-like gel is produced from tetraethoxysilane (TEOS), ethanol, and water in a multistage, acidically catalyzed synthesis process. The gel is processed in a spinning tower: “We press it through fine nozzles at constant temperatures and humidity levels,” explains Walther Glaubitt, the inventor of the silica gel fibers. “This produces fine endless threads that are collected on a traversing table and spun in a specific pattern to produce a roughly A4-sized multi-layer textile web.” For more information: Dipl.-Ing. Walther Glaubitt, Fraunhofer Institute, Wurzburg, Germany; tel: 49 931 4100406; fax: 49 931 4100-698; monika. [email protected]; http://www. fraunhofer.de/EN/press/pi/2008/05/ ResearchNews5s2008Topic3.jsp.

A porous glass implant that dissolves in the body, releasing calcium that encourages damaged bones to re-grow, is being developed at Imperial College, London, with the Universities of Kent and Warwick. The implant is designed to act as an immediate replacement for the missing bone, carrying out tasks such as bearing weight. The implant is made of cloudy-looking glass containing pores similar to the inner layer of bone, which has a honeycomb-like structure. These pores contain calcium, the building block of Invibio Biomaterial bone. Once in place, the implant reacts with Solutions announces its bodily fluids and gradually dissolves, newly expanded and bonding to existing bone while creating inredesigned website, which stant support, and a scaffold for new bone to provides easy access to grow. The implant dissolves at the same rate polymer material properties and comparisons, medical the new bone grows. It releases other elements application information, such as silicon, which signals the body's bone processing and application growth cells. guidelines, abstracts and The implant, which would be available in various shapes and sizes depending on where papers, case studies, and it was needed, could be used in areas such as hips that are under great stress. more. It also features For more information: Kajal Mallick, University of Warwick, Coventry, England; regulatory, research, and development initiatives. [email protected]; www.warwick.ac.uk. www.invibio.com Wyatt Technology has published an application note to demonstrate the accurate and reliable characterization of polyurethanes in medical applications. Wyatt's powerful Multi-Angle Light Scattering (MALS) detectors were found to provide vital information about the molecular structure of polyurethanes when coupled to the company's innovative on-line ViscoStar viscometer. www.wyatt.com

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Ceramic machining, extrusion achieve new geometries Precision ceramic machining and extrusion techniques that provide sub-micron tolerances and allow previously unavailable geometries have reportedly been developed by Polymer Technologies Inc., Clifton, N.J. The procedure applies to ceramics and other biocompatible materials and produces geometries including: holes as small as ten microns; outer diameters from 0.3 mm up to 5 mm; lengths from 0.5 mm up to 100 mm; and wall thickness from 100 microns up to 2.49 mm. In addition, holes can be configured to various shapes, and tubes can be multi-lumen. For more information: Stan Zalkind, Pilot Precision Ceramics, Trumbull, Conn.; tel: 619/8046733; www.pilot-pre.com/ceramics; www.polymertechnologies.com. www.pilot-pre.com/ ceramics_e/index1_e.htm. ADVANCED MATERIALS & PROCESSES/JULY 2008

You always knew it could be manufactured. You just needed a single-source supplier that could take you from prototype to full market requirements. No one matches Norman Noble’s capabilities and quality for micromachining medical devices and implants. With our proprietary systems, we can manufacture components from virtually any material to the industry’s tightest tolerances.

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MATERIALS Nanofibers serve as scaffold for nerve fibers to grow An engineered material that can be injected into damaged spinal cords could help prevent scars and encourage damaged nerve fibers to grow. The liquid material, developed by Northwestern University materials science professor Samuel Stupp, contains molecules that self-assemble into nanofibers, which act as a scaffold on which nerve fibers grow. The nanofibers break down into nutrients in three to eight weeks. The new work is the first test for the material to heal spinal cord injuries in animals. The researchers stimulated a spinal cord injury in mice and injected the material 24 hours later. They found that the material reduced the size of scars and stimulated the growth of the nerve fibers through the scars. It promoted the growth of both types of nerve fibers that make up the spinal cord: motor fibers that carry signals from the brain to the limbs, and sensory fibers that carry sense signals to the brain. The material encouraged the nerve stem cells to mature into cells that create myelin, an insulating layer around nerve fibers that helps them to conduct signals more effectively. For more information: Samuel Stupp, Northwestern University, Evanston, IL 60208; http://stupp. northwestern.edu.; www.northwestern.edu.

Hydrophilic polyurethanes provide low-friction surfaces Hydrophilic polyurethane coatings for catheters, leads, and endoscopes are being developed to provide particularly low-friction surfaces that are also resistant to mechanical and thermal stresses, according to Bayer MaterialScience, Germany. The new dispersions and solutions can be applied to medical devices or implants by means of spraying, dipping, or virtually any other method. Samples are currently being provided to certain customers and should to be ready by Fall 2008. For more information: Dr. Michael Mager, Medical Coatings and Adhesives, Bayer MaterialScience, Leverkusen, Germany; tel: +49 21430-76944; fax: +49 214-30-67779; www.bayermaterialscience.com. 58

ADVANCED MATERIALS & PROCESSES/JULY 2008

Finally, a supplier with materials and production. A victory for all hips, knees and shoulders!

W

ith increasing demand for orthopedic implants in markets around the world, the pressures for differentiation and high quality combined with production efficiency continue to rise. Responding to the market as quickly as possible is essential. Cooperation with the right partner all along the value chain can help to ensure an advantage.

clinical designs into a product that can be manufactured efficiently. We work with you to identify full production routes as well as tailor programs with an extensive range of processes including casting in air or vacuum, forging, powder technology and machining expertise.

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A partnership with Sandvik gives you our full commitment to meet your key business objectives in the production of implants and instruments. Based on our unique expertise in materials and contract manufacturing, there are many ways that we can support your product design efforts. We can, for example, advise on the suitability of materials as it pertains to achieving your desired implant and instrument characteristics. Through prototyping, we can help you translate your

Cross-functional teams are ready to advise and assist you on factors that can make all the difference in getting the product to market rapidly and efficiently. With international resources and a local field presence, we can respond to urgent needs of a quick turnaround as well as handle the demands of a global launch.

The Sandvik R&D team employs over 2,000 people, with a unique knowledge base in metallurgy and coatings. We have a proven track record in materials development, casting, machining and forging technologies. Sandvik is a global business with a solid history of success and growth, so you have the security of dealing with a stable company that has the capability to invest for the future. At the same time, we work locally in small teams, drawing on our broad resources to ensure you meet your timelines and commercial objectives. For all those hips, knees and shoulders, Sandvik can be a winning partner.

STRATEGIC PARTNERSHIP Combining scientific research with practical manufacturing experience, we’ll give you our total support in developing the optimal products.

www.smt.sandvik.com/medical

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DEVICES Heart aid could be implanted without invasive surgery An implantable pump that is about the size of a AA battery has been developed by CircuLite Inc., Saddle Brook, N.J. It could ultimately be implanted through a catheterization procedure that is far less invasive than the operations to place today's pumps. Called Synergy Pocket Circulatory Assist Device, a combination of magnetic and hydrostatic forces suspends the Multi-bearing acetabular rotor. Because it is designed for patients in an earlier stage of heart failure, whose hearts can still pump a modest amount of blood on cup system features their own, the Synergy pump gets by on a porous coating smaller, less powerful motor. Unlike imSmith & Nephew Inc. Orplantable VADs, which rest deep inside the thopaedic Reconstruction busichest cavity, the Synergy pump is small ness announces the global enough to be placed near the skin's surface. launch of the R3 Acetabular The CircuLite pump is powered by a roughly System, an advanced multifour-pound battery pack worn at the waist. bearing acetabular cup system Future versions will have an even smaller battery, about the size of used in total hip replacement a Razr cell phone. procedures. The R3 Acetabular For more information: Gail Farnan, Circulite Inc., 250 Pehle Avenue, Cup features Stiktite porous Saddle Brook, NJ 07663; 201/543-2430; http://www.circulite.net. coating designed to enhance fix-

Porous silicon nanomachines deliver drugs to cancer cells

ation and bony ingrowth. The multi-bearing cup, in addition to providing flexibility for surgeons, provides a foundation designed to reduce wear and the subsequent need for revision surgery. Optimized inserts accommodate larger head sizes and help the R3 system achieve a greater range of motion. R3 modular resurfacing system and ceramic-on-ceramic system are currently awaiting FDA approval in the U.S. For more information: Smith & Nephew, 1450 Brooks Road, Memphis, TN 38116; tel: 901/ 396-2121; www.smith-nephew. com.

A porous silicon nanomachine that can capture and store anticancer drugs inside tiny pores and release them into cancer cells in response to light are under development by researchers from the Nano Machine Center of the California NanoSystems Institute at the University of California at Los Angeles. Known as a "nanoimpeller," the device is the first light-powered nanomachine that operates inside a living cell, a development that has strong implicaSt. Jude Medical Inc. tions for cancer treatment. announces a partnership The nanomachine is made of mesoporous silica with the Microsoft Corp. Health Solutions Group to nanoparticles in which the interiors of the pores research the integration of are coated with azobenzene, a chemical that can data from implantable oscillate between two different conformations upon devices with patient- light exposure. Operation of the nanoimpeller was controlled, personal health demonstrated in a variety of human cancer cells, records. St. Jude Medical and Microsoft will work with including colon and pancreatic cancer cells. The physicians to determine the nanoparticles were placed in human cancer cells optimal level of integration in vitro and taken up in the dark. When light was (between the Merlin.net™ directed at the particles, the nanoimpeller mechaPatient Care Network and Microsoft® HealthVault) that nism took effect and released the contents. The pores of the particles can be loaded with cargo molecules, such as dyes or antiwill allow physicians to efficiently and confidentially cancer drugs. In response to light exposure, a wagging motion occurs, causing the cargo share device information molecules to escape from the pores and attack the cell. Confocal microscopic images with their patients. showed that the impeller operation can be regulated precisely by the intensity of the www.sjm.com light, the excitation time, and the specific wavelength. For more information: Jeffrey Zink, UCLA, Los Angeles, CA 90025; tel: 310/825-1001; Medtronic Inc. has received FDA approval for [email protected]; http://www.cnsi.ucla.edu. the Talent Abdominal Stent Graft on the CoilTrac Delivery System. It consists of a woven polyester membrane supported by a tubular metal lattice, and is specifically indicated for endovascular treatment of abdominal aortic aneurysms with or without iliac involvement. www.medtronic.com

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Hybrid hearing aid/cochlear implant differentiates sounds A hybrid hearing aid/cochlear implant device is reportedly being evaluated as part of a multi-site, national study by otolaryngologists at UT Southwestern Medical Center, Dallas, Tex. Already approved in Europe, the Duet Electric-Acoustic System, or EAS, targets borderline cases for which hearing aids don't adequately differentiate sounds, but for whom some natural hearing remains. Initial studies suggest a synergistic effect is achieved by maintaining the natural hearing and coupling it with the cochlear implant, particularly for distinguishing speech in noisy environments. The device both amplifies low frequencies and electronically stimADVANCED MATERIALS & PROCESSES/JULY 2008

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DEVICES ulates middle and high frequencies. Still in the investigational stage, the device is made by Med-El Corp., which conducts the initial patient screening for the trial. For more information: Russell Rian, UT Southwestern Medical Center, Dallas, TX 75390; tel: 214/648-3111; [email protected]; http://www.utsouthwestern.org/earnosethroat.

Rechargeable neurostimulator battery could last ten years Both FDA and European CE Mark approval have reportedly been received for St. Jude Medical’s Eon Mini, a rechargeable neurostimulator designed to treat chronic pain of the trunk or limbs. Slightly larger than a silver dollar, the device has a 10 mm profile and weighs about one ounce (29 grams). It is reportedly the only small rechargeable neurostimulator to receive a ten-year battery longevity approval by the FDA. The device should provide sustainable therapy and maintain a reasonable recharge interval for ten years of service at high settings. For more information: Kathleen Janasz, St. Jude Medical Inc., One Lillehei Plaza, St. Paul, MN 551179983; tel: 651/415-7042; www.sjm.com.

Stent controls release of drug-polymer compositions A new stent that incorporates hundreds of small holes that act as reservoirs into which drug-polymer compositions can be loaded is available from Conor Medsystems, Menlo Park, Calif. The stent is designed to enhance control of the rate and direction of drug delivery, enable a wider range of drug therapies, and potentially increase the range of clinical applications of drug eluting stents. The ability to vary the structure of the drug inlay within the reservoirs can potentially deliver a broad range of compounds, including fat-soluble drugs, water-soluble drugs, proteins, peptides, and oligonucleotides. For more information: Conor Medsystems LLC, 1003 Hamilton Court, Menlo Park, CA 94025; tel: 650/614-4100; fax: 650/614-4125; www.conormed. com.

Spinal implant treats multiple stages of degeneration The Zimmer DTO implant and OPTIMA ZS transition screw have been cleared to provide stabilization and immobilization to the lumbar and sacral spine as an adjunct to fusion, according to Zimmer Holdings Inc., Warsaw, Ind. The implant combines a Dynamic Stabilization System with the rigid stabilization of the OPTIMA ZS Spinal System to offer a new segmental solution for treating different stages of spinal degeneration at contiguous levels. For more information: Brad Bishop, Zimmer Orthopaedics, Warsaw, IN 46580; tel: 574/372-4291; [email protected]; www.zimmer.com.

Coated nanoparticles deliver drugs to interior of cells Coated nanoparticles that can slip inside a cell without triggering its self-protective mechanism have been developed at the Massachusetts Institute of Technology, Cambridge. Prof. Francesco Stellacci and his colleagues coated gold nanoparticles six nanometers in diameter with alternating stripes of hydrophobic and hydrophilic molecules, mimicking the ordered structure of the peptides researchers have tried to use in the past. They then labeled the gold nanoparticles with fluorescent dye and tested them on mouse immune cells. The group found that the nanoparticles entered the cells and distributed themselves throughout the cytosol, the cell's internal fluid, without killing the cell. For more information: Francesco Stellacci, MIT, Cambridge, MA 02139; tel: 617/ 452-3704; frstella@ mit.edu; www.mit.edu. 62

ADVANCED MATERIALS & PROCESSES/JULY 2008

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TESTING/R&D Innovation center planned for joint replacement materials

The Kansas Bioscience Authority, Wichita, Kan., is set to decide whether to invest $50 million over ten years to create a new hip replacement center with products developed by aircraft and medical scientists. The center would develop artificial hips and Lawrence Berkeley other joints from lightweight comLab, Berkeley, Calif., says posites, or resins, similar to those althat new composite ready being developed for the airmaterials developed for craft industry. The project would be bone implants and bone tissue engineering are a combined venture of Via Christi, now available for the National Institute for Aviation licensing. These include Research at Wichita State Univerinjectable hydrogel- sity, and the University of Kansas. based biodegradable For more information: Tom bone replacement Thornton, Kansas Bioscience Aumaterials, composites with graded thority, 25501 West Valley Parkway, microstructures for Suite 100, Olathe, KS 66061; tel: 913/ orthopedic implants and 397-8300; info@kansasbioauthority. bone tissue engineering, mineralization of org; www.kansasbioauthority.org. biocompatible scaffolds, peptides for the controllable promotion or inhibition of bone growth, and graded bioactive glass and glass/ceramic coatings for metal bone implants. www.lbl.gov

Imaging yields insights into polymers for cancer treatment

Researchers at Purdue University have discovered a possible new pathway for anti-tumor drugs to kill cancer cells and proposed how to improve the design of tiny drugdelivery particles for nanomedicine. The synthetic "polymer micelles" are drug-delivery spheres 60 to 100 nanometers in diameter, or roughly 100 times smaller than a red blood cell. The spheres harbor drugs in their inner core and contain an outer shell made of polyethylene glycol. The researchers used an imaging technique called Förster resonance energy transfer imaging, or FRET, to make two key discoveries: how fluorescent molecules mimicking the cancer drug paclitaxel enter tumor cells; and how the micelles break down in the blood before they have a chance to deliver the drug to cancer cells. A critical feature of micelles is that they combine two types of polymers, one hydrophobic and the other hydrophilic. The hydrophobic core was loaded with a green dye and the hydrophilic portion labeled with a red dye. Experiments showed that "core-loaded” fluorescent molecules mimicking the drug entered cancer cells within 15 minutes, suggesting a new drug-delivery pathway to kill tumor cells.

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For more information: Ji-Xin Cheng, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907; tel: 765/494-4335; [email protected]; www.purdue.edu.

Biomaterials screened through libraries of porous scaffolds A novel three-dimensional screening method for analyzing interactions between cells and new biomaterials could cut initial search times by more than half, report researchers from the National Institute of Standards and Technology (NIST) and Rutgers University. The technique, an advance over flat, twodimensional screening methods, enables rapid assessment of the biocompatibility and other properties of materials designed for repairing — or even rebuilding — damaged tissues and organs. In what may be a first, the team demonstrated how to screen cell-material interactions in a biologically representative, but systematically altered, threedimensional environment. The pivotal step in the experiment was making libraries of miniature porous scaffolds that are bone-like in structure but vary incrementally in chemical composition. For more information: Carl G. Simon Jr., NIST, 100 Bureau Drive, Gaithersburg, MD 20899-8543; [email protected]; www.nist.gov.

Bioabsorbable drug eluting stent Data from the first clinical trial of a fully bioabsorbable drug eluting stent for the treatment of coronary artery disease is available in The Lancet, reports Abbott Vascular, part of Abbott Laboratories, Abbott Park, Ill. The coronary stent is made of polylactic acid, a biocompatible material that is commonly used in medical implants such as dissolvable sutures. The positive results from this clinical trial form a strong basis for the development of additional bioabsorbable stent platforms with the potential to eliminate some of the restrictions of metallic stents in areas such as vessel imaging and vessel remodeling. For more information: Karin Bauer, Abbott Medical, Santa Clara, CA 95054; tel: 408/845-3887; www.abbottvascular.com. ADVANCED MATERIALS & PROCESSES/JULY 2008

Medpor Porous Biomaterial Sebastien Henry Porex Surgical Inc. Newnan, Georgia

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edpor is a biomaterial consisting of porous high-density polyethylene (pHDPE). It is one of the few biomaterials that can be used to reconstruct complex cranial defects or in cosmetic surgery to augment the skeleton, such as in chin augmentation surgery. In addition, it can be made in many different shapes, and can further be trimmed and carved intra-operatively to provide the best possible fit and cosmesis. It has excellent biocompatibility and good mechanical properties, which makes it a suitable biomaterial for a wide range of non load-bearing craniofacial applications. These mechanical properties come, however, at the expense of flexibility. Indeed, thicker Medpor implants are rigid and cannot be bent easily like silicone implants. One of Medpor’s key attributes is its porosity. Open-cell, interconnected pores of 100 microns or more allow tissue ingrowth throughout the implants. This tissue ingrowth provides several advantages. It fixates the implants in place, thus limiting the risk of implant migration post-operatively. It integrates the implants within the host tissue, and minimizes capsule formation around the implants. Tissue ingrowth within Medpor implants was also shown in the animal model to minimize the risk of experimentally-induced infection compared to implants made of ePTFE, which is a much less porous material that undergoes only superficial tissue ingrowth. However, in cases when a Medpor implant needs to be removed weeks or months after surgery, tissue ingrowth can render the removal of the implant difficult. For this reason, some surgeons may prefer nonporous implants. Other advantages include its availability, the fact that it does not require a second surgical site (to harvest autologous tissue), and that it does not carry any risk of disease transmission, as opposed to xenografts such as bovine-derived tissue. Facial implants Medpor implants are used in virtually all areas of the face. In the orbit, it repairs the orbital floor and wall, and replaces volume in enucleated or eviscerated sockets where the eye has been removed. In the latter case, spheres are implanted and covered with thin tissue onto which a prosthetic eye, which is made to look like the healthy, contra-lateral eye, can be placed for cosmetic purposes. In severe trauma or cancer cases where most of the orbit has to be removed, pre-shaped implants can be used to reconstruct the orbit. Since tissue irradiated in cancer therapy has been compromised, using Medpor in ADVANCED MATERIALS & PROCESSES/JULY 2008

15

these areas may be problematic. When augmentation of the orbital rim is desired, pre-shaped implants are also available. In rhinoplasty, or plastic surgery of the nose, a wide range of implants is available. In primary surgeries, they improve the aesthetics of the nose, or in secondary cases they replace or support tissue in noses that have been too aggressively corrected in a previous surgery. In other parts of the face, implants augment the bony skeleton in the chin, mandible, and malar areas. One of the most challenging reconstruction cases for surgeons is the ear. One in 6,000 to 12,000 newborns has an ear deformity known as microtia, which manifests itself by the absence of the external cartilaginous ear. To reconstruct the missing ear, surgeons typically harvest rib cartilage from the patient and shape it into an ear. This is a tedious surgery that does not always yield good results from a cosmetic standpoint and that requires a chest surgery to harvest the rib cartilage. Medpor is one of the few biomaterials that serves as an alternative to rib cartilage to reconstruct microtic ears. Pre-shaped ears in left and right configurations and in various sizes are available to surgeons. They can significantly minimize OR time and provide excellent cosmetic results in the hands of experienced surgeons. Small and large cranial defects can be repaired with a wide range of pre-shaped implants. They are available to surgeons in a range of shapes and sizes, depending on the area of the cranium they need to repair or reconstruct. In addition, Medpor implants can be customized to a patient’s specific needs. This is an especially useful feature when bony defects are so large and complex that pre-shaped implants would render the surgery too difficult and would yield less-than-desirable results. When a customized implant is needed, CT scans of the patient are used to model the defect, and an implant that will fit correctly within the defect can be created. MPMD For more information: Sebastien Henry, Porex Surgical Inc., 15 Dart Road, Newnan, GA 30265; tel: 678/479-1738; [email protected]; www.porex.com.

Medpor is the result of ten years of research that was conducted in the 1970’s and early 80’s by the late Barry Sauer (DVM). Dr. Sauer was looking for a porous implant material whose porosity would allow bone to grow within the implant, thus providing better implant integration within host tissue. Dr. Sauer’s research showed that pHDPE was not strong enough for load-bearing applications, but that it was very suitable for non load-bearing applications in the head and face. Blocks and sheets that were cut and carved by surgeons were the first configurations, and later preformed shapes were designed to minimize the time spent by surgeons carving and trimming. Today, Porex Surgical offers more than 300 implant configurations that span five surgical specialties (ENT/facial plastic, plastic, oculoplastic, oral maxillofacial, and neurosurgery) and that are available in over 50 countries. 65

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Novel Nanocomposites for Bone Regeneration Eduardo Saiz and Antoni P. Tomsia Lawrence Berkeley National Laboratory

Janice S. Lee, Mahesh H. Mankani, Sally J. Marshall, and Grayson W. Marshall University of California at San Francisco

Ulrike G.K. Wegst Drexel University

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trategies for bone repair are currently based on the use of autografts or alloplastic (synthetic) materials. Both approaches have severe shortcomings. This article summarizes Bone grafting requires a second a paper that the authors surgical site and risks to the patient, are to present at the and the amount of available bone is 2008 Materials Science limited. On the other hand, synthetic bio& Technology materials often have integration probConference and lems with the host tissue, and can reExhibition in Pittsburgh, sult in infection, foreign-body October 5-9. reactions, and extrusion or loss of the For more information, implanted material. Their outcome visit is time-limited and unpredictable. The deficiencies of current treatwww.matscitech.org. ments and the search for alternatives have motivated an increasing interest in the development of tissue engineering therapies for the treatment of bone defects. Most of these approaches require a porous scaffold to provide cell support and guide bone regeneration. Multiple physical and biological requirements should be addressed by a bone scaffold. • It must supply a porous matrix with interconnected porosity and tailored surface chemistry for cell growth and proliferation, and the transport of nutrients and metabolic waste. • It must possess sufficient strength and stiffness to prevent fracture under physiological loads during integration and healing. • It should be resorbed or remodeled in a predictable way, with controlled osteogenic activity, and produce only metabolically acceptable substances. • Once in vivo, it should substitute, at least temporarily, for natural tissue, and • It should present no risk of rejection or foreignbody reaction. • Its mechanical properties should match those of the host tissues, and • The strength and stability of the material-tissue interface should be maintained while the material is resorbed or remodeled. A major obstacle in the development of effective 66

Fig. 1 — Solid freeform fabrication techniques that are precise and reproducible would be able to fabricate customdesigned scaffolds with complex architectures. These techniques include direct ink-jet printing, robotic-assisted deposition or robocasting (in the figure), and hot-melt printing. These technologies typically involve “building” structures layer-by-layer following a computer design, or image sources such as MRI.

bone tissue engineering therapies has been the inability to create scaffolds that combine these stringent physical and biological conditions. Clinical success with currently available biomaterials is temporary and limited and does not approach that obtainable with autologous bone, despite its limitations documented above. The emerging consensus is that designing the optimum scaffold is a balancing act that can only be approached through the combination of complex material designs incorporating pore gradients and different material combinations with sophisticated functional capabilities through surface engineering, cell encapsulation, and controlled chemical release. Process challenges Progress in the development of new scaffolds has been hampered, in part, by the limitations in processing techniques. Current technologies are unable to produce materials designed at different length scales (from nano- to macroscopic), while incorporating various organic and inorganic components with tailored surfaces, and drug delivery vehicles at different locations within the scaffold. For the fabrication of macroporous materials, abundant established techniques can be adopted, including solvent casting/particle leaching, phase separation, solvent evaporation, fiber bonding to form a polymer mesh, and freeze-drying. However, these techniques fail to provide the required degree of structural control. In addition, we still lack basic design criteria to guide the design of scaffolds able Continued on page 20 ADVANCED MATERIALS & PROCESSES/JULY 2008

Materials Knowledge Leads to Better Medical Devices

Attend one of ASM’s upcoming seminars to gain the materials knowledge you need to become an innovator in your industry! Polymer Considerations in Medical Device Design Jennifer M. Hoffman, PhD

Seminars at a Glance Stainless Steels, Cobalt-Chromium and Titanium Alloys for Medical Devices Phillip J. Andersen, PhD Phillip J. Andersen, PhD

Nitinol for Medical Devices Presented by SMSTSM

Jennifer M. Hoffman, PhD

Medical Device Design Validation and Failure Analysis Brad James, PhD, PE Scott Russell Inorganic PVD Coatings and Surface Treatments for Medical Devices Dr. David Glocker

Scott Russell

Brad James, PhD, PE

Seminar Dates: Materials Selection: Meeting Functional Requirements of Medical Devices Michael N. Helmus, PhD

Ft. Wayne, Indiana

May 19-23, 2008

Minneapolis, Minnesota

June 23-27, 2008

Cleveland, Ohio

August 4, 2008

Dr. David Glocker

Michael N. Helmus, PhD

Stanford, California

September 8-12, 2008

Miami, Florida

December 8-12, 2008

You may attend one or more of the full-day seminars or the entire five-day series. Multiple students from your organization can sign up and receive a discount. For details, contact [email protected], or call 800.336.5152 or 440.338.5151, ext. 0. Visit us online at www.asminternational.org/training

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These articles summarize papers that the authors are to present at the 2008 Materials Science & Technology Conference and Exhibition in Pittsburgh, October 5 - 9. For more information, visit www.matscitech.org.

Synthesis of Nanocrystalline Hydroxyapatite Using Microwave Radiation Samar J. Kalita and Saurabh Verma University of Central Florida, Orlando, Florida

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anocrystalline bioceramics are a new focus bone tissue engineering research. Nanostructured ceramics provide unique size-dependent properties; a large surface to volume ratio, and unusual chemical/electronic synergistic effects resulting from ultrahigh component dispersion. In particular, hydroxyapatite (HAp) bioceramic has a crystal structure similar to that of native bone and teeth minerals. It is the material of choice in many orthopedic and dental formulations because it elicits a favorable biological response and forms a strong bond with the surrounding tissues. HAp is sensitive to nonstoichiometry and impurities due to its complex composition and crystal structure [Ca10(PO4)6(OH)2, P63/m]. For this reason, the conventionally synthesized HAp lacks phase purity, stoichiometry, and homogeneity. The aim of our study was to synthesize phase-pure, homogeneous, bioactive HAp powder in the lower-end of the nano regime using microwave radiation, which offers several advantages. Nano-biomaterials promote osteoblast adhesion and proliferation, osteointegration, and the deposition of calcium-containing minerals on the surface of these materials. Furthermore, nanocrystalline HAp is expected to exhibit improved bioactivity and homogeneous resorption in vivo. Nanocrystalline HAp powder was synthesized with calcium nitrate tetrahydrate and sodium phosphate dibasic anhydrous as starting materials. The microwave power of 600 W and mole ratio of Ca/P in the starting chemicals, served as the factors in HAp synthesis. The powder was characterized via XRD, SEM, HR-TEM, EDS, TG/DTA, and FT-IR techniques. Results established a highly crystalline nanopowder with elemental composition of calcium and phosphorus in the HAp phase, which possessed mixed (elliptical and rod-shape) morphology. The TEM micrograph shown in Fig. 1 confirmed the formation of nanocrystalline powders of different morphologies. These included rod-shaped (~5 nm in diameter and ~15 nm in length) and elliptical (16 nm x 26 nm). The average crystallite size

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Fig. 1 — TEM micrograph of nanocrystalline hydroxyapatite powder.

determined from the XRD peaks using the Scherrer’s formula was calculated to be 12 nm. TEM results are in agreement with this crystallite size information. Unique advantages associated with microwave synthesis of ceramics helped in the synthesis of fine crystalline phase-pure HAp powder. These advantages include shorter synthesis time, rapid heating, fast reaction, easy reproducibility, narrow particle distribution, high yield, high purity, efficient energy transformation, and through-the-volume heating. Microwave heating is different from conventional heating, in which the heat is generated internally within the material instead of originating from an external heating source and subsequent radiative transfer. FT-IR confirmed the apatite structure of the powder. TG analysis showed 23% weight loss upon heating up to 1200°C (2190°F), contributed by the removal of adsorbed/lattice water, and decarboxylation of HAp. Remarkably lower initial dehydroxylation temperature (570°C) was observed compared to results reported in literature for conventional micron size HAp. MPMD For more information: Samar J. Kalita, Department of Mechanical, Materials and Aerospace Engineering, University of Central Florida, Orlando, FL 32816-2450; tel: 407/823-3159; fax: 407/823-0208; [email protected]; www.ucf.edu.

ADVANCED MATERIALS & PROCESSES/JULY 2008

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Porous NiTi with Superelastic or Shape-Memory Properties Ampika Bansiddhi and David C. Dunand Northwestern University Evanston, Illinois

ADVANCED MATERIALS & PROCESSES/JULY 2008

Fig. 1 — Scanning electron microscopic micrographs of NiTi foam polished cross-sections showing open porous structure at low magnification (left) and high magnification (right). 400 Stress, MPa

NiTi

with 30 to 50% interconnected porosity (90% open-pore ratio) and 100 to 400 micron pore size has been fabricated by a new foam replication process. Prealloyed NiTi powders are densified in the presence of NaCl powders by hot isostatic pressing at temperatures above the melting point of the NaCl space holder (800°C, 1470°F). The NaCl space holder can be fully removed by water dissolution or vacuum evaporation without unacceptable residual or contamination. Empty space left after removal of NaCl becomes pores whose fraction, size, shape, and connectivity are controllable through the initial volume fraction and geometry of the NaCl space holders. The pores maintained the angular shape of the original NaCl particles, indicating that substantial NiTi densification occurred prior to NaCl melting (Fig. 1). With this technique, higher porosity and connectivity can be achieved by the choice of spaceholder content and geometries, while thinner NiTi walls are well-densified without pore collapse, which is problematic in a simple sintering approach with transient space holders. Subsequent sintering after NaCl removal at temperatures above the limits of the HIP process can also further optimize densification in the NiTi structure. Molten space holders offer significantly greater flexibility in processing, relative to other existing solid place holders (fluorides or oxides), by enabling cheaper and more low-melting space-holders with high solubility in water. For example, NaCl could be used for foams of technologically-important highmelting-point materials, including the NiTi alloy studied here. Furthermore, for porous NiTi to serve as a bone-replacement implant, this method offers precise control over many foam geometrical parameters that are crucial to the performance of the implant. The NiTi foams exhibit superelasticity or shapememory properties, depending on the exact Ni/Ti ratio. Higher nickel content could be applied directly to the technique (although the method was originally demonstrated using porous shape-memory NiTi) to create low-modulus, superelastic NiTi foam. In general, high compressive yield strength with very low stiffness (4%) are observed. For example, martensitic

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