Medical Device Materials VI Proceedings from the Materials & Processes for Medical Devices Conference August 8–10, 2011 Hilton Minneapolis Minneapolis, Minnesota, USA Sponsored by ASM International® Materials Park, OH 44073-0002 www.asminternational.org Copyright  2013 by ASM International® All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the written permission of the copyright owner. First printing, February 2013 Great care is taken in the compilation and production of this book, but it should be made clear that NO WARRANTIES, EXPRESS OR IMPLIED, INCLUDING, WITHOUT LIMITATION, WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, ARE GIVEN IN CONNECTION WITH THIS PUBLICATION. 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ISBN-13: 978-1-62708-009-5 ISBN-10: 1-62708-009-0 SAN: 204-7586 ASM International® Materials Park, OH 44073-0002 www.asminternational.org Printed in the United States of America Contents Poster Session Plasma Sterilization of Ultrasound Contrast Agents ............................................................ 1 L. Albala, Drexel University, Philadelphia, PA, USA   Inducing the Bone Growth on Different Titanium Alloys ...................................................... 4 J. Mirza Rosca1, D. Herrera Santana1, D. Gonzalez Martin2 (1) Las Palmas de Gran Canaria University, Canary Islands, Spain (2) Technological Institute of Canarias, Canary Islands, Spain A Novel Polymeric Composite for Orthopaedic Applications .............................................. 7 A.O. Tiamiyu1, S.A. Ibitoye2, I. A. Inyang2 (1) University of Cape Town, South Africa (2) Obafemi Awolowo University, Nigeria Passive Layer on Some Titanium Alloys ............................................................................. 11 J. Mirza Rosca, D. Herrera Santana, A. Santana Lopez Las Palmas de Gran Canaria University, Canary Islands, Spain Fracture Mechanics and Micro Crack Detection in Bone — A Short Communication ........................................................................................................ 15 A.M. Al-Mukhtar1, C. Konke2 (1) Technische Universitat Bergakademie Freiberg, Germany (2) Bauhaus-Universitat Weimar, Germany ADSC Cells with Different Medium in Polycaprolactone/Hydroxyapatite Whiskers Scaffolds an Initial Study ..................................................................................... 20 G.B.C. Cardoso, S.L.F. Ramos, C.A.C. Zavaglia, P. B. Rego, S.T.O. Saad, A.C.F. Arruda, State University of Campinas, Brazil A Microstructural Overview of Oxide Ceramics for Medical Implants .............................. 24 A. Nield, J. Haftel, S. Hughes C5 Medical Werks, LLC, Grand Junction, CO, USA Mechanical Performances of Biomedical Beta-type Titanium Alloy Through Heat Treatment and Severe Plastic Deformation ....................................... 27 T. Akahori1, M. Niinomi2, M. Nakai2, H. Yilmazer2, H. Fukui3, Y. Todaka4 (1) Meijo University, Japan (2) Tohoku University, Japan (3) Aichi-Gakuin University, Japan (4) Toyohashi University of Technology, Japan iv Fabrication Processes for Medical Devices — I Electropolishing and Throughmask ElectroEtching of Nitinol Stents and Other Materials in an Aqueous Electrolyte ....................................................... 31 M. Inman1, E.J. Taylor1, A. Lozano-Morales2, L. Zardiackas3 (1) Faraday Technology, Clayton, OH, USA (2) Eltron Research, Boulder, CO, USA (3) University of Mississippi Medical Center, Jackson, MS, USA Effect of Thermo-Set Process on MP35N Cable .................................................................. 37 B. Li, H. Zhang, L. Wang, Medtronic Corporation, Minneapolis, MN, USA Evaluation of Metal Injection Molded 17-4 PH Stainless Steel for Instruments ................ 41 A. Craft, D. Campbell, B. Aboud, DePuy Orthopaedics, Inc., Warsaw, IN, USA Materials Modeling Designing with Materials — Applying Materials Data and Rational Materials Selection Methodologies in Medical Device Design ........................................... 47 S. Egan, S. Warde, Granta Design, Cambridge, UK Effect of Strain Rate on Nitinol Constitutive Modeling in the Clinically Relevant Strain Range ............................................................... 52 P. Briant, R. Siskey, A. Rau, S. Easley, B. James Exponent Inc., Menlo Park, CA, USA Fatigue Life and Durability of Medical Devices — I Why are Implantable Cardioverter-Defibrillators and Pacemakers being Revised Today? ..................................................................................... 57 J.A. Hanzlik1,2, J.D. Patel1,2, S.M. Kurtz1,2, Q.C. Horn2, Y.P. Shkolnikov2, J.A. Ochoa2, B.B. Pavri3, A.J. Greenspon3, (1) Drexel University, Philadelphia, PA, USA (2) Exponent Inc., Seattle, WA, USA (3) Thomas Jefferson University Hospital, Philadelphia, PA, USA Comparative Failure Analysis of Retrieved UHMWPE Tibial Components ....................... 63 N. Camacho, S.W. Stafford, L. Trueba Jr. University of Texas, El Paso, TX, USA Advanced Materials and Emerging Technologies — I Qualification of Hot Isostatic Pressing Processes ............................................................. 69 K. Rivard, A. Craft, T. Smith, B. Aboud DePuy Orthopaedics, Inc., Warsaw, IN, USA v Bioactive Improving the Bioresponse to Polymers Using Zirconium and Tantalum Hybridization ................................................................................ 74 J. Jarrell1, J. Walters2, N. Thomas2, M. Young2, P. Tran3, N. Tran3, R. Hayda3, C. Born3 (1) BioIntraface, Inc., East Providence, RI, USA (2) Brown University, Providence, RI, USA (3) Orthopaedic Trauma Research, Providence, RI, USA Fatigue Life and Durability of Medical Devices — II Ultrasonic Detection of Defects in Multilayered Ceramic Capacitors for Active Implantable Medical Devices ........................................................... 80 S.A. Kim1, W.L. Johnson1, G.S. White1, R. Roberts2 (1) National Institute of Standards and Technology, Boulder, CO, USA (2) Vishay Corp., Columbus, NE, USA Medical Device Feedthrough Fatigue Characterization ...................................................... 86 J. Popp, J. Taylor, J. Hendrickson, Meditronic Inc., Minneapolis, MN, USA Prediction of Hip Prosthesis Fatigue Properties — Influence of the Process .................. 92 M. Puget1, C. Doudard1, S. Calloch1 F. Boucher2 (1) Laboratoire Brestois de Mecanique et des Systemes, France (2) Stryker Benoist Girard, France Fabrication Processes for Medical Devices — III The Functionality of Ti-15Mo in Creating 3-D Porous Surfaces via Laser Powder Deposition for the Use in Dental Prosthetics .............................................. 98 J. Fuerst1, K. Kennedy1, M. Carter1, J. Sears1, D.J. Medlin2 (1) South Dakota School of Mines and Technology, Rapid City, SD, USA (2) Engineering Systems Incorporated, Omaha, NE, USA Corrosion In-vitro Degradation and Cytocompatibility Assessment of Mg-Zn and Mg-Zn-Ca Alloys ................................................................................................ 104 P. Gill, N. Munroe, R. Dua, S. Ramaswamy, Florida International University, Miami, FL, USA Potentiodynamic and Potentiostatic Characterization of CVD Alumina Coating for Orthopaedic Implant Wear Reduction ............................................................ 108 R. Overholser, E. Gulley, B. Smith DePuy Orthopaedics Inc., Warsaw, IN, USA Fabrication Processes for Medical Devices — IV Improved Resolution and Mechanical Properties of Porous Coatings and Cellular Structures in Ti6Al4V Manufactured with Electron Beam Melting ........................................................................ 113 S. Fager Franzén, M. Svensson, U. Ackelid, I. Elfström Arcam AB, Sweden vi Influence of Interstitials on Material Properties of TI6AL4V Fabricated with Electron Beam Melting (ebm®) ................................................................ 119 M. Svensson, Arcam AB, Sweden Next Generation of Bio Materials Surface Integrity of Biodegradable Orthopedic Magnesium-Calcium Alloy Processed by High Speed Machining ....................................................................... 125 M. Salahshoor, Y.B. Guo, The University of Alabama, Tuscaloosa, AL, USA Materials Research & Development — I Phase Transformation Study on MP35N Wire for Lead Conductor ................................. 131 B.Q. Li, D. Sorensen, T. Steigauf, Medtronic, Minneapolis, MN, USA Factors Causing Compressive Damage-Induced Cracking in Nitinol ............................ 139 A. Chinubhai, A. Kueck, P. Saffari, K. Senthilnathan, L. Vien, A.R. Pelton, Nitinol Devices & Components, Fremont, CA, USA Surface Engineering of Medical Devices Bioactive Hybrid Material Surface Treatments for Infection Resistant Implants without Drugs ...................................................................................... 143 J. Jarrell1, N. Thomas2, M. Young2, C. Baker2, J. Morgan2, P. Tran3, N. Tran3, R. Hayda3, C. Born3 (1) BioIntraface, Inc., East Providence, RI, USA (2) Brown University, Providence, RI, USA (3) Orthopaedic Trauma Research, Providence, RI, USA Evaluation of Diffusion Hardened Oxidized Zr-2.5wt%Nb for Hard-on-Hard Articulation in Total Hip Arthroplasty ........................................................ 149 V. Pawar, C. Weaver, A. Parikh, S. Jani, Smith and Nephew Inc., Memphis, TN, USA Adsortion of Fibronectin into Titanium Implant Surface .................................................. 153 P.A. Gravina1, C.N. Elias1, F.C. Silva2, (1) Instituto Militar de Engenharia, Brazil (2) Instituto de Biofísica, Brazil LASER Powder Deposition of Titanium – Tantalum Alloy Structured Interfaces for Use in Orthopedic Devices ............................................. 159 J. Fuerst1, M. Carter1, M. Huber1, J. Sears1 D.J. Medlin2, G.F. Vander Voort3 (1) South Dakota School of Mines and Technology, Rapid City, SD, USA (2) Engineering Systems Incorporated, Omaha, NE, USA (3) Vander Voort Consulting, Wadsworth, IL, USA vii Materials Research & Development — II Young’s Modulus Change due to Deformation-Induced Phase Transformation in Beta-type Titanium Alloys for Biomedical Applications ................... 165 M. Nakai, M. Niinomi, X.L. Zhao, X.F. Zhao Tohoku University, Sendia, Japan Improved Properties of Light Alloys (Ti-, Ti-Alloys) Using Near-Nano and Nano-Based Materials for Biomedical Applications ............................... 169 C. Melnyk1, B. Weinstein1, D. Grant1, R. Gansert2 (1) California Nanotechnologies Inc., Cerritos, CA, USA (2) Advanced Materials & Technology Services, Inc., Simi Valley, CA, USA Characterization of Microstructure and Dynamic Mechanical Properties of Biomedical Nitinol Alloy ........................................................... 175 J.E. McKinney, J.Z. Snyder, Y.B. Guo The University of Alabama, Tuscaloosa, AL, USA Materials Research & Development — III Design and Optimization of a Permeation Testing System for Polymer Coatings ............................................................................................. 181 A. Verwolf, National Institute of Standards and Technology, Boulder, CO, USA Author Index ......................................................................................................................... 187 viii Medical Device Materials VI Proceedings from the Materials and Processes for Copyright © 2013 ASM International® Medical Devices Conference All rights reserved August 8–10, 2011, Minneapolis, Minnesota, USA www.asminternational.org Plasma Sterilization of Ultrasound Contrast Agents L. Albala Drexel University, Philadelphia, PA, USA Abstract Ultrasound-targeted microbubble destruction is a non-invasive method of administering drugs. UCA are less than 6 µm in The presence of contrast agents in ultrasound imaging has diameter and show enhanced permeation and retention effects made a substantial impact on account of the physical in vascular circulation. Non-ionic surfactant-based similarities between tissues and fluids in the human body. microbubbles can be ‘loaded’ in a variety of different ways Perfluorocarbon gas-filled microbubbles have been shown to with drugs (electrostatic binding, encapsulation within the possess great viability as both ultrasound contrast agents hydrophobic core, etc.), allowing for simultaneous imaging (UCA) and as therapeutic targeted drug-delivery vehicles. and drug delivery aimed at targeted drug release. Ultrasound PFC gas has extremely low solubility (in blood), the bubbles sonication causes a contraction and expansion of the bubbles are safe in concordance with the human body and are small (corresponding to the sound waves’ harmonic oscillation), enough (less than 6µm) to pass through the smallest vessels, which, at clinical ultrasound frequencies, can cause the bubble and most importantly, their acoustical impedance greatly to implode, thereby releasing its contents. enhances contrast. Ultrasound can be applied to a specific area of the body (e.g. a An important consideration of anything injected and tumor/mass) where the bubbles in circulation need to release circulating in the human body is its sterility, especially to their contents. The force of the microbubbles’ destruction is avoid risk of infection (and satisfy FDA requirements). Short also known to cause transient pore opening, which allows for of production in a “clean” facility, microbubbles are far from enhanced drug uptake. Microbubbles of different types are sterile. This focus of this experiment is to employ gas plasma being applied clinically already for enhanced ultrasound to sterilize bubbles freeze-dried for storage. The goal is to imaging, and the importance of future applications is clear, in identify the ideal plasma setting to sterilize the sample. terms of delivering medication in high concentration to the target, sparing toxicity to the rest of the body. Sterility was difficult to achieve with this UCA, but poly lactic acid bubbles can be sterilized with similar setup [2], perhaps The sterility of contrast agents is of utmost importance. The due to non-sterile pre-plasma injection of PFC gas. More possible complications and confusion that can arise with studies need to be done to understand sterilization possibilities bacteriological infections or reactions are unacceptable. The with surfactant bubbles. goal is to sterilize two important types of surfactant-based microbubbles—both are made with a combination of Span 60 Introduction and a either Polysorbate/Tween 80 or Vitamin E. The microbubble solution is flash-frozen in liquid nitrogen and The microbubbles are generated in a solution by sonication, vacuum-dried to achieve the final product, a powder. This is and stabilized by a layer of nonionic surfactant molecules. The the medium that is sterilized because packaging, storing, and combination of surfactants has a certain hydrophile-lipophile sterilization applications of microbubbles show that balance to reduce head-group repulsion. These bubbles are conservation in a solid powder state after freeze-drying is highly echogenic and small enough to pass through the likely favorable. pulmonary capillary bed. Plasma gas is the chosen method of sterilization because of the low probability that it will react with the bubbles and of its low-thermal nature. Plasma is a partially ionized gas mainly composed of ions, electrons, and radicals. In turn, radicals disrupt the metabolism of microorganisms, thus making this permeating gas medium ideal in annihilating bacteria. This experiment explored the different power setting and durations of plasma setting of a bench-top plasma cleaner for the optimal sterilization setting. Figure 1: Proposed molecular arrangement of the surfactants by Wheatley et. Al. [5]. 1 Microbubble stability and echogenicity in an ultrasound bath could mean that there are either fewer microbubbles or that and sterility tests are done to ensure that incubation in RPMI they survive the ultrasound less: growth media does not cause contamination. Results have shown possibility for sterilization in addition to maintenance of echogenicity, though future work with plasma- treated liquids seems to be a feasible solution in the manufacturing process of the microbubbles Primary Goals  Maximize retention of enhancement with appropriate SE61 and ST68 bubble size after sterilization of freezedried bubble solutions.  Maintain sterile conditions in RPMI growth media up to 48 hours after incubation with plasma-sterilized bubbles.  Avoid compromising echogenicity and stability of the bubbles Figure 2: Acoustic response; the response of different amounts of reconstituted microbubbles per liter. while maintaining sterility by optimizing sterilization settings. Methodology Microbubble Manufacture: Span60, NaCl, and PBS are mixed with either Tween80 or TPGS to form ST68 or SE61 suspensions. Suspensions are autoclaved and bubbles are generated by sonication (3 min, 110 W) and purging with PFC. Wash and gravity separation of microbubbles at 4º C with 3 cold PBS washes. Pipetted 2ml of bubbles in lyophilization vials with 2 ml glucose/PBS solution (maintain 1:1) and freeze-dry. Injected PFC gas into vials. 0.05g of powder are transferred to vials. Plasma sterilized at appropriate settings. Bubbles reconstituted with RPMI media to test size, echogenicity, or sterility. Figure 3: Acoustic stability; the response of a fixed amount of Plasma Sterilization Process: Extracted cap on lyophilization reconstituted microbubbles per liter over a period of time. vials to open position. With a rubber band, wrapped Kimwipe around vial so opening is covered. Connected plasma cleaner As for contamination of microbubbles, all the controls showed to gas tank, inserted vials into chamber. Initiated vacuum no contamination under microscopy examination. Controls inside chamber, turned on machine and allowed gas in for were simply petri dishes with RPMI medium. This confirmed chosen time. Turned off vacuum, allowed gas to enter and that the experimenter’s aseptic method was adequate. An pressure to equalize. Opened chamber, quickly closed caps increasing trend of plasma treatment led to an increasing and placed samples in container sprayed with alcohol. number of sterile dishes: Acoustic Setup: 5 MHz Transducer focused through an Table 1: The percentage of uncontaminated petri dishes with acoustic window in vessel with 50 ml PBS. Signal amplified respect to plasma sterilization setting: to 40 dB and analyzed using Labview [1]. Sterility Testing: Another portion of plasma sterilized samples are reconstituted with RPMI media and incubated in small petri dishes for 48 hours at 37 C. Microscopy was used to explore for bacteria contamination. Data & Results Microbubbles maintained a diameter from 1 to 3 microns (tested using dynamic light scattering). As for echogenicity, it seems that various settings of plasma gas do not cause significant loss in response. However, the duration of echogenic response is slightly decreased over time, which 2 Conclusions References Sterility can be obtained, but consistency needs to be 1. Wheatley, M. A., F. Forsberg, K. Oum, R. Ro, D. El-Sherif, achieved. For most samples, non-sterilized UCA maintained Ultrasonics 44, 360 (Nov, 2006). superior echogenicity and stability. Enhancement tends to 2. Wheatley, M. A., J. R. Eisenbrey, and J. Hsu. "Plasma decrease for higher plasma times and/or intensities. Finally, Sterilization of Poly Lactic Acid Ultrasound Contrast Agents: the rate of sterile samples is higher with increased time in Surface Modification and Implications for Drug plasma. Delivery." Ultrasound in Medicine & Biology 35.11 (2009): Future Work 1845-862. 3. Solis, Carl, Flemming Forsberg, and Margaret A. Wheatley. There are a few process modifications that appear promising, "Preserving Enhancement in Freeze-dried Contrast Agent such as aseptically evacuating vials and injecting sterile PFC ST68: Examination of Excipients." International Journal of gas after sterilization. Another interesting technique would be employing novel plasma technology [4] to suspend ions in Pharmaceutics 396 (2010): 30-38. solution and utilizing this solution in the final steps of 4. Joshi, Suresh, et al. "Effect of Liquid Modified by Non- manufacture to achieve, ideally, a ‘self-sterilizing’ solution. Equilibrium Atmospheric Pressure Plasmas on Bacteria Inactivation Rates".IEEE , 2010. 1-1. Furthermore, an analysis of sterilization and stability when 5. Wheatley, M. "Structural Studies on Stabilized sterilized with different gases would be useful. The Microbubbles: Development of a Novel Contrast Agent for aforementioned plasma technology could be used as well for possible sterilization of fresh (not freeze-dried) bubbles. With Diagnostic Ultrasound." Reactive Polymers 25.2-3 (1995): continued progress, contamination and proliferation analysis 157-66. should be done with standard blood agar tests. 3