Implantable Microelectromechanical Systems Research Articles

Implementation of an epicardial implantable MEMS sensor for continuous and real-time postoperative assessment of left ventricular activity in adult minipigs over a short- and long-term period.

The sensing of left ventricular (LV) activity is fundamental in the diagnosis and monitoring of cardiovascular health in high-risk patients after cardiac surgery to achieve better short- and long-term outcome. Conventional approaches rely on noninvasive measurements even if, in the latest years, invasive microelectromechanical systems (MEMS) sensors have emerged as a valuable approach for precise and continuous monitoring of cardiac activity. The main challenges in designing cardiac MEMS sensors are represented by miniaturization, biocompatibility, and long-term stability. Here, we present a MEMS piezoresistive cardiac sensor capable of continuous monitoring of LV activity over time following epicardial implantation with a pericardial patch graft in adult minipigs. In acute and chronic scenarios, the sensor was able to compute heart rate with a root mean square error lower than 2 BPM. Early after up to 1 month of implantation, the device was able to record the heart activity during the most important phases of the cardiac cycle (systole and diastole peaks). The sensor signal waveform, in addition, closely reflected the typical waveforms of pressure signal obtained via intraventricular catheters, offering a safer alternative to heart catheterization. Furthermore, histological analysis of the LV implantation site following sensor retrieval revealed no evidence of myocardial fibrosis. Our results suggest that the epicardial LV implantation of an MEMS sensor is a suitable and reliable approach for direct continuous monitoring of cardiac activity. This work envisions the use of this sensor as a cardiac sensing device in closed-loop applications for patients undergoing heart surgery.

Novel Fabrication Technology for Clamped Micron-Thick Titanium Diaphragms Used for the Packaging of an Implantable MEMS Acoustic Transducer.

Micro-Electro-Mechanical Systems (MEMS) acoustic transducers are highly sophisticated devices with high sensing performance, small size, and low power consumption. To be applied in an implantable medical device, they require a customized packaging solution with a protecting shell, usually made from titanium (Ti), to fulfill biocompatibility and hermeticity requirements. To allow acoustic sound to be transferred between the surroundings and the hermetically sealed MEMS transducer, a compliant diaphragm element needs to be integrated into the protecting enclosure. In this paper, we present a novel fabrication technology for clamped micron-thick Ti diaphragms that can be applied on arbitrary 3D substrate geometry and hence directly integrated into the packaging structure. Stiffness measurements on various diaphragm samples illustrate that the technology enables a significant reduction of residual stress in the diaphragm developed during its deposition on a polymer sacrificial material.

Piezoelectric MEMS—evolution from sensing technology to diversified applications in the 5G/Internet of Things (IoT) era

The rapid development of the fifth-generation mobile networks (5G) and Internet of Things (IoT) is inseparable from a large number of miniature, low-cost, and low-power sensors and actuators. Piezoelectric microelectromechanical system (MEMS) devices, fabricated by micromachining technologies, provide a versatile platform for various high-performance sensors, actuators, energy harvesters, filters and oscillators (main building blocks in radio frequency front-ends for wireless communication). In this paper, we provide a comprehensive review of the working mechanism, structural design, and diversified applications of piezoelectric MEMS devices. Firstly, various piezoelectric MEMS sensors are introduced, including contact and non-contact types, aiming for the applications in physical, chemical and biological sensing. This is followed by a presentation of the advances in piezoelectric MEMS actuators for different application scenarios. Meanwhile, piezoelectric MEMS energy harvesters, with the ability to power other MEMS devices, are orderly enumerated. Furthermore, as a representative of piezoelectric resonators, Lamb wave resonators are exhibited with manifold performance improvements. Finally, the development trends of wearable and implantable piezoelectric MEMS devices are discussed.

Magnetoelectric and Multiferroic Properties of BaTiO3/NiFe2O4/BaTiO3 Heterostructured Thin Films Grown by Pulsed Laser Deposition Technique

Development of lead-free BaTiO3/NiFe2O4/BaTiO3 (BTO/NFO/BTO) trilayer structure thin films is significant for the realization of eco-friendly and implantable microelectromechanical systems (MEMS)-based devices. In the present work, we report BTO/NFO/BTO trilayer structure as a representative ferroelectric/ferromagnetic/ferroelectric (FE/FM/FE) system deposited on Pt(111)/TiO2/SiO2/Si using Pulsed Laser Deposition (PLD) technique. We report the ferroelectric, magnetic, and ME properties of BTO/NFO/BTO trilayer nanoscale heterostructure having dimensions 140/80/140 nm, at room temperature. High room temperature dielectric constant ~2145 at 100 Hz with low dielectric loss ~0.05 at 1 MHz is observed. Further, the deposited (BTO/NFO/BTO) tri-layered thin films showed magnetoelectric, multiferroic behavior with remanent polarization of 8.63 μCcm−2 at about 0.25 MV/cm and a reasonably high saturation magnetization of ~16 emu/cm3 at ~10 kOe is witnessed at room temperature. Tri-layered films have shown interesting magnetoelectric (ME) coupling coefficient (αE) ~54.5 mV/cm Oe at room temperature.

In Vitro Biocompatibility of Piezoelectric K0.5Na0.5NbO3 Thin Films on Platinized Silicon Substrates.

Lead-free piezoelectric ceramics like K0.5Na0.5NbO3 (KNN) represent an emerging class of biomaterials for medical technology, as they can be used as components in implantable microelectromechanical systems (MEMS) and bioactive scaffolds for tissue stimulation. Such functional materials can act as working components in future in vivo devices, and their addition to current implant designs can greatly improve the biological interaction between host and implant. Despite this, only a few reports have studied the biocompatibility of these materials with living cells. In this work, we investigate the biological response of two different cell lines grown on KNN thin films, and we demonstrate excellent biocompatibility of the KNN films with the cells. Undoped and 0.5 mol % CaTiO3-doped KNN thin films with nanometer-sized roughness were deposited on platinized silicon (SiPt) substrates, and cell proliferation, viability, and morphology of human 161BR fibroblast cells and rat Schwann cells grown on the KNN films and SiPt substrates were investigated and compared to glass control samples. The results show that proliferation rates for the cells grown on the KNN thin films were equally high or higher than those on the glass control samples, and no cytotoxic effect from either the films or the substrate was observed. The work demonstrates that KNN thin films on SiPt substrates are very promising candidates for components in implantable medical devices.

Packaging Technology for an Implantable Inner Ear MEMS Microphone.

Current cochlear implant (CI) systems provide substantial benefits for patients with severe hearing loss. However, they do not allow for 24/7 hearing, mainly due to the external parts that cannot be worn in all everyday situations. One of the key missing parts for a totally implantable CI (TICI) is the microphone, which thus far has not been implantable. The goal of the current project was to develop a concept for a packaging technology for state-of-the-art microelectromechanical systems (MEMS) microphones that record the liquid-borne sound inside the inner ear (cochlea) as a microphone signal input for a TICI. The packaging concept incorporates requirements, such as biocompatibility, long-term hermeticity, a high sensing performance and a form factor that allows sensing inside the human cochlea and full integration into the existing CI electrode array. The present paper (1) describes the sensor packaging concept and the corresponding numerical and experimental design verification process and (2) gives insight into new engineering solutions for sensor packaging. Overall, a packaging concept was developed that enables MEMS microphone technology to be used for a TICI system.

Cytotoxicity of ultraviolet-C radiation on a heterogeneous population of human glioblastoma multiforme cells: Meta-analysis

Current treatment strategies for glioblastoma multiforme are limited due to early recurrence and heterogeneity of the cell population that causes a varied response to treatment. Ultraviolet-C (UVC) radiation may be a potential adjuvant treatment that could theoretically be delivered locally by implantable micro-electromechanical systems that sense and kill early recurrence and/or minimally residual cancer. in vitro irradiation experiments are limited because they commonly use a single cell line. Therefore other methods are required to investigate cytotoxicity across a heterogeneous population of GBM. A meta-analysis was conducted to assess the cytotoxic effects of UVC radiation on human GBM cell lines, with or without genetic modification, in monolayer to simulate a heterogeneous model. 16 publications were included using 14 different cell lines and 19 gene vectors. Effect sizes were calculated for cell survival, viability, apoptosis and proliferation. Univariate meta-regression was used to investigate the effects of radiant exposure (J/m2) and timing on cytotoxicity. UVC resulted in a 70.9% (CI: 63.6%-78.2%) reduction in survival, 16.6% (CI: 10.8%-22.4%) increase in apoptosis, 32.0% (CI: 9.95%-54.2%) reduction in viability, and 413.8% (CI: 95.7%-731.9%) reduction in proliferation of GBM cell lines compared to controls. Radiant exposure was significantly associated with survival (R2 = 0.486, p < 0.0001) but not with apoptosis or viability. This study provides more data on the therapeutic translational potential of UVC to a more clinically-realistic context. Overall, UVC is cytotoxic to GBM cell lines in aggregate and may be clinically useful when combined with genetic modification or other adjuvant treatments.

Effects of Ultraviolet Radiation on Glioma: Systematic Review.

Glioblastoma multiforme is the most aggressive primary brain tumor. Treatment is largely palliative, with current strategies unable to prevent inevitable tumor recurrence. Implantable micro-electromechanical systems are becoming more feasible for the management of several human diseases. These systems may have a role in detecting tumor recurrence and delivering localized therapies. One potential therapeutic tool is ultraviolet (UV) light. This systematic review assesses the effects of UV light on glioma cells. A total of 47 publications are included. The large majority were in vitro experiments conducted on human glioblastoma cell lines in monolayer. In these cells, UV light was shown to induce apoptosis and the expression of genes or activation of proteins that modulate cell death, repair, and proliferation. The nature and magnitude of cellular response varied by UV wavelength, dose, cell line, and time after irradiation. UVC (wavelength 100-280 nm) was most effective at inducing apoptosis, and this effect was dose dependent. The included studies had varied methodologies, complicating reconciliation of results. Further work will be required to determine the best regime of UV irradiation for therapeutic use. J. Cell. Biochem. 118: 4063-4071, 2017. © 2017 Wiley Periodicals, Inc.

Si-Integrated Secondary Li-Ion Micro Batteries with Side-By-Side Electrodes for the Application As Buffers in Self-Sufficient Energy Harvesting Micro Systems

Lithium-ion cell chemistries, with their quite high energy densities, are naturally interesting candidates for the application as buffers in future self-sufficient energy-harvesting microelectronic systems [1, 2]. For these applications, thin film or 3D micro batteries could come into consideration [3, 4], although they might be comparatively expensive. Another promising approach that may limit production cost is the fabrication of micro batteries on a silicon wafer, where a vast number of batteries can be produced in one batch.Previously we have investigated a concept involving the integration of conventional stacked electrodes and a porous polymer separator in a silicon glass package [5]. In this study, a design with the anode and the cathode lying side by side, separated by a narrow silicon spacer, has been implemented. This design facilitates assembly and encapsulation considerably since no polymer separator is needed and both electrodes can be contacted from downside. Geometry can be adapted to meet balancing requirements for different electrode materials.Figure 1: Schematic profile of a battery with side-by-side electrode setup (arrows: paths of Li-ion movement)The production process for this kind of micro battery has been described in detail elsewhere [6]. Briefly, wet chemical etching of a Si-wafer of {110} crystal orientation is applied to form long and narrow cavities with vertical sidewalls at the long sides and a slope at the front sides. Such geometry ensures a good utilization of area (i.e. high specific capacity) at a high geometric accuracy as well as an easy contacting of the current collectors. The structured substrate is oxidized and passivated against Li-diffusion prior to the deposition of the active materials and the electrolyte by micro dispensing [7]. Finally, the device is almost hermetically sealed by the attachment of a glass lid (fig 1.).To obtain a high energy density, we have applied graphite as the anode material and nickel cobalt manganese oxide as the cathode material (LixC6 / Liy(Ni1/2Co1/5Mn3/10)O2). The fabricated single cells show a reproducible rate capability and cycling performance during continuous cycling between 4.1 and 3V (fig. 2). Due to the long paths for Li ion movement and the relatively thick electrodes the impedance of such cells is naturally higher as compared to cells with stacked electrodes. However, utilizing the special mechanical properties of silicon as a battery housing material it is possible to further decrease the width of the cavities for the electrodes (wcav) and the separator (wsep) substantially which is expected to result in improved rate capabilities. Furthermore, by fabricating cells with interdigital electrodes and narrow separators it is possible to enlarge the specific capacity per area, tailoring batteries for specific applications.The fabricated micro batteries have convential (i.e. non-thin-film) electrodes with a thickness in the range of around 50…150 µm. This is interesting for applications where a small volume, high capacity energy supply is needed. Examples are small energy autarkic sensors, e.g. implantable sensors for medical applications [8], or miniaturized sensor networks. Such applications are usually linked to radio modules for transmitting information. We can show that during pulsed discharge the system performance is less influenced by the relatively thick electrodes due to relaxation effects, resulting in higher extractable energies that are several times higher than during continuous discharge of the cells.Fig. 2: Cycling performance and rate capability of a cell with wcav=1.8mm, wsep=0.2mm, d1=0.15mm, d2=0.1mm The fabricated structures could be used in materials research, e.g. for high-throughput screening and in-operando electrode surface studies by applying different lid materials.REFERENCES[1] Belleville, M. et al., Energy autonomous sensor systems: Towards a ubiquitous sensor technology, Microelectronics Journal, 41, 11 (2010) pp. 740-745.[2] Hahn, R. Autonomous energy supply for electronic grains and wireless sensors, Frequenz, no. 3-4, pp. 87-91, 2004.[3] Hahn, R. und K. Marquardt, Secondary Microbatteries for Energy Harvesting Microsystems, In IDTEchEx Energy Harvesting Conference 2010 (Munich, Germany, 2010). May 26-27, 2010.[4] Hahn, R. Microbatteries for Energy Storage. In 4th SINANO device modeling summer school (Bertinoro, Italy, 2010). Jul. 19-23, 2010. [5] M. Thunman et al, Discharge Performance Dependence on Electrode Thickness for Li4Ti5O12/LiMn2O4 Cells for Application in Wafer-Integrated Microbatteries, ECS Trans. 2012 volume 41, issue 41, 147-157; doi: 10.1149/1.4717972.[6] K. Hoeppner et al., Design, Fabrication and Testing of Silicon-integrated Li-ion Secondary Micro Batteries with Side-by-Side Electrodes, Proceedings of PowerMEMS, London, 2013.[7] K. Hoeppner et al., Development and Investigation of Electrode Slurries for the Batch Fabrication of Li-ion Secondary Micro Batteries, EnMat Conference, 2013, Abstr. No 3276.[8] F. Albano et al., A fully integrated microbattery for an implantable microelectromechanical system, Journal of Power Sources, 185 (2008), pp. 1524–1532.

An Electrochemically Actuated MEMS Device for Individualized Drug Delivery: an In Vitro Study

Individualized disease treatment is a promising branch for future medicine. In this work, we introduce an implantable microelectromechanical system (MEMS) based drug delivery device for programmable drug delivery. An in vitro study on cancer cell treatment has been conducted to demonstrate a proof-of-concept that the engineered device is suitable for individualized disease treatment. This is the first study to demonstrate that MEMS drug delivery devices can influence the outcome of cancer drug treatment through the use of individualized disease treatment regimes, where the strategy for drug dosages is tailored according to different individuals. The presented device is electrochemically actuated through a diaphragm membrane and made of polydimethylsiloxane (PDMS) for biocompatibility using simple and cost-effective microfabrication techniques. Individualized disease treatment was investigated using the in vitro programmed delivery of a chemotherapy drug, doxorubicin, to pancreatic cancer cell cultures. Cultured cell colonies of two pancreatic cancer cell lines (Panc-1 and MiaPaCa-2) were treated with three programmed schedules and monitored for 7 days. The result shows that the colony growth has been successfully inhibited for both cell lines among all the three treatment schedules. Also, the different observations between the two cell lines under different schedules reveal that MiaPaCa-2 cells are more sensitive to the drug applied. These results demonstrate that further development on the device will provide a promising novel platform for individualized disease treatment in future medicine as well as for automatic in vitro assays in drug development industry.

Ultra-thin layer packaging for implantable electronic devices

State of the art packaging for long-term implantable electronic devices generally uses reliable metal and glass housings; however, these are limited in the miniaturization potential and cost reduction. This paper focuses on the development of biocompatible hermetic thin-film packaging based on poly-para-xylylene (Parylene-C) and silicon oxide (SiOx) multilayers for smart implantable microelectromechanical systems (MEMS) devices. For the fabrication, a combined Parylene/SiOx single-chamber deposition system was developed. Topological aspects of multilayers were characterized by atomic force microscopy and scanning electron microscopy. Material compositions and layer interfaces were analyzed by Fourier transform infrared spectrometry and x-ray photoelectron spectroscopy. To evaluate the multilayer corrosion protection, water vapor permeation was investigated using a calcium mirror test. The calcium mirror test shows very low water permeation rates of 2 × 10−3 g m−2 day−1 (23 °C, 45% RH) for a 4.7 µm multilayer, which is equivalent to a 1.9 mm pure Parylene-C coating. According to the packaging standard MIL-STD-883, the helium gas tightness was investigated. These helium permeation measurements predict that a multilayer of 10 µm achieves the hermeticity acceptance criterion required for long-term implantable medical devices.

Approaches and Challenges of Engineering Implantable Microelectromechanical Systems (MEMS) Drug Delivery Systems for in Vitro and in Vivo Applications

Despite the advancements made in drug delivery systems over the years, many challenges remain in drug delivery systems for treating chronic diseases at the personalized medicine level. The current urgent need is to develop novel strategies for targeted therapy of chronic diseases. Due to their unique properties, microelectromechanical systems (MEMS) technology has been recently engineered as implantable drug delivery systems for disease therapy. This review examines the challenges faced in implementing implantable MEMS drug delivery systems in vivo and the solutions available to overcome these challenges.

Implantable MEMS compressive stress sensors: Design, fabrication and calibration with application to the disc annulus

Physiological stresses are fundamental to biomechanical testing, mechanobiological analyses, implant design, and tissue engineering. The purpose of this study was to design, fabricate, and evaluate compressive stress sensors packaged for extended , in vivo implantation in the annulus of the intervertebral disc. A commercial microelectromechanical systems (MEMS) pressure sensor die was selected as the active element for a custom stress sensor. The sensor die was modified and packaged to protect the electrical system from the biochemical and biomechanical environment. Completed sensors were calibrated under hydrostatic pressure and solid contact compression. Calibrations were performed before and after 8 weeks of in vivo implantation in a porcine disc. For the two reported sensors, stress and voltage were linearly correlated over a range of 0–1.8 MPa with less than 5% change in sensitivity. Sensitivity to solid contact stress was within 10% of that from hydrostatic pressure. In contrast to most previous studies, in which disc pressure was measured in the fluidic nucleus pulposus, these sensors may be used to measure in vivo dynamic compressive stresses in the annulus at magnitudes typical of the musculoskeletal system in a large animal over a relatively long post-operative time.

A fully integrated microbattery for an implantable microelectromechanical system

The Wireless Integrated Microsystems Engineering Research Center’s Intraocular Sensor (WIMS-ERC IOS) was studied as a model system for an integrated, autonomous implantable device. In the present study, we had four objectives: (1) select and designing an optimized power supply for the WIMS-IOS; (2) develop a fabrication technique allowing small scale, low-cost, and integrable fabrication for CMOS systems, and experimentally demonstrate a microscopic power source; (3) map capacity and lifetime of several fabricated microbatteries; (4) determine the effects of miniaturization on capacity, lifetime and device architecture. Physical vapor deposition (PVD) was used to deposit thin layers (≤1 μm) of metal sequentially onto glass substrates (SiO 2, as used in the device). To map the influence of size over cell capacity and cycle life, we fabricated and tested five stand-alone cells using a Solartron ® 1470E battery tester and a Maccor ® 4000 series tester. A sixth battery was fabricated to investigate the effects of system integration, variable discharge rate and size reduction simultaneously. The highest experimental capacity among the larger cells O(cm 2) was 100 μAh, achieved by IOS-C-1 at 250 μA (1.4 C) discharge. Among O(mm 2) cells, IOS-M-1 achieved the highest capacity (2.75 μAh, ∼76% of theoretical) at 2.5 μA discharge (0.7 C rate).

Electrochemical and antimicrobial properties of diamondlike carbon-metal composite films

Implants containing antimicrobial metals may reduce morbidity, mortality, and healthcare costs associated with medical device-related infections. We have deposited diamondlike carbon–silver (DLC–Ag), diamondlike carbon–platinum (DLC–Pt), and diamondlike carbon–silver–platinum (DLC–AgPt) thin films using a multicomponent target pulsed laser deposition process. Transmission electron microscopy of the DLC–silver and DLC–platinum composite films revealed that the silver and platinum self-assemble into nanoparticle arrays within the diamondlike carbon matrix. The diamondlike carbon–silver film possessed hardness and Young’s modulus values of 37 GPa and 331 GPa, respectively. The diamondlike carbon-metal composite films exhibited passive behavior at open-circuit potentials. Low corrosion rates were observed during testing in a phosphate-buffered saline (PBS) electrolyte. In addition, the diamondlike carbon–metal composite films were found to be immune to localized corrosion below 1000 mV (SCE). DLC–silver–platinum films demonstrated exceptional antimicrobial properties against Staphylococcus bacteria. It is believed that a galvanic couple forms between platinum and silver, which accelerates silver ion release and provides more robust antimicrobial activity. Diamondlike carbon–silver–platinum films may provide unique biological functionalities and improved lifetimes for cardiovascular, orthopaedic, biosensor, and implantable microelectromechanical systems.

Visualization of the intact interface between neural tissue and implanted microelectrode arrays

This research presents immunohistochemical strategies for assessing the interactions at the immediate interface between micro-scale implanted devices and the surrounding brain tissue during inflammatory astrogliotic reactions. This includes preparation, microscopy and analysis techniques for obtaining images of the intimate contact between neural cells and the surface of implantable micro-electromechanical systems (MEMS) devices. The ability to visualize the intact interface between an implant and the surrounding tissue allows researchers to examine tissue that is unchanged from its native implanted state. Conversely, current popular techniques involve removing the implant. This tends to cause damage to the tissue immediately surrounding the implant and can hinder one's ability to differentiate inflammatory responses to the implant versus physical damage occurring from removal of the implant from the tissue. Due to advances in microscopy and staining techniques, it is now possible to visualize the intact tissue–implant interface. This paper presents the development of imaging techniques for visualizing the intact interface between neural tissue and implanted devices. This is particularly important for understanding both the acute and chronic neuroinflammatory responses to devices intended for long-term use in a prosthetic system. Non-functional, unbonded devices were imaged in vitro and in vivo at different times post-implantation via a range of techniques. Using these techniques, detailed interactions could be seen between delicate cellular processes and the electrode surface, which would have been destroyed using conventional histology processes.

Design and Testing of an Impedance-Based Sensor for Monitoring Drug Delivery

A new impedance-based sensor to monitor drug delivery from an implantable microelectromechanical systems (MEMS) device has been fabricated and tested. The sensor consists of two electrodes on opposing sides of a pyramidal drug reservoir. The dissolution of the drug and advance of solution into the reservoir cause the impedance to change over time. A 100 times scale model of the sensor was constructed to examine the effects of electrode geometry on solution resistance. An equivalent circuit was formulated to interpret the impedance signal in terms of the resistance and double-layer capacitance of the solution in the reservoir. The circuit was validated by impedance measurements on reservoirs filled with phosphate-buffered saline solutions of varying concentrations. The sensor was then used to monitor the dissolution of the model drug mannitol from the drug delivery MEMS device. The measured solution resistance and double-layer capacitance are related to the rate of transport of drug from the device, making this sensor a potential instrument for noninvasive monitoring of drug transport from the implant in vivo. Experimental results agree closely with the expected values of capacitance, resistance, and dissolution time calculated from physical parameters. © 2004 The Electrochemical Society. All rights reserved.

Evaluation of MEMS materials of construction for implantable medical devices

Medical devices based on microelectro-mechanical systems (MEMS) platforms are currently being proposed for a wide variety of implantable applications. However, biocompatibility data for typical MEMS materials of construction and processing, obtained from standard tests currently recognized by regulatory agencies, has not been published. Likewise, the effects of common sterilization techniques on MEMS material properties have not been reported. Medical device regulatory requirements dictate that materials that are biocompatibility tested be processed and sterilized in a manner equivalent to the final production device. Material, processing, and sterilization method can impact the final result. Six candidate materials for implantable MEMS devices, and one encapsulating material, were fabricated using typical MEMS processing techniques and sterilized. All seven materials were evaluated using a baseline battery of ISO 10993 physicochemical and biocompatibility tests. In addition, samples of these materials were evaluated using a scanning electron microscope (SEM) pre- and post-sterilization. While not addressing all facets of ISO 10993 testing, the biocompatibility and SEM data indicate few concerns about use of these materials in implant applications.