Implantable Medical Devices Research Articles

Risk of infections related to endovascular catheters and cardiac implantable devices in hemodialysis patients.

Patients requiring dialysis are extremely vulnerable to infectious diseases. The high burden of comorbidities and weakened immune system due to uremia and previous immunosuppressive therapy expose the patient on dialysis to more infectious events than the general population. The infectious risk is further increased by the presence of endovascular catheters and implantable cardiologic devices. The former is generally placed as urgent vascular access for dialysis and in subjects requiring hemodialysis treatments without autogenous arteriovenous fistula. The high frequency of cardiovascular events also increases the likelihood of implanting indwelling implantable cardiac devices (CIED) such as pacemakers (PMs) and defibrillators (ICDs). The simultaneous presence of CVC and CIED yields an increased risk of developing severe prosthetic device-associated bloodstream infections often progressing to septicemia. Although, antibiotic therapy is the mainstay of prosthetic device-related infections, antibiotic resistance of biofilm-residing bacteria reduces the choice of infection eradication. In these cases, the resolution of the infection process relies on the removal of the prosthetic device. Compared to CVC removal, the extraction of leads is a more complex procedure and poses an increased risk of vessel tearing. As a result, the prevention of prosthetic device-related infection is of utmost importance in hemodialysis (HD) patients and relies principally on avoiding CVC as vascular access for HD and placement of a new class of wireless implantable medical devices. When the combination of CVC and CIED is inevitable, prevention of infection, mainly due translocation of skin bacteria, should be a mandatory priority for healthcare workers.

Calcium‐dependent antimicrobials: Nature‐inspired materials and designs

Bacterial infection remains a major complication answering for the failures of various implantable medical devices. Tremendous extraordinary advances have been published in the design and synthesis of antimicrobial materials addressing this issue; however, the clinical translation has largely been blocked due to the challenge of balancing the efficacy and safety of these materials. Here, calcium's biochemical features, natural roles in pathogens and the immune systems, and advanced uses in infection medications are illuminated, showing calcium is a promising target for developing implantable devices with less infection tendency. The paper gives a historical overview of biomedical uses of calcium and summarizes calcium's merits in coordination, hydration, ionization, and stereochemistry for acting as a structural former or trigger in biological systems. It focuses on the involvement of calcium in pathogens' integrity, motility, and metabolism maintenance, outlining the potential antimicrobial targets for calcium. It addresses calcium's uses in the immune systems that the authors can learn from for antimicrobial synthesis. Additionally, the advances in calcium's uses in infection medications are highlighted to sketch the future directions for developing implantable antimicrobial materials. In conclusion, calcium is at the nexus of antimicrobial defense, and future works on taking advantage of calcium in antimicrobial developments are promising in clinical translation.

Analyzing Emerging Trends in Wireless Implantable Medical Devices (IMDs): A Bibliometric Study

In the present era of advanced medical technology, there has been a significant increase in the utilization of wireless-based implantable medical devices (IMDs) in various biomedical applications, including health diagnosis, monitoring, recording, treatment, and other clinical concerns. It is essential to closely examine the research trends in wireless IMD topics to understand their growth trajectory. This can be achieved through the utilization of bibliometric reviews. While there are numerous experimental studies and survey papers on the topic, there is a dearth of review papers that utilize a bibliometric approach. Therefore, this study aims to conduct a bibliometric analysis to identify emerging research trends in wireless IMDs for biomedical applications for the first time. An analysis was conducted on 1,650 articles retrieved from the Scopus database from its inception until September 2023. The study used tools such as VOS Viewer to measure performance and science map parameters, and Tableau Cloud to visually enhance the analysis process. This research endeavor allowed us to analyze historical trends, influential papers, top journals, institutions, countries, and authors within this field. The top three influential journals in this field are IEEE Transactions on Biomedical Circuits and Systems, IEEE Transactions on Antenna and Propagation, and IEEE access. The National University of Singapore is the most productive institution in terms of overall publications. The United States, China, and India make significant contributions to overall publications. Finally, we also examined the most significant keywords and current research areas within this field.

Review on structural optimization techniques for additively manufactured implantable medical devices

Recent developments in additive manufacturing (AM) have led to significant opportunities in the design and fabrication of implantable medical devices due to the advantages that AM offers compared to conventional manufacturing, such as high customizability, the ability to fabricate highly complex shapes, good dimensional accuracy, a clean build environment, and reduced material usage. The study of structural design optimization (SDO) involves techniques such as Topology Optimization (TO), Shape Optimization (SHO), and Size Optimization (SO) that determine specific parameters to achieve the best measurable performance in a defined design space under a given set of loads and constraints. Integration of SDO techniques with AM leads to utmost benefits in designing and fabricating optimized implantable medical devices with enhanced functional performance. Research and development of various lattice structures represents a powerful method for unleashing the full potential of additive manufacturing (AM) technologies in creating medical implants with improved surface roughness, biocompatibility, and mechanical properties. Furthermore, the integration of artificial intelligence (AI) and machine learning (ML) in structural optimization has expanded opportunities to improve device performance, adaptability, and durability. The review is meticulously divided into two main sections, reflecting the predictability of the implant’s internal structure: (a) unpredictable interior topology, which explores topology-based optimization techniques, and (b) predictable inner topology, concentrating on lattice structures. The analysis of the reviewed literature highlights a common focus on addressing issues such as stress shielding, osseointegration enhancement, customization to individual needs, programmable functionalities, and weight reduction in implant designs. It emphasizes significant advances in reducing stress shielding effects, promoting osseointegration, and facilitating personalized implant creation. The review provides a detailed classification of optimization methods, with each approach scrutinized for its unique contribution to overcoming specific challenges in medical implant design, thus leading to more advanced, effective, and patient-oriented implantable devices.

Biodegradable triboelectric nanogenerator as a implantable power source for embedded medicine devices

Implantable medical devices have played an important role in human medicine in recent decades. However, traditional implanted devices require battery replacement and a second surgery for device removal, which can cause pain to the patient. This work presents a biodegradable triboelectric nanogenerator (BI-TENG) made from both natural and synthetic biodegradable materials that is utilized to collect mechanical energy in vivo and transduce it into electricity. Reed film and polylactic acid were chosen among different biodegradable materials as the triboelectric layers due to having the best generator output performance by providing voltages that reached 368 V. The biocompatibility of the friction layer and the device was verified via a blood test. After implantation in mice, the BI-TENG exhibited an open-circuit voltage of 0.176 V and a short-circuit current of 192 nA as generated from body movement. The BI-TENG was connected to an interdigital electrode to generate an electric field, which stimulated the accelerated release of doxorubicin (DOX) from red blood cells in targeted drug delivery systems. After stopping the electric field, the release of DOX normalized, facilitating the precise killing of cancer cells. Our work demonstrates the broad potential of BI-TENGs in the field of cancer treatment.

Analyzing the Trends and Global Growth of Energy Harvesting for Implantable Medical Devices (IMDs) Research—A Bibliometric Approach

Implantable medical devices (IMDs) play a crucial role in improving individuals’ well-being and ensuring their safety by providing real-time health data monitoring for recovery. The use of energy harvesting (EH) technology has become increasingly popular among researchers because it offers the potential to extend the battery life of IMDs and reduce their weight. This study successfully examined the expansion of EH in the field of IMDs, the distribution of publications across different countries, and the identification of the most influential authors for potential research collaborations. A bibliometric analysis was conducted to evaluate two metrics: performance and science mapping. Data was collected from the Scopus database from the initial publications until October 2023, encompassing 250 articles published in Englishlanguage journals. The titles, keywords, and abstracts of these publications were analyzed and interpreted using VOS Viewer (version 1.6.19). Furthermore, network analysis using VOS Viewer enabled the identification of key research clusters. The findings reveal a continuous increase in EH for research on infectious and parasitic diseases over the 15-year period from 2008 to 2023. The United States and the University of Bern are recognized as the leading contributors to this field, based on their country and institutional contributions, respectively. The author with the most published papers and citations hails from China. Additionally, this study identifies several opportunities for collaboration with countries, institutions, authors, and research hotspots in EH for IMDs that benefit the reader.

Advances in Antimicrobial Coatings for Preventing Infections of Head-Related Implantable Medical Devices

During surgery and after, pathogens can contaminate indwelling and implanted medical devices, resulting in serious infections. Microbial colonization, infection, and later biofilm formation are major complications associated with the use of implants and represent major risk factors in implant failure. Despite the fact that aseptic surgery and the use of antimicrobial medications can lower the risk of infection, systemic antibiotic use can result in a loss of efficacy, increased tissue toxicity, and the development of drug-resistant diseases. This work explores the advancements in antimicrobial coatings for head-related implantable medical devices, addressing the critical issue of infection prevention. It emphasizes the significance of these coatings in reducing biofilm formation and microbial colonization and highlights various techniques and materials used in creating effective antimicrobial surfaces. Moreover, this article presents a comprehensive overview of the current strategies and future directions in antimicrobial coating research, aiming to improve patient outcomes by preventing head-related implant-associated infections.

Laser etching of on-chip ultra-high stability flexible micro MnO2//Zn batteries

Micro zinc batteries have great potential in fields such as smart clothing, wearable devices, and implantable medical devices, due to their high-energy density and biocompatibility, etc. However, the side reactions in Zn anode have limited their lifespan. Here we design a high stable fork-finger-shaped electrode using laser etching to obtain MnO2//Zn flexible miniature zinc ion batteries. And then, a carbon slurry is introduced to inhibit hydrogen evolution to suppress the detachment of the zinc anode. Compared with Au/PET interface, the PET/C interface had lower water retention and higher hydrogen evolution production barrier based on first-principles calculation. The interdigital electrode based on PET/C/Au had good stability. The micro MnO2–Zn flexible battery showed high specific capacity of 0.091 mAh/cm2 at 0.1 mA. After 5000 cycles at 0.5 mA, the capacity retention rate reached 83.6%. This study of interdigital electrode by laser etching brings an inspired universal pathway to fabricate a reversible Zn anode for micro-zinc storage systems.

Ultrathin, Transferred Layers of Silicon Oxynitrides as Tunable Biofluid Barriers for Bioresorbable Electronic Systems.

Bio/ecoresorbable electronic systems create unique opportunities in implantable medical devices that serve a need over a finite time period and then disappear naturally to eliminate the need for extraction surgeries. A critical challenge in the development of this type of technology is in materials that can serve as thin, stable barriers to surrounding ground water or biofluids, yet ultimately dissolve completely to benign end products. This paper describes a class of inorganic material (silicon oxynitride, SiON) that can be formed in thin films by plasma-enhanced chemical vapor deposition for this purpose. In vitro studies suggest that SiON and its dissolution products are biocompatible, indicating the potential for its use in implantable devices. A facile process to fabricate flexible, wafer-scale multilayer films bypasses limitations associated with the mechanical fragility of inorganic thin films. Systematic computational, analytical, and experimental studies highlight the essential materials aspects. Demonstrations in wireless light-emitting diodes both in vitro and in vivo illustrate the practical use of these materials strategies. The ability to select degradation rates and water permeability through fine tuning of chemical compositions and thicknesses provides the opportunity to obtain a range of functional lifetimes to meet different application requirements.

Radiopacity Enhancements in Polymeric Implant Biomaterials: A Comprehensive Literature Review.

Polymers as biomaterials possess favorable properties, which include corrosion resistance, light weight, biocompatibility, ease of processing, low cost, and an ability to be easily tailored to meet specific applications. However, their inherent low X-ray attenuation, resulting from the low atomic numbers of their constituent elements, i.e., hydrogen (1), carbon (6), nitrogen (7), and oxygen (8), makes them difficult to visualize radiographically. Imparting radiopacity to radiolucent polymeric implants is necessary to enable noninvasive evaluation of implantable medical devices using conventional imaging methods. Numerous studies have undertaken this by blending various polymers with contrast agents consisting of heavy elements. The selection of an appropriate contrast agent is important, primarily to ensure that it does not cause detrimental effects to the relevant mechanical and physical properties of the polymer depending upon the intended application. Furthermore, its biocompatibility with adjacent tissues and its excretion from the body require thorough evaluation. We aimed to summarize the current knowledge on contrast agents incorporated into synthetic polymers in the context of implantable medical devices. While a single review was found that discussed radiopacity in polymeric biomaterials, the publication is outdated and does not address contemporary polymers employed in implant applications. Our review provides an up-to-date overview of contrast agents incorporated into synthetic medical polymers, encompassing both temporary and permanent implants. We expect that our results will significantly inform and guide the strategic selection of contrast agents, considering the specific requirements of implantable polymeric medical devices.

High-Performance Wireless Power and Data Transmission System for Medical Implant Devices Using ASK Modulation

Wireless power and data transmission (WPDT) solutions for medical implants are highly desired. However, achieving a high-power transmission efficiency and data rate simultaneously over an inductive link remains a significant challenge. This paper presents an innovative WPDT circuit that incorporates additional MOSFETs with an inductor in a Class-E power amplifier (PA), achieving amplitude-shift keying (ASK) modulation to address this issue. Firstly, the efficiency of the inductive power transmission link and Class-E PA was analyzed, providing design insights. Then, leveraging the insights, the proposed circuit was designed in such a way that it could effectively switch between two load networks to maintain high transfer efficiency for ASK modulation. Based on the load networks, the relationship between introducing the inductor’s value and the data modulation index (MI) was derived to help achieve the desired high-power transmission efficiency. Additionally, the design and calculation of the proposed circuit are also presented. Finally, the proposed circuit was validated through simulations and experiments, demonstrating a power delivery to a load of 84.1 mW with a power transmission efficiency of 70.8% at a data rate and carrier frequency of 3 Mbps and 16 MHz, respectively. Furthermore, the bit error rate (BER) is less than 10−6 with an MI of 10%.

PUFchain 3.0: Hardware-Assisted Distributed Ledger for Robust Authentication in Healthcare Cyber-Physical Systems.

This article presents a novel hardware-assisted distributed ledger-based solution for simultaneous device and data security in smart healthcare. This article presents a novel architecture that integrates PUF, blockchain, and Tangle for Security-by-Design (SbD) of healthcare cyber-physical systems (H-CPSs). Healthcare systems around the world have undergone massive technological transformation and have seen growing adoption with the advancement of Internet-of-Medical Things (IoMT). The technological transformation of healthcare systems to telemedicine, e-health, connected health, and remote health is being made possible with the sophisticated integration of IoMT with machine learning, big data, artificial intelligence (AI), and other technologies. As healthcare systems are becoming more accessible and advanced, security and privacy have become pivotal for the smooth integration and functioning of various systems in H-CPSs. In this work, we present a novel approach that integrates PUF with IOTA Tangle and blockchain and works by storing the PUF keys of a patient's Body Area Network (BAN) inside blockchain to access, store, and share globally. Each patient has a network of smart wearables and a gateway to obtain the physiological sensor data securely. To facilitate communication among various stakeholders in healthcare systems, IOTA Tangle's Masked Authentication Messaging (MAM) communication protocol has been used, which securely enables patients to communicate, share, and store data on Tangle. The MAM channel works in the restricted mode in the proposed architecture, which can be accessed using the patient's gateway PUF key. Furthermore, the successful verification of PUF enables patients to securely send and share physiological sensor data from various wearable and implantable medical devices embedded with PUF. Finally, healthcare system entities like physicians, hospital admin networks, and remote monitoring systems can securely establish communication with patients using MAM and retrieve the patient's BAN PUF keys from the blockchain securely. Our experimental analysis shows that the proposed approach successfully integrates three security primitives, PUF, blockchain, and Tangle, providing decentralized access control and security in H-CPS with minimal energy requirements, data storage, and response time.

Implantable pH Sensing System Using Vertically Stacked Silicon Nanowire Arrays and Body Channel Communication for Gastroesophageal Reflux Monitoring.

Silicon nanowires (SiNWs) are emerging as versatile components in the fabrication of sensors for implantable medical devices because of their exceptional electrical, optical, and mechanical properties. This paper presents a novel top-down fabrication method for vertically stacked SiNWs, eliminating the need for wet oxidation, wet etching, and nanolithography. The integration of these SiNWs into body channel communication (BCC) circuits was also explored. The fabricated SiNWs were confirmed to be capable of forming arrays with multiple layers and rows. The SiNW-based pH sensors demonstrated a robust response to pH changes, and when tested with BCC circuits, they showed that it was possible to quantize based on pH when transmitting data through the human body. This study successfully developed a novel method for SiNW fabrication and integration into BCC circuits, which could lead to improvements in the reliability and efficiency of implantable medical sensors. The findings demonstrate significant potential for bioelectronic applications and real-time biochemical monitoring.

Piezoelectric polymer based acoustic energy harvester for implantable medical devices

Wireless implantable devices (WIDs) have the potential to revolutionize biomedical sensing, but their power supplies face significant challenges. Traditional energy transfer methods such as inductive and RF have limitations due to associated tissue losses. This work demonstrates a promising approach to this problem, using a flexible implantable ultrasound energy harvester (IUEH) made of biocompatible Poly (vinylidene fluoride-co-trifluoro ethylene) (P(VDF-TrFe)) free-standing film. Unlike commonly used piezoceramic devices, IUEH can be fabricated using economical solution processing methods such as spin coating. In addition, the PVDF-TrFE Ultrasound energy harvesters are rarely reported in the literature. The device performance of the polymer IUEH was investigated in air, water, and animal meat tissue, and the results show that it can generate a power output of 1.1 mW cm−2 in meat, and 1.4 mW cm−2 in water at 80 kHz. The device fabricated using a free-standing piezoelectric thin film, offers an optimum output that is comparable to other P(VDF-TrFe) based high-frequency devices. Additionally, its flexible design, lower costs, and biocompatibility make it a promising alternative to lead-based devices; thus, offering safety, affordability, and quick customization, while promoting minimally invasive procedures and driving innovation in medical device development.

A mm-sized acoustic wireless implantable neural stimulator based on a piezoelectric micromachined ultrasound transducer

Implantable medical devices are increasingly being used to perform electrophysiological stimulation, thus calling for wireless implantable neural stimulators for which wireless power transfer is needed. Compared with radio frequency and inductive coupling wireless power transfer methods, acoustic wireless power transfer features lower attenuation, a smaller size and a higher safe power threshold. This paper demonstrates the design, fabrication, assembly and characterization of a mm-sized acoustic wireless implantable neural stimulator based on a piezoelectric micromachined ultrasound transducer. Ex vivo experiments in water are conducted to characterize the power transfer link, showing improvement of the power transfer efficiency by more than two times with a matching circuit. Following FDA guidelines, the wireless implantable neural stimulator achieves a 3.24 μW output power in tissue. The feasibility for rat sciatic nerve stimulation is successfully demonstrated in vivo by the implantable prototype with a size of 5 × 5.5 × 2.5 mm3. The proposed solution has the potential to shrink the entire implanted system to a monolithic transducer-IC chip, paving the way toward an acoustic wireless implantable neural stimulator with higher levels of biocompatibility, integration and miniaturization.

Ultrananocrystalline diamond (UNCD™) coating for new-generation implantable medical devices/prostheses

Ultrananocrystalline diamond (UNCD™) coating for new-generation implantable medical devices/prostheses In this materials science piece, Orlando Auciello, describes the development of a unique multifunctional/best biocompatible ultrananocrystalline diamond (UNCDTM) coating for new-generation implantable medical devices and prostheses. Materials’ surfaces of vital medical devices, such as silicon (Si) microchip (artificial retina) implanted on human retina, restoring partial vision to people blinded by genetically induced photoreceptors degeneration, and metallic dental implants, are attacked chemically by eyes’ fluids or oral fluids respectively. Metallic stents/artificial heart valves, inside human blood vessels, activate blood enzymes, inducing coagulation, and fibrinolytic, leading to thrombus formation (i.e., blood clot in blood vessels, obstructing blood flow or loosed clot getting stuck in arteries/veins’ walls, causing life-threatening stroke/heart attack.

Fibroblasts and osteoblasts behavior after contact with different titanium surfaces used as implant abutment: An in vitro experimental study

BackgroundThe goal of this in vitro study was to compare three different surfaces: two types of implant surfaces commercially available ([a] smooth/machined and [b] acid-treated surface) versus (c) anodized surface. Discs were manufactured with commercially pure titanium (CP) grade IV, which were subsequently analyzed by scanning microscopy and fibroblastic and osteoblastic cell cultures. MethodsNinety-nine discs (5 × 2 mm) were manufactured in titanium grade IV and received different surface treatments: (i) Mach group: machined; (ii) AA group: double acid etch; and (iii) AN group: anodizing treatment. Three discs from each group were analyzed by Scanning Electron Microscopy (SEM) to obtain surface topography images and qualitatively analyzed by EDS. Balb/c 3T3 fibroblasts and pre-osteoblastic cells (MC3T3-E1 lineage) were used to investigate each group's biological response (n = 10/cellular type). The data were compared statistically using the ANOVA one-way test, considered as a statistically significant difference p < 0.05. ResultsThe AA group had numerous micropores with diameters between 5 and 10 μm, while nanopores between 1 and 5 nm were measured in the AN group. The EDX spectrum showed a high titanium concentration in all the analyzed samples. The contact angle and wetting tension were higher in the AA, whereas similar results were observed for the other groups. A lower result was observed for base width in the AA, which was higher in the other two groups. The AN showed the best values in the fibroblast cells, followed by Mach and AA; whereas, in the culture of the MC3T3 cells, the result was precisely the opposite (AA > Mach > AN). There was similar behavior for cell adhesion for the test groups (Mach and AN), with greater adhesion of Balb/c 3T3 fibroblasts compared to MC3T3 cells; in the AA group, there was greater adherence for MC3T3 cells compared to Balb/c 3T3 fibroblasts. ConclusionsThe findings suggest that different surface characteristics can produce different biological responses, possibly cell-line dependent. These findings have important implications for the design of implantable medical devices, where the surface characteristics can significantly impact its biocompatibility.

RF energy harvesters for wireless sensors, state of the art, future prospects and challenges: a review.

The power consumption of portable gadgets, implantable medical devices (IMDs) and wireless sensor nodes (WSNs) has reduced significantly with the ongoing progression in low-power electronics and the swift advancement in nano and microfabrication. Energy harvesting techniques that extract and convert ambient energy into electrical power have been favored to operate such low-power devices as an alternative to batteries. Due to the expanded availability of radio frequency (RF) energy residue in the surroundings, radio frequency energy harvesters (RFEHs) for low-power devices have garnered notable attention in recent times. This work establishes a review study of RFEHs developed for the utilization of low-power devices. From the modest single band to the complex multiband circuitry, the work reviews state of the art of required circuitry for RFEH that contains a receiving antenna, impedance matching circuit, and an AC-DC rectifier. Furthermore, the advantages and disadvantages associated with various circuit architectures are comprehensively discussed. Moreover, the reported receiving antenna, impedance matching circuit, and an AC-DC rectifier are also compared to draw conclusions towards their implementations in RFEHs for sensors and biomedical devices applications.

Upconversion 3D Bioprinting for Noninvasive In Vivo Molding.

Tissue engineered bracket materials provide essential support for the physiological protection and therapeutics of patients. Unfortunately, the implantation process of such devices poses the risk of surgical complications and infection. In this study, an upconversion nanoparticles (UCNPs)-assisted 3D bioprinting approach is developed to realize in vivo molding that is free from invasive surgery. Reasonably designed UCNPs, which convert near-infrared (NIR) photons that penetrate skin tissues into blue-violet emission (300-500 nm), induce a monomer polymerization curing procedure in vivo. Using a fused deposition modeling coordination framework, a precisely predetermined trajectory of the NIR laser enables the manufacture of implantable medical devices with tailored shapes. A proof of the 3D bioprinting of a noninvasive fracture fixation scaffold is achieved successfully, thus demonstrating an entirely new method of in vivo molding for biomedical treatment.

An area efficient inductorless super-regenerative receiver front-end for biomedical implant devices

Wearable and implantable medical devices are of great importance in diagnosis and treatment as they provide continuous monitoring and data collection. Considering the comfort of the patient and ease-of-operation, these devices require wireless data transmission. In this work, a novel area and energy efficient inductorless super-regenerative receiver (SRR) is proposed for medical implants dedicated to patient monitoring and treatment. The proposed SRR was fabricated in UMC CMOS 180 nm technology. The SRR occupies only 0.072mm2 which corresponds to an order of magnitude area reduction compared to the state-of-the-art. The SRR achieves −70dBm sensitivity and the highest data rate is 4Mbps. 3.22nJ/b energy efficiency is obtained with 12.9mW power consumption from a 1.8V power supply.