Next-generation Medical Devices Research Articles

Integrated Devices: A New Regulatory Pathway to Promote Revolutionary Innovation.

Policy Points Current medical device regulatory frameworks date back half a century and are ill suited for the next generation of medical devices that involve a significant software component. Existing Food and Drug Administration efforts are insufficient because of a lack of statutory authority, whereas international examples offer lessons for improving and harmonizing domestic medical device regulatory policy. A voluntary alternative pathway built upon two-stage review with individual component review followed by holistic review for integrated devices would provide regulators with new tools to address a changing medical device marketplace.

Biobased, self-healing, and recyclable polyurethane derived hydrogel-elastomer hybrids for efficient lubrication

Developing biobased hydrogel-elastomer hybrids with stable lubrication derived from self-healing and recyclable polymer matrix poses a key challenge in the field of medical devices. Herein, we reported a novel hydrogel-elastomer hybrid incorporating a tung oil (TO)-based, self-healing, and recyclable polyurethane (PU) substrate that exhibits exceptional hydrophilic and lubricating properties. Initially, a series of UV-curable PU elastomers containing dynamic hindered urea bonds (HUBs) derived from renewable TO were prepared. By adjusting the ratios of the cross-linking agent TO-based polyol and the chain-extending agent polytetramethyleneglycol, the mechanical and thermal properties of these elastomers could be tuned well. The as-prepared PU elastomers demonstrated remarkable dynamic properties, attributed to the dissociation and recombination of HUBs, enabling efficient self-healing and effective recycling through solvent or hot-pressing methods while preserving their mechanical properties. Furthermore, functional hydrogel-elastomer hybrids were obtained by applying UV-initiated polymerization method to generate hydrogel coatings onto the optimized PU elastomer surface. Compared to the pristine PU material, the resulting hydrogel-elastomer hybrids exhibited excellent lubricity in aqueous environments, resulting from the formation of a robust hydration layer facilitated by electrostatic forces. Overall, our current research work provides key design inspiration for developing next-generation medical devices from sustainable and recyclable functional biomaterials.

Synthesis and characterization of biodegradable seaweed-based paper battery for sustainable energy storage

This article deals with the design and development of a seaweed-based paper battery, synthesized using different material coatings. Batteries have a high potential to power up the next generation of medical devices, electronics and hybrid vehicles but it require high working capacity. With the presence of several deficiencies like a regular, fluctuating voltage, spill out and damage issues, itching and irritation during human direct contact with wet and non-paper batteries, a need for dry and paper-based batteries has arisen. The design and fabrication of paper-based batteries with enhanced electrochemical and structural stability play a pivotal role to fix the above-mentioned problems. A battery made up of seaweed paper offers remarkable capacity with better performance and also helps to avoid the use of wood-based paper. The battery has been prepared with different materials of cathode and electrolyte, which are further tested for identifying an optimum match in terms of generated voltage. A biodegradability test and toxicity test were performed which ensured the eco-friendly nature of the proposed battery. The proposed battery is made of nanocomposites, which can pack more power into smaller spaces. Moreover, it is found that there is a reduction of weight by 58%, an enhancement of 16.7% in voltage capacity and eco-friendly compared to conventional AA 1.5–3.5 V Li-on battery.

Hybrid Ti6Al4V/Silk Fibroin Composite for Load-Bearing Implants: A Hierarchical Multifunctional Cellular Scaffold.

Despite the tremendous technological advances that metal additive manufacturing (AM) has made in the last decades, there are still some major concerns guaranteeing its massive industrial application in the biomedical field. Indeed, some main limitations arise in dealing with their biological properties, specifically in terms of osseointegration. Morphological accuracy of sub-unital elements along with the printing resolution are major constraints in the design workspace of a lattice, hindering the possibility of manufacturing structures optimized for proper osteointegration. To overcome these issues, the authors developed a new hybrid multifunctional composite scaffold consisting of an AM Ti6Al4V lattice structure and a silk fibroin/gelatin foam. The composite was realized by combining laser powder bed fusion (L-PBF) of simple cubic lattice structures with foaming techniques. A combined process of foaming and electrodeposition has been also evaluated. The multifunctional scaffolds were characterized to evaluate their pore size, morphology, and distribution as well as their adhesion and behavior at the metal–polymer interface. Pull-out tests in dry and hydrated conditions were employed for the mechanical characterization. Additionally, a cytotoxicity assessment was performed to preliminarily evaluate their potential application in the biomedical field as load-bearing next-generation medical devices.

Engaging Early-Career Physicians in Medical Device Innovation and Entrepreneurship.

Engaging Early-Career Physicians in Medical Device Innovation and Entrepreneurship.

Emerging trends in biliary stents: a materials and manufacturing perspective.

Biliary stent technology has come a long way since its inception. There have been significant advancements in the materials used, and design and deployment strategies. Options have expanded from plastic and metallic stents to a wider variety of materials and manufacturing technologies to offer several options to clinicians, including self-expandable metallic stents and bioresorbable stents. Bioresorbable biliary stents are still in the early stages of clinical adoption. This review encompasses the materials currently used for biliary stents and the significant developments in the past few years in the resorbable materials for use as biliary stents. We critically discuss the emerging trends in the development of new resorbable materials for fabricating biliary stents. We then assess the developments in drug-eluting stents and advanced manufacturing technologies that could be leveraged for biliary stents. Challenges in the paths for translation for the future, such as pre-clinical and clinical trials, are highlighted. Finally, we present future directions that could drive the biliary stent market to meet the increasingly complex and diverse clinical needs of patients.

In vivo degradation and endothelialization of an iron bioresorbable scaffold

Detection of in vivo biodegradation is critical for development of next-generation medical devices such as bioresorbable stents or scaffolds (BRSs). In particular, it is urgent to establish a nondestructive approach to examine in vivo degradation of a new-generation coronary stent for interventional treatment based on mammal experiments; otherwise it is not available to semi-quantitatively monitor biodegradation in any clinical trial. Herein, we put forward a semi-quantitative approach to measure degradation of a sirolimus-eluting iron bioresorbable scaffold (IBS) based on optical coherence tomography (OCT) images; this approach was confirmed to be consistent with the present weight-loss measurements, which is, however, a destructive approach. The IBS was fabricated by a metal-polymer composite technique with a polylactide coating on an iron stent. The efficacy as a coronary stent of this new bioresorbable scaffold was compared with that of a permanent metal stent with the name of trade mark Xience, which has been widely used in clinic. The endothelial coverage on IBS was found to be greater than on Xience after implantation in a rabbit model; and our well-designed ultrathin stent exhibited less individual variation. We further examined degradation of the IBSs in both minipig coronary artery and rabbit abdominal aorta models. The present result indicated much faster iron degradation of IBS in the rabbit model than in the porcine model. The semi-quantitative approach to detect biodegradation of IBS and the finding of the species difference might be stimulating for fundamental investigation of biodegradable implants and clinical translation of the next-generation coronary stents.

Fiber Bragg Gratings for Medical Applications and Future Challenges: A Review

In the last decades, fiber Bragg gratings (FBGs) have become increasingly attractive to medical applications due to their unique properties such as small size, biocompatibility, immunity to electromagnetic interferences, high sensitivity and multiplexing capability. FBGs have been employed in the development of surgical tools, assistive devices, wearables, and biosensors, showing great potentialities for medical uses. This paper reviews the FBG-based measuring systems, their principle of work, and their applications in medicine and healthcare. Particular attention is given to sensing solutions for biomechanics, minimally invasive surgery, physiological monitoring, and medical biosensing. Strengths, weaknesses, open challenges, and future trends are also discussed to highlight how FBGs can meet the demands of next-generation medical devices and healthcare system.

Interfacing human induced pluripotent stem cell-derived neurons with designed nanowire arrays as a future platform for medical applications.

Nanostructured substrates such as nanowire arrays form a powerful tool for building next-generation medical devices. So far, human pluripotent stem cell-derived neurons-a revolutionary tool for studying physiological function and modeling neurodegenerative diseases-have not been applied to such innovative substrates, due to the highly demanding nature of stem cell quality control and directed differentiation procedures to generate specialized cell types. Our study closes this gap, by presenting electrophysiologically mature human pluripotent stem cell-derived neurons on a set of nanowires in different patterns and growth densities after only four weeks of maturation-thereof 14 to 16 days on the nanowire arrays. While cell viability is maintained on all nanowire substrates, the settling regime of the cells can be controlled and tuned by the nanowire density from a fakir-like state to a complete nanowire wrapping state. Especially, full electrophysiological integrity of the neurons independent of the settling regime has been revealed by patch clamp experiments showing characteristic action potentials. Based on these results, our protocol has the potential to open new pathways in stem cell research and regenerative medicine utilizing human stem cell-derived neurons on tailor-made nanostructured substrates.

Ultra-Long-Term Reliable Encapsulation Using an Atomic Layer Deposited HfO2/Al2O3/HfO2 Triple-Interlayer for Biomedical Implants

Long-term packaging of miniaturized, flexible implantable medical devices is essential for the next generation of medical devices. Polymer materials that are biocompatible and flexible have attracted extensive interest for the packaging of implantable medical devices, however realizing these devices with long-term hermeticity up to several years remains a great challenge. Here, polyimide (PI) based hermetic encapsulation was greatly improved by atomic layer deposition (ALD) of a nanoscale-thin, biocompatible sandwich stack of HfO2/Al2O3/HfO2 (ALD-3) between two polyimide layers. A thin copper film covered with a PI/ALD-3/PI barrier maintained excellent electrochemical performance over 1028 days (2.8 years) during acceleration tests at 60 °C in phosphate buffered saline solution (PBS). This stability is equivalent to approximately 14 years at 37 °C. The coatings were monitored in situ through electrochemical impedance spectroscopy (EIS), were inspected by microscope, and were further analyzed using equivalent circuit modeling. The failure mode of ALD Al2O3, ALD-3, and PI soaking in PBS is discussed. Encapsulation using ultrathin ALD-3 combined with PI for the packaging of implantable medical devices is robust at the acceleration temperature condition for more than 2.8 years, showing that it has great potential as reliable packaging for long-term implantable devices.

An Innovative Deep Learning Algorithm for Drowsiness Detection from EEG Signal

The development of detection methodologies for reliable drowsiness tracking is a challenging task requiring both appropriate signal inputs and accurate and robust algorithms of analysis. The aim of this research is to develop an advanced method to detect the drowsiness stage in electroencephalogram (EEG), the most reliable physiological measurement, using the promising Machine Learning methodologies. The methods used in this paper are based on Machine Learning methodologies such as stacked autoencoder with softmax layers. Results obtained from 62 volunteers indicate 100% accuracy in drowsy/wakeful discrimination, proving that this approach can be very promising for use in the next generation of medical devices. This methodology can be extended to other uses in everyday life in which the maintaining of the level of vigilance is critical. Future works aim to perform extended validation of the proposed pipeline with a wide-range training set in which we integrate the photoplethysmogram (PPG) signal and visual information with EEG analysis in order to improve the robustness of the overall approach.

Mechanism of Acceleration of Iron Corrosion by a Polylactide Coating.

Strong and biodegradable materials are key to the development of next-generation medical devices for interventional treatment. Biodegradable polymers such as polylactide (PLA) have controllable degradation profiles, but their mechanical strength is much weaker than some metallic materials such as iron; on the other hand, tuning the corrosion rate of iron to a proper time range for biomedical applications has always been a challenge. Very recently, we have achieved a complete corrosion of iron stent in vivo within the clinically required time frame by combining a PLA coating, which provides a new biomaterial type for the next-generation biodegradable coronary stents termed as a metal-polymer composite stent. The underlying mechanism of accelerating iron corrosion by a PLA coating remains an open fundamental topic. Herein, we investigated the corrosion mechanism of an iron sheet under a PLA coating in the biomimetic in vitro condition. The Pourbaix diagram (potential vs pH) was calculated to present the thermodynamic driving force of iron corrosion in the biomimetic aqueous medium. Electrochemical methods were applied to track the dynamic corrosion process and inspect various potential cues influencing iron corrosion. The present work reveals that acceleration of iron corrosion by the PLA coating arises mainly from decreasing the local pH owing to PLA hydrolysis and from alleviating the deposition of the passivation layer by the polymer coating.

Leveraging Big Data for Personalized Treatment of Anxiety and Depression: Review and Possible Future Directions

The combination of big data, machine learning and medical devices can be very effective in determining a personalized treatment plan, as exemplified through our literature review. We focus in particular on considering this combination within context of treatment of anxiety and depression. However, since the required amount and type of data (for determining such an individualized treatment plan) may not be available, we establish the need of developing enhanced biosensors to produce such data. We also argue for development of next generation of medical devices that can deliver such a personalized treatment plan for anxiety and depression. Moreover, evidence is presented to support the utility of bio-markers as potentially useful clinical tools to enhance treatment response for depression.

The intelligent OR: design and validation of a context-aware surgical working environment

Interoperability of medical devices based on standards starts to establish in the operating room (OR). Devices share their data and control functionalities. Yet, the OR technology rarely implements cooperative, intelligent behavior, especially in terms of active cooperation with the OR team. Technical context-awareness will be an essential feature of the next generation of medical devices to address the increasing demands to clinicians in information seeking, decision making, and human-machine interaction in complex surgical working environments. The paper describes the technical validation of an intelligent surgical working environment for endoscopic ear-nose-throat surgery. We briefly summarize the design of our framework for context-aware system's behavior in integrated OR and present example realizations of novel assistance functionalities. In a study on patient phantoms, twenty-four procedures were implemented in the proposed intelligent surgical working environment based on recordings of real interventions. Subsequently, the whole processing pipeline for context-awareness from workflow recognition to the final system's behavior is analyzed. Rule-based behavior that considers multiple perspectives on the procedure can partially compensate recognition errors. A considerable robustness could be achieved with a reasonable quality of the recognition. Overall, reliable reactive as well as proactive behavior of the surgical working environment can be implemented in the proposed environment. The obtained validation results indicate the suitability of the overall approach. The setup is a reliable starting point for a subsequent evaluation of the proposed context-aware assistance. The major challenge for future work will be to implement the complex approach in a cross-vendor setting.

The use of engineered protein materials in electrochemical devices.

Bioelectrochemical technologies have an important and growing role in healthcare, with applications in sensing and diagnostics, as well as the potential to be used as implantable power sources and be integrated with automated drug delivery systems. Challenges associated with enzyme-based electrodes include low current density and short functional lifetimes. Protein engineering is emerging as a powerful tool to overcome these issues. By taking advantage of the ability to precisely define protein sequences, electrodes can be organized into high performing structures, and enable the next generation of medical devices.

Zwitterionic surface grafting of epoxylated sulfobetaine copolymers for the development of stealth biomaterial interfaces

Most biomaterials have a lack of a simple, efficient and robust antifouling modification approach that limits their potential for biomedical applications. The challenge is to develop a universal surface grafting solution to meet the antifouling requirement. In this work, a new formulation of zwitterionic sulfobetaine-based copolymer, ploy(glycidyl methacrylate-co-sulfobetaine methacrylate) (poly(GMA-co-SBMA)), is designed as a chemical for grafting onto material and is introduced for the surface zwitterionization of versatile biomaterials, including ceramic, metal, and plastics. The grafting principle used to stabilize the poly(GMA-co-SBMA) on the target surfaces is based the base-induced ring opening reaction between epoxied and hydroxyl groups. A universal surface modification procedure was developed and performed from an optimized sequence of ultra-violet ozone pretreatment and trimethylamine-catalyzed zwitterionization on a selective case of versatile surfaces including silicon wafer, ceramic glass, titanium, steel, and polystyrene. The prepared poly(GMA-co-SBMA) with an optimum PGMA/PSBMA ratio of 0.23 and a molecular weight of 25kDa exhibited the best resistance to fibrinogen adsorption with over 90% reduction as well as blood cell activation, tissue cell adhesion and bacterial attachment on the zwitterionic copolymer grafted surfaces. The developed antifouling grafting introduces a universal modification method to generate zwitterionic interfaces on versatile biomaterial substrates, providing great potential for application in medical device coating. Statement of SignificanceA simple, efficient and robust antifouling modification approach is critical for many scientific interests and industrial applications. In current stage, the existing available zwitterionic modifications suffer from the lack of universal surface grafting solution to achieve the antifouling requirement on versatile biomaterial substrates. In this study, we synthesized and characterized a new zwitterionic sulfobetaine-based copolymer, ploy(glycidyl methacrylate-co-sulfobetaine methacrylate) (poly(GMA-co-SBMA)), which is designed as chemical grafting onto material and introduced for the surface zwitterionization of versatile biomaterials, including ceramic, metal, and plastics. This research have a promising opportunity for the application of stealth biomaterial interfaces on the next generation of medical devices.

Soft hydrogels interpenetrating silicone--A polymer network for drug-releasing medical devices.

Materials for the next generation of medical devices will require not only the mechanical stability of current devices, but must also possess other properties such as sustained release of drugs in a controlled manner over a prolonged period of time. This work focuses on creating such a sophisticated material by forming an interpenetrating polymer network (IPN) material through modification of silicone elastomers with a poly(2-hydroxyethyl methacrylate) (PHEMA)-based hydrogel. IPN materials with a PHEMA content in the range of 13%-38% (w/w) were synthesized by using carbon dioxide-based solvent mixtures under high pressure. These IPNs were characterized with regard to microstructure as well as ability of the hydrogel to form a surface-connected hydrophilic carrier network inside the silicone. A critical limit for hydrogel connectivity was found both via simulation and by visualization of water uptake in approximately 25% (w/w) PHEMA, indicating that entrapment of gel occurs at low gel concentrations. The optimized IPN material was loaded with the antibiotic ciprofloxacin, and the resulting drug release was shown to inhibit bacterial growth when placed on agar, thus demonstrating the potential of this IPN material for future applications in drug-releasing medical devices.

Chemical sensors for breath gas analysis: the latest developments at the Breath Analysis Summit 2013

Profiling the body chemistry by means of volatile organic compounds (VOCs) in the breath opens exciting new avenues in medical diagnostics. Gas sensors could provide ideal platforms for realizing portable, hand-held breath testing devices in the near future. This review summarizes the latest developments and applications in the field of chemical sensors for diagnostic breath testing that were presented at the Breath Analysis Summit 2013 in Wallerfangen, Germany. Considerable progress has been made towards clinically applicable breath testing devices, especially by utilizing chemo-sensitive nanomaterials. Examples of several specialized breath testing applications are presented that are either based on stand-alone nanomaterial-based sensors being highly sensitive and specific to individual breath compounds over others, or on combinations of several highly specific sensors, or on experimental nanomaterial-based sensors arrays. Other interesting approaches include the adaption of a commercially available MOx-based sensor array to indirect breath testing applications, using a sample pre-concentration method, and the development of compact integrated GC-sensor systems. The recent trend towards device integration has led to the development of fully integrated prototypes of point-of-care devices. We describe and compare the performance of several prototypes that are based on different sensing technologies and evaluate their potential as low-cost and readily available next-generation medical devices.

The art of engineering viral nanoparticles.

Viral nanotechnology is an emerging and highly interdisciplinary field in which viral nanoparticles (VNPs) are applied in diverse areas such as electronics, energy and next-generation medical devices. VNPs have been developed as candidates for novel materials, and are often described as "programmable" because they can be modified and functionalized using a number of techniques. In this review, we discuss the concepts and methods that allow VNPs to be engineered, including (i) bioconjugation chemistries, (ii) encapsulation techniques, (iii) mineralization strategies, and (iv) film and hydrogel development. With all these techniques in hand, the potential applications of VNPs are limited only by the imagination.

형상기억합금(SMA) 스티어링 카테터의 반응속도 향상을 위한 펠티어 열전소자의 열전기적 특성 평가

Actuation using a shape memory alloy (SMA) is considered to be an important technology that will play a leading role in market for next-generation medical devices because an SMA actuator can accurately imitate skillful and delicate hand movements. However, SMA actuators have not been successfully used because of problems in control design caused by the nonlinear hysteresis effect of SMA, which leads to inaccuracies in control systems. In order to overcome the effect, the authors invented a SMA actuator, which could actively and rapidly cool down and heat up, by combining a SMA catheter and a TE module using the Peltier effect. In order to evaluate the TE characteristics of our TE module system, the changes in the temperature with 1) incremental increases in a continuous electric current and 2) the appearance of a discontinuous constant or reverse current are discussed in this paper.