Medical Device Applications Research Articles

Moderating cellular inflammation using 2-dimensional titanium carbide MXene and graphene variants.

The effective control of microbial and metabolically derived biological toxins which negatively impact physical health remains a key challenge for the 21st century. 2-Dimensional graphene and MXene nanomaterials are relatively new additions to the field of biomedical materials with superior external surface areas suited to adsorptive remediation of biological toxins. However, relatively little is known about their physiological interactions with biological systems and, to date, no comparative biological studies have been done. This study compares titanium carbide MXene (Ti3C2Tx) in multilayered and delaminated forms with graphene variants to assess the impact of variable physical properties on cellular inflammatory response to endotoxin stimulus. No significant impact on cell metabolism or induction of inflammatory pathways leading to cell death was observed. No significant increase in markers of blood cell activation and haemolysis occurred. Whilst graphene nanoplatelets (GNP), graphene oxide (GO) and Ti3C2Tx showed insignificant antibacterial activity towards Escherichia coli, silver nanoparticle-modified GO (GO-Ag) induced bacterial cell death and at a lower dose than silver nanoparticles. All nanomaterials significantly reduced bacterial endotoxin induced THP-1 monocyte IL-8, IL-6 and TNF-α cytokine production by >99%, >99% and >80% respectively, compared to control groups. This study suggests the utility of these nanomaterials as adsorbents in blood contacting medical device applications for removal of inflammatory cytokines linked to poor outcome in patients with life-threatening infection.

Bluetooth Signal Attenuation Analysis in Human Body Tissue Analogues

Wireless communications for ingestible and implantable medical device applications are integral for the embedded systems employed to these ends. The Bluetooth protocol is of major interest given its ubiquitous nature in consumer electronic devices. Here the effectiveness of Bluetooth in such applications is examined with a custom-designed Bluetooth system. The radio frequency (RF) attenuation testing was conducted in a variety of different media, including water, meat, ballistic gel, and fat. The RF signal attenuation was found to be the highest in meat and ballistic gel, less in water and least severe in fat. The measured distances at which signal integrity was still maintained provide necessary information for designing and implementing Bluetooth based medical devices and function as evidence for the feasibility of Bluetooth enabled systems for such communications.

Estudo do biocompósito de P3HB/nanodiamante para aplicação em dispositivos médicos, parte 2: citotoxicidade in vitro e testes de biocompatibilidade

Na Parte 1 deste trabalho, foi apresentado um novo nanocompósito biodegradável e biocompatível com matriz polimérica de poli-hidroxibutirato (PHB) carregado com nanopartículas de diamante (ND) obtido, pela primeira vez, sob conhecimento dos autores, a partir da técnica de vaporização de solvente (técnica sob pedido de patente) para aplicação em acessórios médicos. As propriedades mecânicas, térmicas e morfológicas, como também a eficiência da técnica na homogeneidade e dispersão da carga na matriz polimérica confirmada através de modelos mecânicos foram investigadas na Parte 1 do artigo. Na Parte 2, testes in vitro foram feitos para testar a citotoxicidade e biocompatibilidade do nanocompósito. Os testes resultaram na ausência de resposta inflamatória em culturas de fibroblastos e macrófagos para todas as composições do nanocompósitos estudados.

Effect of Material on the Mechanical Properties of Additive Manufactured Thermoplastic Parts

Additive manufacturing (AM) also called 3D printing, is an emerging process in the manufacturing sector with increasing new applications in aerospace, prototyping, medical devices and product development, among others. The resistance of the AM part is determined by the chosen material and the printing parameters. As novel materials and AM methods are continuously being developed, there is a need for the development and mechanical characterization of suitable materials for 3D printing. In this study, the influence of the material and the 3D-printing parameters on the mechanical properties of additive manufactured thermoplastic parts was investigated. Three different filaments that are commercially available: Polylactic acid (PLA), acrylonitrile butadiene styrene (ABS) and Tritan were used. Tensile and flexural tests were carried out, in accordance to ASTM standards, to investigate and compare the mechanical properties of the AM parts as a function of material used. The results showed that the type of filaments had the greatest influence on the mechanical properties of the AM parts. The maximum strength and stiffness were obtained for the PLA specimens. Tritan displayed the highest deformation, while the PLA manifested the lowest deformation capacity. The mechanical properties of the printed parts also depend on the printing parameters. The parameters used in this work are a good compromise between the printing time and the mechanical properties.

Effects of in vivo application of an overnight patch containing Allium cepa, allantoin, and pentaglycan on hypertrophic scars and keloids: Clinical, videocapillaroscopic, and ultrasonographic study.

Several therapeutic approaches have been described for their treatment of hypertrophic scars and keloids, but to date, the optimal treatment has not been established yet. Our in vivo study was conducted to evaluate the effect of a medical device consisting in an adhesive patch containing onion extract (Allium cepa) 10%, allantoin 1%, and pentaglycan 4% (Kaloidon patch) on hypertrophic scars and keloids. Thirty-nine patients with hypertrophic scars and seven patients with keloids were asked to apply an adhesive patch containing Allium cepa, allantoin, and pentaglycan once/day for at least 8 h consecutively, for 24 weeks. Patients were reevaluated 6 weeks (T6), 12 weeks (T12), and 24 weeks (T24) after starting the treatment through POSAS scale v 2.0, ultrasonographic, and videocapillaroscopic assessment. The investigated medical device was able to induce a significant improvement of POSAS starting from T12, with a positive amelioration trend until T24. However the patient-assessed POSAS sub-items showed improvement already after 6 weeks, whereas a significant improvement of the observer-assessed POSAS sub-items was observed only after 12 weeks (P < .001). Ultrasonography and intravital videocapillaroscopy confirmed a significant improvement of skin scars thickness (P < .001) and vascularization (P < .001) after 12 weeks of medical device application at least, with increasing improvement until T24. Applying an adhesive patch containing Allium cepa, allantoin, and pentaglycan once a day for at least 8 consecutive hours seems to be able to improve the clinical and morphological characteristics of the scars of the skin in 24 weeks.

Anti-inflammatory potential of Portuguese thermal waters

In light of Medical Hydrology, thermal waters (TW) are all-natural mineral waters that emerge inside a thermal resort and have therapeutic applications. Their beneficial effect has been empirically recognized for centuries, being indicated for symptom alleviation and/or treatment of several diseases, almost all associated with inflammation. Indeed, an anti-inflammatory effect has been attributed to many different Portuguese TW but there is no scientific validation supporting this empiric knowledge. In the present study, we aimed to investigate the anti-inflammatory properties of 14 TW pertaining to thermal centers located in the Central Region of Portugal, and grouped according to their ionic profile. Mouse macrophage cells stimulated with lipopolysaccharide (LPS), a Toll-like receptor 4 agonist, were exposed to culture medium prepared in TW. Metabolism, nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression levels and the scavenging capacity of TW, were investigated in vitro. 11 out of 14 TW reduced NO production and/or iNOS expression, and/or scavenging activity, in macrophages exposed to LPS. The sulphated/calcic TW did not show any effect on at least one of the inflammatory parameters evaluated. Two sulphurous/bicarbonate/sodic TW and the sulphurous/chlorinated/sodic TW promoted an increase in NO production and/or iNOS expression. Our results validate, for the first time, the anti-inflammatory properties of Portuguese TW, supporting their therapeutic use in the treatment of inflammation-related diseases and promoting their putative application in cosmetic products and medical devices.

Application of Artificial Intelligence Technology in Oncology: Towards the Establishment of Precision Medicine.

Simple SummaryArtificial intelligence (AI) technology has been advancing rapidly in recent years and is being implemented in society. The medical field is no exception, and the clinical implementation of AI-equipped medical devices is steadily progressing. In particular, AI is expected to play an important role in realizing the current global trend of precision medicine. In this review, we introduce the history of AI as well as the state of the art of medical AI, focusing on the field of oncology. We also describe the current status of the use of AI for drug discovery in the oncology field. Furthermore, while AI has great potential, there are still many issues that need to be resolved; therefore, we would provide details on current medical AI problems and potential solutions.In recent years, advances in artificial intelligence (AI) technology have led to the rapid clinical implementation of devices with AI technology in the medical field. More than 60 AI-equipped medical devices have already been approved by the Food and Drug Administration (FDA) in the United States, and the active introduction of AI technology is considered to be an inevitable trend in the future of medicine. In the field of oncology, clinical applications of medical devices using AI technology are already underway, mainly in radiology, and AI technology is expected to be positioned as an important core technology. In particular, “precision medicine,” a medical treatment that selects the most appropriate treatment for each patient based on a vast amount of medical data such as genome information, has become a worldwide trend; AI technology is expected to be utilized in the process of extracting truly useful information from a large amount of medical data and applying it to diagnosis and treatment. In this review, we would like to introduce the history of AI technology and the current state of medical AI, especially in the oncology field, as well as discuss the possibilities and challenges of AI technology in the medical field.

Sung Wan Kim - Early events in blood/material interactions

Sung Wan Kim's initial efforts as an independent investigator were focused on improving the understanding of the early events in blood/material interactions with the goal to develop blood compatible materials for application in medical devices and prostheses. These initial efforts were centered around blood protein adsorption on biomaterials and related mechanisms of thrombus formation (thrombosis). Ultimately, Sung Wan's efforts were expanded to studies of the non-thrombogenic nature of heparinized biomaterials, prostaglandin biomaterials, and block copolymer systems. These studies were supported by two NIH grants for 22 and 19 years, respectively, and a NIH Career Development Award. Moreover, these studies resulted in over 140 peer-reviewed publications and training of many students and postdoctoral scientists. The intent of this paper is to identify key concepts, papers, and contributions by Sung Wan and his colleagues that fall within the four aforementioned research categories. In this context, many of Sung Wan's early efforts contributed directly to Utah's biomaterials efforts and the Total Artificial Heart program at the time, while providing the foundation for the productive international Triangle Collaboration as well as his following work in polymer-controlled drug releasing systems.

Performance of OLED under mechanical strain: a review

OLEDs with convenient portability, low power consumption, and mechanical flexibility have successfully demonstrated their wide range of applications in display, lighting, and medical devices. With the biological requirement and continuous development of electronic technology, the OLEDs have opened up new possibilities for wearable electronic devices. Plentiful reports have revealed the progress of OLED devices with excellent performance of mechanical strain, involving flexible electrodes, processing technology, and advanced fabrication. In this review, the OLED processing methods are systematically discussed, and the development of flexible electrodes has been focused in terms of mechanical strain. In addition, the OLED performance with flexible electrodes also is described. The review provides a comprehensive understanding of OLEDs that can withstand the mechanical strain and achieve commercial maturity.

Epidermal Electronics: Ultrathin, Stretchable, and Breathable Epidermal Electronics Based on a Facile Bubble Blowing Method (Adv. Electron. Mater. 11/2020)

A novel bubble blowing method is proposed to fabricate ultrathin, stretchable, and breathable epidermal electronics by Xianqing Yang and co-workers in article number 2000306. The ultrathin epidermal electrode can be conformably attached to human skin for high-quality electromyogram signal recording. It shows the potentiality in applications of future conformal wearable medical devices and human-computer interfaces.

Reconfigurable multifunctional ferrofluid droplet robots

Magnetically actuated miniature soft robots are capable of programmable deformations for multimodal locomotion and manipulation functions, potentially enabling direct access to currently unreachable or difficult-to-access regions inside the human body for minimally invasive medical operations. However, magnetic miniature soft robots are so far mostly based on elastomers, where their limited deformability prevents them from navigating inside clustered and very constrained environments, such as squeezing through narrow crevices much smaller than the robot size. Moreover, their functionalities are currently restricted by their predesigned shapes, which is challenging to be reconfigured in situ in enclosed spaces. Here, we report a method to actuate and control ferrofluid droplets as shape-programmable magnetic miniature soft robots, which can navigate in two dimensions through narrow channels much smaller than their sizes thanks to their liquid properties. By controlling the external magnetic fields spatiotemporally, these droplet robots can also be reconfigured to exhibit multiple functionalities, including on-demand splitting and merging for delivering liquid cargos and morphing into different shapes for efficient and versatile manipulation of delicate objects. In addition, a single-droplet robot can be controlled to split into multiple subdroplets and complete cooperative tasks, such as working as a programmable fluidic-mixing device for addressable and sequential mixing of different liquids. Due to their extreme deformability, in situ reconfigurability and cooperative behavior, the proposed ferrofluid droplet robots could open up a wide range of unprecedented functionalities for lab/organ-on-a-chip, fluidics, bioengineering, and medical device applications.

Regulatory Frameworks for Development and Evaluation of Artificial Intelligence-Based Diagnostic Imaging Algorithms: Summary and Recommendations.

Although artificial intelligence (AI)-based algorithms for diagnosis hold promise for improving care, their safety and effectiveness must be ensured to facilitate wide adoption. Several recently proposed regulatory frameworks provide a solid foundation but do not address a number of issues that may prevent algorithms from being fully trusted. In this article, we review the major regulatory frameworks for software as a medical device applications, identify major gaps, and propose additional strategies to improve the development and evaluation of diagnostic AI algorithms. We identify the following major shortcomings of the current regulatory frameworks: (1) conflation of the diagnostic task with the diagnostic algorithm, (2) superficial treatment of the diagnostic task definition, (3) no mechanism to directly compare similar algorithms, (4) insufficient characterization of safety and performance elements, (5) lack of resources to assess performance at each installed site, and (6) inherent conflicts of interest. We recommend the following additional measures: (1) separate the diagnostic task from the algorithm, (2) define performance elements beyond accuracy, (3) divide the evaluation process into discrete steps, (4) encourage assessment by a third-party evaluator, (5) incorporate these elements into the manufacturers’ development process. Specifically, we recommend four phases of development and evaluation, analogous to those that have been applied to pharmaceuticals and proposed for software applications, to help ensure world-class performance of all algorithms at all installed sites. In the coming years, we anticipate the emergence of a substantial body of research dedicated to ensuring the accuracy, reliability, and safety of the algorithms.

Diamond in medical devices and sensors: An overview of diamond surfaces

AbstractSignificant challenges arise when the human body is damaged, diseased and unable to repair itself. Current biomaterials for biomedical devices have limitations to restore function, while materials for implants and sensors often invoke a large foreign body response. Therefore, there is a need to develop suitable biomaterials in the fields of medical devices and sensors. Diamond is emerging due to its many favourable properties including biocompatibility, antimicrobial capability, antifouling properties, electrical conductivity and chemical functionalization capability. Thin film coatings of diamond can be fabricated by chemical vapour deposition, or by particle coatings with nanodiamond materials. Hybrid/composite diamond materials include soft materials such as those processed by electrospinning and melt extrusion, as well as hard materials such as those processed by additive manufacturing. Additive manufacturing is a developing area for diamond biomaterial fabrication and can include both hard and soft materials. The fabrication method used will depend on the properties required of the biomaterial, as well as the application. In this mini‐review, recent progress on using diamond in medical devices and sensors is outlined, with particular emphasis on fabrication methods. We highlight selected applications from recent literature and, in closing, make comments and suggestions to advance the field and direction of diamond application in medical devices and sensors.

CMOS High-Efficiency Wireless Battery Charging System With Global Power Control Through Backward Data Telemetry for Implantable Medical Devices

A high-efficiency CMOS wireless battery charging system with battery voltage tracking and global power control through the proposed pulsed load-shift keying (PLSK) backward data telemetry technique is designed. The power transmitted from the adaptively controlled power transmitter (ACPT) for battery charging is automatically adjusted with the battery voltage tracking through the PLSK backward data telemetry. Therefore, the generated rectifier output voltage is only slightly larger than battery voltage and tracks with battery voltage during the charging time of linear battery charger. Experimental result shows that the average receiver efficiency with battery voltage tracking from 3.3 V to 4.2 V and global power control is 90.9% which is 14.9% higher than that without these techniques and 28.9% higher than that in the prior work. The measured power loss is 8 mW (4.44%) under the maximum output power of 180 mW and with the PLSK data rate of 211 kbps. The proposed wireless battery charging system with a single pair of coils at the resonant frequency of 13.56 MHz is suitable for the applications of implantable medical devices.

In-situ monitoring the effect of acoustic vibration in the form of music on the motility of Escherichia coli

In this work, a new analytical approach combining optical microscope with software was carried out to study the effect of music on bacteria and to explore its potential mechanism. The stimulation of classical music (Flight of the Bumblebee) with different frequencies (range from 55 Hz to 4186 Hz) and tempos (range from 25 BPM to 250 BPM) was transmitted in the form of vibration by the apparatus which was bone conduction to Escherichia coli MG1655. The increment of E. coli motility affected by Flight of the Bumblebee was quantified by two approaches. One was indirect motility assay and the other was the in-situ monitoring on the swimming behavior of E. coli under the optical microscope. The in-situ monitoring was conducted by combining optical microscope with software which enabled real-time observation on the swimming behavior of E. coli. Both results showed that different frequencies and tempos of musical vibration affected the motility to a different extent. With comparison, it was found that the music with higher frequency and faster tempo could enhance more on the motility. Above findings suggest this new analytical approach could be applied for investigating the motility of E. coli, and also a potential mechanism to modulate biological cells for future digital therapeutic and medical device applications.

Creating CRISPR-responsive smart materials for diagnostics and programmable cargo release.

Materials that sense and respond to biological signals in their environment have a broad range of potential applications in drug delivery, medical devices and diagnostics. Nucleic acids are important biological cues that encode information about organismal identity and clinically relevant phenotypes such as drug resistance. We recently developed a strategy to design nucleic acid-responsive materials using the CRISPR-associated nuclease Cas12a as a user-programmable sensor and material actuator. This approach improves on the sensitivity of current DNA-responsive materials while enabling their rapid repurposing toward new sequence targets. Here, we provide a comprehensive resource for the design, synthesis and actuation of CRISPR-responsive hydrogels. First, we provide guidelines for the synthesis of Cas12a guide RNAs (gRNAs) for in vitro applications. We then outline methods for the synthesis of both polyethylene glycol-DNA (PEG-DNA) and polyacrylamide-DNA (PA-DNA) hydrogels, as well as their controlled degradation using Cas12a for the release of cargos, including small molecules, enzymes, nanoparticles and living cells within hours. Finally, we detail the design and assembly of microfluidic paper-based devices that use Cas12a-sensitive hydrogels to convert DNA inputs into a variety of visual and electronic readouts for use in diagnostics. Following the initial validation of the gRNA and Cas12a components (1 d), the synthesis and testing of either PEG-DNA or PA-DNA hydrogels require 3-4 d of laboratory time. Optional extensions, including the release of primary human cells or the design of the paper-based diagnostic, require an additional 2-3 d each.

A feasible approach to obtain near-infrared (NIR) emission from binuclear platinum(II) complexes containing centrosymmetric isoquinoline ligand in PLEDs

Abstract Organic light-emitting diodes (OLEDs) of deep-red (DR)/near-infrared (NIR) emission have become an emerging hot topic in applications for medical and night-vision devices. In this article, one novel symmetrical binuclear platinum(II) complexes as well as its mononuclear analogues, namely (DIQB)[Pt(DPM)]2 and (DIQB)Pt(DPM), involving big rigid planar ligand 1,4-di(isoquinolin-1-yl)benzene (DIQB) and auxiliary ligand dipivaloylmethanato (DPM), were successfully synthesized and characterized. Intrinsic DR emission peaked at 618 nm with a photoluminescence quantum yield (Φ) of 2.42% and lifetime of 0.37 μs was obtained in the (DIQB)Pt(DPM) solution. Wondrously, an outstandingly 112 nm red-shifted emission peaked at 730 nm with a Φ of 0.77% and lifetime of 0.26 μs was observed in (DIQB)[Pt(DPM)]2 solution. Density functional theory (DFT/TD-DFT) calculations were carried out to reveal the emission process and a predominant 3ILCT/3MLCT characteristics. As a result, the emission of platinum(II) complexes is tuned from DR to NIR via appending an additional platinum(II) ion. OLEDs based on (DIQB)Pt(DPM) exhibited an efficient DR emission at 666 nm with a maximum external quantum efficiency (EQE) of 2.86% and a brightness of 1632 cd/cm2 at dopant concentration of 3 wt %, In contrast, an outstandingly 80 nm red-shifted NIR emission at 746 nm with a EQE of 0.58% and a radiance of up to 10036 mW/Sr/m2 was obtained for the (DBIQ)[Pt(DPM)]2 device at the same dopant concentration. Moreover, the efficiency roll-off was efficiently inhibited in the (DIQB)[Pt(DPM)]2-doped devices. This work demonstrates that binuclear platinum(II) complexes dominated by centrosymmetric type C∧N-C∧N tetradentate big rigid planar ligand is an effective strategy for obtaining NIR luminescent materials.

Biocompatibility of a Marine Collagen-Based Scaffold In Vitro and In Vivo

Scaffold material is essential in providing mechanical support to tissue, allowing stem cells to improve their function in the healing and repair of trauma sites and tissue regeneration. The scaffold aids cell organization in the damaged tissue. It serves and allows bio mimicking the mechanical and biological properties of the target tissue and facilitates cell proliferation and differentiation at the regeneration site. In this study, the developed and assayed bio-composite made of unique collagen fibers and alginate hydrogel supports the function of cells around the implanted material. We used an in vivo rat model to study the scaffold effects when transplanted subcutaneously and as an augment for tendon repair. Animals’ well-being was measured by their weight and daily activity post scaffold transplantation during their recovery. At the end of the experiment, the bio-composite was histologically examined, and the surrounding tissues around the implant were evaluated for inflammation reaction and scarring tissue. In the histology, the formation of granulation tissue and fibroblasts that were part of the inclusion process of the implanted material were noted. At the transplanted sites, inflammatory cells, such as plasma cells, macrophages, and giant cells, were also observed as expected at this time point post transplantation. This study demonstrated not only the collagen-alginate device biocompatibility, with no cytotoxic effects on the analyzed rats, but also that the 3D structure enables cell migration and new blood vessel formation needed for tissue repair. Overall, the results of the current study proved for the first time that the implantable scaffold for long-term confirms the well-being of these rats and is correspondence to biocompatibility ISO standards and can be further developed for medical devices application.

Nanofibrillation and characterization of sugarcane bagasse agro-waste using water-based steam explosion and high-pressure homogenization

Sugarcane bagasse waste, consisting of approximately 40–50% cellulose, has been widely used in a number of industries. The extraction and defibrillation of nanometer-scale cellulose fibers from such waste using strong chemical solutions have been extensively investigated. However, the using of strong chemical solutions can cause adverse effects to the fibers as well as negatively affect the environment. Some evidence has shown that mechanical treatments, such as steam explosion and high-pressure homogenization, are environmentally friendly when compared with chemical treatment techniques. This work aimed to isolate the cellulose nanofibers from sugarcane bagasse waste using steam explosion pretreatment at various temperatures (195, 200, 205, and 210 °C) and durations (5, 10, and 15 min) before passing through a microfluidizer within 12 passes of 200 mL cellulose suspension. The mean separation analysis using Duncan’s Multiple Range test showed that higher temperatures significantly improved the efficiency of non-cellulosic substances reduction, as evidenced by an increment of whiteness index (81.39–90.02), thermal degradation temperature (313.92–326.34 °C) and crystallinity index (74.27–81.42%). The obtained cellulose nanofibers exhibited very fine diameter within the range of 3–7 nm, had a high cellulose content (92.74 ± 0.14%) and a low density (0.8989 g/cm3). The obtained cellulose nanofibers could be applied in various fields such as medical, cosmetic, food packaging, and electronic device applications.

Effects of deposition and annealing conditions on the crystallisation of NiTi thin films by e‐beam evaporation

This Letter demonstrates the effects of deposition and annealing conditions on the crystallisation of nickel–titanium (NiTi) thin films deposited by the e-beam evaporation. NiTi thin films of 0.5 μm thick are fabricated on P-type (110) silicon substrates using the e-beam evaporation technique. With the characterisations using the X-ray diffraction method, the results indicate that low e-beam deposition rate and argon employed annealing procedures can be beneficial to the formation of NiTi crystalline structure. Additionally, the as-deposited NiTi thin films without annealing procedures are amorphous, when deposited on the substrates at low temperatures. The differential scanning calorimetry studies show NiTi thin films formed by the e-beam evaporation are Ni-rich. Furthermore, SEM images illustrate that high-precision patterned NiTi thin film microstructures can be fabricated by combining with the e-beam evaporation and lift-off resist methods, without any wet or dry etching procedures. The proposed fabrication process for NiTi thin film microstructures shows great potential for application in shape memory alloy medical devices, as well as the micro-robotics.