Medical Device Applications Research Articles

Automated manufacturing system for carbon fiber-based twisted and coiled artificial muscles (TCAMs)

Carbon Fiber (CF) Twisted and Coiled Artificial Muscles (TCAMs) can replace traditional actuators in robotics and medical devices applications. CF TCAMs are currently made through a time-consuming and inconsistent manual process. This paper proposes a novel automated manufacturing system to produce CF-based TCAMs with repeatable and tailored geometry. This system reduces manufacturing time from 24 h to only 3 min, and experiments demonstrates that the system is capable of manufacturing TCAMs with repeatable performance. The maximum deviation of the output contraction between different TCAMs is reduced by 66%. This automated and scalable process will foster the use of TCAMs in several applications.

Nitric Oxide-Releasing Silicone Oil with Tunable Payload for Antibacterial Applications

Bacterial infections are a hurdle to the application of medical devices, and in the United States alone, more than one million infection cases are reported annually from indwelling medical devices. Infections not only affect the function of medical devices but also risk the lives and health of patients. Nitric oxide (NO) has been used as an antibacterial therapy that kills bacteria without causing resistance and provides many therapeutic effects such as anti-inflammation, antithrombosis, and angiogenesis. Silicone oils have been widely utilized in manufacturing consumer goods, healthcare products, and medical products. Specifically, liquid silicone oils are used as a medical lubricant that creates lubricated interfaces between medical devices and the exterior physiological environment to improve the performance of medical devices. Herein, we report the first primary S-nitrosothiol-based NO-releasing silicone oil (RSNO-Si) that exhibits proactive antibacterial effects. S-nitrosothiol silicone oils (RSNO-Si) were synthesized and the NO payloads ranged from 34.0 to 603.9 μM. The increased NO payload induced higher-viscosity RSNO-Si oils, as RSNO0.1-Si, RSNO0.5-Si, and RSNO1-Si had viscosities of 12.8 ± 0.1 cP, 32.0 ± 0.2 cP, and 35.1 ± 0.3 cP, respectively. RSNO-Si-SR interfaces were fabricated by infusing silicone rubber (SR) in RSNO-Si oil, and the resulting RSNO-Si-SR disks demonstrated NO release without NO donor leaching. RSNO0.1-Si-SR, RSNO0.5-Si-SR, and RSNO1-Si-SR exhibited maximum NO flux at 0.8, 6.5, and 21.5 × 10 -10 mol cm-2 min-1 in 24 h, respectively. RSNO-Si-SR disks also demonstrated 97.45, 95.40, and 96.08% of inhibition against S. aureus in a 4 h bacterial adhesion assay. Considering the easy synthesis, simple fabrication of non-leaching NO-releasing interfaces, tunable payloads, NO flux levels, and antimicrobial effects, RSNO-Si oils exhibited their potential use as platform chemicals for creating antimicrobial medical device surfaces and other antibacterial materials.

A Short Review: Chemistry of Curcumin and Its Metal Complex Derivatives

This review covers recent progress in the synthesis of curcumin and the bioactivity of semisynthetic and synthetic analogs of curcumin. The review also shows how curcumin is a useful intermediate for the synthesis of more complex organic molecules; historical perspective; the process of preparing the metal complexes and characterization the produced complexes using various spectral and other techniques; shows the importance of curcumin and its derivatives for their potential applications in medical devices and broad-spectrum of medical application such as antibiotic ointment, alternative therapeutics, antifungal, and antibacterial activities.

A miniaturized low frequency direct-current magnetic-bias-integrated magnetoelectric wireless power transfer system with enhanced energy conversion efficiency

Wireless power transfer (WPT), which transfers energy without a physical link, has recently received significant research interest. Due to the advantages of small dimension, low operation frequency, and low transmission loss, magnetoelectric WPT (ME-WPT) has been shown to be a promising technology for internet of things (IoT) and implantable medical device (IMD) applications. However, ME-WPT requires a direct-current (DC) magnetic bias for optimal performance and prior arts have implemented large electromagnets, Helmholtz coils, or externally positioned magnet bias systems, which increase the system dimension. Furthermore, the highest energy conversion efficiency (ECE) reported by prior ME-WPT studies is 0.62%, which needs to be improved. In this paper, we present an ME-WPT system with a novel miniaturized ME-WPT receiver and a spiral coil based transmitter. Four DC magnets are integrated onto the ME-WPT receiver to significantly reduce its dimension while providing a DC magnetic bias of 190 Oe for optimal performance. Electrochemical polarization characterizations are introduced to analyze the performance of the WPT receiver, which reveal that a maximum output power of 4.096 mW is obtained. A record ECE of 2.64% is reported, the highest among all ME-WPTs to date. The output power is improved by at least 49.3 times compared with the ME-WPT without integrated DC magnets. The influence of the input voltage and the distance between transmitter/receiver on the performance of the ME-WPT system is studied, which shows that the output power increases as the distance decreases and the input voltage increases. The proposed ME-WPT system with integrated DC magnets has potential applications in IoT and IMDs.

Nitric Oxide-Releasing Nanofibrous Scaffolds Based on Silk Fibroin and Zein with Enhanced Biodegradability and Antibacterial Properties.

Clinical applications of scaffolds and implants have been associated with bacterial infection resulting in impaired tissue regeneration. Nanofibers provide a versatile structure for both antimicrobial molecule delivery and tissue engineering. In this study, the nitric oxide (NO) donor molecule S-nitrosoglutathione (GSNO) and the natural biodegradable polymer zein (ZN) were combined with silk fibroin (SF) to develop antibacterial and biodegradable nanofibrous scaffolds for tissue engineering applications. The compatibility and intermolecular interactions of SF and ZN were studied using differential scanning calorimetry and Fourier transform infrared spectroscopy. The incorporation of ZN increased the hydrophobicity of the fibers and resulted in a more controlled and prolonged NO release profile lasting for 48 h. Moreover, the degradation kinetics of the fibers was significantly improved after blending with ZN. The results of tensile testing indicated that the addition of ZN and GSNO had a positive effect on the strength and stretchability of SF fibers and did not adversely affect their mechanical properties. Finally, due to the antibacterial properties of both NO and ZN, the SF-ZN-GSNO fibers showed a synergistically high antibacterial efficacy with 91.6 ± 2.5% and 77.5 ± 3.1% reduction in viability of adhered Staphylococcus aureus and Escherichia coli after 24 h exposure, respectively. The developed NO-releasing fibers were not only antibacterial but also non-cytotoxic and successfully enhanced the proliferation and growth of fibroblast cells, which was quantitatively studied by a CCK-8 assay and visually observed through fluorescent staining. Overall, SF-ZN-GSNO fibers developed in this study were biodegradable and highly antibacterial and showed great cytocompatibility with fibroblasts, indicating their promising potential for a range of tissue engineering and medical device applications.

Systematic Exploration of a Catalytic Metal–Organic Framework/Polyurethane Composite for Medical Device Applications: Effects of MOF Particle Size, MOF Loading, and Polymer Concentration on Composite Material Activity

The metal–organic framework (MOF) CuBTTri, H3[(Cu4Cl)3(BTTri)8] (where H3BTTri = 1,3,5-tris(1H-1,2,3-triazol-5-yl)benzene), is a promising catalyst for the development of antithrombotic medical device materials via localized nitric oxide (NO) generation from endogenous S-nitrosothiols. This work evaluates the effects of three key parameters of CuBTTri-embedded polyurethane composite materials—MOF preparation/particle size, MOF loading, and polymer concentration—on the rate of NO generation. We discovered that CuBTTri preparation and particle size have a significant impact on NO generation. Specifically, hand-ground MOF particles (0.3 ± 0.1 µm diameter) generate NO at greater rates compared to larger as-prepared, raw MOF particles (0.4 ± 0.2 µm diameter) and smaller, filtered MOF particles (0.2 ± 0.1 µm diameter) for composite materials. This finding contradicts previous research for CuBTTri powder which found that the smaller the particles, the greater the catalytic rate. In examining the effects of MOF loading and polymer concentration, our data show that increasing these parameters generally results in increased rates of NO generation; though thresholds appear to exist in which increasing these parameters results in diminishing returns and impedes NO generation capacity for certain composite formulations. We found that polymer concentration is the key determinant of water absorptivity and statistically significant decreases in water uptake accompany statistically significant increases in NO generation. It was also found that formulations with relatively high MOF loadings and low polymer concentrations or low MOF loadings and high polymer concentrations inhibit the rate of NO generation. In summary, this research provides a framework for more strategic selections of key parameters when fabricating composite materials for medical device applications.

Research on Automatic Application of Medical Devices

Research on Automatic Application of Medical Devices

Biomedical Applications of Polyhydroxyalkanoate in Tissue Engineering.

Tissue engineering technology aids in the regeneration of new tissue to replace damaged or wounded tissue. Three-dimensional biodegradable and porous scaffolds are often utilized in this area to mimic the structure and function of the extracellular matrix. Scaffold material and design are significant areas of biomaterial research and the most favorable material for seeding of in vitro and in vivo cells. Polyhydroxyalkanoates (PHAs) are biopolyesters (thermoplastic) that are appropriate for this application due to their biodegradability, thermo-processability, enhanced biocompatibility, mechanical properties, non-toxicity, and environmental origin. Additionally, they offer enormous potential for modification through biological, chemical and physical alteration, including blending with various other materials. PHAs are produced by bacterial fermentation under nutrient-limiting circumstances and have been reported to offer new perspectives for devices in biological applications. The present review discusses PHAs in the applications of conventional medical devices, especially for soft tissue (sutures, wound dressings, cardiac patches and blood vessels) and hard tissue (bone and cartilage scaffolds) regeneration applications. The paper also addresses a recent advance highlighting the usage of PHAs in implantable devices, such as heart valves, stents, nerve guidance conduits and nanoparticles, including drug delivery. This review summarizes the in vivo and in vitro biodegradability of PHAs and conducts an overview of current scientific research and achievements in the development of PHAs in the biomedical sector. In the future, PHAs may replace synthetic plastics as the material of choice for medical researchers and practitioners.

A smart antibacterial surface with switchable bacteria-antifouling and killing capabilities

A single layer zwitterionic polymer brush grafted surface with pH-responsive charge reversal capacity was prepared in a simple and widely used strategy. The amide bond of the zwitterionic polymer will break under acidic condition and undergo a charge reversal, resulting the surface to convert from an antifouling zwitterionic surface to a bactericidal cationic surface. The surface we constructed can successfully resist the attachment of initial bacteria at physiological conditions and kill bacteria on demand to defend bacterial infection, showing an attractive application in implantable medical devices.

In vitro hemocompatibility screening of a slippery liquid impregnated surface coating for extracorporeal organ support applications.

Clot formation, infection, and biofouling are unfortunate but frequent complications associated with the use of blood-contacting medical devices. The challenge of blood-foreign surface interactions is exacerbated during medical device applications involving substantial blood contact area and extended duration of use, such as extracorporeal life support (ECLS). We investigated a novel surface modification, a liquid-impregnated surface (LIS), designed to minimize protein adsorption and thrombus development on medical plastics. The hemocompatibility and efficacy of LIS was investigated first in a low-shear model with LIS applied to the lumen of blood incubation vials and exposed to human whole blood. Additionally, LIS was evaluated in a 6 h ex vivo circulation model with swine blood using full-scale ECLS circuit tubing and centrifugal pumps with clinically relevant flow rate (1.5 L/min) and shear conditions for extracorporeal carbon dioxide removal. Under low-shear, LIS preserved fibrinogen concentration in blood relative to control polymers (+40 ± 6 mg/dL vs polyvinyl chloride, p < .0001), suggesting protein adsorption was minimized. A fibrinogen adhesion assay demonstrated a dramatic reduction in protein adsorption under low shear (87% decrease vs polyvinyl chloride, p = .01). Thrombus deposition and platelet adhesion visualized by scanning electron microscopy were drastically reduced. During the 6 h ex vivo circulation, platelets in blood exposed to LIS tubing did not become significantly activated or procoagulant, as occurred with control tubing; and again, thrombus deposition was visually reduced. A LIS coating demonstrated potential to reduce thrombus formation on medical devices. Further testing is needed specialized to clinical setting and duration of use for specific medical target applications.

Developing Integrated Approaches for Testing and Assessment (IATAs) in order to support nanomaterial safety

Due to the unique characteristics of nanomaterials (NM) there has been an increase in their use in nanomedicines and innovative medical devices (MD). Although large numbers of NMs have now been developed, comprehensive safety investigations are still lacking. Current gaps in understanding the potential mechanisms of NM-induced toxicity can make it challenging to determine the safety testing necessary to support inclusion of NMs in MD applications. This article provides guidance for implementation of pre-clinical tailored safety assessment strategies with the aim to increase the translation of NMs from bench development to clinical use. Integrated Approaches to Testing and Assessment (IATAs) are a key tool in developing these strategies. IATAs follow an iterative approach to answer a defined question in a specific regulatory context to guide the gathering of relevant information for safety assessment, including existing experimental data, integrated with in silico model predictions where available and appropriate, and/or experimental procedures and protocols for generating new data to fill gaps. This allows NM developers to work toward current guidelines and regulations, while taking NM specific considerations into account. Here, an example IATA for NMs with potential for direct blood contact was developed for the assessment of haemocompatibility. This example IATA brings together the current guidelines for NM safety assessment within a framework that can be used to guide information and data gathering for the safety assessment of intravenously injected NMs. Additionally, the decision framework underpinning this IATA has the potential to be adapted to other testing needs and regulatory contexts.

A comprehensive study about low-cost and limited bandwidth FMCW bio-radar: detailed analyses on vital signs measurements

Abstract In this study, a bio-radar system has been constituted using a frequency modulated continuous wave (FMCW) radar with low cost and limited bandwidth, taking into account of the lack of range the continuous wave (CW) radar. The displacement and vibration frequencies have been determined at a distance of 3.5–5 m for single and multiple targets via the help of the target test mechanism. Then, the detection of vital signs has been achieved with healthy human subject measurements. For a single human subject, respiration rate (RR) errors at 3.5 m and 5 m distances are 4% and 4.42%, respectively, and 13.25% and 15.16% for heartbeat rate (HR). In multiple targets measurements, although targets do not create an obstacle to each other, a slight deterioration has been observed in the signals and the error rates increase. The results show that bio-radar have a promising future to replace contact devices in medical applications.

Development of Eco-Friendly Nanomembranes of Aloe vera/PVA/ZnO for Potential Applications in Medical Devices.

Due to the current COVID-19 pandemic, there is a crucial need for the development of antimicrobial and antiviral personal protective equipment such as facemasks and gowns. Therefore, in this research we fabricated electrospun nanofibers composite with polyvinyl alcohol, aloe vera, and zinc oxide nanoparticles for end application in medical devices. Electrospun nanofibers were made with varying concentrations of aloe vera (1%, 2%, 3%, 4%) having a constant concentration of ZnO (0.5%) with varying concentrations of ZnO nanoparticles (1%, 2%, 3%, 4%) having a constant concentration of aloe vera (0.5%). To check the morphology and composition, all prepared nanofibers were subjected to different characterization techniques, such as Scanning Electron Microscopy (SEM), and Fourier Transform Infrared Spectroscopy (FTIR). In addition, its antimicrobial activity was checked both with qualitative and quantitative approaches against gram-positive (Staphylococcus aureus) bacteria and gram-negative (Escherichia coli) bacteria. The results suggest that increasing ZnO concentration kills and inhibits bacterial growth more proficiently compared to increasing aloe vera concentration in electrospun nanofibers; the highest antimicrobial was found with 4% ZnO, killing almost 100% of gram-positive (Staphylococcus aureus) bacteria and 99.2% of gram-negative (Escherichia coli) bacteria. These fabricated nanofibers have potential applications in medical devices and would help control the spread of many diseases.

Heating and Cooling Rate Study on Water Cooling Thermal Cycler using Aluminium Block Sample

Temperature measurement has many applications in medical devices. In recent days, body temperature become the main screening procedure to justify people infected by SARS-CoV-2. Related to pandemic situation due to SARS-Cov-2, Polymerase Chain Reaction (PCR) method become the most accurate and reliable detection method. This method employs a device named PCR machine or Thermal Cycler. In this research, we focus to build a Thermal Cycler using a low-cost material such as aluminium and using a liquid coolant as the cooling system. We use 2 types of coolant solution: mineral water and generic liquid coolant. Peltier device in thermal cycler serves as heating and cooling element. In heating rate experiments, generic liquid coolant shows a better result than using mineral water due to specific heat capacity and thermal conductivity of water. In the cooling rate experiments, the water pump is activated to stream the liquid solution, the flow rate of liquid solution is influenced by viscosity of the liquid. Generic liquid coolant has approx. 4,5 times greater viscosity than water. The higher flow rate means better performance for cooling rate. Using 2 pieces of 60-Watt heaters and a 60-Watt chiller and aluminium material as block sample, our research shows a heating and cooling rate up to approx. 0,1°C/s. Compared to commercially thermal cycler, our thermal cycler has a lower wattage; this lower wattage performance has been tradeoff with lower ramping rate. Some factors are suspected become the source of contributors of lower ramping rate.

Smart Bioreso rbable Polymers for Pharmaceuticals and Medical Devices

Smart bioresorbable polymers play a crucial role in pharmaceutical drug delivery and medical device applications. Among several bioresorbable polymers, poly lactic-co-glycolic acid and poly lactic acid are two common synthetic polymers used for various applications. Owing to their stimuli-sensitive behavior, they are called ‘smart polymers.’ Numerous commercial applications have demonstrated the effective use of bioresorbable polymer-based drug delivery systems for the treatment and diagnosis of several diseases and disorders. This review provides an overview of bioresorbable polymers as well as the associated commercial technologies and applications in the United States Food and Drug Administration-approved products and in drug delivery and medical devices.

Fabrication of Titanium Coatings for Medical Device Applications

Titanium is widely used for medical purposes. It related to bone repair because of its favorable mechanical properties and biocompatible ability to osseointegrate in host bone tissue. A good and lasting connection of the implant with the bone tissue is possible when there are sufficient conditions for the bone to grow into the pores of the material, therefore the use of a porous titanium coating may be helpful in solving this problem. In this paper, shrouded plasma spray is used to produce low oxide containing titanium coatings and lower the cost as titanium is a very reactive metal at high temperatures. A solid conical shroud was designed for plasma spray. The titanium coatings were assessed by scanning electron microscopy and energy dispersive X-ray spectroscopy. An analysis in microstructure had been carried out. The results showed that the shroud attachment played an important role in protecting the titanium particles in flight during the process of plasma spraying. An enhanced microstructure with moderate porosity in the titanium coatings plasma sprayed with the shroud was observed. The reduction in air entrainment with the shroud resulted in a good heating of the particles. The plasma-sprayed titanium coating was mainly composed of α-Ti with a low quantity of TiO.

Faces of Pain in Dementia: Learnings From a Real-World Study Using a Technology-Enabled Pain Assessment Tool.

Pain is common in people living with dementia (PLWD), including those with limited verbal skills. Facial expressions are key behavioral indicators of the pain experience in this group. However, there is a lack of real-world studies to report the prevalence and associations of pain-relevant facial micro-expressions in PLWD. In this observational retrospective study, pain-related facial features were studied in a sample of 3,144 PLWD [mean age 83.3 years (SD = 9.0); 59.0% female] using the Face domain of PainChek®, a point-of-care medical device application. Pain assessments were completed by 389 users from two national dementia-specific care programs and 34 Australian aged care homes. Our analysis focused on the frequency, distribution, and associations of facial action units [AU(s)] with respect to various pain intensity groups. A total of 22,194 pain assessments were completed. Of the AUs present, AU7 (eyelid tightening) was the most frequent facial expression (48.6%) detected, followed by AU43 (closing eyes; 42.9%) and AU6 (cheek raising; 42.1%) during severe pain. AU20 (horizontal mouth stretch) was the most predictive facial action of higher pain scores. Eye-related AUs (AU6, AU7, AU43) and brow-related AUs (AU4) were more common than mouth-related AUs (e.g., AU20, AU25) during higher pain intensities. No significant effect was found for age or gender. These findings offer further understanding of facial expressions during clinical pain in PLWD and confirm the usefulness of artificial intelligence (AI)-enabled real-time analysis of the face as part of the assessment of pain in aged care clinical practice.

Slippery Liquid-Like Solid Surfaces with Promising Antibiofilm Performance under Both Static and Flow Conditions.

Biofilms are central to some of the most urgent global challenges across diverse fields of application, from medicine to industries to the environment, and exert considerable economic and social impact. A fundamental assumption in anti-biofilms has been that the coating on a substrate surface is solid. The invention of slippery liquid-infused porous surfaces—a continuously wet lubricating coating retained on a solid surface by capillary forces—has led to this being challenged. However, in situations where flow occurs, shear stress may deplete the lubricant and affect the anti-biofilm performance. Here, we report on the use of slippery omniphobic covalently attached liquid (SOCAL) surfaces, which provide a surface coating with short (ca. 4 nm) non-cross-linked polydimethylsiloxane (PDMS) chains retaining liquid–surface properties, as an antibiofilm strategy stable under shear stress from flow. This surface reduced biofilm formation of the key biofilm-forming pathogens Staphylococcus epidermidis and Pseudomonas aeruginosa by three–four orders of magnitude compared to the widely used medical implant material PDMS after 7 days under static and dynamic culture conditions. Throughout the entire dynamic culture period of P. aeruginosa, SOCAL significantly outperformed a typical antibiofilm slippery surface [i.e., swollen PDMS in silicone oil (S-PDMS)]. We have revealed that significant oil loss occurred after 2–7 day flow for S-PDMS, which correlated to increased contact angle hysteresis (CAH), indicating a degradation of the slippery surface properties, and biofilm formation, while SOCAL has stable CAH and sustainable antibiofilm performance after 7 day flow. The significance of this correlation is to provide a useful easy-to-measure physical parameter as an indicator for long-term antibiofilm performance. This biofilm-resistant liquid-like solid surface offers a new antibiofilm strategy for applications in medical devices and other areas where biofilm development is problematic.

Plasma‐deposited AgOx‐doped TiOx coatings enable rapid antibacterial activity based on ROS generation

AbstractTo enable a rapid‐acting antibacterial mechanism without the release of biocidal substances, TiO2 catalysts have been considered based on the generation of reactive oxygen species (ROS). Doping with dissimilar metals generates electron‐hole pairs with narrow band gaps promoting the production of ROS. Here, plasma technology is investigated to deposit Ag nano islets on defective TiOx films, stabilized by plasma postoxidation suppressing Ag ion release. Importantly, ROS generation is maintained upon storage in the dark yet with diminishing efficacy; however, it can be restored by exposure to visible light. The rapid‐acting antibacterial properties are found to strongly correlate with ROS generation, which can even be maintained by functionalization with hydrophobic plasma polymer films. The cytocompatible coatings offer promising applications for implants and other medical devices.

Design Optimization of Perfluorinated Liquid‐Infused Surfaces for Blood‐Contacting Applications

AbstractTethered‐liquid perfluorocarbon (TLP) coatings show promise for blood‐contacting medical device applications to reduce blood adhesion and delay thrombosis. However, their fabrication and longevity under external fluid flow is not well characterized. A vapor phase silanization reaction leading to the formation of tethered‐perfluorocarbon (TP) layers containing large bumpy aggregates, 300 ± 200 nm thick, on top of an underlying 35 ± 15 nm thick uniform coating is reported. The vapor phase method compares favorably to the well‐established liquid phase deposition to reproducibly create slippery coatings on silicon and polystyrene with very low water sliding angles (2° ± 1°), without the need to control humidity conditions. The TP layer retains perfluorinated lubricants up to 20 000 s–1, using a cone‐and‐plate rheometer, with the higher viscosity lubricant perfluoroperhydrophenanthrene being more resistant to depletion than perfluorodecalin. TLP infused with either of the lubricants effectively reduces adhesion of fibrin from human whole blood relative to TP and control hydrophilic and hydrophobic surfaces. The combination of highly fluorinated TP coatings grafted from the vapor phase to create nanoscale structured surfaces infused with higher viscosity lubricant may be the most suitable combination for clinical applications of liquid‐infused surfaces to reduce thrombosis in blood‐contacting medical devices under flow.