Laser-assisted surface alloying of titanium with silver to enhance antibacterial and bone-cell mineralization properties of orthopedic implants.

Orthopedic device-related infection (ODRI) poses a significant threat to patients with titanium-based implants. The challenge lies in developing antibacterial surfaces that preserve the bulk mechanical properties of titanium implants while exhibiting characteristics similar to bone tissue. In response, we present a two-step approach: silver nanoparticle (AgNP) coating followed by selective laser-assisted surface alloying on commonly used titanium alumina vanadium (TiAl6V4) implant surfaces. This process imparts antibacterial properties without compromising the bulk mechanical characteristics of the titanium alloy. Systematic optimization of laser beam power (8-40 W) resulted in an optimized surface (32 W) with uniform TiAg alloy formation. This surface displayed a distinctive hierarchical mesoporous textured surface, featuring cauliflower-like nanostructures measuring between 5-10 nm uniformly covering spatial line periods of 25 µm while demonstrating homogenous elemental distribution of silver throughout the laser processed surface. The optimized laser processed surface exhibited prolonged superhydrophilicity (40 days) and antibacterial efficacy (12 days) against Staphylococcus aureus and Escherichia coli. Additionally, there was a significant twofold increase in bone mineralization compared to the pristine Ti6Al4V surface (p < 0.05). Rockwell hardness tests confirmed minimal (<1%) change in bulk mechanical properties compared to the pristine surface. This innovative laser-assisted approach, with its precisely tailored surface morphology, holds promise for providing enduring antibacterial and osteointegration properties, rendering it an optimal choice for modifying load-bearing implant devices without altering material bulk characteristics.

Sticker-Type Remote Monitoring System for Early Risk Detection of Catheter Associated Urinary Tract Infections.

A substantial number of critically ill patients in intensive care units (ICUs) rely on indwelling urinary catheters (IDCs), demanding regular monitoring of urine bags. This process increases the workload for healthcare providers and elevates the risk of exposure to contagious diseases. Moreover, IDCs are a primary cause of catheter-associated urinary tract infections (UTIs) in ICU patients whose delayed detection can have life-threatening complications. To address this, we have developed a Sticker Type Antenna for Remote Sensing (STARS) system capable of measuring urine flow rate and conductivity as early-risk markers for UTIs, alongside tracking patients' urine bag status to facilitate medical automation for healthcare providers. STARS comprises a simple, low-cost, disposable antenna module for contactless measurements of urine volume and conductivity, and a reusable wireless module for real-time data transmission. Systematic studies on STARS revealed its stable performance within physiologically relevant ranges of urine volume (0 to 2000 ml) and conductivity (5 to 40 mS/cm) in urine bags. As a proof-of-concept, STARS was tested in artificially created healthy and infected urine specimens to validate its non-contact sensing performance in detecting the onset of UTIs in catheterized patients within a hospital-like environment. STARS represents the first application of a real-time, contactless, wireless monitoring platform for simultaneous urine bag management and early risk detection of UTIs.

Smart capsule for monitoring inflammation profile throughout the gastrointestinal tract.

Inflammatory bowel disease (IBD) has become alarmingly prevalent in the last two decades affecting 6.8 million people worldwide with a starkly high relapse rate of 40% within 1 year of remission. Existing visual endoscopy techniques rely on subjective assessment of images that are error-prone and insufficient indicators of early-stage IBD, rendering them unsuitable for frequent and quantitative monitoring of gastrointestinal health necessary for detecting regular relapses in IBD patients. To address these limitations, we have implemented a miniaturized smart capsule (2.2 cm × 11 mm) that allows monitoring reactive oxygen species (ROS) levels as a biomarker of inflammation for quantitative and frequent profiling of inflammatory lesions throughout the gastrointestinal tract. The capsule is composed of a pH and oxidation reduction potential (ORP) sensor to track the capsule's location and ROS levels throughout the gastrointestinal tract, respectively, and an optimized electronic interface for wireless sensing and data communication. The designed sensors provided a linear and stable performance within the physiologically relevant range of the GI tract (pH: 1-8 and ORP: -500 to +500 mV). Additionally, systematic design optimization of the wireless interface electronics offered an efficient sampling rate of 10 ms for long-running measurements up to 48 h for a complete evaluation of the entire gastrointestinal tract. As a proof-of-concept, the capsule the capsule's performance in detecting inflammation risks was validated by conducting tests on in vitro cell culture conditions, simulating healthy and inflamed gut-like environments. The capsule presented here achieves a new milestone in addressing the emerging need for smart ingestible electronics for better diagnosis and treatment of digestive diseases.

Ozone as a Topical Treatment for Infected Dermal Wounds.

Dermal wound infections are a rising source of morbidity and mortality in patients worldwide as new and worsening complications reduce the efficacy of traditional treatments. These challenges in wound care are increasingly caused by comorbidities such as obesity and diabetes as well as surging rates of antibiotic resistance. As a result, there is an urgent need for alternative treatment options. Gaseous ozone has shown great promise as a potential new treatment for infected dermal wounds. In this brief review of current wound therapy techniques found in the literature, an in-depth discussion of the mechanisms, benefits, and results of topical ozone gas as a therapy for infected dermal wounds is presented. This includes studies of ozone applied to wounds performed in vitro, in vivo, and clinical settings, as well as the use of ozone as an adjunct therapy for increasing the efficacy of traditional treatments. The overwhelming evidence suggests that ozone exhibits significant antimicrobial properties and has been shown to promote wound healing factors, especially when applied between 5-60 ppm. As such, this promising alternative therapy warrants a significant investment of time and resources to fully utilize ozone as an effective treatment against antibiotic resistant bacteria and other rising challenges in wound treatment.

Biocompatibility and Safety Assessment of Combined Topical Ozone and Antibiotics for Treatment of Infected Wounds.

Wound infections with antibiotic-resistant bacteria, particularly the Gram-negative strains, pose a substantial health risk for patients with limited treatment options. Recently topical administration of gaseous ozone and its combination with antibiotics through portable systems has been demonstrated to be a promising approach to eradicate commonly found Gram-negative strains of bacteria in wound infections. However, despite the significant impact of ozone in treating the growing number of antibiotic-resistant infections, uncontrolled and high concentrations of ozone can cause damage to the surrounding tissue. Hence, before such treatments could advance into clinical usage, it is paramount to identify appropriate levels of topical ozone that are effective in treating bacterial infections and safe for use in topical administration. To address this concern, we have conducted a series of in vivo studies to evaluate the efficacy and safety of a portable and wearable adjunct ozone and antibiotic wound therapy system. The concurrent ozone and antibiotics are applied through a wound interfaced gas permeable dressing coated with water-soluble nanofibers containing vancomycin and linezolid (traditionally used to treat Gram-positive infections) and connected to a portable ozone delivery system. The bactericidal properties of the combination therapy were evaluated on an ex vivo wound model infected with Pseudomonas aeruginosa, a common Gram-negative strain of bacteria found in many skin infections with high resistance to a wide range of currently available antibiotics. The results indicated that the optimized combination delivery of ozone (4 mg h-1) and topical antibiotic (200 µg cm-2) provided complete bacteria eradication after 6 h of treatment while having minimum cytotoxicity to human fibroblast cells. Furthermore, in vivo local and systemic toxicity studies (e.g., skin monitoring, skin histopathology, and blood analysis) on pig models showed no signs of adverse effects of ozone and antibiotic combination therapy even after 5 days of continuous administration. The confirmed efficacy and biosafety profile of the adjunct ozone and antibiotic therapy places it as a strong candidate for treating wound infection with antimicrobial-resistant bacteria and further pursuing human clinical trials.

Cold Atmospheric Plasma-Assisted Direct Deposition of Polypyrrole-Ag Nanocomposites for Flexible Electronic Sensors.

Conductive polymers and their composite materials have attracted considerable interest due to their potential applications in sensors, actuators, drug delivery systems, and energy storage devices. Despite their wide range of applications, many challenges remain primarily with respect to the complex synthesis and time-consuming manufacturing steps that are often required in the fabrication process of various devices with conductive polymers. Here, we demonstrate the novel use of cold atmospheric plasma (CAP)-assisted deposition technologies as a solvent-free and scalable approach for in situ polymerization and direct deposition of conductive polypyrrole-silver (PPy-Ag) nanocomposites onto the desired substrates under atmospheric conditions. In this study, a systematic approach with different precursor composition mixtures containing pyrrole as the monomer and AgNO3 as the photoinitiator was investigated to assess the effect of precursor composition on the final chemical, electrical, and mechanical properties of the PPy-Ag nanocomposite thin-film coatings which were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and cyclic bending tests. The characterizations indicated the possibility of fabricating PPy-Ag nanocomposite films with tunable degrees of polymerization and Ag nanoparticle loading by simply varying the percentage of AgNO3 in precursor composition mixtures. Finally, as a proof of concept, the potential use of the PPy-Ag nanocomposite films with different Ag nanoparticle loading percentages was assessed for humidity sensing by measuring their level of change in electrical resistance in the relative humidity range of 12-60%. It is envisioned that the developed CAP-assisted deposition technology can provide a new stepping stone toward scalable additive manufacturing of various functional nanocomposite films for different low-cost and flexible electronic applications.

Organ-on-a-Chip Platform with an Integrated Screen-Printed Electrode Array for Real-Time Monitoring Trans-Epithelial Barrier and Bubble Formation.

Cellular tight junctions play a key role in establishing a barrier between different compartments of the body by regulating the selective passage of different solutes across epithelial and endothelial tissues. Over the past decade, significant efforts have been conducted to develop more clinically relevant "organ-on-a-chip" models with integrated trans-epithelial electrical resistance (TEER) monitoring systems to help better understand the fundamental underpinnings of epithelial tissue physiology upon exposure to different substances. However, most of these platforms require the use of high-cost and time-consuming photolithography processes, which limits their scalability and practical implementation in clinical research. To address this need, we have developed a low-cost microfluidic platform with an integrated electrode array that allows continuous real-time monitoring of TEER and the risk of bubble formation in the microfluidic system by using scalable manufacturing technologies such as screen printing and laser processing. The integrated printed electrode array exhibited excellent stability (with less than ∼0.02 Ω change in resistance) even after long-term exposure to a complex culture medium. As a proof of concept, the fully integrated platform was tested with HMT3522 S1 epithelial cells to evaluate the tight barrier junction formation through TEER measurement and validated with standard immunostaining procedures for Zonula occludens-1 protein. This platform could be regarded as a stepping stone for the fabrication of disposable and low-cost organ and tissue-on-a-chip models with integrated sensors to facilitate studying the dynamic response of epithelial tissues to different substances in more physiologically relevant conditions.

Printed graphene-based electrochemical sensor with integrated paper microfluidics for rapid lidocaine detection in blood.

Topical lidocaine patches are commonly used to relieve pain and suffering in various clinical and household settings. Despite its extensive use, excessive skin absorption during numbing or pain reduction procedures can cause systemic toxicity, which can lead to life-threatening conditions. Rapid and reliable monitoring of escalating levels of lidocaine in the blood could help management/prevention of lidocaine overdose and its associated complications. To address this need, here we have developed a disposable point-of-care (POC) diagnostic platform composed of an integrated graphene-based electrochemical sensor with paper-based microfluidics for rapid detection of lidocaine levels in serum and blood samples. The fabrication process takes advantage of advanced, scalable manufacturing techniques, including printing, laser processing, and nondestructive near infrared (NIR) drying. The sensitivity tests of the platform revealed a sensitivity of ∼0.2 µA µM-1 towards lidocaine concentrations in the clinically relevant range (1-100 µM) in both complex matrix fluids of serum and blood with high cross specificity in the presence of the interfering analytes. This proof-of-concept platform could be regarded as the first step toward the development of low-cost and translational POC devices that could help in better pain management and reduce potential side effects or misuse of analgesics.

Wearable adjunct ozone and antibiotic therapy system for treatment of Gram-negative dermal bacterial infection.

The problematic combination of a rising prevalence of skin and soft tissue infections and the growing rate of life-threatening antibiotic resistant infections presents an urgent, unmet need for the healthcare industry. These evolutionary resistances originate from mutations in the bacterial cell walls which prevent effective diffusion of antibiotics. Gram-negative bacteria are of special consideration due to the natural resistance to many common antibiotics due to the unique bilayer structure of the cell wall. The system developed here provides one solution to this problem through a wearable therapy that delivers and utilizes gaseous ozone as an adjunct therapy with topical antibiotics through a novel dressing with drug-eluting nanofibers (NFs). This technology drastically increases the sensitivity of Gram-negative bacteria to common antibiotics by using oxidative ozone to bypass resistances created by the bacterial cell wall. To enable simple and effective application of adjunct therapy, ozone delivery and topical antibiotics have been integrated into a single application patch. The drug delivery NFs are generated via electrospinning in a fast-dissolve PVA mat without inducing decreasing gas permeability of the dressing. A systematic study found ozone generation at 4 mg/h provided optimal ozone levels for high antimicrobial performance with minimal cytotoxicity. This ozone treatment was used with adjunct therapy delivered by the system in vitro. Results showed complete eradication of Gram-negative bacteria with ozone and antibiotics typically used only for Gram-positive bacteria, which showed the strength of ozone as an enabling adjunct treatment option to sensitize bacteria strains to otherwise ineffective antibiotics. Furthermore, the treatment is shown through biocompatibility testing to exhibit no cytotoxic effect on human fibroblast cells.

Electrochemical sensor for rapid detection of fentanyl using laser-induced porous carbon-electrodes.

The growing pervasiveness of opioid-based drugs such as fentanyl and its analogs represent a foremost hazard to the civilian population and burden on the first responders and clinicians. Thus, to enable a rapid and low-cost surveillance system to detect fentanyl in a non-ideal environment, we demonstrate the use of laser-induced nano-porous carbon structures directly onto commercially available polyimide sheets for rapid and cost-effective manufacturing of electrochemical sensors for fentanyl detection. The porous carbon surface instigated by various laser energy densities was analyzed towards morphological, vibrational, and fentanyl sensing properties. The results showed that laser carbonized electrode (LCE) prepared with 31 J/cm2 laser energy densities showed the highest level of porosity, surface roughness, and thereby enhanced sensitivity towards fentanyl detection by square-wave voltammetry (SWV) with a 1 µM limit of detection. This new disposable sensor strip offers an information-rich electrochemical fingerprint of fentanyl oxidation at + 0.526 V (vs Ag/AgCl) on the surface of laser carbonized electrodes with high linear (R2 = 0.99) sensitivity (0.025 µA⋅µM-1⋅cm-2) and reproducibility (RSD = 5%), within the clinically relevant working range of 20-200 µM with similar performance in both PBS and serum samples. The laser carbonized electrode surface was further found to be selective towards fentanyl concentrations in the presence of various cutting agents. This technology could provide a new route towards scalable manufacturing of cost-effective sensors for rapid detection of opioid misuse and potentially save the lives from systemic side effects.