Muscle dysfunction and muscle atrophy are common complications resulting from Chronic Obstructive Pulmonary Disease (COPD). The evaluation of the peripheral muscles can be carried out through the assessment of their structural components from ultrasound images or their functional components through isometric and isotonic strength tests. This evaluation, performed mainly on the quadriceps muscle, is not only of great interest for diagnosis, prognosis and monitoring of COPD, but also for the evaluation of the benefits of therapeutic interventions. In this work, bioimpedance spectroscopy technology is proposed as a low-cost and easy-to-use alternative for the evaluation of peripheral muscles, becoming a feasible alternative to ultrasound images and strength tests for their application in routine clinical practice. For this purpose, a laboratory prototype of a bioimpedance device has been adapted to perform segmental measurements in the quadriceps region. The validation results obtained in a pseudo-randomized study in patients with COPD in a controlled clinical environment which involved 33 volunteers confirm the correlation and correspondence of the bioimpedance parameters with respect to the structural and functional parameters of the quadriceps muscle, making it possible to propose a set of prediction equations. The main contribution of this manuscript is the discovery of a linear relationship between quadriceps muscle properties and the bioimpedance Cole model parameters, reaching a correlation of 0.69 and an average error of less than 0.2 cm regarding the thickness of the quadriceps estimations from ultrasound images, and a correlation of 0.77 and an average error of 3.9 kg regarding the isometric strength of the quadriceps muscle.

This article describes the development of a system forin vivomeasurements of lead body burden in mice using109Cd K x-ray fluorescence (XRF). This K XRF system could facilitate early-stage studies on interventions that ameliorate or reverse organ tissue damage from lead poisoning by reducing animal numbers through a cross-sectional study approach. A novel mouse phantom was developed based on a mouse atlas and 3D-printed using PLA plastic with plaster of Paris \'bone\' inserts. PLA plastic was found to be a good surrogate for soft tissue in XRF measurements and the phantoms were found to be good models of mice. As expected, lead detection limits varied with mouse size, mouse orientation, and mouse position with respect to the source and detector. The work suggests that detection limits of 10 to 20μg Pb per g bone mineral may be possible for a 2 to 3 hour XRF measurement in a single animal, an adequate limit for some pre-clinical studies. The109Cd K XRF mouse measurement system was also modeled using the Monte Carlo code MCNP. The combination of experiment and modeling found that contrary to expectation, accurate measurements of lead levels in mice required calibration using mouse-specific calibration standards due to the coherent scatter peak normalization failing when small animals are measured. MCNP modeling determined that this was because the coherent scatter signal from soft tissue, which until now has been assumed negligible, becomes significant when compared to the coherent scatter signal in bone in small animals. This may have implications for some human measurements. This work suggests that109Cd K x-ray fluorescence measurements of lead body burden are precise enough to make the system feasible for small animals if appropriately calibrated. Further work to validate the technology\'s measurement accuracy and performancein vivowill be required.

Substrates or encapsulants in soft and stretchable formats are key components for transient, bioresorbable electronic systems; however, elastomeric polymers with desired mechanical and biochemical properties are very limited compared to non-transient counterparts. Here, we introduce a bioresorbable elastomer, poly(glycolide-co-ε-caprolactone) (PGCL), that contains excellent material properties including high elongation-at-break (< 1300%), resilience and toughness, and tunable dissolution behaviors. Exploitation of PGCLs as polymer matrices, in combination with conducing polymers, yields stretchable, conductive composites for degradable interconnects, sensors, and actuators, which can reliably function under external strains. Integration of device components with wireless modules demonstrates elastic, transient electronic suture system with on-demand drug delivery for rapid recovery of post-surgical wounds in soft, time-dynamic tissues.

A stent implantation is a standard medical procedure for treating coronary artery diseases. Over the years, various different designs have been explored for the stents which come with a range of limitations, including late in-stent restenosis (due to low radial strength), foreshortening, radial recoil, etc. Contrary, stents with auxetic design, characterized by a negative Poisson\'s ratio, display unique deformation characteristics that result in enhanced mechanical properties in terms of its radial strength, radial recoil, foreshortening, and more. In this study, we have analysed a novel double arrowhead (DA) auxetic stent that aims to overcome the limitations associated with traditional stents, specifically in terms of radial strength, foreshortening, and radial recoil. The parametric analysis was done initially on the DA\'s unit ring structure to optimize the design by evaluating the effect of three design parameters (angle, amplitude, and width) on the mechanical characteristics (radial strength and radial recoil) using finite element analysis. The width of the strut was found to be the primary determinant of the stent structure\'s properties. Consequently, the angle and width were found to have the least effect on altering the stent\'s mechanical properties. After performing the parametric analysis, optimal design factors were selected to design the full-length DA auxetic stent. The mechanical characteristics of the DA auxetic stent were assessed and compared in a case study with the Cypher™ commercial stent. The radial strength of DA auxetic stent was found to be 7.26 N/mm, which is more than double the Cypher™ commercial stent\'s radial strength. Additionally, the proposed stent possesses reduced radial recoil property and completely eliminates the stent foreshortening issue, which shows the superior mechanical properties of the proposed auxetic stent and its potential as a promising candidate for future stent designs.

Cellular response to mechanical stimuli is a crucial factor for maintaining cell homeostasis. The interaction between the extracellular matrix and mechanical stress plays a significant role in organizing the cytoskeleton and aligning cells. Tools that apply mechanical forces to cells and tissues, as well as those capable of measuring the mechanical properties of biological cells, have greatly contributed to our understanding of fundamental mechanobiology. These tools have been extensively employed to unveil the substantial influence of mechanical cues on the development and progression of various diseases. In this report, we present an economical and high-performance uniaxial cell stretching device. This paper reports the detailed operation concept of the device, experimental design, and characterization. The device was tested with MDA-MB-231 breast cancer cells. The experimental results agree well with previously documented morphological changes resulting from stretching forces on cancer cells. Remarkably, our new device demonstrates comparable cellular changes within 30 min compared with the previous 2 h stretching duration. This third-generation device significantly improved the stretching capabilities compared with its previous counterparts, resulting in a remarkable reduction in stretching time and a substantial increase in overall efficiency. Moreover, the device design incorporates an open-source software interface, facilitating convenient parameter adjustments such as strain, stretching speed, frequency, and duration. Its versatility enables seamless integration with various optical microscopes, thereby yielding novel insights into the realm of mechanobiology.

New therapeutic strategies and paradigms are direly needed to treat pancreatic cancer. The absence of a suitable pre-clinical animal model of pancreatic cancer is a major limitation to biomedical device and therapeutic development. Traditionally, pigs have proven to be ideal models, especially in the context of designing human-sized instruments, perfecting surgical techniques and optimizing clinical procedures for use in humans. However, pig studies have typically focused on healthy tissue assessments and are limited to general safety evaluations because of the inability to effectively model human tumors.
Here, we establish an orthotopic porcine model of human pancreatic cancer using RAG2/IL2RG double-knockout immunocompromised pigs and treat the tumors ex vivo and in vivo with histotripsy.
Using these animals, we describe the successful engraftment of Panc-1 human pancreatic cancer cell line tumors and characterize their development. To illustrate the utility of these animals for therapeutic development, we determine for the first time, the successful targeting of in situ pancreatic tumors using histotripsy. Treatment with histotripsy resulted in partial ablation in vivo and reduction in collagen content in both in vivo tumor in pig pancreas and ex vivo patient tumor.
This study presents a first step toward establishing histotripsy as a non-invasive treatment method for pancreatic cancer and exposes some of the challenges of ultrasound guidance for histotripsy ablation in the pancreas. Simultaneously, we introduce a highly robust model of pancreatic cancer in a large mammal model that could be used to evaluate a variety biomedical devices and therapeutic strategies.

Hydrogels based on natural polysaccharides can have unique properties and be tailored for several applications, which may be mainly limited by the fragile structure and weak mechanical properties of this type of system. We successfully prepared cryogels made of newly synthesized kefiran exopolysaccharide-chondroitin sulfate (CS) conjugate via carbodiimide-mediated coupling to overcome these drawbacks. The freeze-thawing procedure of cryogel preparation followed by lyophilization is a promising route to fabricate polymer-based scaffolds with countless and valuable biomedical applications. The novel graft macromolecular compound (kefiran-CS conjugate) was characterized through 1H-NMR and FTIR spectroscopy-which confirmed the structure of the conjugate, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)-which mirrored good thermal stability (degradation temperature of about 215 °C) and, finally, gel permeation chromatography-size exclusion chromatography (GPC-SEC)-which proved an increased molecular weight due to chemical coupling of kefiran with CS. At the same time, the corresponding cryogels physically crosslinked after the freeze-thawing procedure were investigated by scanning electron microscopy (SEM), Micro-CT, and dynamic rheology. The results revealed a prevalent contribution of elastic/storage component to the viscoelastic behavior of cryogels in swollen state, a micromorphology with micrometer-sized open pores fully interconnected, and high porosity (ca. 90%) observed for freeze-dried cryogels. Furthermore, the metabolic activity and proliferation of human adipose stem cells (hASCs), when cultured onto the developed kefiran-CS cryogel, was maintained at a satisfactory level over 72 h. Based on the results obtained, it can be inferred that the newly freeze-dried kefiran-CS cryogels possess a host of unique properties that render them highly suitable for use in tissue engineering, regenerative medicine, drug delivery, and other biomedical applications where robust mechanical properties and biocompatibility are crucial.

Subchondroplasty is a new minimally invasive surgical technique developed to treat bone marrow lesions (BML) and early osteoarthritis (OA). During the procedure, engineered calcium phosphate compound (CPC) is injected. It is claimed by the manufacturer that during the healing process, the CPC is replaced with new bone. The purpose of this study was to verify the replacement of CPC with new bone after subchondroplasty for the first time in humans. A 76-year old woman was referred for resistant medial knee pain. Standing radiographs showed varus knee OA and magnetic resonance imaging (MRI) revealed BML. She was treated with subchondroplasty of medial femoral condyle. Excellent relief of pain was achieved after procedure. Afterwards, the pain worsened, the radiographs confirmed the OA progression and the patient was treated with a total knee arthroplasty (TKA) 4 years after primary procedure. The resected bone was examined histologically and with micro-computed tomography (CT). Histologically, bone trabeculae of subcortical bone were embedded in the amorphous mass. However, no signs of CPC resorption and/or bone replacement have been found with micro-CT. In short term, excellent pain relief could be expected after the subchondroplasty procedure. However, there was no replacement of CPC with bone and the technique probably did not influence the natural process of knee OA.

The mechanisms of deep-hole microdrilling of pure Mg material were experimentally studied in order to find a suitable setup for a novel intraocular drug delivery device prototyping. Microdrilling tests were performed with 0.20 mm and 0.35 mm microdrills, using a full factorial design in which cutting speed vc and feed fz were varied over two levels. In a preliminary phase, the chip shape was evaluated for low feeds per tooth down to 1 μm, to verify that the chosen parameters were appropriate for machining. Subsequently, microdrilling experiments were carried out, in which diameter, burr height and surface roughness of the drilled holes were examined. The results showed that the burr height is not uniform along the circumference of the holes. In particular, the maximum burr height increases with higher cutting speed, due to the thermal effect that plasticizes Mg. Hole entrance diameters are larger than the nominal tool diameters due to tool runout, and their values are higher for high vc and fz. In addition, the roughness of the inner surface of the holes increases as fz increases.

This paper presents the design, development, and testing of an IoT-enabled smart stick for visually impaired people to navigate the outside environment with the ability to detect and warn about obstacles. The proposed design employs ultrasonic sensors for obstacle detection, a water sensor for sensing the puddles and wet surfaces in the user\'s path, and a high-definition video camera integrated with object recognition. Furthermore, the user is signaled about various hindrances and objects using voice feedback through earphones after accurately detecting and identifying objects. The proposed smart stick has two modes; one uses ultrasonic sensors for detection and feedback through vibration motors to inform about the direction of the obstacle, and the second mode is the detection and recognition of obstacles and providing voice feedback. The proposed system allows for switching between the two modes depending on the environment and personal preference. Moreover, the latitude/longitude values of the user are captured and uploaded to the IoT platform for effective tracking via global positioning system (GPS)/global system for mobile communication (GSM) modules, which enable the live location of the user/stick to be monitored on the IoT dashboard. A panic button is also provided for emergency assistance by generating a request signal in the form of an SMS containing a Google maps link generated with latitude and longitude coordinates and sent through an IoT-enabled environment. The smart stick has been designed to be lightweight, waterproof, size adjustable, and has long battery life. The overall design ensures energy efficiency, portability, stability, ease of access, and robust features.