Modeling Self-Rollable Elastomeric Films for Building Bioinspired Hierarchical 3D Structures.

In this work, an innovative model is proposed as a design tool to predict both the inner and outer radii in rolled structures based on polydimethylsiloxane bilayers. The model represents an improvement of Timoshenko's formula taking into account the friction arising from contacts between layers arising from rolling by more than one turn, hence broadening its application field towards materials based on elastomeric bilayers capable of large deformations. The fabricated structures were also provided with surface topographical features that would make them potentially usable in different application scenarios, including cell/tissue engineering ones. The bilayer design parameters were varied, such as the initial strain (from 20 to 60%) and the bilayer thickness (from 373 to 93 µm). The model matched experimental data on the inner and outer radii nicely, especially when a high friction condition was implemented in the model, particularly reducing the error below 2% for the outer diameter while varying the strain. The model outperformed the current literature, where self-penetration is not excluded, and a single value of the radius of spontaneous rolling is used to describe multiple rolls. A complex 3D bioinspired hierarchical elastomeric microstructure made of seven spirals arranged like a hexagon inscribed in a circumference, similar to typical biological architectures (e.g., myofibrils within a sarcolemma), was also developed. In this case also, the model effectively predicted the spirals' features (error smaller than 18%), opening interesting application scenarios in the modeling and fabrication of bioinspired materials.

Erythro-Magneto-HA-Virosome: A Bio-Inspired Drug Delivery System for Active Targeting of Drugs in the Lungs.

Over the past few decades, finding more efficient and selective administration routes has gained significant attention due to its crucial role in the bioavailability, absorption rate and pharmacokinetics of therapeutic substances. The pulmonary delivery of drugs has become an attractive target of scientific and biomedical interest in the health care research area, as the lung, thanks to its high permeability and large absorptive surface area and good blood supply, is capable of absorbing pharmaceuticals either for local deposition or for systemic delivery. Nevertheless, the pulmonary drug delivery is relatively complex, and strategies to mitigate the effects of mechanical, chemical and immunological barriers are required. Herein, engineered erythrocytes, the Erythro-Magneto-Hemagglutinin (HA)-virosomes (EMHVs), are used as a novel strategy for efficiently delivering drugs to the lungs. EMHV bio-based carriers exploit the physical properties of magnetic nanoparticles to achieve effective targeting after their intravenous injection thanks to an external magnetic field. In addition, the presence of hemagglutinin fusion proteins on EMHVs' membrane allows the DDS to anchor and fuse with the target tissue and locally release the therapeutic compound. Our results on the biomechanical and biophysical properties of EMHVs, such as the membrane robustness and deformability and the high magnetic susceptibility, as well as their in vivo biodistribution, highlight that this bio-inspired DDS is a promising platform for the controlled and lung-targeting delivery of drugs, and represents a valuable alternative to inhalation therapy to fulfill unmet clinical needs.

Thermal Analysis of Paraffin-Embedded Tissue Blocks for Anatomic Pathology Processes.

We analyze temperature dynamics in anatomic pathology samples to identify the most efficient refrigeration method and to predict the time available for optimal sectioning before sample heating, thus getting appropriate information for a correct diagnosis by anatomopathologists. A thermal finite element (FE) analysis was carried out with comsolmultiphysics to evaluate temperature variations in paraffin-embedded tissues, i.e., muscle, bone and fat, and the corresponding thermal stresses. Experiments with different tissues and thermocouple-based measurements allowed validating the FE simulations. Simulations allowed to estimate the time needed to bring the sample at the optimal temperature for sectioning (-8 to -4 °C) in different conditions: refrigeration on a cold plate, refrigeration in a cooled environment, and refrigeration in an environment with forced convection. Among the three cooling methods tested, the forced convection at -20 °C and with an air-flow speed of 5 m/s resulted in the shortest cooling time. As compared to the other methods, thermal stresses can be modulated by varying the air-flow speed. For the different conditions, the time needed for the surface of the tissue block to exit from a temperature corresponding to an optimal cutting, when leaving the sample exposed to room temperature after refrigeration, ranged from 12 to 310 s. We quantify the time needed to adequately refrigerate paraffin-embedded tissue samples and the time available before they leave the optimal temperature window for sectioning. We also evaluate the maximum stress attained in the paraffin block during the cooling and the heating transients. This information will help optimize anatomic pathology processes.

Comparative analysis of occlusion methods for artificial sphincters.

An artificial sphincter is a device that replaces the function of the biological sphincter by occluding the relative biological lumen. The investigation of occlusion methods for artificial sphincters is crucial for a reliable and effective design of such devices. The compression induced onto the tissue by a certain pressure depends on the biomechanical and physiological features of the lumen and on the specific occlusion method. A numerical model and an experimental evaluation are presented here to assess the efficiency of different occlusion methods. Numerical models of circumferential occlusion and clamping occlusion methods to simulate the compression of the biological lumen were developed. Results revealed a relationship between the efficiency of the occlusion method and the physiological condition of the lumen. With differences related to the testing setup, this relationship was also confirmed experimentally by conducting tests on biological simulators. We analyzed the occlusion method to adopt as the physiological pressure (ie, leakage pressure values) changed. In particular, we focused on the urinary incontinence, which is a dysfunction involving the external sphincter surrounding the urethra. In this scenario, we demonstrated that a clamping occlusion is an efficient method to compress the urethra, whose physiological pressures range between 4 and 12 kPa. The clamping occlusion method resulted up to 35% more efficient in terms of sealing pressure than the circumferential one for a closing pressure varying between 2.3 and 11.5 kPa.

High-Resolution SPECT Imaging of Stimuli-Responsive Soft Microrobots.

Untethered small-scale robots have great potential for biomedical applications. However, critical barriers to effective translation of these miniaturized machines into clinical practice exist. High resolution tracking and imaging in vivo is one of the barriers that limit the use of micro- and nanorobots in clinical applications. Here, the inclusion of radioactive compounds in soft thermoresponsive magnetic microrobots is investigated to enable their single-photon emission computed tomography imaging. Four microrobotic platforms differing in hydrogel structure and four 99m Tc[Tc]-based radioactive compounds are investigated in order to achieve optimal contrast agent retention and optimal imaging. Single microrobot imaging of structures as low as 100 µm in diameter, as well as tracking of shape switching from tubular to planar configurations by inclusion of 99m Tc[Tc] colloid in the hydrogel structure, is reported.

Soft Hydrogel Zwitterionic Coatings Minimize Fibroblast and Macrophage Adhesion on Polyimide Substrates.

Minimizing the foreign body reaction to polyimide-based implanted devices plays a pivotal role in several biomedical applications. In this work, we propose materials exhibiting nonbiofouling properties and a Young's modulus reflecting that of soft human tissues. We describe the synthesis, characterization, and in vitro validation of poly(carboxybetaine) hydrogel coatings covalently attached to polyimide substrates via a photolabile 4-azidophenyl group, incorporated in poly(carboxybetaine) chains at two concentrations of 1.6 and 3.1 mol %. The presence of coatings was confirmed by attenuated total reflectance Fourier transform infrared spectroscopy. White light interferometry was used to evaluate the coating continuity and thickness (between 3 and 6 µm under dry conditions). Confocal laser scanning microscopy allowed us to quantify the thickness of the swollen hydrogel coatings that ranged between 13 and 32 µm. The different hydrogel formulations resulted in stiffness values ranging from 2 to 19 kPa and led to different fibroblast and macrophage responses in vitro. Both cell types showed a minimum adhesion on the softest hydrogel type. In addition, both the overall macrophage activation and cytotoxicity were observed to be negligible for all of the tested material formulations. These results are a promising starting point toward future advanced implantable systems. In particular, such technology paves the way for novel neural interfaces able to minimize the fibrotic reaction, once implanted in vivo, and to maximize their long-term stability and functionality.

Artificial Sphincters to Manage Urinary Incontinence: A Review.

Urinary incontinence affects more than 300 million people worldwide. The implantation of a medical device called an artificial urinary sphincter (AUS) is the gold standard treatment when conservative and minimally invasive therapies fail. In this article, the AUSs (extra-urethral and endo-urethral sphincters) available on the market, both presented at the research level and filed as patents, are reviewed. The ability of the different solutions to effectively replace the natural sphincter are discussed, together with advantages and some possible side effects, such as tissue atrophy, overall invasiveness of the implant, and so forth. Finally, future research priorities are discussed for both endo-urethral and extra-urethral approaches considering key engineering aspects, such as materials, compression and closure mechanisms, and implantation methods, with the long-term aim of developing an effective, reliable, durable, and minimally invasive AUS capable of restoring a normal quality of life for incontinent patients.

Untethered magnetic millirobot for targeted drug delivery.

This paper reports the design and development of a novel millimeter-sized robotic system for targeted therapy. The proposed medical robot is conceived to perform therapy in relatively small diameter body canals (spine, urinary system, ovary, etc.), and to release several kinds of therapeutics, depending on the pathology to be treated. The robot is a nearly-buoyant bi-component system consisting of a carrier, in which the therapeutic agent is embedded, and a piston. The piston, by exploiting magnetic effects, docks with the carrier and compresses a drug-loaded hydrogel, thus activating the release mechanism. External magnetic fields are exploited to propel the robot towards the target region, while intermagnetic forces are exploited to trigger drug release. After designing and fabricating the robot, the system has been tested in vitro with an anticancer drug (doxorubicin) embedded in the carrier. The efficiency of the drug release mechanism has been demonstrated by both quantifying the amount of drug released and by assessing the efficacy of this therapeutic procedure on human bladder cancer cells.

MEMS sensor technologies for human centred applications in healthcare, physical activities, safety and environmental sensing: a review on research activities in Italy.

Over the past few decades the increased level of public awareness concerning healthcare, physical activities, safety and environmental sensing has created an emerging need for smart sensor technologies and monitoring devices able to sense, classify, and provide feedbacks to users' health status and physical activities, as well as to evaluate environmental and safety conditions in a pervasive, accurate and reliable fashion. Monitoring and precisely quantifying users' physical activity with inertial measurement unit-based devices, for instance, has also proven to be important in health management of patients affected by chronic diseases, e.g., Parkinson's disease, many of which are becoming highly prevalent in Italy and in the Western world. This review paper will focus on MEMS sensor technologies developed in Italy in the last three years describing research achievements for healthcare and physical activity, safety and environmental sensing, in addition to smart systems integration. Innovative and smart integrated solutions for sensing devices, pursued and implemented in Italian research centres, will be highlighted, together with specific applications of such technologies. Finally, the paper will depict the future perspective of sensor technologies and corresponding exploitation opportunities, again with a specific focus on Italy.

A sensorized Nuss bar for patient-specific treatment of Pectus Excavatum.

Pectus Excavatum is an anatomical deformation characterized by a depression of the anterior chest wall. Nuss technique (representing the current clinical golden standard) consists in the introduction of a corrective metal bar, in order to raise the sternum in its anatomic natural position. Nowadays, the bar plays purely a mechanical/corrective action and is kept implanted for about three years, supporting up to a maximum force of 250 N. Our study aims at optimizing the procedure of correction, in terms of monitoring the bar effect, minimizing the body response, and facilitating the bar removal. The sensorized Nuss bar prototype inserted in a platform for telemedicine described in this article is able to monitor in vitro pressure data variations, with more than 150 discrete measurements during the operating period. This behavior is promising for future clinical applications, in which the device could be exploited to monitor the forces at work, thus, providing a customized therapeutic protocol, which in turn may optimize the period of implant. The sensorized bar was also provided with a polymeric coating, able to influence human dermal fibroblast behavior in vitro. This highlights the possibility to minimize, in future in vivo applications, tissue fibrotic responses.

Effects of padel activity and proprioception training on soccer players in an off-season period.

BACKGROUND: Off-season periods imply considerable changes in the fitness status of soccer players. So far, no studies evaluated the effects of proprioception-focused training during soccer off-season periods. In this work, we assessed how much some players' abilities (static and dynamic balance, reaction times, quickness, strength, and technical skills) were affected by proprioception training and padel activity during an off-season period of 12 weeks. METHODS: Twenty-eight non-professional adult male soccer players were organized into three groups: a group carried out regular padel activity, ~2 h once a week. Another group underwent a regular proprioception training program, ~ 20 min, twice a week. The third group did not perform any specific activity (control). Static and dynamic balance, reaction times, quickness, strength, and technical skills were evaluated at three time-points: before starting, after 6 weeks, and after 12 weeks. RESULTS: Both padel activity and specific proprioception training carried out for 12 weeks significantly improved players' monopodalic static balance with eyes open and dynamic balance. No significant effects of these training regimens were found on monopodalic static balance with eyes closed, visual and acoustic reaction times, acyclic quickness, and strength. Furthermore, proprioception training considerably improved technical skills. CONCLUSIONS: Coaches may use padel activity and proprioception exercises for off-season programs featured by ease of execution, low training volume, and high compliance.

Triggerable Patches for Medical Applications.

Medical patches have garnered increasing attention in recent decades for several diagnostic and therapeutic applications. Advancements in material science, manufacturing technologies, and bioengineering have significantly widened their functionalities, rendering them highly versatile platforms for wearable and implantable applications. Of particular interest are triggerable patches designed for drug delivery and tissue regeneration purposes, whose action can be controlled by an external signal. Stimuli-responsive patches are particularly appealing as they may enable a high level of temporal and spatial control over the therapy, allowing high therapeutic precision and the possibility to adjust the treatment according to specific clinical and personal needs. This review aims to provide a comprehensive overview of the existing extensive literature on triggerable patches, emphasizing their potential for diverse applications and highlighting the strengths and weaknesses of different triggering stimuli. Additionally, the current open challenges related to the design and use of efficient triggerable patches, such as tuning their mechanical and adhesive properties, ensuring an acceptable trade-off between smartness and biocompatibility, endowing them with portability and autonomy, accurately controlling their responsiveness to the triggering stimulus and maximizing their therapeutic efficacy, are reviewed.

Quantitative analysis of interface pressures in transfemoral prosthetic sockets.

BACKGROUND: Among the different factors affecting socket comfort, the pressure applied on residual limb tissues is a crucial parameter for the success or failure of any prosthetic device. However, only a few incomplete data are available on people with transfemoral amputation, in this regard. This work aims at filling this gap in the literature. METHODS: Ten people with transfemoral amputation wearing 3 different socket designs were recruited in this study: 2 ischial containment sockets featured by proximal trim lines that contain the ischial tuberosity and ramus and greater trochanter, 2 subischial sockets with proximal trim lines under the ischium level, and 6 quadrilateral sockets with proximal trim lines that contain the greater trochanter and create a horizontal seat for the ischial tuberosity. The pressure values at the anterior, lateral, posterior, and medial areas of the socket interface were recorded during 5 locomotion tasks (ie, horizontal, ascent, and descent walking, upstairs and downstairs) by using an F-Socket System (Tekscan Inc., Boston, MA). Gait segmentation was performed by exploiting plantar pressure, which was acquired by an additional sensor under the foot. Mean and standard deviation of minimum and maximum values were calculated for each interface area, locomotion task, and socket design. The mean pressure patterns during different locomotion tasks were reported, as well. RESULTS: Considering all subjects irrespective of socket design, the mean pressure range resulted 45.3 (posterior)-106.7 (posterior) kPa in horizontal walking; 48.3 (posterior)-113.8 (posterior) kPa in ascent walking; 50.8 (posterior)-105.7 (posterior) kPa in descent walking; 47.9 (posterior)-102.9 (lateral) kPa during upstairs; and 41.8 (posterior)-84.5 (anterior) kPa during downstairs. Qualitative differences in socket designs have been found. CONCLUSIONS: These data allow for a comprehensive analysis of pressures acting at the tissue-socket interface in people with transfemoral amputation, thus offering essential information for the design of novel solutions or to improve existing ones, in this field.

Ultrasound Imaging in Knee Osteoarthritis: Current Role, Recent Advancements, and Future Perspectives.

While conventional radiography and MRI have a well-established role in the assessment of patients with knee osteoarthritis, ultrasound is considered a complementary and additional tool. Moreover, the actual usefulness of ultrasound is still a matter of debate in knee osteoarthritis assessment. Despite that, ultrasound offers several advantages and interesting aspects for both current clinical practice and future perspectives. Ultrasound is potentially a helpful tool in the detection of anomalies such as cartilage degradation, osteophytes, and synovitis in cases of knee osteoarthritis. Furthermore, local diagnostic and minimally invasive therapeutic operations pertaining to knee osteoarthritis can be safely guided by real-time ultrasound imaging. We are constantly observing a growing knowledge and awareness among radiologists and other physicians, concerning ultrasound imaging. Ultrasound studies can be extremely useful to track the response to various therapies. For this specific aim, tele-ultrasonography may constitute an easy tool aiding precise and repeated follow-up controls. Moreover, raw radio-frequency data from US backscattering signals contain more information than B-mode imaging. This paves the way for quantitative in-depth analyses of cartilage, bone, and other articular structures. Overall, ultrasound technologies and their rapid evolution have the potential to make a difference at both the research and clinical levels. This narrative review article describes the potential of such technologies and their possible future implications.

Arthroscopic device with bendable tip for the controlled extrusion of hydrogels on cartilage defects.

Advanced tools for the in situ treatment of articular cartilage lesions are attracting a growing interest in both surgery and bioengineering communities. The interest is particularly high concerning the delivery of cell-laden hydrogels. The tools currently available in the state-of-the-art hardly find an effective compromise between treatment accuracy and invasiveness. This paper presents a novel arthroscopic device provided with a bendable tip for the controlled extrusion of cell-laden hydrogels. The device consists of a handheld extruder and a supply unit that allows the extrusion of hydrogels. The extruder is equipped with a disposable, bendable nitinol tip (diameter: 4 mm, length: 92 mm, maximum bending angle: 90°) that guarantees access to hard-to-reach areas of the joint, which are difficult to get to, with conventional arthroscopic instruments. The tip accommodates a biocompatible polymer tube that is directly connected to the cartridge containing the hydrogel, whose plunger is actuated by a volumetric or pneumatic supply unit (both tested, in this study). Three different chondrocyte-laden hydrogels (RGD-modified Vitrogel®, methacrylated gellan gum, and an alginate-gelatine blend) were considered. First, the performance of the device in terms of resolution in hydrogel delivery was assessed, finding values in the range between 4 and 102 µL, with better performance found for the pneumatic supply unit and no significant differences between straight tip and bent tip conditions. Finite element simulations suggested that the shear stresses and pressure levels generated during the extrusion process were compatible with a safe deposition of the hydrogels. Biological analyses confirmed a high chondrocyte viability over a 7-day period after the extrusion of the three cell-laden hydrogel types, with no differences between the two supply units. The arthroscopic device was finally tested ex vivo by nine orthopedic surgeons on human cadaver knees. The device allowed surgeons to easily deliver hydrogels even in hard-to-reach cartilage areas. The outcomes of a questionnaire completed by the surgeons demonstrated a high usability of the device, with an overall preference for the pneumatic supply unit. Our findings provide evidence supporting the future arthroscopic device translation in pre-clinical and clinical scenarios, dealing with osteoarticular treatments.

Usability Assessment of Technologies for Remote Monitoring of Knee Osteoarthritis.

Goal: To evaluate the usability of different technologies designed for a remote assessment of knee osteoarthritis. Methods: We recruited eleven patients affected by mild or moderate knee osteoarthritis, eleven caregivers, and eleven clinicians to assess the following technologies: a wristband for monitoring physical activity, an examination chair for measuring leg extension, a thermal camera for acquiring skin thermographic data, a force balance for measuring center of pressure, an ultrasound imaging system for remote echographic acquisition, a mobile app, and a clinical portal software. Specific questionnaires scoring usability were filled out by patients, caregivers and clinicians. Results: The questionnaires highlighted a good level of usability and user-friendliness for all the technologies, obtaining an average score of 8.7 provided by the patients, 8.8 by the caregivers, and 8.5 by the clinicians, on a scale ranging from 0 to 10. Such average scores were calculated by putting together the scores obtained for the single technologies under evaluation and averaging them. Conclusions: This study demonstrates a high level of acceptability for the tested portable technologies designed for a potentially remote and frequent assessment of knee osteoarthritis.

Urinary Continence Restoration Through an Endourethral Device: A 3-Month Pilot Study on 10 Patients.

Background: Stress urinary incontinence (SUI) is a widespread and frustrating condition that affects millions of people worldwide, with severe consequences on patients' quality of life and health care systems' costs. Currently, the most severe cases of SUI are treated using implanted (and rather invasive) extraurethral artificial sphincters. The authors propose an innovative, minimally invasive endourethral device for the treatment of SUI. Methods: Ten patients with SUI were enrolled in three Italian centers and underwent device implantation. After 10, 30, 60, and 90 days, correct device position was confirmed by ultrasonography. Improvements in continence and quality of life were evaluated through a 24-hour pad-test, an International Consultation on Incontinence Questionnarie-Short Form (ICI-Q) and a custom checklist. The device was explanted after 90 days. Results: The proposed device was successfully implanted and explanted in 8 out of 10 patients. The results of the pad-test, ICI-Q, and custom checklist demonstrated remarkable improvements in continence (median improvement: 82% with respect to the initial condition) and quality of life (mean reduction of the impact of urine losses on the quality of life: 61%). No major pain or discomfort was reported. Conclusions: The results demonstrate the efficacy of the proposed endourethral artificial sphincter in addressing SUI. The proposed device was successfully implanted and explanted in a short time (∼10 minutes) without intrinsic side effects and without triggering pain or discomfort.

Ultrasound Stimulation of Piezoelectric Nanocomposite Hydrogels Boosts Chondrogenic Differentiation in Vitro, in Both a Normal and Inflammatory Milieu.

The use of piezoelectric nanomaterials combined with ultrasound stimulation is emerging as a promising approach for wirelessly triggering the regeneration of different tissue types. However, it has never been explored for boosting chondrogenesis. Furthermore, the ultrasound stimulation parameters used are often not adequately controlled. In this study, we show that adipose-tissue-derived mesenchymal stromal cells embedded in a nanocomposite hydrogel containing piezoelectric barium titanate nanoparticles and graphene oxide nanoflakes and stimulated with ultrasound waves with precisely controlled parameters (1 MHz and 250 mW/cm2, for 5 min once every 2 days for 10 days) dramatically boost chondrogenic cell commitment in vitro. Moreover, fibrotic and catabolic factors are strongly down-modulated: proteomic analyses reveal that such stimulation influences biological processes involved in cytoskeleton and extracellular matrix organization, collagen fibril organization, and metabolic processes. The optimal stimulation regimen also has a considerable anti-inflammatory effect and keeps its ability to boost chondrogenesis in vitro, even in an inflammatory milieu. An analytical model to predict the voltage generated by piezoelectric nanoparticles invested by ultrasound waves is proposed, together with a computational tool that takes into consideration nanoparticle clustering within the cell vacuoles and predicts the electric field streamline distribution in the cell cytoplasm. The proposed nanocomposite hydrogel shows good injectability and adhesion to the cartilage tissue ex vivo, as well as excellent biocompatibility in vivo, according to ISO 10993. Future perspectives will involve preclinical testing of this paradigm for cartilage regeneration.

Wearable and implantable pancreas substitutes.

A lifelong-implanted and completely automated artificial or bioartificial pancreas (BAP) is the holy grail for type 1 diabetes treatment, and could be a definitive solution even for other severe pathologies, such as pancreatitis and pancreas cancer. Technology has made several important steps forward in the last years, providing new hope for the realization of such devices, whose feasibility is strictly connected to advances in glucose sensor technology, subcutaneous and intraperitoneal insulin pump development, the design of closed-loop control algorithms for mechatronic pancreases, as well as cell and tissue engineering and cell encapsulation for biohybrid pancreases. Furthermore, smart integration of the mentioned components and biocompatibility issues must be addressed, bearing in mind that, for mechatronic pancreases, it is most important to consider how to recharge implanted batteries and refill implanted insulin reservoirs without requiring periodic surgical interventions. This review describes recent advancements in technologies and concepts related to artificial and bioartificial pancreases, and assesses how far we are from a lifelong-implanted and self-working pancreas substitute that can fully restore the quality of life of a diabetic (or other type of) patient.

Low-intensity pulsed ultrasound increases neurotrophic factors secretion and suppresses inflammation inin vitromodels of peripheral neuropathies.

Objective. In this study, we aimed to verify the beneficial effects of low-intensity pulsed ultrasound (LIPUS) stimulation on two cell types: H2O2-treated RSC96 Schwann cells and THP-1 macrophages, used to model neuropathic inflammation.Approach. Using a set-up guaranteeing a fine control of the ultrasound dose at the target, different frequencies (38 kHz, 1 MHz, 5 MHz) and different intensities (20, 100, 500 mW cm-2) were screened to find the most effective experimental conditions for triggering beneficial effects on metabolic activity and release of neurotrophic cytokines (ß-nerve growth factor, brain-derived neurotrophic factor, glial cell-derived neurotrophic factor) of RSC96 cells. The combination of parameters resulting the optimal one was applied to evaluate anti-inflammatory effects in terms of reactive oxygen species (ROS) and tumor necrosis factor-α(TNF-α) production, also investigating a possible anti-oxidant activity and mechanotransduction pathway for the anti-inflammatory process. The same optimal combination of parameters was then applied to THP-1 cells, differentiated into M1 and M2 phenotypes, to assess the effect on the expression and release of pro-inflammatory markers (TNF-α, interleukin (IL)-1ß, IL-6, IL-8) and anti-inflammatory ones (IL-10 and CD206).Main results.5 MHz and 500 mW cm-2were found as the optimal stimulation parameters on RSC96 cells. Such parameters were also found to suppress ROS and TNF-αin the same cell line, thus highlighting a possible anti-inflammatory effect, involving the NF-kB pathway. An anti-oxidant effect induced by LIPUS was also observed. Finally, the same LIPUS parameters did not induce any differentiation towards the M1 phenotype of THP-1 cells, whereas they decreased TNF-αand IL-8 gene expression, reduced IL-8 cytokine release and increased IL-10 cytokine release in M1-polarized THP-1 cells.Significance.This study represents the first step towards the use of precisely controlled LIPUS for the treatment of peripheral neuropathies.