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.

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.

A magnetic endourethral sphincter against stress urinary incontinence: preliminary pilot study in humans.

BACKGROUND: Urinary incontinence (UI) is a common and frustrating condition that affects patients' quality of life as well as the Healthcare systems. Currently, the most severe cases of UI are treated using implanted, invasive artificial sphincters. We propose an innovative, minimally invasive magnetic endourethral sphincter for the treatment of stress UI (SUI) in patients for whom previous medical and surgical treatments have failed. METHODS: Six patients with severe SUI were enrolled at a single center and underwent cystoscopic sphincter implantation. After 10 days, correct device position was confirmed by ultrasonography. The sphincter was explanted after 28 days. RESULTS: In all patients, the sphincter was successfully implanted using an endoscopic approach. One patient reached the end of the pilot test (28 days) with the sphincter correctly placed. Patients' responses on the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form questionnaire improved from a score of 18 out of 21 at the screening visit (UI without reasons) to a score of 3 out of 21 (almost perfect continence). No major pain and discomfort were reported. CONCLUSIONS: This study showed the feasibility of sphincter implantation, explantation, and overall tolerability, although a redesign of the sphincter distal part is needed.

A Novel Approach for Multiple Material Extrusion in Arthroscopic Knee Surgery.

Articular cartilage defects and degenerative diseases are pathological conditions that cause pain and the progressive loss of joint functionalities. The most severe cases are treated through partial or complete joint replacement with prostheses, even if the interest in cartilage regeneration and re-growth methods is steadily increasing. These methods consist of the targeted deposition of biomaterials. Only a few tools have been developed so far for performing these procedures in a minimally invasive way. This work presents an innovative device for the direct deposition of multiple biomaterials in an arthroscopic scenario. The tool is easily handleable and allows the extrusion of three different materials simultaneously. It is also equipped with a flexible tip to reach remote areas of the damaged cartilage. Three channels are arranged coaxially and a spring-based dip-coating approach allows the fabrication and assembly of a bendable polymeric tip. Experimental tests were performed to characterize the tip, showing the ability to bend it up to 90° (using a force of ~ 1.5 N) and to extrude three coaxial biomaterials at the same time with both tip straight and tip fully bent. Rheometric analysis and fluid-dynamic computational simulations were performed to analyze the fluids' behavior; the maximum shear stresses were observed in correspondence to the distal tip and the channel convergence chamber, but with values up to ~ 1.2 kPa, compatible with a safe extrusion of biomaterials, even laden with cells. The cells viability was assessed after the extrusion with Live/Dead assay, confirming the safety of the extrusion procedures. Finally, the tool was tested arthroscopically in a cadaveric knee, demonstrating its ability to deliver the biomaterial in different areas, even ones that are typically hard-to-reach with traditional tools.

PDMS and DLC-coated unidirectional valves for artificial urinary sphincters: Opening performance after 126 days of immersion in urine.

In this work, unidirectional valves made of bare polydimethylsiloxane (PDMS) and PDMS provided with a micrometric diamond-like carbon (DLC) coating were fabricated and characterized, in terms of surface properties and opening pressure. The valve performance was also tested over 1250 repeated cycles of opening/closure in water, finding a slight decrease in the opening pressure after such cycles (10%) for the PDMS valves, while almost no variation for the PDMS + DLC ones. The valves were then immersed in urine for 126 days, evaluating the formation of encrustations and the trend of the opening pressure over time. Results showed that PDMS valves were featured by a thin layer of encrustations after 126 days, but the overall encrustation level was much smaller than the one shown by PDMS in static conditions. Furthermore, the opening pressure was almost not affected by such a thin layer of crystals. DLC-coated valves showed even less encrustations at the same time-point, with no significant loss of performance over time, although they were featured by a higher variability. These results suggest that most encrustations can be removed by the mechanical action of the valve during daily openings/closures. Such a self-cleaning behavior with respect to a static condition opens exciting scenarios for the long-term functionality of mobile devices operating in the urinary environment.

Smart Implantable Artificial Bladder: An Integrated Design for Organ Replacement.

Substituting the natural bladder with an artificial solution, after cancer and other pathologies, is an ambitious challenge in biomedical engineering. In this work we propose a fully implantable smart artificial bladder system (ABS) that collects urinary fluids and provides the subject with real-time feedback on the implant status. To achieve long term duration, the ABS was designed to be unstretchable in order to be treated with urine resistant coatings and included built-in passive check valves preventing reflux to kidneys. To estimate the amount of fluid collected, the ABS was provided with four electromagnetic distance sensing units and a control unit. An algorithm implemented on an embedded controller enabled the reconstruction of the bladder volume through sensors readings. A wireless data transfer system allows for providing a real-time feedback to the subject. Bench tests validated volume reconstruction accuracy and ex-vivo experiments verified the implantability of the proposed device on a human cadaver, proving the reliability of a Bluetooth data transmission system and paving the way towards an in-body/out-body communication. The proposed solution has the potential to overcome the limitations of currently available replacement strategies towards a new generation of implantable devices for lost organ functions replacement.

A Coupled FEM-SPH Modeling Technique to Investigate the Contractility of Biohybrid Thin Films.

Biohybrid actuators have the potential to overcome the limitations of traditional actuators employed in robotics, thanks to the unique features of living contractile muscle cells, which can be used to power artificial elements. This paper describes a computational approach for the estimation of the contractile capabilities of skeletal muscle cell-powered biohybrid actuators based on polymeric thin films. The proposed model grounds on the coupling between finite element modeling and smooth particle hydrodynamics. This allows describing the overall condition, including the viscous forces caused by the surrounding liquid medium, in which biohybrid systems are normally immersed. The model is calibrated by analyzing the contractile behavior of polydimethylsiloxane films coupled with skeletal muscle cells, reported in the literature as muscular thin films. Afterward, it is applied to poly (D, L-lactic acid) thin films to explore the behavior of these systems, due to myotubes cultured on them, evaluating the role of thickness, tissue maturation status, and hydrostatic pressure on the contractile performance. These results pave the way toward a novel optimization approach of biohybrid robot design relying on the simulation of all the boundary conditions, thus reducing the need for extensive trial-and-error efforts.

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.

Biohybrid Actuators Based on Skeletal Muscle-Powered Microgrooved Ultrathin Films Consisting of Poly(styrene-block-butadiene-block-styrene).

This paper describes a biohybrid actuator consisting of a microgrooved thin film, powered by contractile, aligned skeletal muscle cells. The system was made of a thermoplastic elastomer [SBS, poly(styrene-block-butadiene-block-styrene)]. We prepared SBS thin films with different thicknesses (0.5-11.7 µm) and Young's moduli (46.7-68.6 MPa) to vary their flexural rigidity. The microgrooves on the SBS thin film resembled the microstructure of the extracellular matrix of muscle and facilitated the alignment and differentiation of skeletal muscle cells. Electrical stimulation was applied to self-standing biohybrid thin films to trigger their contraction, enabled by the low flexural rigidity of the SBS thin film. Finite element model simulations were also examined to predict their contractile behavior. We achieved the prediction of displacements, which were rather close to the actual values of the SBS thin film: the discrepancy was <5% on the X axis. These results pave the way for in silico prediction of the contractile capabilities of elastomeric thin films. This study highlights the potential of microgrooved SBS thin films as ultraflexible platforms for biohybrid machines.

Novel Nanostructured Coating on PDMS Substrates Featuring High Resistance to Urine.

Artificial urinary devices are commonly employed to restore the lost functionalities of the urinary system, due to diseases, disfunctions or organ resections. However, the long-term operation of these devices in the urinary system is affected by encrustations. In this paper, three different nanostructured coatings, based on diamondlike carbon (DLC), molybdenum disulfide (MoS2) and Tungsten disulfide (WS2), were deposited on polydimethylsiloxane substrates, an elastomer suitable for coating different kinds of urinary devices, and tested in terms of resistance to urinary encrustations. DLC coatings were deposited using plasma enhanced-chemical vapor deposition (T < 180 °C), whereas MoS2 and WS2 coatings were achieved through self-assembly at room temperature. All coatings showed good adhesion and stability on PDMS substrate over one month, relatively small roughness, a strongly hydrophobic behavior, and low surface energy. After immersion in artificial urine formulations and continuous mechanical agitation for 4 weeks, WS2 coating resulted the most resistant to encrustations. This material had been never investigated in the urinary context. Our results pave the way to the adoption of WS2 coatings for developing long-lasting stable urinary devices.

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.

Pressure mapping with textile sensors for compression therapy monitoring.

Compression therapy is the cornerstone of treatment in the case of venous leg ulcers. The therapy outcome is strictly dependent on the pressure distribution produced by bandages along the lower limb length. To date, pressure monitoring has been carried out using sensors that present considerable drawbacks, such as single point instead of distributed sensing, no shape conformability, bulkiness and constraints on patient's movements. In this work, matrix textile sensing technologies were explored in terms of their ability to measure the sub-bandage pressure with a suitable temporal and spatial resolution. A multilayered textile matrix based on a piezoresistive sensing principle was developed, calibrated and tested with human subjects, with the aim of assessing real-time distributed pressure sensing at the skin/bandage interface. Experimental tests were carried out on three healthy volunteers, using two different bandage types, from among those most commonly used. Such tests allowed the trends of pressure distribution to be evaluated over time, both at rest and during daily life activities. Results revealed that the proposed device enables the dynamic assessment of compression mapping, with a suitable spatial and temporal resolution (20 mm and 10 Hz, respectively). In addition, the sensor is flexible and conformable, thus well accepted by the patient. Overall, this study demonstrates the adequacy of the proposed piezoresistive textile sensor for the real-time monitoring of bandage-based therapeutic treatments.