Strong Sustainability of Medical Technologies: A Medical Taboo? The Case of Disposable Endoscopes.

This paper aims to question the sustainability of biomedical engineering practices. The strong sustainability framework is applied to the evaluation and development of medical technologies through the definition of clinical sustainability. A roadmap for developing and evaluating medical technologies in this respect is derived from this framework, as a first step toward a multidisciplinary evaluation tool. On this basis, the current trend towards disposable endoscopes is analyzed and discussed. This highlights the subtle balance between economic, clinical, social, and environmental factors, the lack of evidence at these multiple levels, and the need for multidisciplinarity. This paper concludes with the need to assess all aspects of sustainability and identify and quantify the trade-offs, instead of focusing on one or two key indicators, to have more relevant information in order to make better and more effective decisions. Towards sustainable healthcare, we outline two paths of action: (1) providing evidence that is lacking on the environmental impact of existing or currently developed medical technologies and (2) clarifying the premises and visions underlying our practices.Clinical Relevance- This work provides insights regarding the strong sustainability of medical technologies. This clinical framework may help clinicians and developers in decision-making to reduce indirect negative ecological, social, and health impacts.

Urinary bladder phantom mimicking mechanical properties and pressure during filling.

Objective.Phantoms that mimic healthy or diseased organ properties can complement animal models for surgical planning, training, and medical device development. If urodynamic studies rely on pressure-volume curves to assess lower urinary tract symptoms, there is an unsatisfied need for a bladder phantom that accurately mimics the bladder stretching capabilities and compliant behaviour during physiological filling.Approach.We demonstrate the suitability of water-soluble 3D-printed moulds as a versatile method to fabricate accurate phantoms with anatomical structures reconstructed from medical images. We report a phantom fabricated with silicone rubber. A wire net limits the silicone expansion to model the cystometric capacity. A mathematical model describes the pressure increase due to passive hyperelastic properties.Main results.The phantom reproduces the bladder's mechanical properties during filling. The pressure-volume curve measured on the phantom is typical of cystometric studies, with a compliance of 25.2 ± 1mlcmH2O-1.The root-mean-square error between the theoretical model and experimental data is 2.7cmH2O.The compliance, bladder wall thickness, cystometric capacity and pressure near the cystometric capacity of the phantom can be tuned to mimic various pathologies or human variability.Significance.The manufacturing method is suitable for fabricating bladder and other soft and hollow organ phantoms. The mathematical model provides a method to determine design parameters to model healthy or diseased bladders. Soft hollow organ phantoms can be used to complement animal experimentations for developing and validating medical devices aiming to be anchored on these organs or monitor their activity through pressure and strain measurement.

Cold atmospheric plasma differentially affects cell renewal and differentiation of stem cells and APC-deficient-derived tumor cells in intestinal organoids.

Cold atmospheric plasma (CAP) treatment has been proposed as a potentially innovative therapeutic tool in the biomedical field, notably for cancer due to its proposed toxic selectivity on cancer cells versus healthy cells. In the present study, we addressed the relevance of three-dimensional organoid technology to investigate the biological effects of CAP on normal epithelial stem cells and tumor cells isolated from mouse small intestine. CAP treatment exerted dose-dependent cytotoxicity on normal organoids and induced major transcriptomic changes associated with the global response to oxidative stress, fetal-like regeneration reprogramming, and apoptosis-mediated cell death. Moreover, we explored the potential selectivity of CAP on tumor-like Apc-deficient versus normal organoids in the same genetic background. Unexpectedly, tumor organoids exhibited higher resistance to CAP treatment, correlating with higher antioxidant activity at baseline as compared to normal organoids. This pilot study suggests that the ex vivo culture system could be a relevant alternative model to further investigate translational medical applications of CAP technology.

Magnet and wire remodeling for the treatment of candy cane syndrome: first case series of a new approach (with video).

BACKGROUND AND AIMS: Candy cane syndrome (CCS) is an adverse event (AE) from gastrectomy or gastric bypass and end-to-side anastomosis to a jejunal loop. Preferential passage of food to the blind loop induces early satiety, pain, and regurgitation. An endoscopic device that combines 2 magnets and a self-retractable wire was designed to perform progressive septotomy with marsupialization. We evaluated the clinical safety and efficacy of this treatment in CCS. METHODS: Consecutive patients presenting with symptoms associated with CCS after gastrectomy or Roux-en-Y gastric bypass were treated with the MAGUS (Magnetic Gastrointestinal Universal Septotome) system. Weight, dysphagia, pain scores, 12-item Short Form Survey quality of life physical and mental scores, GERD Health-Related Quality of Life, and Eckardt score were measured at baseline and 1 and 3 months postprocedure. Satisfaction with therapy and AEs were monitored during follow-up. RESULTS: Fourteen consecutive patients with CCS were enrolled in the study. Thirteen MAGUS systems migrated within 28 days after achieving uneventful complete septotomy. In 1 patient the magnet had to be collected from the right-sided colon after 1 month. Treatment was completed in a single endoscopy session. Dysphagia score (2 [1-3] vs 1 [1-1], P = .02), pain score (7 [6-8] vs 1 [0-1], P = .002), Eckardt score (5 [3-8] vs 1 [0-2], P = .002), GERD Health-Related Quality of Life score (37 [29-45] vs 8 [6-23], P = .002), and quality of life physical and mental scores were all significantly improved at 3 months. No device or procedure-related serious AEs were observed. One patient died during follow-up from evolution of oncologic disease. CONCLUSIONS: Endoluminal septotomy using a retractable wire and magnet system in CCS is feasible and safe, with rapid improvement of symptoms. (Clinical trial registration number: NCT04480216.).

Magnets and a self-retractable wire for endoscopic septotomies: from concept to first-in-human use.

BACKGROUND: A medical device that allows simple and safe performance of an endoscopic septotomy could have several applications in the gastrointestinal (GI) tract. We have developed such a device by combining two magnets and a self-retractable wire to perform a progressive septotomy by compression of the tissues. We describe here the concept, preclinical studies, and first clinical use of the device for the treatment of symptomatic epiphrenic esophageal diverticulum (EED). METHODS: The MAGUS (MAgnetic Gastrointestinal Universal Septotome) device was designed based on previous knowledge of compression anastomosis and currently unmet needs. After initial design, the feasibility of the technique was tested on artificial septa in pigs. A clinical trial was then initiated to assess the feasibility and safety of the technique. RESULTS: Animal studies showed that the MAGUS can perform a complete septotomy at various levels of the GI tract. In two patients with a symptomatic EED, uneventful complete septotomy was observed within 28 and 39 days after the endoscopic procedure. CONCLUSIONS: This new system provides a way of performing endoluminal septotomy in a single procedure. It appears to be effective and safe for managing symptomatic EED. Further clinical applications where this type of remodeling of the GI tract could be beneficial are under investigation.

Impact of adaptive gastric electrical stimulation on weight, food intake, and food intake rate in dogs.

BACKGROUND: Gastric electrical stimulation (GES) has been studied for decades as a promising treatment for obesity. Stimulation pulses with fixed amplitude and pulse width are usually applied, but these have limitations with regard to overcoming habituation to GES and inter-subject variation. This study aims to analyze the efficacy of an adaptive GES protocol for reducing food intake and maintaining lean weight in dogs. METHODS: Six beagle dogs were implanted with a remotely programmable gastric stimulator. An adaptive protocol was designed to increase the stimulation energy proportionally to the excess of food consumption, with respect to the dogs' maintenance energy requirements. After surgery and habituation to experimental conditions, the dogs went through both a control and a stimulation period of 4 weeks each, in a randomized order. The stimulation parameters were adapted daily. Body weight, food intake, food intake rate, and postprandial cutaneous electrogastrograms (EGG) were recorded to assess the effect of adaptive GES. RESULTS: Adaptive GES decreased food intake and food intake rate (p < 0.05) resulting in weight maintenance. In the absence of GES, the dogs gained weight (p < 0.05). Postprandial EGG dominant frequency was accelerated by GES (p < 0.05). The strategy of adapting the stimulation energy was effective in causing significant mid-term changes. CONCLUSION: Adaptive GES is effective for reducing food intake and maintaining lean weight. The proposed adaptive strategy may offer benefits to counter habituation and adapt to inter-subject variation in clinical use of GES for obesity.

A Soft Pneumatic Two-Degree-of-Freedom Actuator for Endoscopy.

The rise of soft robotics opens new opportunities in endoscopy and minimally invasive surgery. Pneumatic catheters offer a promising alternative to conventional steerable catheters for safe navigation through the natural pathways without tissue injury. In this work, we present an optimized 6 mm diameter two-degree-of-freedom pneumatic actuator, able to bend in every direction and incorporating a 1 mm working channel. A versatile vacuum centrifugal overmolding method capable of producing small geometries with a variety of silicones is described, and meter-long actuators are extruded industrially. An improved method for fiber reinforcement is also presented. The actuator achieves bending more than 180° and curvatures of up to 0.1 mm-1. The exerted force remains below 100 mN, and with no rigid parts in the design, it limits the risks of damage on surrounding tissues. The response time of the actuator is below 300 ms and therefore not limited for medical applications. The working space and multi-channel actuation are also experimentally characterized. The focus is on the study of the influence of material stiffness on mechanical performances. As a rule, the softer the material, the better the energy conversion, and the stiffer the material, the larger the force developed at a given curvature. Based on the actuator, a 90 cm long steerable catheter demonstrator carrying an optical fiber is developed, and its potential for endoscopy is demonstrated in a bronchial tree phantom. In conclusion, this work contributes to the development of a toolbox of soft robotic solutions for MIS and endoscopic applications, by validating and characterizing a promising design, describing versatile and scalable fabrication methods, allowing for a better understanding of the influence of material stiffness on the actuator capabilities, and demonstrating the usability of the solution in a potential use-case.

Optimization and assessment of a novel gastric electrode anchoring system designed to be implanted by minimally invasive surgery.

A novel electrode anchoring design and its implantation procedure, aiming for a minimally invasive solution for gastric electrical stimulation, are presented. The system comprises an anchor made of a flexible body embedding two needle-shaped electrodes. The electrodes can easily switch from a parallel position - to pierce the stomach - to a diverging position - enabling them to remain firmly anchored into the muscular layer of the stomach. Key device parameters governing anchoring stability were assessed on a traction test bench, and optimal values were derived. The device was then implanted in six dogs by open surgery to assess its anchoring durability in vivo. Computed tomography images showed that the electrodes remained well placed within the dogs' gastric wall over the entire assessment period (more than one year). Finally, a prototype of a surgical tool for the minimally invasive device placement was manufactured, and the anchoring procedure was tested on a dog cadaver, providing the proof of concept of the minimally invasive implantation procedure. The use of our electrode anchoring system in long-term gastric electrical stimulation is promising in terms of implantation stability (the anchor withstands a force up to 0.81 N), durability (the anchor remains onto the stomach over one year) and minimal invasiveness of the procedure (the diameter of the percutaneous access is smaller than 12 mm). Moreover, the proposed design could have clinical applications in other hollow organs, such as the urinary bladder.

Optimization of Phase-Change Material-Elastomer Composite and Integration in Kirigami-Inspired Voxel-Based Actuators.

Phase-change material-elastomer composite (PCMEC) actuators are composed of a soft elastomer matrix embedding a phase-change fluid, typically ethanol, in microbubbles. When increasing the temperature, the phase change in each bubble induces a macroscopic expansion of the matrix. This class of actuators is promising for soft robotic applications because of their high energy density and actuation strain, and their low cost and easy manufacturing. However, several limitations must be addressed, such as the high actuation temperature and slow actuation speed. Moreover, the lack of a consistent design approach limits the possibility to build PCMEC-based soft robots able to achieve complex tasks. In this work, a new approach to manufacture PCMEC actuators with different fluid-elastomer combinations without altering the quality of the samples is proposed. The influence of the phase-change fluid and the elastomer on free elongation and bending is investigated. We demonstrate that choosing an appropriate fluid increases the actuation strain and speed, and decreases the actuation temperature compared with ethanol, allowing PCMECs to be used in close contact with the human body. Similarly, by using different elastomer materials, the actuator stiffness can be modified, and the experimental results showed that the curvature is roughly proportional to the inverse of Young's modulus of the pure matrix. To demonstrate the potential of the optimized PCMECs, a kirigami-inspired voxel-based design approach is proposed. PCMEC cubes are molded and reinforced externally by paper. Cuts in the paper induce anisotropy into the structure. Elementary voxels deforming according to the basic kinematics (bending, torsion, elongation, compression and shear) are presented. The combination of these voxels into modular and reconfigurable structures could open new possibilities towards the design of flexible robots able to perform complex tasks.

Design, characterization and optimization of a soft fluidic actuator for minimally invasive surgery.

PURPOSE: In minimally invasive surgery and endoscopy, the rise of soft robotics, using materials of similar softness as biological soft tissues, opens many new opportunities. Soft actuated catheters could become an alternative to current steerable catheters, by minimizing the risk of damage to surrounding tissues while enhancing the possibilities to navigate in confined space and to reach remote locations. Fluidic actuators present the advantage to be safe, since they do not require rigid parts nor voltage, to be lightweight, and to allow the reduction of the number of parts needed for a given movement. This work presents the design, development and characterization of a soft fluidic bending actuator for a steerable catheter. METHODS: A silicone prototype of 5 mm diameter has been designed. It has one degree of freedom in bending and achieves a radius of curvature below 10 mm. A numerical model has been developed and compared to the experimental results. RESULTS: Despite an overestimation of the bending, the numerical model properly captures the behaviour of the actuator. This allowed to identify and validate the key design parameters of the actuator, namely the ratio between the pressure channel surface and the actuator cross-section surface. Based on the results, an optimized design has been developed and numerically implemented. The miniaturization and the potential to carry devices with non-negligible bending stiffness have also been discussed. CONCLUSION: In this work, a proof of concept of a soft fluidic actuator for a steerable catheter has been designed, developed and characterized. It showed promising results concerning the feasibility of a miniaturized actuator with two degrees of freedom.

In Vivo Validation of a Less Invasive Gastrostimulator.

Gastrointestinal stimulator implants have recently shown promising results in helping obese patients lose weight. However, to place the implant, the patient currently needs to undergo an invasive surgical procedure. We report a less invasive procedure to stimulate the stomach with a gastrostimulator. After attempting fully endoscopic implantation, we more recently focused on a single incision percutaneous procedure. In both cases, the challenges in electronic design of the implant are largely similar. This article covers the work achieved to meet these and details the in vivo validation of a gastrostimulator aimed to be endoscopically placed and anchored to the stomach.

The larynx ruler to measure height and profile of vocal folds: a proof of concept.

INTRODUCTION: Glottic leakage during phonation is a direct consequence of unilateral vocal fold (VF) paralysis. This air leakage can be in the horizontal plane and in the vertical plane. Presently, there is no easily applicable medical device allowing noninvasive, office-based measurement of the relative vertical position of the VFs. The larynx ruler (LR) is a laser-based measuring device that could meet the previously stated need, using a flexible endoscope. This study represents a proof of concept regarding the use of the LR in assessing VF relative positions in the vertical plane. MATERIALS AND METHODS: One fresh male human cadaver larynx, free of neurologic and anatomic disease, was explored with the LR system through the operative channel of a flexible gastroenterology video-endoscope. The tip of the video-endoscope was located in the laryngeal vestibule. The right crico-arytenoid joint was posteriorly disarticulated. Tilting of the VF was obtained by pulling or pushing the arytenoid cartilage with a mosquito forceps fixed to the stump of the previously sectioned superior tip of the posterior crico-arytenoid muscle allowing anterior and posterior tilting of the arytenoid cartilage in order to induce an elevation or a depression of the VF process. Ten "push" and ten "pull" sessions were performed. The distance from the tip of the video-endoscope to each illuminated pixel of the laser beam was recorded. The level difference between the left and right VFs was measured for each recording. RESULTS: Data provided by the LR were consistently in accordance with the movements applied on the VFs. The accuracy of 0.2 mm of the LR is compatible with the envisioned applications for the human larynx. CONCLUSION: The LR system represents a feasible technique to evaluate respective vertical position of VFs in the human larynx. Technical limitations were identified that will require improvements before experimental use on human beings.

A Study on Cross-Talk Nerve Stimulation: Electrode Placement and Current Leakage Lid.

Cross-talk phenomena should be avoided when stimulating nerves. One option to limit the current spread is to use tripolar electrodes, but at the cost of increasing the number of wires connection. This should be avoided since cables must be thin and compliant. We investigated the impact of the central electrode position and of current spread due to a gap between book and lid on cross-talk, in a set of tripolar or quasi-tripolar configurations..

Design and Implementation of a Less Invasive Gastrostimulator.

Gastrointestinal stimulator implants have recently shown positive results in helping obese patients lose weight. However, to place the implant, the patient currently needs to undergo an invasive surgical procedure. Our team is aiming for a less invasive procedure to stimulate the stomach with a gastrostimulator. Attempts covered fully endoscopic implantation and, more recently, we have focussed on a single incision laparoscopic procedure. Whatever the chosen implantation solution, the electronic design of the implant system shares many challenges. This paper covers the work achieved to meet these.

Review of patents for microneedle application devices allowing fluid injections through the skin.

Microneedles have been developed in the past few years as a new means of transdermal drug delivery. They indeed present many advantages compared to injections using hypodermic needles (reduced risk of contamination and epidermic reactions), but mostly bring comfort and compliance to patients. Microneedles may be plain, opening pathways for medications to dissolve into the skin, or hollow, allowing fluid to actually enter the dermis or the hypodermis. This review focuses on the latter type of microneedles and two issues with their application: first, ensuring correct insertion into the skin (controlled and repeatable insertion depth, mainly); and second, ensuring correct fluid delivery to the dermis (controlled infusion rate). This paper thus focuses on recently published patents for hollow microneedle applicators-i.e., microneedles applicators that allow fluid delivery to the skin. Descriptions are given of several of the most relevant patents concerning this. The benefits and drawbacks of the different solutions are also described.

Hollow polymer microneedles array resistance and insertion tests.

Microneedles are developed in order to become the transdermal administration method of the future. They however still face numerous challenges. This paper addresses the challenge to effectively insert the microneedle arrays into membranes. A recently proposed model membrane and test method for microneedles insertion, published in International Journal of Pharmaceutics, is used in this aim. A moulded 4 by 4 hollow polymer microneedle array developed at the Université Libre de Bruxelles is tested for insertion using this model. Results show that the array is extremely resistant to insertion, it can withstand very high forces and even multiple insertions without blunting. Different insertion tests were performed on a folded in eight Parafilm® film because it exhibits excellent similarity to porcine skin. The insertion force, the insertion speed and the holding time of the array against membranes must be optimised in order to get efficient reliable insertions at, at least, 500µm depth.

Comparison between two capillary forces models.

Surface tension effects are dominant in miniaturization. Therefore, a lot of capillary forces models have been recently discussed in the literature. The work reported in this paper intends to prove the equivalence between two methods which are very widespread in capillary forces computation at equilibrium: the energetic method based on the derivation of the total interfacial energy and a second method summing both pressure and tension terms obtained from the meniscus profile (based on the Laplace equation). The results are supported by different qualitative arguments, an analytical proof in the case of a prism-plate configuration, numerical simulation, and experiments in the case of two millimetric spheres.

Parameters ruling capillary forces at the submillimetric scale.

This paper reviews the way to compute capillary forces between two solids by numerically integrating the Laplace equation describing the shape of an axially symmetric meniscus at equilibrium. The numerical results of the proposed model have been experimentally validated with a test bed able to measure forces of about 1 mN with an accuracy of about 1 microN. Thanks to the simulation tool and the test bed, the influence of the following parameters has been studied: surface tension, solid geometry, volume of liquid, materials, separation distance between both solids, and surrounding environment. The way to compute the force from a given meniscus geometry has been clarified as far as the "Laplace" and "tension" contributions are concerned.