Lymphaticovenous anastomosis in rabbits: A novel live experimental animal model for supermicrosurgical training.

BACKGROUND: Lymphaticovenous anastomosis is widely used in lymphedema management. Although its effectiveness in reducing edema in patients can be clinically observed, evaluating the long-term outcomes of this technique can be complex. This study established an animal model to assess the outcomes of lymphaticovenous anastomosis technique at 15 and 30-days post-surgery using indocyanine green lymphography, Patent Blue V dye injection, and histopathological examination. METHODS: An experimental model was established in the hindlimbs of 10 rabbits using the popliteal vein and afferent lymphatic vessels in the popliteal area. The subjects were divided into two groups: the first group (n = 5) underwent patency assessment at 0 and 15 days, and the second group (n = 5) at 0 and 30-days, resulting in 20 anastomoses. Patency was verified at 0, 15, and 30-days using indocyanine green lymphography and Patent Blue V injection. Histopathological examinations were performed on the collected anastomosis samples. RESULTS: The patency rate was 90% (19/20) initially, 60% (6/10) at 15 days post-surgery, and 80% (8/10) at 30-days. The average diameter of lymphatic vessels and veins was 1.0 mm and 0.8 mm, respectively. The median number of collateral veins was 3; the median surgical time was 65.8 min. Histopathology revealed minimal endothelial damage and inflammatory responses due to the surgical sutures, with vascular inflammation and thrombosis in a single case. Local vascular neoformations were observed. CONCLUSION: This study highlights the reliability and reproducibility of using rabbits as experimental models for training in lymphaticovenous anastomosis technique owing to the accessibility of the surgical site and dimensions of their popliteal vasculature.

A Serious Game for Cognitive Stimulation of Older People With Mild Cognitive Impairment: Design and Pilot Usability Study.

Background: Cognitive stimulation of older people helps prevent, and even treat, age-related diseases, such as mild cognitive impairment. Playing games reduces the probability of experiencing this pathology, which is related to the loss of the ability to carry out some instrumental activities of daily living. Objective: This work describes the design and development of a serious game for the cognitive stimulation of older people, with exercises related to the daily life task of shopping. A pilot study for its preliminary usability validation is also presented. Methods: The designed serious game includes 4 exercises consisting of shopping in a hypermarket, ordering products, making payments, and organizing the purchase, thus dealing with the most frequent cognitive problems of older people associated with episodic declarative memory, naming, calculation, and organization, respectively. Results: A total of 19 older people participated in the pilot study for the usability validation of the serious game. They indicated that they like the aesthetic and interesting topic of the game. They reported that it provides a high level of entertainment and could be useful in daily life for mental stimulation. The participants found the serious game to be intuitive, but the ease of use and readability of the instructions could be improved. Conclusions: This study suggests that the innovative serious game developed could be accepted by older people for their cognitive stimulation to prevent or treat mild cognitive impairment, although a long-term intervention study should be performed as future work. Its ecological validity design, with everyday tasks, adaptable levels of difficulty, and motivational mechanisms, is a differentiating factor compared to similar serious games.

Colonic Electrical Stimulation for Chronic Constipation: A Perspective Review.

Chronic constipation affects around 20% of the population and there is no efficient solution. This perspective review explores the potential of colonic electric stimulation (CES) using neural implants and methods of bioelectronic medicine as a therapeutic way to treat chronic constipation. The review covers the neurophysiology of colonic peristaltic function, the pathophysiology of chronic constipation, the technical aspects of CES, including stimulation parameters, electrode placement, and neuromodulation target selection, as well as a comprehensive analysis of various animal models highlighting their advantages and limitations in elucidating the mechanistic insights and translational relevance for CES. Finally, the main challenges and trends in CES are discussed.

An implantable magnetic drive mechanism for non-invasive arteriovenous conduit blood flow control.

OBJECTIVE: Hemodialysis patients usually receive an arteriovenous fistula (AVF) in the arm as vascular access conduit to allow dialysis 2-3 times a week. This AVF introduces the high flow necessary for dialysis, but over time the ever-present supraphysiological flow is the leading cause of complications. This study aims to develop an implantable device able to non-invasively remove the high flow outside dialysis sessions. METHODS: The developed prototype features a magnetic ring allowing external coupling and torque transmission to non-invasively control an AVF valve. Mock-up devices were implanted into arm and sheep cadavers to test sizes and locations. The transmission torque, output force, and valve closure are measured for different representative skin thicknesses. RESULTS: The prototype was placed successfully into arm and sheep cadavers. In the prototype, a maximum output force of 78.9±4.2 N, 46.7±1.9 N, 25.6±0.7 N, 13.5±0.6 N and 6.3±0.4 N could be achieved non-invasively through skin thicknesses of 1-5 mm respectively. The fistula was fully collapsible in every measurement through skin thickness up to the required 4 mm. CONCLUSION: The prototype satisfies the design requirements. It is fully implantable and allows closure and control of an AVF through non-invasive torque transmission. In vivo studies are pivotal in assessing functionality and understanding systemic effects. SIGNIFICANCE: A method is introduced to transfer large amounts of energy to a medical implant for actuation of a mechanical valve trough a closed surface. This system allows non-invasive control of an AVF to reduce complications related to the permanent high flow in conventional AVFs.

Biopolymers for Tissue Engineering: Crosslinking, Printing Techniques, and Applications.

Currently, tissue engineering has been dedicated to the development of 3D structures through bioprinting techniques that aim to obtain personalized, dynamic, and complex hydrogel 3D structures. Among the different materials used for the fabrication of such structures, proteins and polysaccharides are the main biological compounds (biopolymers) selected for the bioink formulation. These biomaterials obtained from natural sources are commonly compatible with tissues and cells (biocompatibility), friendly with biological digestion processes (biodegradability), and provide specific macromolecular structural and mechanical properties (biomimicry). However, the rheological behaviors of these natural-based bioinks constitute the main challenge of the cell-laden printing process (bioprinting). For this reason, bioprinting usually requires chemical modifications and/or inter-macromolecular crosslinking. In this sense, a comprehensive analysis describing these biopolymers (natural proteins and polysaccharides)-based bioinks, their modifications, and their stimuli-responsive nature is performed. This manuscript is organized into three sections: (1) tissue engineering application, (2) crosslinking, and (3) bioprinting techniques, analyzing the current challenges and strengths of biopolymers in bioprinting. In conclusion, all hydrogels try to resemble extracellular matrix properties for bioprinted structures while maintaining good printability and stability during the printing process.

EASIER: A new model for online learning of minimally invasive surgery skills.

INTRODUCTION: Technology Enhanced Learning (TEL) can provide the tools to safely master minimally invasive surgery (MIS) skills in patient-free environments and receive immediate objective feedback without the constant presence of an instructor. However, TEL-based systems tend to work isolated from one another, focus on different skills, and fail to provide contents without a sound pedagogical background. OBJECTIVE: The objective of this descriptive study is to present in detail EASIER, an innovative TEL platform for surgical and interventional training, as well as the results of its validation. METHODS: EASIER provides a Learning Management System (LMS) for institutions and content creators that can connect and integrate TEL "external assets" (virtual reality simulators, augmented box trainers, augmented videos, etc.) addressing different skills. The platform integrates all skills under an Assessment Module that measures skills' progress in different courses. Finally, it provides content creators with a pedagogical model to scaffold contents while retaining flexibility to approach course design with different training philosophies in mind. Three courses were developed and hosted in the platform to validate it with end-users in terms of usability, performance, learning results in the courses and student self-perception on learning. RESULTS: In total 111 volunteers completed the validation. The study was limited due to the COVID-19 pandemic, which limited access to external assets (virtual reality simulators). Nevertheless, usability was rated with 73.1 in the System Usability Scale. Most positive aspects on performance were easiness to access the platform, easiness to change the configuration and not requiring additional plug-ins to use the platform. The platform was rated above average in the six scales of the User Experience Questionnaire. Overall, student results improved significantly across the three courses (p < 0.05). CONCLUSIONS: This study provides, within its limitations, evidence on the usefulness of the EASIER platform for distance learning of MIS skills. Results show the potential impact of the platform and are an encouraging boost for the future, especially in the aftermath of the COVID-19 pandemic.

Clinical Validation Benchmark Dataset and Expert Performance Baseline for Colorectal Polyp Localization Methods.

Colorectal cancer is one of the leading death causes worldwide, but, fortunately, early detection highly increases survival rates, with the adenoma detection rate being one surrogate marker for colonoscopy quality. Artificial intelligence and deep learning methods have been applied with great success to improve polyp detection and localization and, therefore, the adenoma detection rate. In this regard, a comparison with clinical experts is required to prove the added value of the systems. Nevertheless, there is no standardized comparison in a laboratory setting before their clinical validation. The ClinExpPICCOLO comprises 65 unedited endoscopic images that represent the clinical setting. They include white light imaging and narrow band imaging, with one third of the images containing a lesion but, differently to another public datasets, the lesion does not appear well-centered in the image. Together with the dataset, an expert clinical performance baseline has been established with the performance of 146 gastroenterologists, who were required to locate the lesions in the selected images. Results shows statistically significant differences between experience groups. Expert gastroenterologists' accuracy was 77.74, while sensitivity and specificity were 86.47 and 74.33, respectively. These values can be established as minimum values for a DL method before performing a clinical trial in the hospital setting.

Three-Dimensionally Printed Hydrogel Cardiac Patch for Infarct Regeneration Based on Natural Polysaccharides.

Myocardial infarction is one of the more common cardiovascular diseases, and remains the leading cause of death, globally. Hydrogels (namely, those using natural polymers) provide a reliable tool for regenerative medicine and have become a promising option for cardiac tissue regeneration due to their hydrophilic character and their structural similarity to the extracellular matrix. Herein, a functional ink based on the natural polysaccharides Gellan gum and Konjac glucomannan has, for the first time, been applied in the production of a 3D printed hydrogel with therapeutic potential, with the goal of being locally implanted in the infarcted area of the heart. Overall, results revealed the excellent printability of the bioink for the development of a stable, porous, biocompatible, and bioactive 3D hydrogel, combining the specific advantages of Gellan gum and Konjac glucomannan with proper mechanical properties, which supports the simplification of the implantation process. In addition, the structure have positive effects on endothelial cells' proliferation and migration that can promote the repair of injured cardiac tissue. The results presented will pave the way for simple, low-cost, and efficient cardiac tissue regeneration using a 3D printed hydrogel cardiac patch with potential for clinical application for myocardial infarction treatment in the near future.

Computational simulation-based comparative analysis of standard 3D printing and conical nozzles for pneumatic and piston-driven bioprinting.

Bioprinting is an application of additive manufacturing that can deliver promising results in regenerative medicine. Hydrogels, as the most used materials in bioprinting, are experimentally analyzed to assure printability and suitability for cell culture. Besides hydrogel features, the inner geometry of the microextrusion head might have an equal impact not only on printability but also on cellular viability. In this regard, standard 3D printing nozzles have been widely studied to reduce inner pressure and get faster printings using highly viscous melted polymers. Computational fluid dynamics is a useful tool capable of simulating and predicting the hydrogel behavior when the extruder inner geometry is modified. Hence, the objective of this work is to comparatively study the performance of a standard 3D printing and conical nozzles in a microextrusion bioprinting process through computational simulation. Three bioprinting parameters, namely pressure, velocity, and shear stress, were calculated using the level-set method, considering a 22G conical tip and a 0.4 mm nozzle. Additionally, two microextrusion models, pneumatic and piston-driven, were simulated using dispensing pressure (15 kPa) and volumetric flow (10 mm3/s) as input, respectively. The results showed that the standard nozzle is suitable for bioprinting procedures. Specifically, the inner geometry of the nozzle increases the flow rate, while reducing the dispensing pressure and maintaining similar shear stress compared to the conical tip commonly used in bioprinting.

Personalized tissue-engineered veins - long term safety, functionality and cellular transcriptome analysis in large animals.

Tissue engineering is a promising methodology to produce advanced therapy medicinal products (ATMPs). We have developed personalized tissue engineered veins (P-TEV) as an alternative to autologous or synthetic vascular grafts utilized in reconstructive vein surgery. Our hypothesis is that individualization through reconditioning of a decellularized allogenic graft with autologous blood will prime the tissue for efficient recellularization, protect the graft from thrombosis, and decrease the risk of rejection. In this study, P-TEVs were transplanted to vena cava in pig, and the analysis of three veins after six months, six veins after 12 months and one vein after 14 months showed that all P-TEVs were fully patent, and the tissue was well recellularized and revascularized. To confirm that the ATMP product had the expected characteristics one year after transplantation, gene expression profiling of cells from P-TEV and native vena cava were analyzed and compared by qPCR and sequencing. The qPCR and bioinformatics analysis confirmed that the cells from the P-TEV were highly similar to the native cells, and we therefore conclude that P-TEV is functional and safe in large animals and have high potential for use as a clinical transplant graft.

Animal model assessment of a new design for a coated mitomycin-eluting biodegradable ureteral stent for intracavitary instillation as an adjuvant therapy in upper urothelial carcinoma.

BACKGROUND: A major limitation in the treatment of upper urinary tract urothelial carcinoma is the limited use of adjuvant therapy due to the drawbacks of current techniques for intracavitary instillation. The aim was to assess, in a large animal model, a biodegradable ureteral stent coated with silk fibroin for mitomycin release, i.e. BraidStent-SF-MMC. METHODS: A total of 14 female pigs with a solitary kidney underwent initial urinalysis, blood chemistry, nephrosonographic, and contrast fluoroscopy assessment of the urinary tract. Later, the BraidStent-SF-MMC was placed retrogradely to assess the mitomycin urine concentration from 0-48 hours. Follow-up was performed weekly until complete stent degradation to assess the macroscopic and microscopic changes in the urinary tract, stent complications. RESULTS: The drug eluting stent released mitomycin for the first 12 h. The main complication was the release of obstructive ureteral coating fragments during the first to third week in 28.5 and 7.1% of animals, respectively, related to urinary pH<7.0, which destabilized the stent coating. Another complication was ureteral strictures between the fourth and sixth week in 21%. The stents were completely degraded by 6-7 weeks. There were no stent-related systemic toxic effects. The success rate was 67.5% and the complication rate was 25.7%. CONCLUSIONS: For the first time, we have shown that a biodegradable anti-cancer drug eluting stent, BraidStent-SF-MMC, provides controlled and well-tolerated release of mitomycin into the upper urinary tract in an animal model. Mitomycin release from a silk fibroin coating could be a compelling approach for adjuvant chemotherapy instillation in upper tract urothelial carcinoma management.

Supplementation of culture medium with quercetin improves mouse blastocyst quality and increases the expression of HIF-1α protein.

Regarding the low number of embryos that reach the blastocyst stage when cultured in vitro, this study aimed to evaluate the effects of quercetin on pre-implantation mouse (Mus musculus) embryos obtained using in vitro fertilization, especially during the passage from morula to blastocyst. Furthermore, we studied whether quercetin also affected the expression of hypoxia-inducible factor 1α (HIF-1α). The culture medium for the embryos was supplemented with quercetin, for long or short periods of time, and then the development potential, total cell number, apoptosis rates and expression of HIF-1α were studied to determine the effect of quercetin. Embryos failed to develop when cultured for long periods of time with quercetin, implying the possible toxic effects of this, alternatively antioxidant, compound. However, a short culture from morula to blastocyst significantly improved the development potential of in vitro produced embryos, increasing the final total cell number and reducing the apoptosis rate, observing similar results to those embryos cultured in low-oxygen concentrations or developed in utero. Furthermore, in embryos treated with quercetin for 2 or 4 h we found an increase in HIF-1α compared with untreated embryos. This work could imply a way to use quercetin in fertility clinics to improve the production of healthy blastocysts and, consequently, increase the success rates in assisted reproduction techniques.

Fetal Endoscopic Third Ventriculostomy Is Technically Feasible in Prenatally Induced Hydrocephalus Ovine Model.

BACKGROUND: Congenital obstructive hydrocephalus generates progressive irreversible fetal brain damage by ventricular enlargement and incremental brain tissue compression that leads to maldevelopment and poor clinical outcomes. Intrauterine treatments such as ventriculo-amniotic shunting have been unsuccessfully tried in the eighties. OBJECTIVE: To assess if prenatal endoscopic third ventriculostomy (ETV) is feasible in a large animal model and optimize this technique for ventricular decompression and potential arrest of fetal brain damage in fetal lambs. METHODS: We generated hydrocephalus in 50 fetal lambs by injecting a polymeric agent into the cisterna magna at midgestation (E85). Subsequently, 3 weeks later (E105), fetal ETV was performed using a small rigid fetoscope. The endoscopy entry point was located anterior to the coronal suture, 7 mm from the midline. RESULTS: We obtained clear visualization of the enlarged lateral ventricles by endoscopy in the hydrocephalic fetal lambs. The floor of the third ventricle was bluntly perforated and passed with the scope for a successful ETV. Total success was achieved in 32/50 cases (64%). Causes of failure were blurred vision or third ventricle obliteration by BioGlue in 10/50 (20%) cases, anatomic misdirection of the endoscope in 5 (10%) cases, 2 cases of very narrow foramen of Monro, and 1 case of choroid plexus bleeding. If we exclude the cases artificially blocked by the polymer, we had a successful performance of prenatal-ETV in 80% (32/40) of hydrocephalic fetuses. CONCLUSION: Despite the inherent difficulties arising from ovine brain anatomy, this study shows that innovative fetal ETV is technically feasible in hydrocephalic fetal lambs.

Development of Silk Fibroin Scaffolds for Vascular Repair.

Silk fibroin (SF) is a biocompatible natural protein with excellent mechanical characteristics. SF-based biomaterials can be structured using a number of techniques, allowing the tuning of materials for specific biomedical applications. In this study, SF films, porous membranes, and electrospun membranes were produced using solvent-casting, salt-leaching, and electrospinning methodologies, respectively. SF-based materials were subjected to physicochemical and biological characterizations to determine their suitability for tissue regeneration applications. Mechanical analysis showed stress-strain curves of brittle materials in films and porous membranes, while electrospun membranes featured stress-strain curves typical of ductile materials. All samples showed similar chemical composition, melting transition, hydrophobic behavior, and low cytotoxicity levels, regardless of their architecture. Finally, all of the SF-based materials promote the proliferation of human umbilical vein endothelial cells (HUVECs). These findings demonstrate the different relationship between HUVEC behavior and the SF sample's topography, which can be taken advantage of for the design of vascular implants.

Effects of Cardiac Stem Cell on Postinfarction Arrhythmogenic Substrate.

Clinical data suggest that cardiosphere-derived cells (CDCs) could modify post-infarction scar and ventricular remodeling and reduce the incidence of ventricular tachycardia (VT). This paper assesses the effect of CDCs on VT substrate in a pig model of postinfarction monomorphic VT. We studied the effect of CDCs on the electrophysiological properties and histological structure of dense scar and heterogeneous tissue (HT). Optical mapping and histological evaluation were performed 16 weeks after the induction of a myocardial infarction by transient occlusion of the left anterior descending (LAD) artery in 21 pigs. Four weeks after LAD occlusion, pigs were randomized to receive intracoronary plus trans-myocardial CDCs (IC+TM group, n: 10) or to a control group. Optical mapping (OM) showed an action potential duration (APD) gradient between HT and normal tissue in both groups. CDCs increased conduction velocity (53 ± 5 vs. 45 ± 6 cm/s, p < 0.01), prolonged APD (280 ± 30 ms vs. 220 ± 40 ms, p < 0.01) and decreased APD dispersion in the HT. During OM, a VT was induced in one and seven of the IC+TM and control hearts (p = 0.03), respectively; five of these VTs had their critical isthmus located in intra-scar HT found adjacent to the coronary arteries. Histological evaluation of HT revealed less fibrosis (p < 0.01), lower density of myofibroblasts (p = 0.001), and higher density of connexin-43 in the IC+TM group. Scar and left ventricular volumes did not show differences between groups. Allogeneic CDCs early after myocardial infarction can modify the structure and electrophysiology of post-infarction scar. These findings pave the way for novel therapeutic properties of CDCs.

Intrapericardial cardiosphere-derived cells hinder epicardial dense scar expansion and promote electrical homogeneity in a porcine post-infarction model.

The arrhythmic substrate of ventricular tachycardias in many structural heart diseases is located in the epicardium, often resulting in poor outcomes with currently available therapies. Cardiosphere-derived cells (CDCs) have been shown to modify myocardial scarring. A total of 19 Large White pigs were infarcted by occlusion of the mid-left anterior descending coronary artery for 150 min. Baseline cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement sequences was obtained 4 weeks post-infarction and pigs were randomized to a treatment group (intrapericardial administration of 300,000 allogeneic CDCs/kg), (n = 10) and to a control group (n = 9). A second CMR and high-density endocardial electroanatomical mapping were performed at 16 weeks post-infarction. After the electrophysiological study, pigs were sacrificed and epicardial optical mapping and histological studies of the heterogeneous tissue of the endocardial and epicardial scars were performed. In comparison with control conditions, intrapericardial CDCs reduced the growth of epicardial dense scar and epicardial electrical heterogeneity. The relative differences in conduction velocity and action potential duration between healthy myocardium and heterogeneous tissue were significantly smaller in the CDC-treated group than in the control group. The lower electrical heterogeneity coincides with heterogeneous tissue with less fibrosis, better cardiomyocyte viability, and a greater quantity and better polarity of connexin 43. At the endocardial level, no differences were detected between groups. Intrapericardial CDCs produce anatomical and functional changes in the epicardial arrhythmic substrate, which could have an anti-arrhythmic effect.

Development and evaluation of different electroactive poly(vinylidene fluoride) architectures for endothelial cell culture.

Tissue engineering (TE) aims to develop structures that improve or even replace the biological functions of tissues and organs. Mechanical properties, physical-chemical characteristics, biocompatibility, and biological performance of the materials are essential factors for their applicability in TE. Poly(vinylidene fluoride) (PVDF) is a thermoplastic polymer that exhibits good mechanical properties, high biocompatibility and excellent thermal properties. However, PVDF structuring, and the corresponding processing methods used for its preparation are known to significantly influence these characteristics. In this study, doctor blade, salt-leaching, and electrospinning processing methods were used to produce PVDF-based structures in the form of films, porous membranes, and fiber scaffolds, respectively. These PVDF scaffolds were subjected to a variety of characterizations and analyses, including physicochemical analysis, contact angle measurement, cytotoxicity assessment and cell proliferation. All prepared PVDF scaffolds are characterized by a mechanical response typical of ductile materials. PVDF films displayed mostly vibration modes for the a-phase, while the remaining PVDF samples were characterized by a higher content of electroactive ß-phase due the low temperature solvent evaporation during processing. No significant variations have been observed between the different PVDF membranes with respect to the melting transition. In addition, all analysed PVDF samples present a hydrophobic behavior. On the other hand, cytotoxicity assays confirm that cell viability is maintained independently of the architecture and processing method. Finally, all the PVDF samples promote human umbilical vein endothelial cells (HUVECs) proliferation, being higher on the PVDF film and electrospun randomly-oriented membranes. These findings demonstrated the importance of PVDF topography on HUVEC behavior, which can be used for the design of vascular implants.

Effect of the addition of 4OHE2 and quercetin in culture media on ROS levels and gene expression in mouse blastocysts.

AIMS: The main objective of this work is to elucidate whether Quercetin (Qc) and 4-Hidroxistradiol (4OHE2 ) decrease the level of reactive oxygen species (ROS) in in vitro obtained embryos and to analyse which genes are activated under the treatments that could explain this improvement. METHODS: Oxidative stress was induced during embryo culture by H2 O2 treatment and ROS production was measured and compared with embryos treated with Qc or 4OHE2 . Gene expression was analysed by Q-PCR in control embryos obtained in utero (IU) or by IVF and compared with the levels found in embryos cultured with Qc or 4OHE2 to determine the effect of these compounds. KEY RESULTS: Qc strongly reduces ROS levels in embryos after a treatment of 4h. On the contrary, 4OHE2 had no effect in reducing ROS levels in embryos. The addition of these molecules to the culture media upregulate several hypoxia-related genes when Qc is added to the culture media, and implantation-related genes when 4OHE2 is used. CONCLUSIONS: Qc is a very strong antioxidant molecule that when used for short periods of time during culture can reduce ROS levels and improve embryo quality by activating antioxidant enzymes. 4OHE2 supplementation, despite having no effects in reducing ROS levels, acts directly in the molecular signalling implicated in the implantation process and could be also considered as a supplement for embryo culture during IVF. IMPLICATIONS: Proper supplementation of the culture media could greatly improve the quality of embryos cultured in vitro , resulting in better results in IVF clinics.

Biodegradable ureteral stents: in vitro assessment of the degradation rates of braided synthetic polymers and copolymers.

OBJECTIVES: The control and predictability of degradation rates and the absence of obstructive phenomena are two main challenges for research regarding biodegradable ureteral stents. The objectives are to assess the degradation performance and safety of braided combinations of three synthetic biodegradable polymers and copolymers; and to evaluate the interference of a heparin dip coating on degradation and bacterial colonization. METHODS: The hydrolysis of polyglycolic acid (PGA), poly lactic-co-glycolic acid (PLGA) and Glycomer™ 631 is assessed in this in vitro study that comprises ten groups. Stent samples present a braided arrangement and are incubated in porcine urine that undergoes analysis and exchange every 48 h until degradation. Coating is carried out with sodium heparin via dip coating and determination of the heparin release is carried out by ELISA test. Variables of study are stent mass, mass fold change, degradation time, bacterial colonization and concentration of heparin released in artificial urine. RESULTS: There is statistical significance in degradation times between all materials except between the Glycomer™ 631 alone and combined with PGA. Mass fold change analysis of the Glycomer™ 631 evidences an increasing trend of its mass during degradation. The combination of Glycomer™ 631 and PGA presents a progressive and gradual degradation, where PGA degrades at week 3 while Glycomer™ 631 remains intact until its fragmentation at the late stage of degradation. Heparin coating has no significant impact on mean degradation times and trends in any group, nor on bacteriuria rates; heparin concentration decreases significantly after 72 h. Products of degradation are released steadily with minimum dimensions. CONCLUSIONS: The combination of synthetic biodegradable polymers and copolymers with different degradation rates provides a gradual staged degradation. Heparin dip coating is a safe and feasible technique to coat biodegradable ureteral stents without interfering in degradation rates although it does not have a significant effect on the onset of bacterial colonization.

Can effective pedagogy be ensured in minimally invasive surgery e-learning?

INTRODUCTION: Effectiveness of e-learning diminishes without the support of a pedagogical model to guide its use. In minimally invasive surgery (MIS), this has been reported as a limitation when technology is used to deliver contents without a sound pedagogical background. MATERIAL AND METHODS: We describe how a generic pedagogical model, the 3D pedagogy framework, can be used for setting learning outcomes and activities in e-learning platforms focused on MIS cognitive skills. A demonstrator course on Nissen fundoplication was developed following the model step-by-step in the MISTELA learning platform. Course design was informed by Kolb's Experiential learning model. Content validation was performed by 13 MIS experts. RESULTS: Ten experts agreed on the suitability of content structuring done according to the pedagogical model. All experts agreed that the course provides means to assess the intended learning outcomes. CONCLUSIONS: This work showcases how a general-purpose e-learning framework can be accommodated to the needs of MIS training without limiting the course designers' pedagogical approach. Key advances for its success include: (1) proving the validity of the model in the wider scope of MIS skills and (2) raising awareness amongst stakeholders on the need of developing training plans with explicit, rather than assumed, pedagogical foundations. Abbreviations: MIS: minimally invasive surgery; TEL: technology enhanced learning.