Islet-on-a-chip for the study of pancreatic β-cell function

Diabetes mellitus is a significant public health problem worldwide. It encompasses a group of chronic disorders characterized by hyperglycemia, resulting from pancreatic islet dysfunction or as a consequence of insulin-producing β-cell death. Organ-on-a-chip platforms have emerged as technological systems combining cell biology, engineering, and biomaterial technological advances with microfluidics to recapitulate a specific organ’s physiological or pathophysiological environment. These devices offer a novel model for the screening of pharmaceutical agents and to study a particular disease. In the field of diabetes, a variety of microfluidic devices have been introduced to recreate native islet microenvironments and to understand pancreatic β-cell kinetics in vitro. This kind of platforms has been shown fundamental for the study of the islet function and to assess the quality of these islets for subsequent in vivo transplantation. However, islet physiological systems are still limited compared to other organs and tissues, evidencing the difficulty to study this “organ” and the need for further technological advances. In this review, we summarize the current state of islet-on-a-chip platforms that have been developed so far. We recapitulate the most relevant studies involving pancreatic islets and microfluidics, focusing on the molecular and cellular-scale activities that underlie pancreatic β-cell function.This review received financial support from the European Research Council program under grants ERC-StG-DAMOC (714317), the Spanish Ministry of Economy and Competitiveness, through the “Severo Ochoa” Program for Centres of Excellence in R&D (SEV-2016-2019) and “Retos de investigación: Proyectos I+D+i” (TEC2017-83716-C2-2-R), the CERCA Programme/Generalitat de Catalunya (2017-SGR-1079), and Fundación Bancaria “la Caixa”- Obra Social “la Caixa” (project IBEC-La Caixa Healthy Ageing)

Influence de plusieurs paramèters de dessin et procès sur le largueur et la résistance du structure tissée

El proceso de tisaje genera unas contracciones en las estructuras tejidas, y estas estructuras tienen unas resistencias que dependen principalmente, y para unos ilados determinados, de unos parámetros geométricos (parámetros relacionados con la geometría de la estructura). En este trabajo se estudia la influencia del coeficiente de ligadura por trama, densidad de trama y, también, de la tensión de la urdimbre en el tisaje sobre el ancho del tejido resultante (y por lo tanto la contracción respecto al ancho de trabajo en el peine del telar) y sus resistencias, de urdimbre y trama. En este trabajo se establecen los modelos de regresión de las resistencias sobre los parámetros indicados; atendiendo a la información obtenida se propone unos niveles óptimos para obtener unas resistencias máximas.The weaving process generates contractions in the woven structures, and these structures have resistances that depend mainly, and for some specifics yarns, of several geometric parameters (parameters related with the geometry of the structure). The present work studies the influence of the interlacing, filling density and, also, of the tension of the warp in the weaving on the width of the fabric (and therefore the contraction regarding the work width in the comb of the loom) and its tensile strength, of warp and weft.In this work, linear models predicting tensile strength response were established; on the basis of the data obtained it’s proposed some good levels to find the maximum tensile strength.Le processus de tissage crée des contractions dans les structures textiles qui ont une certaine résistance qui dépend principalement, et pour quelques fils donnés, des paramètres géométriques de celles-ci. Cette étude se pendre sur l´influence du coefficient du liaison sens trame, sur la densité de trame et, également, sur la tension de la chaîne en tissage sur le largueur du tissu (et par conséquence, la contraction du tissu sur le largeur du peigne au travail) et sa résistance, en sens chaîne et trame. Cette étude établie les modèles de régression de résistance à la traction sur les paramètres indiqués; compte tenu de l´information obtenue, il est proposé quelques bons niveaux obtenir résistances maximales

Cellulose-based scaffolds enhance pseudoislets formation and functionality

In vitro research for the study of type 2 diabetes (T2D) is frequently limited by the availability of a functional model for islets of Langerhans. To overcome the limitations of obtaining pancreatic islets from different sources, such as animal models or human donors, immortalized cell lines as the insulin-producing INS1E β-cells have appeared as a valid alternative to model insulin-related diseases. However, immortalized cell lines are mainly used in flat surfaces or monolayer distributions, not resembling the spheroid-like architecture of the pancreatic islets. To generate islet-like structures, the use of scaffolds appeared as a valid tool to promote cell aggregations. Traditionally-used hydrogel encapsulation methods do not accomplish all the requisites for pancreatic tissue engineering, as its poor nutrient and oxygen diffusion induces cell death. Here, we use cryogelation technology to develop a more resemblance scaffold with the mechanical and physical properties needed to engineer pancreatic tissue. This study shows that carboxymethyl cellulose (CMC) cryogels prompted cells to generate β-cell clusters in comparison to gelatin-based scaffolds, that did not induce this cell organization. Moreover, the high porosity achieved with CMC cryogels allowed us to create specific range pseudoislets. Pseudoislets formed within CMC-scaffolds showed cell viability for up to 7 d and a better response to glucose over conventional monolayer cultures. Overall, our results demonstrate that CMC-scaffolds can be used to control the organization and function of insulin-producing β-cells, representing a suitable technique to generate β-cell clusters to study pancreatic islet function

Reconstrucción mamaria con prótesis prepectorales

Introducción: Tras la realización de una mastectomía, existen diversas técnicas de reconstrucción mamaria, una de ellas es mediante el uso de implantes mamarios, siendo la técnica más utilizada la colocación de las prótesis en el plano retropectoral pero, recientemente se está cuestionando utilizar la técnica prepectoral por su menor alteración funcional y dolor postoperatorio. Pacientes y Métodos: Nuestra serie se compone de 7 pacientes, 14 mamas, a las que se les ha realizado mastectomía en el servicio de cirugía del HCU Lozano Blesa, con reconstrucción protésica prepectoral con colgajo dérmico y malla de Vicryl desde Septiembre de 2017 hasta Febrero de 2018. Resultados: Analizamos las complicaciones precoces que han aparecido en el seguimiento postoperatorio (5 meses de media) y la calidad de vida mediante el formulario BREAST-Q. De las 14 reconstrucciones realizadas, se han producido 5 complicaciones (35%) que incluyen 1 pérdida del implante (7%), 1 necrosis de la piel (7%), 2 seromas (14%) y 1 infección del implante (7%).El dolor postoperatorio en la primera semana tras la cirugía evaluado mediante una escala de 1-10 es, de media, 1,8. Todas ellas han tenido escasa repercusión en la movilidad de la extremidad superior y una rápida reincorporación a su actividad habitual. Las puntuaciones obtenidas en el BREAST-Q son 57.6 en el apartado de satisfacción con la mama, 84.4 en satisfacción con el resultado, 82.8 en bienestar social, 73 en bienestar sexual, 80.8 en bienestar físico, 53.8 en satisfacción con el pezón, 58.2 en satisfacción con la información, 83.8 en satisfacción con el cirujano, 90 en satisfacción con el equipo médico. Conclusiones: La reconstrucción con prótesis prepectoral permite mantener la funcionalidad del músculo pectoral, se asocia a bajas tasas de dolor postoperatorio y presenta una elevada satisfacción por parte de las pacientes.<br /

EndoTrainer: a novel hybrid training platform for endoscopic surgery

Purpose Endoscopy implies high demanding procedures, and their practice requires structured formation curricula supported by adequate training platforms. Physical platforms are the most standardised solution for surgical training, but over the last few years, virtual platforms have been progressively introduced. This research work presents a new hybrid, physic-virtual, endoscopic training platform that exploits the benefits of the two kind of platforms combining realistic tools and phantoms together with the capacity of measuring all relevant parameters along the execution of the exercises and of providing an objective assessment performance. Methods The developed platform, EndoTrainer, has been designed to train and assess surgical skills in hysteroscopy and cystoscopy following a structured curricula. The initial development and validation is focused on hysteroscopic exercises proposed in the Gynaecological Endoscopic Surgical Education and Assessment (GESEA) Certification Programme from The Academy and European Society for Gynaecological Endoscopy (ESGE) and analyses the obtained results of an extensive study with 80 gynaecologists executing 30 trials of the standard 30 degree endoscope navigation exercise. Results The experiments demonstrate the benefits of the presented hybrid platform. Multi-variable statistical analysis points out that all subjects have obtained statistically significant improvement in all relevant parameters: shorter and safer trajectories, improved 30-degree endoscope navigation, accurate positioning over the targets and reduction of the execution time. Conclusion This paper presents a new hybrid approach for training, and evaluating whether it provides an objectivable improvement of camera navigation endoscopic basic skills. The obtained results demonstrate the initial hypothesis: all subjects have improved their camera handling and navigation skills.Peer ReviewedPostprint (published version

The Upper Aptian carbonate platform of Benicàssim-Orpesa (Maestrat Basin, Iberian Chain): depositional model

A Lower Cretaceous (Upper Aptian) succesion of carbonate rocks in the southwestern Maestrat Basin (Iberian Chain) was analysed according to sedimentological and palaeontological criteria. The shallow marine sequence was deposited upon a homoclinal carbonate ramp. Six main facies types were distinguished and grouped into facies belts allowing the elaboration of a conceptual depositional model. The inner ramp is represented by rudist floatstones forming a non-restricted lagoon and bioclastic and peloidal grainstones forming shoals affected by wave base. The middle ramp consists of platestones and domestones of corals that developed in moderate energetic environments, occasionally affected by storms. The outer ramp is characterized by coral sheetstones growth fabrics, wackestones of orbitolines and spiculites indicating deep and poorly light environments probably with nutrient-rich water

Collagen-Tannic Acid Spheroids for β-Cell Encapsulation Fabricated Using a 3D Bioprinter

Type 1 Diabetes results from autoimmune response elicited against β-cell antigens. Nowadays, insulin injections remain the leading therapeutic option. However, injection treatment fails to emulate the highly dynamic insulin release that β-cells provide. 3D cell-laden microspheres have been proposed during the last years as a major platform for bioengineering insulin-secreting constructs for tissue graft implantation and a model for in vitro drug screening platforms. Current microsphere fabrication technologies have several drawbacks: the need for an oil phase containing surfactants, diameter inconsistency of the microspheres, and high time-consuming processes. These technologies have widely used alginate for its rapid gelation, high processability, and low cost. However, its low biocompatible properties do not provide effective cell attachment. This study proposes a high-throughput methodology using a 3D bioprinter that employs an ECM-like microenvironment for effective cell-laden microsphere production to overcome these limitations. Crosslinking the resulting microspheres with tannic acid prevents collagenase degradation and enhances spherical structural consistency while allowing the diffusion of nutrients and oxygen. The approach allows customization of microsphere diameter with extremely low variability. In conclusion, a novel bio-printing procedure is developed to fabricate large amounts of reproducible microspheres capable of secreting insulin in response to extracellular glucose stimuli

In Situ LSPR Sensing of Secreted Insulin in Organ-on-Chip

Organ-on-a-chip (OOC) devices offer new approaches for metabolic disease modeling and drug discovery by providing biologically relevant models of tissues and organs in vitro with a high degree of control over experimental variables for high-content screening applications. Yet, to fully exploit the potential of these platforms, there is a need to interface them with integrated non-labeled sensing modules, capable of monitoring, in situ, their biochemical response to external stimuli, such as stress or drugs. In order to meet this need, we aim here to develop an integrated technology based on coupling a localized surface plasmon resonance (LSPR) sensing module to an OOC device to monitor the insulin in situ secretion in pancreatic islets, a key physiological event that is usually perturbed in metabolic diseases such as type 2 diabetes (T2D). As a proof of concept, we developed a biomimetic islet-on-a-chip (IOC) device composed of mouse pancreatic islets hosted in a cellulose-based scaffold as a novel approach. The IOC was interfaced with a state-of-the-art on-chip LSPR sensing platform to monitor the in situ insulin secretion. The developed platform offers a powerful tool to enable the in situ response study of microtissues to external stimuli for applications such as a drug-screening platform for human models, bypassing animal testing

Protein Supplementation with Short Peptides Prevents Early Muscle Mass Loss after Roux-en-Y-Gastric Bypass

Bariatric surgery; Nutrition supplementation; ProteinCirugía bariátrica; Suplementación nutricional; ProteínaCirurgia bariàtrica; Suplementació nutricional; ProteïnaIntroduction: A significant reduction in fat-free mass (FFM) following bariatric surgery (BS) has been reported, and adequate protein intake is recommended for FFM preservation. Current guidelines of nutritional management after BS recommend complex protein (CP) compounds. However, Roux-en-Y-gastric bypass (RYGB) has a negative impact on CP digestion, leading to protein malabsorption. At present, there is no data regarding the impact of early supplementation with short peptide-based (SPB) or hydroxy methylbutyrate (HMB)-enriched formulas on the evolution of the FFM after the BS. Aim: The aim of this study is to evaluate the effect of nutritional products based on CP, HBM-enriched, or SPB formulas on the FFM of patients that undergo RYGB. Material and methods: This is a prospective interventional study, including three groups of patients (according to the type of protein product) as candidates for BS, recruited between December 2021 and April 2022, matched by age, gender, and BMI. All patients underwent evaluations at baseline and one month post-BS, including: medical history, physical and anthropometric evaluation, bioimpedance, and biochemical analysis. Results: A total of 60 patients were recruited: 63% women, mean age 43.13 ± 9.4 years, and BMI 43.57 ± 4.1 kg/m2. The % of FFM loss from total weight loss (TWL) was significantly lower in the SPB group than CP and HMB groups despite the major %TWL in this group (40.60 ± 17.27 in CP, 34.57 ± 13.15 in HMB, and 19.14 ± 9.38 in SPB, p < 0.001). TWL% was 9.98 ± 1.82 vs. 9.83 ± 2.71 vs. 13.56 ± 4.30, p < 0.001, respectively. Conclusion: In our study, the SPB supplementation prevented almost 50% FFM lost from the TWL than the CP- or HMB-enriched compounds at one month post-BS. These results are significant in the setting of muscle mass preservation after the BS, and have the potential to change the current guidelines for the management of nutritional supplementation after BS.This study was supported by grants from the Instituto de Salud Carlos III (Fondo de Investigacion Sanitaria, PI20/01086). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Canagliflozin: A New Therapeutic Option in Patients That Present Postprandial Hyperinsulinemic Hypoglycemia after Roux-en-Y Gastric Bypass: A Pilot Study

Cirurgia bariàtrica; Teràpia farmacològica; Hipoglucèmia postprandialCirugía bariátrica; Terapia farmacológica; Hipoglucemia posprandialBariatric surgery; Pharmacological therapy; Postprandial hypoglycemiaIntroduction: Roux-en-Y gastric bypass (RYGB) is the most common surgical procedure for morbid obesity. However, it can present serious late complications, like postprandial hyperinsulinemic hypoglycemia (PHH). Recent data suggested an increase in intestinal SGLT-1 after RYGB. However, there is no data on the inhibition of SGLT-1 to prevent PHH in patients with prior RYBG. On this basis, we aimed to evaluate (a) the effect of canagliflozin 300 mg on the response to 100 g glucose overload (oral glucose tolerance test [OGTT]); (b) the pancreatic response after intra-arterial calcium stimulation in the context of PHH after RYGB. Materials and Methods: This is a prospective pilot study including patients (n = 21) with PHH after RYGB, matched by age and gender with healthy controls (n = 5). Basal OGTT and after 2 weeks of daily 300 mg of canagliflozin was performed in all cases. In addition, venous sampling after intra-arterial calcium stimulation of the pancreas was performed in 10 cases. Results: OGTT after canagliflozin showed a significant reduction of plasma glucose levels (minute 30: 161.5 ± 36.22 vs. 215.9 ± 58.11 mg/dL; minute 60: 187.46 ± 65.88 vs. 225.9 ± 85.60 mg/dL, p < 0.01) and insulinemia (minute 30: 95.6 ± 27.31 vs. 216.35 ± 94.86 mg/dL, p = 0.03; minute 60: 120.85 ± 94.86 vs. 342.64 ± 113.32 mIU/L, p < 0.001). At minute 180, a significant reduction (85.7%) of the rate of hypoglycemia was observed after treatment with canagliflozin (p < 0.00001). All cases presented normal pancreatic response after intra-arterial calcium administration. Conclusion: Canagliflozin (300 mg) significantly decreased glucose absorption and prevented PHH after 100 g OGTT in patients with RYGB. Our results suggest that canagliflozin could be a new therapeutic option for patients that present PHH after RYGB.There were no funding sources