Synergy between 3D-extruded electroconductive scaffolds and electrical stimulation to improve bone tissue engineering strategies.

In this work, we propose a simple, reliable, and versatile strategy to create 3D electroconductive scaffolds suitable for bone tissue engineering (TE) applications with electrical stimulation (ES). The proposed scaffolds are made of 3D-extruded poly(ε-caprolactone) (PCL), subjected to alkaline treatment, and of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), anchored to PCL with one of two different crosslinkers: (3-glycidyloxypropyl)trimethoxysilane (GOPS) and divinyl sulfone (DVS). Both cross-linkers allowed the formation of a homogenous and continuous coating of PEDOT:PSS to PCL. We show that these PEDOT:PSS coatings are electroconductive (11.3-20.1 S cm-1), stable (up to 21 days in saline solution), and allow the immobilization of gelatin (Gel) to further improve bioactivity. In vitro mineralization of the corresponding 3D conductive scaffolds was greatly enhanced (GOPS(NaOH)-Gel - 3.1 fold, DVS(NaOH)-Gel - 2.0 fold) and cell colonization and proliferation were the highest for the DVS(NaOH)-Gel scaffold. In silico modelling of ES application in DVS(NaOH)-Gel scaffolds indicates that the electrical field distribution is homogeneous, which reduces the probability of formation of faradaic products. Osteogenic differentiation of human bone marrow derived mesenchymal stem/stromal cells (hBM-MSCs) was performed under ES. Importantly, our results clearly demonstrated a synergistic effect of scaffold electroconductivity and ES on the enhancement of MSC osteogenic differentiation, particularly on cell-secreted calcium deposition and the upregulation of osteogenic gene markers such as COL I, OC and CACNA1C. These scaffolds hold promise for future clinical applications, including manufacturing of personalized bone TE grafts for transplantation with enhanced maturation/functionality or bioelectronic devices.

A Novel Approach for Design and Manufacturing of Curvature-Featuring Scaffolds for Osteochondral Repair.

Osteochondral (OC) defects affect both articular cartilage and the underlying subchondral bone. Due to limitations in the cartilage tissue's self-healing capabilities, OC defects exhibit a degenerative progression to which current therapies have not yet found a suitable long-term solution. Tissue engineering (TE) strategies aim to fabricate tissue substitutes that recreate natural tissue features to offer better alternatives to the existing inefficient treatments. Scaffold design is a key element in providing appropriate structures for tissue growth and maturation. This study presents a novel method for designing scaffolds with a mathematically defined curvature, based on the geometry of a sphere, to obtain TE constructs mimicking native OC tissue shape. The lower the designed radius, the more curved the scaffold obtained. The printability of the scaffolds using fused filament fabrication (FFF) was evaluated. For the case-study scaffold size (20.1 mm × 20.1 mm projected dimensions), a limit sphere radius of 17.064 mm was determined to ensure printability feasibility, as confirmed by scanning electron microscopy (SEM) and micro-computed tomography (µ-CT) analysis. The FFF method proved suitable to reproduce the curved designs, showing good shape fidelity and replicating the expected variation in porosity. Additionally, the mechanical behavior was evaluated experimentally and by numerical modelling. Experimentally, curved scaffolds showed strength comparable to conventional orthogonal scaffolds, and finite element analysis was used to identify the scaffold regions more susceptible to higher loads.

Comparing the psychometric properties of two primary school Computational Thinking (CT) assessments for grades 3 and 4: The Beginners' CT test (BCTt) and the competent CT test (cCTt).

Introduction: With the increasing amount of research around Computational Thinking (CT) and endeavors introducing CT into curricula worldwide, assessing CT at all levels of formal education is of utmost importance to ensure that CT-related learning objectives are met. This has contributed to a progressive increase in the number of validated and reliable CT assessments for K-12, including primary school. Researchers and practitioners are thus required to choose among multiple instruments, often overlapping in their age validity. Methods: In this study, we compare the psychometric properties of two of these instruments: the Beginners' CT test (BCTt), developed for grades 1-6, and the competent CT test (cCTt), validated for grades 3-4. Classical Test Theory and Item Response Theory (IRT) were employed on data acquired from 575 students in grades 3-4 to compare the properties of the two instruments and refine the limits of their validity. Results: The findings (i) establish the detailed psychometric properties of the BCTt in grades 3-4 for the first time, and (ii) through a comparison with students from the same country, indicate that the cCTt should be preferred for grades 3-4 as the cCTt is able to discriminate between students of low and medium ability. Conversely, while the BCTt, which is easier, shows a ceiling effect, it is better suited to discriminate between students in the low ability range. For these grades, the BCTt can thus be employed as a screening mechanism to identify low ability students. Discussion: In addition to providing recomendations for use of these instruments, the findings highlight the importance of comparing the psychometric properties of existing assessments, so that researchers and practitioners, including teachers and policy makers involved in digital education curricular reforms, may take informed decisions when selecting assessments.

Clinical aspects of pancreatogenic diabetes secondary to hereditary pancreatitis.

BACKGROUND: Hereditary pancreatitis is a rare inherited form of pancreatitis, characterized by recurrent episodes of acute pancreatitis with early onset and/or chronic pancreatitis, and presenting brittle diabetes, composed of episodes of nonketotic hyperglycemia and severe hypoglycemia. The existing literature regarding this form of diabetes is scarce. In this report, clinical features of pancreatogenic diabetes secondary to hereditary pancreatitis are presented along with recommendations for appropriate medical treatment. RESULTS: Clinical data from five patients of a family with pancreatogenic diabetes secondary to hereditary pancreatitis were analyzed. The average time between hereditary pancreatitis and diabetes diagnosis was 80 ± 24 months (range: 60-180 months) with a mean age of 25.6 ± 14.7 years (range: 8-42 years), four patients used antidiabetic agents for 46 ± 45 months and all progressed to insulin therapy with a mean dose of 0.71 ± 0.63 IU/kg (range: 0.3-1.76 IU/kg). The glycemic control had a high variability with average capillary blood glucose of 217.00 ± 69.44 mg/dl (range: 145-306 mg/dl) and the average HbA1c was 9.9 ± 1.9% (range: 7.6-11.6%). No ketoacidosis episodes occurred and there were several episodes of hospitalization for severe hypoglycemia. CONCLUSIONS: Diabetes mellitus secondary to hereditary pancreatitis presents with early onset, diverse clinical presentation and with extremely labile glycemic control. Diabetes treatment varies according to the presentation and insulin is frequently necessary for glycemic control.