Additive manufacturing techniques for the production of tissue engineering constructs

‘Additive manufacturing’ (AM) refers to a class of manufacturing processes based on the building of a solid object from three‐dimensional (3D) model data by joining materials, usually layer upon layer. Among the vast array of techniques developed for the production of tissue‐engineering (TE) scaffolds, AM techniques are gaining great interest for their suitability in achieving complex shapes and microstructures with a high degree of automation, good accuracy and reproducibility. In addition, the possibility of rapidly producing tissue‐engineered constructs meeting patient's specific requirements, in terms of tissue defect size and geometry as well as autologous biological features, makes them a powerful way of enhancing clinical routine procedures. This paper gives an extensive overview of different AM techniques classes (i.e. stereolithography, selective laser sintering, 3D printing, melt–extrusion‐based techniques, solution/slurry extrusion‐based techniques, and tissue and organ printing) employed for the development of tissue‐engineered constructs made of different materials (i.e. polymeric, ceramic and composite, alone or in combination with bioactive agents), by highlighting their principles and technological solutions. Copyright © 2012 John Wiley & Sons, Ltd.     

AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs

Phenotypic changes induced by extracellular vesicles have been implicated in mesenchymal stromal cell–promoted recovery of AKI. MicroRNAs are potential candidates for cell reprogramming toward a proregenerative phenotype. The aim of this study was to evaluate whether microRNA deregulation inhibits the regenerative potential of mesenchymal stromal cells and derived extracellular vesicles in a model of glycerol-induced AKI in severe combined immunodeficient mice. We generated mesenchymal stromal cells depleted of Drosha to alter microRNA expression. Drosha-knockdown cells produced extracellular vesicles that did not differ from those of wild-type cells in quantity, surface molecule expression, and internalization within renal tubular epithelial cells. However, these vesicles showed global downregulation of microRNAs. Whereas wild-type mesenchymal stromal cells and derived vesicles administered intravenously induced morphologic and functional recovery in AKI, the Drosha-knockdown counterparts were ineffective. RNA sequencing analysis showed that kidney genes deregulated after injury were restored by treatment with mesenchymal stromal cells and derived vesicles but not with Drosha-knockdown cells and vesicles. Gene ontology analysis showed in AKI an association of downregulated genes with fatty acid metabolism and upregulated genes with inflammation, matrix-receptor interaction, and cell adhesion molecules. These alterations reverted after treatment with wild-type mesenchymal stromal cells and extracellular vesicles but not after treatment with the Drosha-knockdown counterparts. In conclusion, microRNA depletion in mesenchymal stromal cells and extracellular vesicles significantly reduced their intrinsic regenerative potential in AKI, suggesting a critical role of microRNAs in recovery after AKI.     

Risk of Adverse Pregnancy Outcomes in Women with CKD

CKD is increasingly prevalent in pregnancy. In the Torino-Cagliari Observational Study (TOCOS), we assessed whether the risk for adverse pregnancy outcomes is associated with CKD by comparing pregnancy outcomes of 504 pregnancies in women with CKD to outcomes of 836 low-risk pregnancies in women without CKD. The presence of hypertension, proteinuria (>1 g/d), systemic disease, and CKD stage (at referral) were assessed at baseline. The following outcomes were studied: cesarean section, preterm delivery, and early preterm delivery; small for gestational age (SGA); need for neonatal intensive care unit (NICU); new onset of hypertension; new onset/doubling of proteinuria; CKD stage shift; “general” combined outcome (preterm delivery, NICU, SGA); and “severe” combined outcome (early preterm delivery, NICU, SGA). The risk for adverse outcomes increased across stages (for stage 1 versus stages 4–5: “general” combined outcome, 34.1% versus 90.0%; “severe” combined outcome, 21.4% versus 80.0%; P<0.001). In women with stage 1 CKD, preterm delivery was associated with baseline hypertension (odds ratio [OR], 3.42; 95% confidence interval [95% CI], 1.87 to 6.21), systemic disease (OR, 3.13; 95% CI, 1.51 to 6.50), and proteinuria (OR, 3.69; 95% CI, 1.63 to 8.36). However, stage 1 CKD remained associated with adverse pregnancy outcomes (general combined outcome) in women without baseline hypertension, proteinuria, or systemic disease (OR, 1.88; 95% CI, 1.27 to 2.79). The risk of intrauterine death did not differ between patients and controls. Findings from this prospective study suggest a “baseline risk” for adverse pregnancy-related outcomes linked to CKD.     

Psychometric characteristics of the mutuality scale in heart failure patients and caregivers

Background

Higher patient-caregiver mutuality is associated with improved patient and caregiver outcomes, but no studies have tested the psychometric characteristics of the mutuality scale (MS) in heart failure (HF) patient and caregiver population.