Adaptable test bench for ASTM-compliant permeability measurement of porous scaffolds for tissue engineering.

Intrinsic permeability describes the ability of a porous medium to be penetrated by a fluid. Considering porous scaffolds for tissue engineering (TE) applications, this macroscopic variable can strongly influence the transport of oxygen and nutrients, the cell seeding process, and the transmission of fluid forces to the cells, playing a crucial role in determining scaffold efficacy. Thus, accurately measuring the permeability of porous scaffolds could represent an essential step in their optimization process. In literature, several methods have been proposed to characterize scaffold permeability. Most of the currently adopted approaches to assess permeability limit their applicability to specific scaffold structures, hampering protocols standardization, and ultimately leading to incomparable results among different laboratories. The content of novelty of this study is in the proposal of an adaptable test bench and in defining a specific testing protocol, compliant with the ASTM International F2952-22 guidelines, for reliable and repeatable measurements of the intrinsic permeability of TE porous scaffolds. The developed permeability test bench (PTB) exploits the pump-based method, and it is composed of a modular permeability chamber integrated within a closed-loop hydraulic circuit, which includes a peristaltic pump and pressure sensors, recirculating demineralized water. A specific testing protocol was defined for characterizing the pressure drop associated with the scaffold under test, while minimizing the effects of uncertainty sources. To assess the operational capabilities and performance of the proposed test bench, permeability measurements were conducted on PLA scaffolds with regular (PS) and random (RS) micro-architecture and on commercial bovine bone matrix-derived scaffolds (CS) for bone TE. To validate the proposed approach, the scaffolds were as well characterized using an alternative test bench (ATB) based on acoustic measurements, implementing a blind randomized testing procedure. The consistency of the permeability values measured using both the test benches demonstrated the reliability of the proposed approach. A further validation of the PTB's measurement reliability was provided by the agreement between the measured permeability values of the PS scaffolds and the theory-based predicted permeability value. Once validated the proposed PTB, the performed measurements allowed the investigation of the scaffolds' transport properties. Samples with the same structure (guaranteed by the fused-deposition modeling technique) were characterized by similar permeability values, and CS and RS scaffolds showed permeability values in agreement with the values reported in the literature for bovine trabecular bone. In conclusion, the developed PTB and the proposed testing protocol allow the characterization of the intrinsic permeability of porous scaffolds of different types and dimensions under controlled flow regimes, representing a powerful tool in view of providing a reliable and repeatable framework for characterizing and optimizing scaffolds for TE applications.

The distinguishing electrical properties of cancer cells.

In recent decades, medical research has been primarily focused on the inherited aspect of cancers, despite the reality that only 5-10% of tumours discovered are derived from genetic causes. Cancer is a broad term, and therefore it is inaccurate to address it as a purely genetic disease. Understanding cancer cells' behaviour is the first step in countering them. Behind the scenes, there is a complicated network of environmental factors, DNA errors, metabolic shifts, and electrostatic alterations that build over time and lead to the illness's development. This latter aspect has been analyzed in previous studies, but how the different electrical changes integrate and affect each other is rarely examined. Every cell in the human body possesses electrical properties that are essential for proper behaviour both within and outside of the cell itself. It is not yet clear whether these changes correlate with cell mutation in cancer cells, or only with their subsequent development. Either way, these aspects merit further investigation, especially with regards to their causes and consequences. Trying to block changes at various levels of occurrence or assisting in their prevention could be the key to stopping cells from becoming cancerous. Therefore, a comprehensive understanding of the current knowledge regarding the electrical landscape of cells is much needed. We review four essential electrical characteristics of cells, providing a deep understanding of the electrostatic changes in cancer cells compared to their normal counterparts. In particular, we provide an overview of intracellular and extracellular pH modifications, differences in ionic concentrations in the cytoplasm, transmembrane potential variations, and changes within mitochondria. New therapies targeting or exploiting the electrical properties of cells are developed and tested every year, such as pH-dependent carriers and tumour-treating fields. A brief section regarding the state-of-the-art of these therapies can be found at the end of this review. Finally, we highlight how these alterations integrate and potentially yield indications of cells' malignancy or metastatic index.

Computational Study of Potential Galectin-3 Inhibitors in the Treatment of COVID-19.

Galectin-3 is a carbohydrate-binding protein and the most studied member of the galectin family. It regulates several functions throughout the body, among which are inflammation and post-injury remodelling. Recent studies have highlighted the similarity between Galectin-3's carbohydrate recognition domain and the so-called "galectin fold" present on the N-terminal domain of the S1 sub-unit of the SARS-CoV-2 spike protein. Sialic acids binding to the N-terminal domain of the Spike protein are known to be crucial for viral entry into humans, and the role of Galectin-3 as a mediator of lung fibrosis has long been the object of study since its levels have been found to be abnormally high in alveolar macrophages following lung injury. In this context, the discovery of a double inhibitor may both prevent viral entry and reduce post-infection pulmonary fibrosis. In this study, we use a database of 56 compounds, among which 37 have known experimental affinity with Galectin-3. We carry out virtual screening of this database with respect to Galectin-3 and Spike protein. Several ligands are found to exhibit promising binding affinity and interaction with the Spike protein's N-terminal domain as well as with Galectin-3. This finding strongly suggests that existing Galectin-3 inhibitors possess dual-binding capabilities to disrupt Spike-ACE2 interactions. Herein we identify the most promising inhibitors of Galectin-3 and Spike proteins, of which five emerge as potential dual effective inhibitors. Our preliminary results warrant further in vitro and in vivo testing of these putative inhibitors against SARS-CoV-2 with the hope of being able to halt the spread of the virus in the future.