This paper deals with the proposition of a kinetic model for the direct synthesis of DME via CO₂ hydrogenation in view of the necessary optimization of the catalytic system, reactor design, and process strategy. Despite the fact that DME synthesis is typically treated as a mere combination of two separated catalytic steps (i.e., methanol synthesis and methanol dehydration), the model analysis is now proposed by taking into account the improvements related to the process running over a hybrid catalyst in a rational integration of the two catalytic steps, with boundary conditions properly assumed from the thermodynamics of direct DME synthesis. Specifically, the CO₂ activation step at the metal–oxide interface in the presence of ZrO₂ has been described for the first time through the introduction of an ad hoc mechanism based on solid assumptions from inherent studies in the literature. The kinetic modeling was investigated in a tubular fixed-bed reactor operating from 200 to 260 °C between 1 and 50 bar as a function of a gas hourly space velocity ranging from 2500 to 60,000 NL/kg_cat/h, in a stoichiometric CO₂/H₂ feed mixture of 1:3 v/v. A well-detailed elementary mechanism was used to predict the CO₂ conversion rate and identify the key reaction pathways, starting with the analysis of the implicated reactions and corresponding kinetic mechanisms and expressions, and finally estimating the main parameters based on an appropriate modeling of test conditions.

The objective of this study is to demonstrate the potential of a multicompartmental mathematical model to simulate the activity of the gastrointestinal system after the intake of drugs, with a limited number of parameters. The gastrointestinal system is divided into five compartments, modeled as both continuous systems with discrete events (stomach and duodenum) and systems with delay (jejunum, ileum, and colon). The dissolution of the drug tablet occurs in the stomach and is described through the Noyes–Whitney equation, with pH dependence expressed through the Henderson–Hasselbach relationship. The boluses resulting from duodenal activity enter the jejunum, ileum, and colon compartments, where drug absorption takes place as blood flows countercurrent. The model includes only three parameters with assigned physiological meanings. It was tested and validated using data from in vivo experiments. Specifically, the model was tested with the concentration profiles of nine different drugs and validated using data from two drugs with varying initial concentrations. Overall, the outputs of the model are in good agreement with experimental data, particularly with regard to the time of peak concentration. The primary sources of discrepancy were identified in the concentration decay. The model’s main strength is its relatively low computational cost, making it a potentially excellent tool for in silico assessment and prediction of drug adsorption in the intestine.

Growing evidence suggests that impaired gut permeability and gut microbiota alterations are involved in the pathogenesis of Inflammatory Bowel Diseases (IBDs), which include Ulcerative Colitis (UC) and Crohn’s Disease (CD). Vedolizumab is an anti-α4β7 antibody approved for IBD treatment, used as the first treatment or second-line therapy when the first line results in inadequate effectiveness. The aim of this study is to develop a mathematical model capable of describing the pathophysiological mechanisms of Vedolizumab treatment in IBD patients. In particular, the relationship between drug concentration in the blood, colonic mucosal permeability and fecal microbiota composition was investigated and modeled to detect and predict trends in order to support and tailor Vedolizumab therapies. To pursue this aim, clinical data from a pilot study on a cluster of 11 IBD patients were analyzed. Enrolled patients underwent colonoscopy in three phases (before ($t_0$), after 24 weeks of ($t_1)$ and after 52 weeks of ($t_{2 }$) Vedolizumab treatment) to collect mucosal biopsies for transepithelial electrical resistance (TEER) evaluation (permeability to ions), intestinal permeability measurement and histological analysis. Moreover, fecal samples were collected for the intestinal microbiota analysis at the three time points. The collected data were compared to those of 11 healthy subjects at $t_0$, who underwent colonoscopy for screening surveillance, and used to implement a three-compartmental mathematical model (comprising central blood, peripheral blood and the intestine). The latter extends previous evidence from the literature, based on the regression of experimental data, to link drug concentration in the peripheral blood compartment with Roseburia abundance and intestinal permeability. The clinical data showed that Vedolizumab treatment leads to an increase in TEER and a reduction in intestinal permeability to a paracellular probe, improving tissue inflammation status. Microbiota analysis showed increasing values of Roseburia, albeit not statistically significant. This trend was adequately reproduced by the mathematical model, which offers a useful tool to describe the pathophysiological effects of Vedolizumab therapy on colonic mucosal permeability and fecal microbiota composition. The model’s satisfactory predictive capabilities and simplicity shed light on the relationship between the drug, the microbiota and permeability and allow for its straightforward extension to diverse therapeutic conditions.

This study introduces a 3D bioprinted scaffold embedding human Bone Morphogenetic Protein-2 (hBMP-2)-loaded Poly-lactic-co-glycolic Acid nanocarriers (PLGA-NCs) to induce the osteogenic differentiation of human Tendon Stem/Progenitor Cells (TSPCs) harvested from tendon explants. The nanocarriers (120 ± 40 nm) were embedded in a Gelatin Methacryloyl (GelMA) matrix and bioplotted under optimized conditions to preserve cell viability (60%). A 3D dynamic culture system, supported by compartmental modelling, enabled continuous perfusion over 21 days, promoting efficient metabolite exchange and removal of catabolic byproducts. This environment enhanced proliferation and osteogenic differentiation, demonstrated by a 20-fold increase in osteopontin (p < 0.05) and an 8-fold increase in osteocalcin (p < 0.05) expression, along with increased calcium deposition observed via Alizarin Red S staining. In contrast, static monolayer cultures with soluble hBMP-2 (20 ng/mL) showed reduced osteogenic activity. These findings suggest that the engineered scaffold offers a promising strategy for regenerating the bone-tendon interface by leveraging the multipotency of TSPCs in a biomimetic 3D environment.