Emanuele Mauri

Sodium carboxymethylcellulose (NaCMC), a natural agent for low‐impact paper systems, is commonly produced via heterogeneous etherification, yet evaluating its degree of substitution (DS) and substitution dispersity remains challenging and method‐dependent. Here, technical‐grade NaCMC samples were synthesized by high‐solids, solvent‐free reactive extrusion at varying NaOH/sodium monochloroacetate (SMCA)/cellulose ratios, yielding materials with different substitution levels and heterogeneity. A Stoichiometric Data‐Reconciliation (SDR) method was developed as an alternative to direct DS measurements with a stoichiometry‐driven workflow, enabling indirect DS estimation (DS ^SDR ) from reaction mass balances closed using independently quantified by‐products (sodium glycolate and residual SMCA). To resolve substitution heterogeneity, centrifugation‐based fractionation was implemented to isolate high‐, intermediate‐, and low‐substitution populations, providing a mass‐weighted DS (DS ^cent ). Both DS ^SDR and DS ^cent showed good agreement with experimental DS values (DS ^exp ) obtained by ATR‐FTIR, across eight NaCMC formulations. Near‐equimolar NaOH/SMCA maximized DS, whereas higher reagent excess (≥3:1 to cellulose) reduced substitution efficiency. Fractionation revealed dominant high‐substitution populations with progressive enrichment of lower‐substitution fractions upon sedimentation. Complementary morphological and rheological analyses were consistent with the fractionation outcome. Collectively, the combined SDR and fractionation strategy provides an analytically flexible distribution‐aware toolkit for technical NaCMC, enabling improved process‐structure‐property correlations in solvent‐free reactive extrusion.

Ovarian cancer (OC) is one of the leading causes of cancer-related mortality in women, primarily due to the late-stage diagnosis and limited therapeutic efficacy. Three-dimensional (3D) bioprinting enables the fabrication of cell-laden scaffolds that better recapitulate the native spatial organization and may support the investigation of tumor cell behavior. However, high-grade serous ovarian cancer (HG-SOC) cell subtypes remain largely unexplored in bioprinting, and it remains unclear whether a different scaffold composition is required to provide an optimal niche for each subtype. To address these gaps, we developed a 3D bioprinting workflow based on methacrylated gelatin (GelMA) and a hybrid methacrylated hyaluronic acid/methacrylated gelatin formulation (HAGel) to generate constructs containing KURAMOCHI and OVCAR3 HG-SOC cells, alongside SKOV3 as a reference epithelial OC model. Bioink formulations were optimized to achieve reproducible extrusion printing and stable construct formation. Rheological characterization showed a higher storage modulus for HAGel scaffold (approximately 2-fold higher than GelMA), while both formulations remained within a stiffness range suitable for cell culture. GelMA exhibited higher swelling and a broader printability window, whereas HAGel showed reduced water uptake and required more restricted processing conditions to ensure stable bioprinting. Cellular responses were evaluated in terms of viability, proliferation, morphology, and expression of hyaluronic-acid-associated markers (e.g., CD44, MMP-2, and MMP-14). Postprinting viability remained high throughout culture (approximately 80-99% after 14 days), with outcomes depending on both cell line and hydrogel formulation. KURAMOCHI and SKOV3 cells exhibited higher viability and cell density in HAGel, whereas OVCAR3 cells performed better in GelMA, consistent with CD44 expression and MMP trends, reflecting subtype-dependent interactions with the scaffold composition. These findings demonstrate the feasibility of bioprinting HG-SOC cells and show how bioink formulations may contribute to cell-line-dependent response, paving the way for a rational design of constructs for advanced OC in vitro platforms.

This study explores the implementation of a response surface methodology supporting the rational design of hyaluronic acid (HA) - linear polyethyleneimine (LPEI) nanogels via droplet-based microfluidics for the targeted delivery of doxorubicin.

Nanogels (NGs) are versatile polymeric nanocarriers with high drug loading capacity and colloidal stability, making them pivotal candidates for targeted biomedical applications. Surface functionalization with biomolecules is essential for selective targeting therapies; however, conventional covalent conjugation can compromise the activity of sensitive ligands (e.g., proteins and antibodies). The His-tag strategy offers a reversible, oriented binding through coordination with transition metal ions, widely used in protein purification, but scarcely explored for polymeric NG decoration. Here, we developed polyallylamine-based NGs via an emulsion–evaporation process. The NG outer layer was functionalized with lysine-conjugated nitrilotriacetic acid to chelate Ni²⁺ or Co³⁺ ions, enabling the His-tag strategy. To validate this approach, a His-Rhodamine compound was used as a representative His-tag structure, mimicking potential bioactive ligands or motifs. Our results demonstrate that Co³⁺ provides superior His-tag grafting density compared to Ni²⁺, preserving the biocompatibility of the nanoscaffold. The cobalt-complexed NGs were also tested as cisplatin delivery systems, showing enhanced therapeutic performance compared with the administration of the free drug in ovarian cancer cells. Overall, the cobalt-mediated His-tag conjugation proved to be an efficient approach for the noncovalent surface decoration of polymeric NGs, defining a reliable alternative for the functionalization of this type of nanoscaffolds. Owing to the presence of His-tag functionalities in several biomolecules, the proposed strategy can be readily extended to a wide range of His-tag-based species, thus providing a flexible platform for the design of advanced, targeted NGs with improved selectivity and therapeutic potential.

Emerging contaminants such as polar iodinated contrast media (ICMs) are increasingly detected in aquatic environments and remain difficult to remove due to their high solubility, limited sorption affinity, and resilience to conventional treatment. This study presents a comprehensive experimental and modeling investigation aimed at engineering a dually modified montmorillonite (Mt-II) for efficient adsorption of the non-ionic ICM iohexol. Batch and continuous-flow experiments are synergistically integrated with a stochastic multimodel analysis to quantify parameter uncertainty and objectively evaluate competing model formulations using rigorous selection criteria.In batch systems, Mt-II achieves rapid uptake and high removal efficiency (~93%), outperforming pristine and singly modified clays. Equilibrium data are most plausibly described by the Langmuir and Sips isotherms. Otherwise, kinetic analysis identified external film diffusion as the dominant rate-limiting step, indicating accessible engineered sorption sites. Under flow-through column conditions, Mt-II maintains strong performance, solute breakthrough behavior being governed by mass-transfer regimes dependent on sorbent loading, flow rate, and influent concentration. Stochastic modeling supports a conceptual picture according to which the Thomas and Yan models can reliably capture breakthrough dynamics across diverse operating conditions. Importantly, column capacities remain stable even at elevated influent concentrations, suggesting operation near the practical saturation capacity of the newly engineered material.Density-functional electrostatic potential mapping reveal complementary hydrogen-bonding and -interaction domains between iohexol and the Mt-II interlayer, providing mechanistic support for macroscopic adsorption behavior. Collectively, these results establish a mechanistically grounded and statistically robust framework elucidating the behavior of tailored amphiphilic organoclays in the presence of pharmaceuticals such as non-ionic ICMs and advancing their potential application in next-generation water treatment technologies.

Self-assembled PEG–PBAE nanoparticles incorporating disulfide bonds enable glutathione-responsive degradation and on-demand release of physically encapsulated therapeutics.

The accurate prediction of drug release kinetics is crucial for designing effective drug delivery formulations. In this context, controlled drug release from hydrogel matrices is a key strategy to enhance therapeutic outcomes while minimizing side effects. In this study, we develop an advanced mathematical model to describe drug release from nanogels, aiming to accurately represent both standard scenarios where the active compound is fully released and cases where diffusion alone is not sufficient to achieve 100% release. The proposed model is based on Fick's diffusion equation but introduces more realistic boundary conditions by eliminating the perfect sink assumption and incorporating a partition coefficient to account for incomplete drug release. The model was applied to six experimental case studies, varying surface charge, pH of the release environment, and nanogel surface functionalization in order to determine the corresponding diffusion coefficient. The results show good agreement with experimental data, providing a consistent interpretation of the release mechanisms observed in the different case studies. This demonstrates the ability of the model to capture the key factors that influence drug release, making it a valuable tool to support the development of new drug delivery systems. By enabling the prediction and optimization of release profiles, the proposed approach can contribute to the design of tailored delivery strategies to achieve improved therapeutic outcomes.