Daniel Ruiz-Molina

Background: The biology of neuromelanin (NMel) is linked to Parkinson’s disease, in which pigment accumulation and release contribute to dopaminergic cell loss. Rodent brains lack detectable levels of NMel, despite possessing the molecular machinery required for its synthesis. The basis for this absence remains unknown. Objectives: To determine whether long-living rodents accumulate NMel and to test whether lifespan constraints explain the lack of pigmentation in mice and rats. Methods: Histological stains were conducted in brain samples of mole rats of different ages to disclose the potential pigmentation of catecholaminergic centers and to determine the chemical phenotype of pigmented neurons. Results: Mole rats exhibited clear age-dependent NMel accumulation beginning after two years of age, with the highest pigmentation levels observed in neurons of the locus coeruleus. Conclusions: Accumulation of NMel is a slow kinetic process that requires extended longevity. Common laboratory rodents lack pigmented brains simply because they do not live long enough to reach detectable NMel levels.

Herein, we report the synthesis of a pyrrole-based symmetric squaraine (SQL) and its supramolecular organization into nanoparticles (SQLNPs) in aqueous media. The aggregation process, driven by non-covalent interactions, gives rise to J- and H-type assemblies and produces pronounced changes in the optical properties of the squaraine. The resulting nanoparticles display selective colorimetric responses toward Zn²⁺, Hg²⁺ and Pd²⁺ and toward low-molecular-weight thiol-containing compounds, with particularly pronounced sensitivity toward glutathione. The photochemical properties of SQL and SQLNPs were also investigated using complementary reactive-oxygen-species assays. Under the experimental conditions employed, blue-light irradiation produced a detectable radical-type ROS response for the aggregated nanoparticles, whereas no measurable response was observed under orange or red-light irradiation. The absence of detectable singlet-oxygen generation together with the response to radical-sensitive assays is consistent with a predominantly Type I radical-mediated photochemical pathway. Computational analysis further indicates that supramolecular aggregation modifies the electronic structure of SQL, particularly for the H-type aggregate. Finally, SQLNPs display blue-light-dependent phototoxicity toward A549 cells. These results demonstrate how supramolecular organization of a multifunctional squaraine can modulate its optical, sensing and photochemical properties and provide a platform for further development of squaraine-based functional nanomaterials.

Thermoresponsive composites made from phase change material particles embedded in polymer matrices show great promise for regulating sunlight transmittance in smart windows. However, their current performance is hindered by critical limitations. Composites obtained from water-soluble matrices present excellent optical performance, but they exhibit intrinsic poor weathering resistance, as they swell and dissolve upon water exposure (e.g., during rainfall or cleaning with aqueous solutions). In contrast, those prepared from water-resistant curable polymers typically require expensive or custom-made phase change materials, and very often show undesired optical properties (e.g., opaque states at room temperature or below). To address this challenge, in this work we developed novel thermoresponsive composite films comprising readily available paraffin particles dispersed within a cross-linked, water-insoluble acrylate matrix. The resulting materials exhibit excellent resistance to water while preserving the characteristic smart window behavior of paraffin-polymer composites; i.e., they remain transparent at low temperatures due to refractive index matching between the matrix and the solid paraffin particles, and become opaque once this condition is lost upon thermally induced paraffin melting, enabling efficient modulation of solar heating gain. In addition, because paraffin-acrylate films are produced via photopolymerization, they are obtained in a fast, straightforward and scalable manner. These features, combined with their low cost, mechanical flexibility, and multistimuli-responsive behavior, make paraffin-acrylate composites a robust and scalable platform for next-generation smart window technologies.

Herein we report a photocurable tissue sealant obtained through thiol-ene reaction of thiol-functionalized catechol monomers, synthesized through thia-Michael addition, with two polyethylene glycol diacrylate (PEGDA) commercial monomers in the presence of photoinitiator (PI) BAPO. The mixture is directly applied to the tissue and irradiated with both UV light and visible light (blue LED). The adhesion was studied through burst pressure (BP) measurements. Characterizations revealed very fast adhesions for gastrointestinal and external skin tissues (11.3 and 29.6 kPa, respectively), competitive with commercial products. Importantly, in vitro cytotoxicity confirmed the sealant biocompatibility in two cell lines (HaCaT and HFF-1) in two different assays, one incubating a piece of the cured material, and the second one curing the formulation over the cells, hence testing the biocompatibility of the procedure.

Glioblastoma, the most prevalent and aggressive brain tumor, presents significant challenge due to its rapid proliferation, invasive nature, and resistance to conventional therapies. Current treatments, including surgery, radiation, and chemotherapy, frequently lead to recurrence, underscoring the urgent need for innovative solutions. This work develops and evaluates bioinspired adhesive membranes designed as novel strategy to address glioblastoma recurrence post‐surgery. Inspired by mussel adhesion, these membranes exhibit strong bioadhesion in wet environments and incorporate various phenolic‐based compounds. Among tested combinations, a membrane with catechin demonstrates specific cytotoxic effect on human glioblastoma cells. This effect is investigated through in vitro assays using glioblastoma cell lines, including primary cell cultures. Exposure to this membrane induces changes in cell morphology and internal structures, and alterations in cell adhesion and migration. Additionally, the use of glioblastoma spheroids and ex vivo tissues allow us to mimic glioblastoma microenvironment and assess the membrane efficacy. Reactive oxygen species are suggested to play a main role in the cytotoxic effect, counteracted by the antioxidant N‐acetylcysteine. Finally, a comprehensive proteomic study elucidates biological mechanisms underlying the membrane performance. This research highlights the potential of mussel‐inspired advanced scaffolds as a localized approach in glioblastoma therapy, suggesting a path for effective anticancer strategies.

Polyphenols, particularly catechols, represent a significant class of compounds characterized by their versatile physicochemical and biological properties, sourced from both natural origins and industrial by‐products. This review highlights their critical redox properties, which enable both antioxidant activity and controlled reactive oxygen species (ROS) generation. These dual capacities underpin their diverse biomedical applications, including the development of materials like nanoparticles, hydrogels, bioadhesives, coatings, and membranes. The review explores their utility in areas such as antimicrobial strategies, advanced cancer therapy, and tissue regeneration, demonstrating how their ROS modulation drives therapeutic effects. Despite promising preclinical studies, significant challenges persist in clinical translation, encompassing pharmacokinetics, biosafety, regulatory pathways, and manufacturing consistency. Future perspectives emphasize the crucial need for deeper understanding and precise control of ROS dynamics, advanced delivery systems, rational material design, and the integration of artificial intelligence (AI) to accelerate research and clinical validation. This comprehensive review synthesizes the current state, challenges, and future directions for polyphenol‐based biomedical materials.

Polyphenols, particularly catechols, represent a significant class of compounds characterized by their versatile physicochemical and biological properties, sourced from both natural origins and industrial by‐products. This review highlights their critical redox properties, which enable both antioxidant activity and controlled reactive oxygen species (ROS) generation. These dual capacities underpin their diverse biomedical applications, including the development of materials like nanoparticles, hydrogels, bioadhesives, coatings, and membranes. The review explores their utility in areas such as antimicrobial strategies, advanced cancer therapy, and tissue regeneration, demonstrating how their ROS modulation drives therapeutic effects. Despite promising preclinical studies, significant challenges persist in clinical translation, encompassing pharmacokinetics, biosafety, regulatory pathways, and manufacturing consistency. Future perspectives emphasize the crucial need for deeper understanding and precise control of ROS dynamics, advanced delivery systems, rational material design, and the integration of artificial intelligence (AI) to accelerate research and clinical validation. This comprehensive review synthesizes the current state, challenges, and future directions for polyphenol‐based biomedical materials.

Herein, high‐contrast colorless‐to‐colored thermochromic materials are accomplished through novel 3‐component mixtures based on catechol/pyrogallol derivatives (color developer – CD), fatty acid phase change materials (PCM), and leuco dyes. Such components ensure: I) always highly colored hot liquid states, promoted by strong stabilization of the dye open form through hydrogen‐bonding interactions with the CDs’ vicinal ‐hydroxyl groups, as also demonstrated by density functional theory calculations; II) solid mixtures with fully controllable coloration state, which directly relies on the relative length of the alkyl chain of CD (C _CD ) and PCM (C _PCM ). As also rationalized by thermal and spectoscopic measurements, colorless solids are obtained when C _CD is larger than C _PCM (ΔC = C _PCM –C _CD <0), due to self‐assembly and phase segregation of CD molecules from PCMs, preventing their interaction with the dye. Instead, when ΔC≥0, the CD solubilizes in PCMs, developing the color of the co‐dissolved dye. The rule is extendable to several leuco dye families (lactams, lactons, fluorans) and acid PCMs, fostering a tunable hot state color palette and transition temperature. The target transition is also preserved in structured mixtures (solid lipid particles), granting for the preparation of polymer composites and screen‐printed thermochromic patterns, of interest for sensors and invisible security inks.

Accurate, rapid, and remote temperature sensing at the nanoscale is essential for applications ranging from monitoring cellular thermodynamics to thermal management of microelectronic devices. Luminescent nanothermometers are promising candidates; however, their deployment is hindered by limited thermal sensitivity and cross-sensitivity to environmental factors that mimic temperature-induced luminescence changes. We introduce fluorescent chromatic nanoswitchers (CNSs), comprising silica nanocapsules incorporating a fluorescent dye within a thermoresponsive matrix. The matrix undergoes a solid-to-liquid phase transition, yielding an exceptional fluorescence lifetime sensitivity of 19% °C^-1 at 37 °C. Crucially, the lifetime-based thermal readout provided by CNSs is resistant to environmental interference, ensuring reliable, reproducible temperature measurements. To enhance CNS performance, we integrate artificial neural networks (ANNs) for advanced lifetime signal processing, enabling faster and robust thermal readouts. Proof-of-concept experiments show that the synergy between high-sensitivity lifetime-based nanothermometers and ANN-driven analysis paves the way for next-generation thermal sensing technologies, offering improved responsiveness, real-time capabilities, and enhanced accuracy.