Search Results (376)

Background: Gum Arabic (GA) is a natural polysaccharide widely recognized for its antioxidant and anti-inflammatory properties; however, its functional behavior as a biopolymeric gel and the mechanisms underlying its selective effects on cancer-related redox microenvironments remain insufficiently characterized. It is imperative to note that the interaction between its physicochemical properties and its biological activity in colorectal cancer remains to be fully clarified. Methods: This study aimed to evaluate the antineoplastic potential of GA in human colorectal cancer (CRC) cell lines (HT-29 and HCT-116) compared to normal fibroblasts (MRC-5) using the MTS assay. Oxidative stress-related molecular responses were assessed by quantitative PCR analysis of GPX4, GSTA2, CAT, NFKB, and SOD1 expression. In parallel, extracellular concentrations of key metal ions (Fe²⁺, Zn²⁺, Mn²⁺, Mg²⁺, Cu²⁺, and Al³⁺) were quantified following GA exposure. To establish its functional gel characteristics, rheological measurements were performed to assess viscosity and shear-dependent behavior, and USP-compliant in vitro kinetic studies were conducted to evaluate time-dependent release properties. Results: GA induced dose-dependent cytotoxicity in HT-29 and HCT-116 colorectal cancer cells, while MRC-5 fibroblasts exhibited comparatively higher viability across the tested concentration range, indicating reduced sensitivity in normal cells. Rheological analysis revealed concentration- and ion-dependent viscoelastic behavior, identifying a 10% (w/w) GA formulation as optimal due to its balanced low-shear viscosity and controlled shear-thinning properties. Kinetic studies demonstrated a defined, diffusion-governed release profile under physiologically relevant conditions. At the molecular level, significant upregulation of GPX4 and GSTA2 was observed in both cancer cell lines, whereas NFKB expression increased selectively in HT-29 cells, with no notable changes in CAT or SOD1 expression. Additionally, GA treatment resulted in marked increases in Fe²⁺, Zn²⁺, and Mn²⁺ levels, indicating modulation of the redox–ionic microenvironment. Conclusions: These findings demonstrate that GA functions as a natural, ion-responsive biopolymeric system with defined rheological and kinetic properties, capable of selectively targeting colorectal cancer cells through coordinated genetic and ionic regulation of oxidative stress. Collectively, the results position GA as a promising functional gel-based platform for future redox-modulated therapeutic strategies in colorectal cancer. Full article

The development of photocurable hydrogel biomaterial inks with suitable rheology, low cytotoxicity, and tuneable mechanical properties is essential for reliable biofabrication. This study aimed to formulate PEGDA–gelatine–collagen inks using lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) as photoinitiator. Rheological characterisation and flow-model fitting were performed, mechanical stiffness modulation under different light intensities was evaluated, complex structures were printed using direct extrusion and FRESH methodologies, and PEGDA/LAP extractables were quantified by NMR after controlled washing procedures. In vitro assays assessed cell viability and proliferation on the resulting scaffolds. The Herschel–Bulkley model best described the flow behaviour across formulations; while viscoelastic measurements showed that increasing light intensity progressively enhanced hydrogel stiffness, enabling fine control over final mechanical properties. NMR analysis showed that washing removed a substantial fraction of residual LAP, in agreement with the biological findings: fibroblasts failed to survive on unwashed scaffolds but exhibited robust proliferation and recovered their characteristic elongated morphology on washed constructs. Among all inks, PeGeCol_10_2 provided the best combination of shear-thinning behaviour, structural integrity, low residual photoinitiator, and tuneable mechanics. Using this formulation, we successfully printed large anatomical models with high fidelity and excellent handling properties, underscoring its potential for soft-tissue prosthetics and broader tissue-engineering applications. Full article

This review synthetizes experimental evidence on collagen-related bioactivity and the biomaterial potential of plant species native to the Chihuahuan Desert, aiming to identify natural compounds that could enhance next-generation dermal bioinks for 3D bioprinting. A structured search across major databases included studies characterizing plant extracts or metabolites, with reported effects on collagen synthesis, fibroblast activity, inflammation, oxidative balance, or interactions with polymers commonly used in skin-engineering materials being developed. Evidence was organized thematically to reveal mechanistic patterns despite methodological heterogeneity. Several species, among them Larrea tridentata, Opuntia spp., Aloe spp., Matricaria chamomilla, Simmondsia chinensis, Prosopis glandulosa, and Artemisia ludoviciana, repeatedly demonstrated the presence of bioactive metabolites such as lignans, flavonoids, phenolic acids, terpenoids, and polysaccharides. These compounds support pathways central to extracellular matrix repair, including stimulation of fibroblast migration and collagen I/III expression, modulation of inflammatory cascades, antioxidant protection, and stabilization of ECM structures. Notably, several metabolites also influence viscoelastic and crosslinking behaviors, suggesting that they may enhance the printability, mechanical stability, and cell-supportive properties of collagen-, GelMA-, and hyaluronic acid-based bioinks. The review also reflects on the bioethical and sustainability considerations regarding endemic floral resources, highlighting the importance of responsible sourcing, conservation extraction practices, and alignment with international biodiversity and access to benefit/sharing frameworks. Taken together, these findings point to a promising, yet largely unexplored, opportunity: integrating regionally derived phytochemicals into bioinks to create biologically active, environmentally conscious, and clinically relevant materials capable of improving collagen remodeling and regenerative outcomes in 3D-printed skin. Full article

A major objective of this study is to investigate the incorporation of hydroxyapatite nanoparticles (nHA) in a biopolymeric matrix of alginate (Alg) and gelatin (Gel), with particular emphasis understanding how controlled variation in nHA concentration affects rheological, mechanical, printing, and biological performance. Although Alg–Gel blends and nHA-containing hydrogels have been previously explored, a systematic and quantitative correlation between nHA loading, viscoelastic recovery, yield behavior, filament fidelity, and cell viability under optimized bioprinting conditions has not been established. Here, we address this by preparing and evaluating six composite inks (0, 1, 2, 3, 4, and 5% w/v nHA). The parameters of interest included the printing accuracy, the rheological profile, including over 70% viscosity recovery after 10 s in almost all formulations, the elastic modulus, which was over 10 kPa, and the swelling degree. In addition, pre-osteoblastic cells were embedded in these formulations, subsequently bioprinted, and demonstrated viability over 70% after 7 days. The results advance our understanding on the effect of the chemical composition behind the modification of the properties of the composite materials and their applications for biofabrication. This work contributes quantitative insight into how compositional tuning influences the performance of alginate–gelatin–nHA bioinks for extrusion-based bioprinting applications. Full article

Cannabidiol (CBD), the primary bioactive element of cannabis, has shown promise in alleviating pain and inflammation, although mechanisms in periodontal inflammation are not fully understood. To improve its limited solubility and mucosal permeability, the developed chitosan-based mucoadhesive hydrogel incorporating CBD-loaded PLGA nanospheres (CPN hydrogel) was characterized by FT-IR, SEM, particle size, rheological, swelling, and diffusion analyses, followed by biological evaluations, including wound-healing and RT-qPCR-based anti-inflammatory assays. The improved CPN hydrogel had a homogeneous shape, better viscoelastic behavior, and sustained drug release. Over 90% of CBD was released within 96 h, and Franz cell experiments showed improved permeability (124.1 μg/cm² after 72 h). The gellan gum-based mucosal substrate significantly increased adhesion (1137.33 ± 142.25 s) compared to the control groups. Antioxidant studies indicated 73.65% DPPH radical scavenging, whereas antibacterial tests showed more than 99% suppression of Staphylococcus aureus. Furthermore, in vitro studies validated its wound healing and the downregulation of the inflammatory cytokines IL-6 and TNF-α. The results indicate that the CPN-loaded chitosan hydrogel has extended mucosal retention, strong antibacterial activity, and steady release of CBD. This underscores its significant potential as a targeted treatment for inflammatory oral diseases such as gingivitis and periodontitis. Full article

Mechanical loading is a central cue in periodontal tissues, where compression of the periodontal ligament guides remodeling and orthodontic tooth movement (OTM). However, most mechanobiology studies have used two-dimensional cultures with poorly defined loading, and the role of autophagy under realistic three-dimensional compression remains unclear. In this study, we constructed a three-dimensional static compression model by encapsulating human periodontal ligament cells in collagen–alginate–CaSO₄ hydrogels, whose swelling, degradation, and viscoelasticity approximate those of native matrix. When exposed to a controlled static compressive stress, the cells exhibited an early autophagic response with increased ATG7, Beclin1, and LC3-II/LC3-I; accumulation of LC3-positive puncta; and reduced p62 expression between 4 and 8 h. Pharmacological modulation showed that activation of AKT-mTOR signaling suppressed this response, whereas its inhibition further augmented autophagy, identifying AKT-mTOR as a negative regulator of compression-induced autophagy. Together, these findings demonstrate that moderate static compression drives AKT-mTOR-dependent autophagy in periodontal ligament cells and establish a simple hydrogel platform for quantitative studies of periodontal remodeling. Full article

Cell morphology and its mechanical properties are crucial factors in cancer development, affecting migration, invasiveness, and the potential risk of metastasis. However, most studies address these aspects separately, limiting the understanding of how morphological complexity relates to cellular mechanics. This work presents an integrated approach that simultaneously quantifies morphology and viscoelasticity in the human osteosarcoma cell line MG-63. Stress–relaxation experiments and optical imaging of the same cells were performed using a custom-built system that couples Atomic Force Microscopy (AFM) with an inverted optical microscope. Morphometric parameters were extracted from cell contours, while viscoelastic properties were obtained by fitting AFM data to the Fractional Kelvin (FK) and Fractional Zener (FZ) models. Among the morphological descriptors, the Shape Complexity (SC) was proposed. It is derived from the Lobe Contribution Elliptical Fourier Analysis (LOCO-EFA), which captures fine-scale contour features overlooked by conventional metrics. Experimental results show that, in MG-63 cells, higher SC values are associated with greater stiffness, indicating a correlation between cell shape complexity and cell stiffness. Furthermore, loading-rate analysis shows that the FZ model captures strain-rate-dependent stiffening more effectively than the FK model. This methodology provides a first approach to jointly analyzing quantitative morphological parameters and mechanical properties, underlining the importance of combined studies to achieve a comprehensive understanding of cell behavior. Full article

Osteoarthritis (OA) is a multifactorial degenerative joint disease in which aberrant mechanical cues act in concert with metabolic dysregulation and chronic low-grade inflammation, with chondrocyte hypertrophy representing a key pathological event driving cartilage degeneration. Alterations in extracellular matrix (ECM) properties—including mechanical loading, stiffness and viscoelasticity, topological organization, and surface chemistry—regulate hypertrophic differentiation and matrix degradation in a zone-, stage-, and scale-dependent manner. Microscale measurements often reveal localized stiffening in superficial zones during early OA, whereas bulk tissue testing can show softening or heterogeneous changes in deeper zones or advanced stages, highlighting the context-dependent nature of ECM mechanics. These biophysical signals are sensed by integrin-based adhesion complexes, primary cilia, mechanosensitive ion channels (TRP/Piezo), and the actin cytoskeleton–nucleus continuum, and are transduced into intracellular pathways with zone- and stage-specific effects, governing chondrocyte fate under physiological and osteoarthritic conditions. Mechanism-based anti-hypertrophic strategies include biomimetic scaffold design for focal defects, dynamic mechanical stimulation targeting early OA, and multimodal approaches integrating mechanical cues with biochemical factors, gene modulation, drug delivery, or cell-based therapies. Collectively, this review provides an integrated mechanobiological framework for understanding cartilage degeneration and highlights emerging opportunities for disease-modifying interventions targeting chondrocyte hypertrophy. Full article

Systemic anticancer therapy causes a number of side effects; therefore, local drug release devices may play an important role in this area. In this study, we developed polyurethane-dendrimer foams containing different amounts of third-generation poly (amidoamine) dendrimers (PAMAM G3) to evaluate their ability to encapsulate and release the model anticancer drug doxorubicin (DOX), as well as their biocompatibility and effectiveness against normal and cancer cells in vitro. PU–PAMAM foams containing 10–50 wt% PAMAM G3 were prepared using glycerin-based polyether polyol and castor oil as co-components. Structural and rheological analyses revealed that foams containing up to 20 wt% PAMAM G3 exhibited a well-developed porous structure, while higher dendrimer loadings (≥30 wt%) led to irregular cell shapes, pore coalescence, and thinning of cell walls, and indicated a gradual loss of structural integrity. Rheological creep–recovery measurements confirmed the structural findings: moderate PAMAM G3 incorporation (≤20 wt%) increased both the instantaneous and delayed elastic modulus (E₁ ≈ 130–140 kPa; E₂ ≈ 80 kPa) and enhanced elastic recovery, reflecting improved cross-link density and foam stability. Higher dendrimer contents (30–50 wt%) caused a decline in these parameters and higher viscoelastic compliance, indicating a softer, less stable structure. The DOX loading capacity and encapsulation efficiency increased with PAMAM G3 content, reaching maximum values of 35% and 51% for 30–40 wt% PAMAM G3, respectively. However, the most sustained DOX release profiles were observed for matrices containing 20 wt% PAMAM G3. Analysis of cumulative release and kinetic modeling revealed a transition from diffusion-controlled release at low PAMAM contents to burst-dominated release at higher dendrimer loadings. Importantly, matrices containing 10–20 wt% PAMAM G3 also indicated selective anticancer action against squamous cell carcinoma (SCC-15) compared to non-cancerous human keratinocytes (HaCaT). Moreover, the DOX they released effectively destroyed cancer cells. Overall, PU–PAMAM foams containing 10–20 wt% PAMAM G3 provide the most balanced combination of structural stability, controlled drug release, and cytocompatibility. These materials therefore represent a promising platform as passive carriers in drug delivery systems (DDSs), such as local implants, anticancer patches, or bioactive wound dressings. Full article

Children with Hutchinson–Gilford progeria syndrome (HGPS) are born without height and weight abnormalities, and postnatal development is delayed from two months of age. The pathophysiological manifestations of HGPS can be categorized into the three tissue systems that are primarily affected: bone and cartilage, the smooth muscular layer of the vasculature, and the dermis layer. To understand the biology of the syndrome’s complications resulting from the inherited dominant mutation of the LMNA gene, HGPS has to be considered in embryogenesis. Since the development of the primarily affected HGPS tissues involves a simultaneous contribution of mesodermal and neural crest cells, we hypothesized that the stochastic and heterogeneous coexistence of mesoderm and neural crest cells might be crucial for the onset and manifestation of HGPS. In addition, the expression of Lamin A and/or progerin during embryonic development tends to accumulate in the cell nucleus, causing the syndrome manifestation. Then, how and why are infants with the LMNA gene mutation born without severe deviations? Migration is a distinguishing property of mesoderm and neural crest cells, so that they are continuously subjected to mechanical stimuli throughout development and require normal lamina function. However, the viscoelastic property and the mechanosensor capability to respond to mechanical stress of the HGPS cell nucleus are disturbed. Despite the presence of progerin in development, we assume that high levels of Lamin B1 in cells determine the delayed onset of HGPS after birth. We also hypothesized that progerin toxicity could be managed and prevented, potentially allowing for rescue by the presence of Lamin B1. Full article

This paper investigates the flow of a second-grade hybrid nanofluid through a Darcy–Forchheimer porous medium under Cattaneo–Christov heat and mass flux models. The hybrid nanofluid, composed of alumina and copper nanoparticles in water, enhances thermal and mass transport, while the second-grade model captures viscoelastic effects, and the Darcy–Forchheimer medium accounts for both linear and nonlinear drag. Using similarity transformations and the spectral quasilinearisation method, the nonlinear governing equations are solved numerically and validated against benchmark results. The results show that hybrid nanoparticles significantly boost heat and mass transfer, while Cattaneo–Christov fluxes delay thermal and concentration responses, reducing the near-wall temperature and concentration. The distributions of velocity, temperature, concentration, and microorganism density are markedly affected by porosity, the Forchheimer number, the bio-convection Peclet number, and relaxation times. The results illustrate that hybrid nanoparticles significantly increase heat and mass transfer, whereas thermal and concentration relaxation factors delay energy and species diffusion, thickening the associated boundary layers. Viscoelasticity, porous medium resistance, Forchheimer drag, and bio-convection all have an influence on flow velocity and transfer rates, highlighting the subtle link between these mechanisms. These breakthroughs may be beneficial in establishing and enhancing bioreactors, microbial fuel cells, geothermal systems, and other applications that need hybrid nanofluids and non-Fourier/non-Fickian transport. Full article

Bioengineered functional salivary tissues can advance regenerative therapies, preclinical drug testing, and the fundamental understanding of salivary gland dysfunction. Current salivary tissue models are typically Matrigel-based, hydrogel-based or scaffold-free organoid systems, with limited physiological relevance or mimicry of cell-cell and cell-extracellular matrix (ECM) interactions. We previously developed elastin-alginate cryoelectrospun scaffolds (CES) that resemble the topography and viscoelastic properties of healthy salivary ECM, and validated their potential for stromal cell culture, delivery, and in vitro fibrosis modeling. Here, we evaluated the utility of CES to support 3D cocultures of salivary gland epithelial and mesenchymal cells in vitro. We compared CES with honeycomb-like topography (CES-H) to densely packed electrospun nanofibers (NFs) and CES with fibrous topography (CES-F) for their ability to support SIMS epithelial cell attachment, morphology, 3D clustering, phenotype and organization into distinct clusters when cocultured with stromal cells. Both CES-F and CES-H supported epithelial cell attachment and clustering; in particular, CES-H most effectively supported the self-organization of epithelial and stromal cells into distinct 3D clusters resembling the structure of native salivary tissue. Stromal cells were essential for maintaining the phenotype of epithelial cells cultured on CES-H, laying the foundation for the development of in vitro tissue models. Full article

In this work, we report a compact and highly sensitive photoacoustic spectroscopy (PAS) system based on a cone–sphere coupled photoacoustic cell (CSC-PAC) for real-time detection of trace acetylene (C₂H₂) dissolved in transformer oil. The sensing module integrates a conical resonator with a spherical cavity, forming a hybrid structure that effectively enhances photoacoustic confinement and energy coupling efficiency. Finite element thermo-viscoelastic simulations were employed to optimize the cavity geometry and resonance conditions for maximum signal generation. Experimental results demonstrate a strong linear correlation between the photoacoustic signal and C₂H₂ concentration (R² > 0.999), with a sensitivity of 2.45 µV·ppm⁻¹. Allan deviation confirms a detection limit of 18.6 ppb is achieved at a 400 s averaging time, confirming excellent system stability. The miniaturized light-acoustic spectroscopy sensor, with a total volume of 7.5 mL and a rapid response time of 25.5 s, provides a high-performance and field-deployable platform for on-site monitoring of high-voltage power equipment and other industrial applications. Full article

Gelatin-based hydrogels are promising materials for pharmaceutical and biomedical applications due to their biocompatibility, biodegradability, and tunable gel-forming behavior. However, their thermo-sensitivity and limited processability often restrict their practical use in advanced drug delivery or tissue engineering systems. In this study, low-molecular-weight gelatin (LMWG) was obtained from native gelatin through controlled degradation with hydroxylamine, aiming to enhance processability while maintaining functional amino groups for crosslinking. Hydrogels prepared from both native gelatin and LMWG were crosslinked with genipin, a natural and biocompatible compound, and comprehensively characterized in terms of structural, mechanical, and biological properties. LMWG exhibited superior processability, remaining liquid at room temperature, which facilitates the preparation of different formulations and the potential incorporation of bioactive compounds into the crosslinked hydrogels. Compared with gelatin-genipin hydrogels, LMWG-genipin hydrogels showed higher swelling capacity, slightly increased porosity, and improved flexibility without significant loss of mechanical integrity. Rheological analysis confirmed both hydrogels’ viscoelastic properties with differences in their thermo-sensitive behavior. Cytocompatibility assays using L929 fibroblasts demonstrated low toxicity as well as proliferation of cells seeded on the materials. Overall, the combination of molecular weight modulation and crosslinking by genipin provides a simple and effective strategy to develop gelatin-based hydrogels suitable for pharmaceutical formulations, tissue-engineering scaffolds, and controlled-release systems. Full article

While research on cellular responses to cyclic compression has predominantly focused on proliferation and differentiation, changes in cell orientation and force distribution within the cytoskeleton represent crucial biomechanical aspects that remain less explored. This study aimed to design a programmable device for applying uniaxial cyclic compression to cells and analyze actin filament reorientation following specific compression regimens. A programmable device was developed to apply uniaxial cyclic compression. A finite element model of a viscoelastic cell incorporating actin filaments was developed to evaluate cell membrane strain. Statistical analysis included Pearson correlation to assess the relationship between actin filament orientation and membrane strain, following normality confirmation with the Kolmogorov–Smirnov test. Student’s t-test and one-way ANOVA were used to assess significance between groups. A strong positive correlation was found between the average/peak maximum principal strain on the cell membrane and the angle of actin filaments relative to the cell long axis (r = 0.96, p < 0.05; r = 0.94, p < 0.05, respectively). Cyclic compression reduced the maximum principal strain by reversing the actin filament orientation observed under static compression. This correlated with a significant decrease in cell mortality. Cyclic compression reduces the maximum principal strain on the cell membrane via reorientation of actin filaments, suggesting a cytoprotective effect. These findings provide insight into biomechanical adaptive mechanisms of cells under cyclic compression and could inform the design of bioreactors and rehabilitation devices. Full article