Search Results (10,153)

Background/Objectives: Calcium hydroxyapatite (CaHA)-based injectable materials are widely used as dermal biostimulators. In vitro models allow for controlled comparison of cellular responses and particle characteristics across formulations. This study aimed to compare two commercially available CaHA-based materials in terms of fibroblast metabolic activity, extracellular matrix-related gene expression, and microsphere morphology. Methods: Primary human dermal fibroblasts were exposed to two CaHA-based materials (Sample R and Sample S) at 10 mg/mL. Metabolic activity was assessed using the MTT assay at 24, 36, 48, and 72 h. Type I collagen and elastin gene expression were evaluated by RT-qPCR at 72 h. Microsphere morphology was analyzed by scanning electron microscopy (SEM). Results: Both materials increased fibroblast metabolic activity compared with the control at all time points. Early responses were similar, whereas Sample S showed higher activity at 48 and 72 h. At 72 h, both materials increased collagen and elastin gene expression versus the control, with greater responses observed for Sample S. SEM analysis showed predominantly spherical microspheres in both materials, with qualitative differences in surface microtopography. Conclusions: Under controlled in vitro conditions, both CaHA-based materials were biocompatible and modulated fibroblast metabolic activity and extracellular matrix-related gene expression. Differences in particle surface characteristics may contribute to the observed biological profiles. These findings support further studies incorporating extended incubation periods and protein-level analyses. Full article

Sodium hypochlorite (NaOCl) remains the gold standard irrigant in endodontics due to its proteolytic and antimicrobial properties, whereas hydrogen peroxide (HP) is widely used for internal bleaching because of its oxidative capacity. Both agents have been associated with chemical and structural alterations in dentin; however, the impact of their sequential application on the organic–mineral balance has not been fully elucidated. Objective: To evaluate whether the isolated and sequential application of 5.25% NaOCl and 37.5% HP induces chemical alterations in dentin by analyzing changes in the organic matrix and mineral phase using Fourier-transform infrared spectroscopy (FTIR) and Energy-dispersive X-ray spectroscopy (EDX). Methods: Twenty-four independent dentin sections (n = 6 per group) from six human third molars were distributed using a tooth-balanced allocation into four groups: Control, NaOCl (5.25%, 15 min), HP (37.5%, 30 min), and sequential NaOCl+HP. FTIR assessed organic (amide I, II, III, CH₂) and inorganic (phosphate, carbonate) components through baseline-corrected integrated areas, Full Width at Half Maximum (FWHM), and molecular ratios. Surface elemental composition and the calculated Ca/P atomic ratio were determined by EDX. Multiple sub-measurements per specimen were averaged before statistical analysis. Data were analyzed using Kruskal–Wallis and Mann–Whitney U tests with Bonferroni correction (p < 0.05). Results: FTIR revealed treatment-dependent modifications. NaOCl reduced absorbance in organic-associated bands, indicating collagen degradation, whereas HP altered the mineral phase. The NaOCl+HP group exhibited increased numerical values for integrated band areas, with differences detected in carbonate, phosphate, and amide III bands (p < 0.05), reflecting structural disorganization and modified spectral signal rather than tissue preservation. No differences were detected across the calculated infrared ratios (p > 0.05). EDX showed decreased absolute atomic percentages of Ca, P, and O in the NaOCl+HP group (p < 0.05), indicating structural demineralization, while its stoichiometric Ca/P ratio remained at 1.56. Isolated HP shifted the mineral stoichiometry to the highest numerical Ca/P ratio (1.69; range 1.58–1.80). Fluorine decreased across all treated groups (p < 0.001). Conclusions: Sequential NaOCl and HP application triggers distinct chemical alterations compared to individual treatments, inducing severe structural disorganization of the organic network and absolute mineral depletion of Ca and P. This multi-agent sequence alters dentin stoichiometry, which may compromise the biomechanical integrity of the tissue. Full article

Diabetic foot ulcers (DFUs) are among the most severe complications affecting diabetic patients, and dressing therapy is one of the standard treatments for DFUs. However, traditional dressings are inadequate for addressing the complex microenvironment of DFUs. Consequently, advanced natural polymer-based dressings have attracted extensive research attention in diabetic foot care due to their biocompatibility, low immunogenicity, and biodegradability. These natural polymer materials include collagen, gelatin, chitosan (CS), hyaluronic acid (HA), alginate, and cellulose. This review systematically analyzes the pathophysiological mechanisms underlying the difficult healing of DFUs and the advantages of natural polymer-based dressings in diabetic wound healing, highlights preclinical studies, and synthesizes evidence from clinical research. Moreover, we pinpoint the challenges associated with these dressings and propose future directions for the improvement of diabetic wound care. Full article

Maternal exposure to airborne particulate matter smaller than $2.5$ μm (${\mathrm{PM}}_{2.5}$) has been associated with adverse fetal outcomes, although its effects on intramembranous ossification remain poorly understood. This study evaluated the impact of gestational and pregestational exposure to wood-smoke-derived ${\mathrm{PM}}_{2.5}$ on fetal neurocranial ossification in Sprague–Dawley rats. Females were allocated to four exposure conditions combining filtered air (FA) and non-filtered air (NFA): FA/FA, FA/NFA, NFA/FA, and NFA/NFA. Fetuses were collected at gestational day 21 and analyzed using fetal morphometry, radiography, micro-computed tomography, whole-mount alizarin red skeletal staining, histology, and immunohistochemistry for HIF-1$\alpha$, COL-1, BMP-2, FGF-R1, and TGF-$\beta$. Continuous exposure (NFA/NFA) was associated with reduced fetal weight, shorter crown–rump length, impaired craniofacial mineralization, widened cranial sutural regions, and reduced mineral density, particularly in the occipital and interparietal bones. Histologically, exposed fetuses exhibited abundant osteoid, reduced osteocyte incorporation, and diffuse osteoblastic distribution, consistent with delayed osteogenic maturation. Immunohistochemistry showed increased HIF-1$\alpha$ immunoreactivity, altered TGF-$\beta$ regulation, and reduced COL-1 expression in continuously exposed fetuses, whereas BMP-2 and FGF-R1 showed no significant changes. These findings suggest that maternal exposure to wood-smoke-derived PM_2.5 is associated with delayed fetal neurocranial intramembranous ossification, particularly under continuous exposure. The observed immunohistochemical profile, elevated HIF-1$\alpha$, reduced COL-I, and altered TGF-$\beta$, is consistent with a hypoxia-associated imbalance between extracellular matrix deposition and mineral maturation; however, the underlying mechanistic pathway was not directly functionally tested and should be regarded as a biologically plausible inferential model requiring further experimental validation. Full article

Background and Objectives: Seroma formation is the most common postoperative complication following mastectomy and axillary dissection, negatively affecting wound healing and delaying adjuvant therapy. Despite numerous surgical and pharmacological approaches, no universally effective strategies have been established. This study aimed to comparatively evaluate the effects of porcine dermal collagen (PDC), tranexamic acid (TXA), and thymoquinone (TQ) on seroma formation and tissue repair. Materials and Methods: A randomized controlled experimental study was conducted using 40 female Wistar albino rats that underwent modified radical mastectomy and axillary dissection. All surgical and postoperative procedures were performed in accordance with the institutional animal welfare and ethical guidelines, including postoperative analgesic administration. The animals were divided into four groups: control, PDC, TXA, and TQ (n = 10 each). Seroma volume was measured on postoperative day 14. Histopathological evaluation, immunohistochemical analysis (FGF2, VEGF, TGF-β1, p53), and quantitative real-time PCR were performed to assess tissue remodeling and molecular responses. Results: All treatment groups demonstrated a significant reduction in seroma volume compared to the control group, with the most pronounced decrease observed in the TQ and TXA groups (p < 0.0001), while PDC showed a moderate effect (p < 0.01). Histopathological analysis revealed increased collagen deposition and fibrin formation in the PDC and TQ groups, whereas TXA exhibited a more limited remodeling profile than the others. Immunohistochemical and molecular analyses showed significant upregulation of VEGF across all groups, with broader and more consistent increases in the PDC and TQ groups. TGF-β1 and FGF2 expression demonstrated region-specific increases, particularly in the thoracic tissue. p53 expression remained relatively stable in the TXA group but was elevated in specific regions in the PDC and TQ groups. Importantly, the increased inflammatory infiltration, edema, vascular proliferation, and fibrin deposition observed in the TQ group may reflect not only active tissue remodeling processes but also prolonged inflammatory activation and enhanced fibrotic responses and should therefore be interpreted cautiously. Conclusions: PDC, TXA, and TQ differentially modulate postoperative seroma formation via distinct biological mechanisms. While TXA primarily exerts a targeted anti-seroma effect and PDC enhances extracellular matrix stabilization, TQ is associated with broader angiogenic, inflammatory, and tissue remodeling responses within this preclinical rat model. These findings should be considered exploratory and hypothesis-generating, and additional mechanistic studies and clinical investigations are necessary before definitive therapeutic conclusions can be established regarding the use of TQ in human breast surgery settings. Full article

Background: Kidney disorders are strongly related to metabolic disturbances, including obesity and type 2 diabetes. Excessive intake of sugar and saturated fats promotes lipid accumulation, cellular energy issues and inflammatory responses. Cannabigerol (CBG), a non-psychotropic phytocannabinoid, has recently gained attention for its metabolic, anti-inflammatory and potential protective properties. Methods: The present study investigated the effect of two weeks of CBG administration (last 14 days of the experiment) on fatty acid (FA) composition, FA metabolic pathways and FA transporters in rats subjected to a high-fat high-sucrose diet (HFHS) for 6 weeks. Male Wistar rats were divided into four groups: Control, CBG, HFHS, and HFHS+CBG. Kidney tissue and urine samples were analyzed by gas–liquid chromatography (GLC) for lipid fractions and FA profiles, while protein expression of FA transporters and metabolic enzymes was assessed by immunoblotting. Polysaccharides and collagen fibers were visualized using Periodic Acid-Schiff (PAS) and AZAN staining, respectively. ELISA and colorimetric kits were used to measure urinary albumin and creatinine contents. Results: HFHS feeding altered renal lipid homeostasis, increasing saturated and monounsaturated fatty acids (SFA and MUFA, respectively) levels and affecting desaturation and elongation ratios. CBG supplementation affected renal lipid metabolism by lowering triacylglycerol (TAG) accumulation, restoring polyunsaturated fatty acids (PUFA) in phospholipid (PL) and altering FA ratios, suggesting an improvement in lipid balance. CBG also increased the expression of carnitine palmitoyltransferase 1 (CPT1) and lipoprotein lipase (LPL) and decreased the expression of stearoyl-CoA desaturase 1 (SCD1) and fatty acid synthase (FAS), suggesting a shift toward enhanced FA oxidation and reduced lipogenesis. Conclusions: Overall, CBG exerted good effects on renal lipid metabolism and may mitigate early lipid-mediated injury associated with metabolic kidney disorders. Full article

Liver-on-a-chip (LoC) platforms offer promising alternatives to conventional in vitro and animal models for studying hepatic function and drug response; however, wide variability in cell sources, seeding strategies, extracellular matrices (ECMs), and functional assays limits reproducibility. This study reviews reported 2D and 3D LoC systems to identify commonly used liver cell types, seeding densities, ECM materials, and albumin/urea assay methods. Immortalised HepG2-based models dominate current platforms, with optimal seeding densities typically ranging from ~3 × 10⁶ cells/mL in 2D systems and 0.5–5 × 10⁶ cells/mL in 3D constructs. Collagen I, alone or combined with Matrigel, emerged as the most frequently adopted ECM. Functional assessment across studies highlighted albumin and urea as robust markers, with Abcam ELISA and QuantiChrom DIUR assays providing suitable sensitivity for microfluidic sample volumes. Collectively, this work establishes practical benchmarks for hepatic cell selection, seeding parameters, ECM choice, and assay selection, supporting more standardised and reproducible LoC development. Full article

Background: No preferred treatments for melasma are known, owing to its underlying complicated pathomechanisms; microneedle radiofrequency (MRF) has recently been used to treat melasma. Objectives: We aimed to investigate the effects and pathomechanisms of melasma treated by MRF and identify the possible determining factors for good response. Methods: Therapeutic outcomes were measured using the Melasma Area and Severity Index (MASI) and artificial intelligence-assisted optical coherence tomography (OCT) evaluation for collagen and pigmentation at baseline and 2 months after each treatment. Participants were divided into good- (≥25% reduction in MASI) and poor-response (<25% reduction in MASI) groups after the last MRF treatment. Results: Two patients achieved fair response and three patients achieved poor response. Overall OCT analysis showed that the confetti/granular melanin ratios (melanin aggregation index) decreased, the distance between melanosomes increased, and the size of melanin decreased. The number of dendritic cells (DCs) decreased. In subgroup analysis, the continuity of the basement membrane was improved in the fair-response group, and the melanin aggregation index and the number of DCs were decreased in the poor-response group. A higher baseline confetti/granular melanin ratio trended towards poorer therapeutic response. Conclusions: This pilot study used OCT to assess the therapeutic efficacy of MRF for melasma and identify the characteristics of individuals for whom MRF is effective. The statistical results were exploratory and descriptive. Further large-scale, randomized controlled studies are required to prove the efficacy of MRF in treating melasma and the feasibility of OCT in investigating the treatment response of melasma. Full article

Bipolar vessel sealing systems are widely used in surgery, yet their effectiveness varies depending on the histological composition of the target vessel. In particular, the influence of elastin on seal stability is not well understood. Porcine carotid arteries, which show a pronounced proximal–distal elastin gradient, provide an ideal model for systematic analysis. In this study, fresh porcine carotid arteries were divided into three segments based on vessel diameter (<5 mm, 5–7 mm, >7 mm). Histological EvG staining was used to quantify elastin and collagen content. All vessels (n = 8 per group) were sealed using a bipolar marSeal^® 5 plus device, followed by burst pressure testing and peel force measurements. Elastin content increased significantly from peripheral to central segments (9% → 25% → 42%; p < 0.001), while collagen content remained constant (22 ± 2%). In parallel, seal stability decreased markedly: burst pressures dropped from 723 mmHg to 240 mmHg and to 31.5 mmHg (p < 0.001). Peel forces showed the same trend (1.75 ± 0.07 N → 0.65 ± 0.03 N → 0.26 ± 0.11 N; p < 0.001). Wall thickness showed no proportional relationship to seal quality. Interestingly, the sealing performance of bipolar systems seems to be greatly influenced by the histological structure of the vessel wall. A high elastin content—rising from 9% to 42% along the carotid artery—was associated with a reduction in burst pressure and peel strength. These findings highlight the need to consider tissue composition when selecting sealing methods and support the development of adaptive energy delivery technologies. Full article

Acute or chronic rotator cuff tears are major causes of shoulder dysfunction, motivating the development of scaffolds with tailored thickness and mechanics for supraspinatus tendon regeneration. This study aimed to investigate the effect of bilayer poly(butylene adipate-co-terephthalate) (PBAT) scaffold thickness on the tenogenic differentiation of rat adipose mesenchymal stem cells (r-AdMSCs) and supraspinatus tendon regeneration. Aligned fibers with a diameter of approximately 476 nm were deposited onto randomly oriented layers at different times (4 h; 4S, 6 h; 6S, 8 h; 8S), and scaffolds with increasing thicknesses from 441 µm (4S) to 1132 µm (8S) were produced. Mechanical testing showed comparable tensile strength for 4S and 6S (≈1.9–2.0 MPa) and modulus (5.5–7.3 MPa), while 8S exhibited markedly reduced stiffness (0.5 MPa) and hyper elastic deformation. Mechanical performance across degradation conditions remained strongly thickness-dependent: thinner scaffolds retained integrity and strengthened, with modulus increases during hydrolytic and enzymatic degradation, whereas thicker matrices showed limited remodeling and instability. Rat-AdMSCs’ were cultured on the scaffolds for 21 days. Cell-free and cell-laden mechanical responses further reflected thickness effects: cell-free samples stiffened due to media-induced passive matrix tightening, whereas cell-laden scaffolds showed extracellular matrix (ECM)-driven reinforcement, most prominently in 4S, which reached 2.1 MPa tensile strength with improved elasticity and balanced deformation. The 4S scaffold exhibited the highest tensile strength and significantly increased collagen-1 (col1), tenomodulin (tnmd) and scleraxis (scx) expression compared with the other groups. In conclusion, among all groups, 4S scaffolds demonstrated the most favorable mechanical and biological performance, suggesting that scaffold thickness plays a critical role in regulating tendon regeneration and will become even more suitable when matured in bioreactors. Full article

Bone defects from trauma, tumour resection, infection, and degenerative disease remain a major clinical burden, and autografts face limitations of supply and donor-site morbidity. Three-dimensional (3D) printing offers a route to patient-specific, architecturally defined bone scaffolds, while biopolymers from natural sources provide biodegradability, biocompatibility, and extracellular matrix-mimicking cues consistent with sustainable, green biomaterials science. This review synthesises recent progress in 3D printing of biopolymer-based scaffolds for bone tissue engineering. We first examine the principal feedstocks—alginate, gelatin and gelatin methacryloyl, collagen, chitosan, silk fibroin, cellulose, and microbial polyesters—and their preparation, crosslinking chemistry, and printability. We then compare extrusion, light-based, and indirect printing technologies and the process–property relationships governing resolution, mechanical competence, and cell viability. Composite and functionalisation strategies, including biopolymer–bioceramic hybrids and controlled delivery of growth factors and antimicrobial agents, are analysed as routes to osteoinduction, vascularisation, and infection control. Finally, we evaluate translational performance in preclinical models and outline central challenges of vascularisation, mechanical–degradation matching, scalability, and regulatory standardisation. Biopolymer 3D printing is positioned as a ve rsatile, sustainable platform whose clinical maturation depends on integrated material, structural, and biological design. Full article

Background and Aims: The “quantity” of bone can be evaluated by dual-energy X-ray absorptiometry (DXA) scans, but not its “quality. We aim to study the clinical relevance of urinary-N-terminal telopeptide (NTx) in a retrospective exploratory study. Patients and Methods: The medical records of patients with osteoporosis, osteopenia with or without fractures, and with available urinary NTx were retrospectively reviewed; those on anti-osteoporotic medication before the start of the study were excluded. In all NTx levels, bone-specific alkaline phosphatase (BSAP), parathormone, serum calcium, and vitamin D were measured. In all cases, a recent DXA scan and fracture risk assessment (FRAX) had been performed. Appropriate statistics were applied using SPSS. 15. Results: Included were 93 patients (17.2% males); thirty-one (33.33%) had osteoporosis, 56 (60.21%) osteopenia, whereas 36 (38.7%) had prior or existing fractures. Older participants had lower NTx levels, and females had higher NTx levels, albeit NS. A negative correlation was found between the T-score of the left hip and NTx levels (p = 0.015) but not of the right hip or lumbar spine. In multivariate analysis, NTx levels (p = 0.013) and FRAX (p = 0.001) were significantly associated with fractures. Patients with osteoporosis had higher NTx levels when compared to patients with osteopenia (p = 0.015). NTx at a cut-off value of 207.4 showed a sensitivity of 80.6% and a specificity of 56.1% for the diagnosis of previous fracture with an area under the curve (AUC) of 0.72 (95% CI: 0.61, 0.83). Conclusions: Elevated NTx levels were significantly associated with existing or prior fractures. Combining DXA scan and FRAX, with NTx testing, may provide a comprehensive approach to osteoporosis assessment and treatment. Further prospective studies are warranted to validate its clinical utility. Full article

Background: Eggshell membrane peptides (ESMPs) are natural bioactive compounds with reported chondroprotective properties. However, their regulatory effects on canine chondrocytes remain unclear. This study investigated ESMP in an interleukin-1β (IL-1β)-induced inflammatory model of canine chondrocytes. Methods: Chondrocytes were assigned to control (Cont), IL-1β, and ESMP + IL-1β groups. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. NF-κB p65 nuclear translocation was evaluated by immunofluorescence staining. Real-time quantitative PCR (RT-qPCR) and Western blotting (WB) were used to measure mRNA and protein expression levels, respectively. Results: ESMP inhibited IL-1β-induced NF-κB p65 nuclear translocation and reduced the IL-1β-induced increases in interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and matrix metalloproteinase-13 (MMP-13) at both mRNA and protein levels. ESMP also decreased IL-6, nitric oxide (NO), and prostaglandin E₂ (PGE₂) levels in culture supernatants. ESMP reversed the IL-1β-induced reduction in type II collagen α1 chain (COL2A1) and aggrecan (ACAN) expression at both transcriptional and protein levels. Conclusions: ESMP attenuates IL-1β-induced inflammatory responses and extracellular matrix degradation in canine chondrocytes, potentially associated with suppression of NF-κB p65 nuclear translocation. This supports its potential application in promoting joint health in dogs. Full article

Background: Solriamfetol, a dopamine and norepinephrine reuptake inhibitor widely used in narcolepsy management, has not been thoroughly investigated for its anti-fibrotic and anti-inflammatory properties. Herein, we investigated its potential therapeutic applications and underlying mechanisms in both cellular and murine models of pulmonary fibrosis. Methods: To induce fibrosis, C57BL/6 male mice (six-week-old) were administered bleomycin via the intratracheal route. These animals subsequently received solriamfetol orally once per day at dosages of 3 or 10 mg/kg. Histological and immunohistochemical techniques were employed to evaluate inflammatory cell infiltration, collagen accumulation, and α-smooth muscle actin (α-SMA) expression in bronchoalveolar lavage samples and lung tissue sections. Cytokine levels were measured by ELISA, and gene/protein expression of pro-fibrotic markers, A_2A/A_2B adenosine receptors (ARs), adenylate cyclases (ACs), Epac, K_Ca3.1, and adenosine deaminase (ADA) were assessed via quantitative PCR and Western blot. Electrophysiological recordings evaluated K_Ca3.1 channel activity. Purified ADA and normal human lung fibroblasts (NHLFs) were treated with solriamfetol to assess effects on ADA activity and levels of cAMP and adenosine, respectively. Results: Solriamfetol significantly reduced inflammatory cell infiltration, collagen accumulation, and α-SMA expression in fibrotic lungs. Solriamfetol restored downregulated A_2AAR, A_2BAR, ACs, and Epac, while suppressing ADA expression and activity, resulting in elevated extracellular adenosine and intracellular cAMP. The intervention potentiated Epac signaling and inhibited fibroblast activation. Solriamfetol inhibited the K_Ca3.1 current in fibroblasts and reduced K_Ca3.1 protein expression levels in TGFβ-treated fibroblasts and lung tissues from bleomycin-challenged mice. Notably, these effects were abolished by A_2AAR or A_2BAR antagonists, implying that they occur through AR-mediated pathways. Conclusions: Solriamfetol inhibits ADA and reinforces adenosine–cAMP signaling, suppressing pathological fibroblast activation. These findings suggest its therapeutic utility as a novel anti-fibrotic compound for various fibrotic diseases, including pulmonary fibrosis. Full article

Mineralising avian tendon is a widely used experimental model for studying collagen-guided mineralisation. Yet, the three-dimensional organisation and topology of its internal canal system have never been quantitatively characterised. We combined high-resolution micro-computed tomography (micro-CT) and scanning electron microscopy (SEM) to provide the first morphometric and topological analysis of the canalicular network in mineralised turkey gastrocnemius tendon. micro-CT revealed that unmineralised canals occupy approximately 34.6% of the mineralised tissue volume and form a single continuously connected network (99.8% of void volume), with a connectivity density of ~1.3 × 10² mm⁻³, a fractal dimension of 2.58, a degree of anisotropy DA = 0.87 [BoneJ convention, range 0–1], and a closed-loop topology. SEM revealed marked ultrastructural heterogeneity of the mineral phase across fascicle cross-sections, consistent with graded intrafibrillar-to-interfibrillar deposition. These findings establish the first quantitative morphometric framework for physiologically mineralising collagen tissue and support the use of turkey gastrocnemius tendon as a tractable model for studying mineralisation dynamics, enthesis biology, and the design of biomimetic scaffolds with controlled porosity and anisotropy. Full article