Search Results (4,442)

Background: Diabetic foot ulcers (DFUs) are a major cause of morbidity and lower extremity amputation. Numerous advanced wound therapies with various mechanisms of action have been developed to improve healing outcomes; however, the comparative certainty of evidence supporting these interventions remains unclear. This study evaluates randomized controlled trials (RCTs) of DFU therapies using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Methods: A narrative synthesis of RCTs published between January 2016-January 2026 evaluating therapies for DFUs was performed. For studies that reported 12–week healing outcomes, risk of bias was assessed using the Cochrane Risk of Bias 2 tool and certainty of evidence for each therapy subgroup was evaluated using the GRADE framework. Results: A total of 143 RCTs were included with 45 RCTs undergoing GRADE assessment. The proportion of studies demonstrating statistically significant improvements in 12-week healing rates relative to controls varied and was not reflected in the GRADE assessment. Moderate-certainty evidence was assigned to the hyperbaric oxygen therapy subgroup. Low-certainty evidence was assigned to silver dressings, biosynthetic scaffolds, stem cell therapy, and negative pressure wound therapy. Very low-certainty evidence was assigned to topical oxygen, synthetic structural scaffolds, moisture-retaining dressings, local antimicrobial delivery, placental-derived skin substitutes, platelet-rich plasma, acellular dermal matrices, allografts/xenografts, and off-loading devices. No therapy subgroup was assigned high-certainty evidence. Conclusions: The certainty of evidence supporting DFU therapies varies substantially across intervention categories. These findings highlight the need for larger, methodologically rigorous comparative trials to clarify the effectiveness of DFU therapies and guide evidence-based wound care. Full article

Titanium-based dental implants have evolved significantly, with the development of binary alloys like Ti-15Zr (Roxolid™) representing a pivotal advancement in mechanical performance. Current research focuses on biomimetic surface engineering to further accelerate osseointegration and optimize bone regeneration, particularly in clinically compromised sites. This review constitutes a narrative synthesis of how these strategies replicate the bone extracellular matrix (ECM) through a holistic framework of architectural, mechanical, and biochemical integration. A structured literature search across PubMed, Scopus, and Web of Science (2010–2026) identified relevant studies focusing on the synergy between Ti-15Zr substrates and surface modifications. Evidence confirms that the high fatigue strength of Roxolid™ alloys provides an ideal foundation for advanced, hierarchical surface engineering without compromising structural integrity. This strategy utilizes macro-topography for primary stability, nano-topography for protein adsorption, and bio-functionalization (e.g., RGD peptides and osteogenic ions) to direct mesenchymal stem cell (MSC) differentiation. This synergy accelerates the transition from passive to active osseointegration, effectively bridging the “biological gap” during early healing. Biomimetic engineering transforms implants into instructive biological platforms, improving outcomes for patients with compromised bone quality and facilitating predictable immediate loading protocols. Full article

Inflammatory bowel disease (IBD) represents a growing global health threat that markedly increases colorectal cancer risk, yet conventional immunosuppressive agents achieve mucosal healing in only a limited subset of patients. M2-polarized macrophages have been recognized as crucial regulators of mucosal repair through their ability to maintain intestinal microenvironment homeostasis. Here, we investigated the potential effects and mechanisms of macrophage-derived exosomes (Exos) on epithelial barrier function in a murine model of IBD. Murine colitis was induced by intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by treatment with Exos isolated from IL-33-treated macrophages (IL-33-Exos) or untreated macrophages (PBS-Exos). Our findings showed that IL-33-Exos markedly ameliorated inflammatory intestinal mucosal injury and improved intestinal barrier dysfunction. Concurrently, IL-33-Exos mitigated intestinal epithelial cell damage, thereby preserving intestinal mucosal integrity. Mechanistic studies revealed that the beneficial effects of IL-33-Exos were implicated in upregulation of Wnt/β-catenin signaling in intestinal epithelial cells. Translationally, these findings suggest that IL-33-Exos may promote epithelial repair in experimental colitis, offering a novel therapeutic avenue for clinical management of inflammatory bowel disease. Full article

Cucurbiturils (CB[n]) are rigid glycoluril-based macrocycles possessing well-defined hydrophobic cavities capable of forming stable host–guest complexes in water. Owing to these properties, CB[n]-containing supramolecular polymer gels have attracted increasing attention as functional composite materials in modern materials science. This review summarizes recent progress in the development of cucurbituril-based supramolecular gels, with particular attention to synthetic approaches, network design, and emerging applications. Both conventional acid-catalyzed methods and more sustainable synthetic strategies for cucurbituril preparation and functionalization are discussed. We further consider the role of CB[n] macrocycles as reversible crosslinking units in polymer networks and analyze how host–guest interactions influence the mechanical properties, self-healing behavior, and stimuli responsiveness of the resulting materials. Recent applications in biomedical engineering, soft electronics, and environmental remediation are also highlighted, demonstrating how molecular-level supramolecular interactions can determine the macroscopic performance of these composite systems. The review concludes with perspectives on scalable synthesis, processing integration, and future directions in supramolecular composite materials. Full article

Tremella fuciformis extract (TFE) is used in dermocosmetic formulations due to its moisturising, antioxidant, and skin-supportive properties. The present study compared the effects of commercial TFE and hyaluronic acid (HA) on selected functions of human dermal fibroblasts (HDF). The cells were treated with TFE at concentrations of either 200 µg/mL or 500 µg/mL, or with HA at a concentration of 500 µg/mL. The following parameters were the focus of the study: cell viability, DNA and collagen biosynthesis, prolidase activity, scratch-wound closure, and immunofluorescence of selected signalling- and extracellular matrix-related markers. The findings of this study demonstrate that neither TFE nor HA had any effect on HDF viability. TFE led to a significant increase in DNA biosynthesis at both concentrations, while HA had no significant effect. The synthesis of collagen was found to be considerably elevated by both HA and TFE500, with no such effect observed in the presence of TFE200. Prolidase activity was observed to be highest in the HA group and also elevated in the TFE500 group; however, these results should be regarded as descriptive due to the nature of the pooled-sample data. Immunofluorescence analysis revealed increased phosphorylated protein kinase B (p-AKT) fluorescence in images treated with TFE, while phosphorylated mechanistic target of rapamycin (p-mTOR) remained close to the control level. Higher levels of β1-integrin, Insulin-Like Growth Factor-I Receptor (IGF-1R), prolidase, and phosphorylated Extracellular Signal-Regulated Kinases (p-ERK1/2) fluorescence were also observed in selected groups. The mean scratch-wound closure was found to be highest for TFE500. Overall, TFE was found to be associated with DNA biosynthesis, whereas HA and TFE500 were found to enhance collagen biosynthesis. Further studies are required to confirm biological reproducibility and the mechanism. Full article

Background: The left atrial appendage (LAA) is the predominant site of thrombus formation in atrial fibrillation. Current percutaneous LAA occlusion devices require permanent implants. A catheter-based, non-implant mechanical inversion strategy may offer an alternative approach to stroke prevention. Objectives: To assess the feasibility of vacuum-assisted catheter-based inversion of the LAA using transseptal aspiration in a swine model. Methods: A 59-kg domestic swine underwent transseptal access via the right femoral vein under fluoroscopy, transesophageal echocardiography (TEE), and intracardiac echocardiography (ICE). A 22-F aspiration catheter was advanced into the left atrium and positioned at the LAA apex. Negative pressure was generated manually with a 60-mL syringe attached to the aspiration port, and sequential suction–traction maneuvers were performed to induce LAA inversion. Procedural feasibility, hemodynamic stability, imaging changes, and gross pathology were assessed. Results: LAA suction and inversion were feasible. Sequential negative pressure applications resulted in complete inversion, confirmed by multiplane TEE. A mild, non-hemodynamically significant pericardial effusion occurred. Necropsy showed focal apex injury consistent with catheter stiffness and suction forces. Conclusions: Catheter-based vacuum-assisted LAA inversion was technically feasible in this acute swine experiment. However, chronic survival studies are required to evaluate durability of inversion, tissue healing, thrombogenicity, and long-term safety before clinical translation can be considered. Full article

Background: Osteoporotic vertebral compression fractures (OVCFs) are the most prevalent manifestation of osteoporotic skeletal disease, associated with severe pain, functional decline, and elevated risk of subsequent fractures. Conservative management remains the first-line approach for stable fractures, yet pain control is often suboptimal, and vertebral collapse progresses in up to 37% of patients. Bio-activated orthosilicic acid combined with vitamins D3 and K2 (BioSi-DK) may support fracture healing through complementary mechanisms acting on osteoblast differentiation, collagen synthesis, osteocalcin carboxylation, and mineralization, but its clinical efficacy in OVCFs has not previously been investigated. Methods: A retrospective, multi-center comparative cohort study was conducted in patients aged >50 years with DXA-confirmed osteoporosis and acute thoracolumbar OVCFs (AO Spine OF1-OF2) managed conservatively. Patients receiving BioSi-DK supplementation (two capsules daily for two months, then one capsule daily for four months) in addition to standard conservative treatment were compared with controls receiving conservative treatment alone. Propensity score matching (1:1, sex-exact constraint, caliper 0.3 SD) was applied across twelve pre-specified baseline covariates. The primary outcome was pain intensity at six months, assessed by numerical rating scale (NRS). Secondary outcomes included NRS change, analgesic use, Patient Global Impression of Change (PGIC), requirement for vertebral augmentation (kyphoplasty), MRI marrow edema score (MES), and Genant grade change. Results: After propensity score matching, 38 patients (19 per group) with balanced baseline characteristics were analyzed (mean age 71.2 ± 6.5 years; 89.5% female; mean T-score −2.61 ± 0.32; mean baseline NRS 8.26 ± 0.95). The BioSi-DK group achieved a significantly lower post-treatment NRS score compared with controls (2.05 ± 2.17 vs. 3.84 ± 2.83; p = 0.015; Cohen’s d = −0.71) and a significantly greater mean NRS reduction (−6.21 ± 1.90 vs. −4.42 ± 2.12 points; p = 0.005; d = −0.89). Analgesic discontinuation was more frequent in the BioSi-DK group (68.4% vs. 36.8%; p = 0.068). Kyphoplasty was required in 5.3% of BioSi-DK patients versus 21.1% of controls (p = 0.340; OR = 0.21), and vertebral compression grade remained stable in 100% of supplemented patients versus 84% of controls. At two months, MES improvement by at least one category was more frequently observed in the BioSi-DK group than in controls, suggesting an earlier edema resolution effect; at six months, MES distribution was comparable between groups (p = 0.620). Conclusions: BioSi-DK supplementation as an adjunct to conservative management was associated with a statistically significant and clinically large reduction in pain at six months, with favorable trends in analgesic burden, kyphoplasty requirement, and edema resolution. The safety profile was excellent. These findings support the conduct of prospective, randomized, placebo-controlled trials to confirm BioSi-DK as an effective adjunct therapy for OVCFs. Full article

(1) Background: Customized 3D-printed anatomical healing abutments (AHAs) are increasingly incorporated into digital implant workflows to optimize emergence profile development. However, the influence of tightening torque on their mechanical stability remains poorly understood. This prospective pilot clinical study evaluated the effect of different torque protocols on the stability of 3D-printed AHA placed on intermediate abutments. (2) Materials and Methods: Forty-two patients (52.4 ± 12.3 years) receiving 60 Paltop implants (Paltop Advanced Dental Solutions Ltd., Ashkelon, Israel) were included. Following implant uncovering, all implants received titanium intermediate abutments fabricated from a photopolymerized acrylate-based resin (MAZIC D TEMP; Vericom Co., Ltd., Chuncheon, Republic of Korea), torqued to 35 Ncm, and were allocated to four AHA tightening protocols. Clinical mobility, torque maintenance, and mechanical complications were evaluated at 4, 8, and 12 weeks. Group comparisons were performed using Fisher’s exact test. (3) Results: At 12 weeks, mobility occurred in 5/15 AHA (33.3%) in the hand-tightened group and 1/15 AHA (6.7%) in the 20 Ncm group, whereas no mobility was observed in 15/15 AHA (100%) in both the 25 Ncm and 30 Ncm groups. Mechanical complications differed significantly among groups (Fisher’s exact test, p = 0.047). (4) Conclusions: Tightening torques ≥ 25 Ncm provided superior early mechanical stability of 3D-printed AHA. Full article

Background: Congenital fibular deficiency is a rare longitudinal deficiency of the lower extremity associated with limb-length discrepancy, ankle and foot deformity, soft-tissue imbalance, and functional impairment. Reconstruction may be challenging because bone healing, regenerate maturation, and mechanical stability can be less predictable in selected patients. Case Presentation: A man with congenital fibular deficiency developed chronic distal tibial nonunion after corrective osteotomy at another institution. The nonunion persisted for four years, and the patient presented to our hospital with inability to bear weight and wheelchair dependence. A comprehensive salvage strategy was performed, including Achilles tendon lengthening using the Vulpius technique, removal of retained fixation material, debridement and refreshment of the nonunion site, negative bacteriological cultures, autologous cancellous iliac bone grafting, acute shortening and compression of the docking site, circular external fixation, proximal tibial osteotomy, and gradual lengthening. Low-intensity pulsed ultrasound was applied postoperatively as an adjunctive biological stimulus. Results: Bone union was achieved, and the external fixator was removed approximately one year after surgery. A total lengthening of 78 mm was achieved. At 12-year follow-up, the AOFAS ankle-hindfoot score was 90, ankle range of motion was 5° dorsiflexion and 40° plantarflexion, and the JOA knee score was 95. The patient walked independently without assistive devices and continued to work. Mild residual varus deformity of the proximal tibia was present, but the patient reported no knee pain, ankle pain, or ankle instability, and radiographs showed no progressive osteoarthritic changes. Conclusions: In selected patients with congenital fibular deficiency and chronic nonunion after previous treatment, durable limb salvage may be achieved using an individualized strategy that addresses both biological and mechanical factors. Full article

Lost circulation of wellbore fluids within fissured zones constitutes a primary factor contributing to increased non-productive time (NPT) and restricted rate of penetration (ROP). Conventional gel-based lost circulation materials (LCMs) inherently suffer from a tradeoff between pumpability and in situ fracture retention, and they lack a design methodology quantitatively correlated with drilling engineering parameters. In this study, a shear-responsive gel with a dual physically crosslinked network—combining hydrophobic association and Fe³⁺-mediated ionic coordination—was prepared through a single-step water-based radical polymerization process, utilizing commercially available monomers. By systematically tuning the hydrophobic monomer and Fe³⁺ contents, the gel’s fracture-sealing efficacy, autogenous healing ability, and shear rheological characteristics were evaluated, establishing a quantitative correlation between the critical shear rate and drilling parameters. The empirical data demonstrate that with an increase in the hydrophobic monomer dosage from 0.4 wt% to 1.2 wt%, the critical shear rate decreases from 22.5 s⁻¹ to 8.6 s⁻¹, exhibiting an exponential decay relationship. The optimized formulation, G0.8F0.5, demonstrates a low initial viscosity of 245 mPa·s under high shear conditions, which surges to 6180 mPa·s at a shear rate of 14.2 s⁻¹, achieving a thickening factor of 29.4. Upon incubation at 80 °C for a duration of 12 h, the formulated gel restores 94.9% of its mechanical tensile strength and 96.3% of its fracture strain, whereas the Fe³⁺-free control sample fails to heal. In dynamic plugging tests using a 3 mm fracture plate, G0.8F0.5 achieves a breakthrough pressure of 12.8 MPa with a minimal fluid loss of 98 mL. The LCM forms a monolithic gel block positioned at the middle-to-rear section of the fracture, outperforming conventional gel counterparts. Drilling hydraulics simulations reveal that deploying this gel reduces the annular equivalent circulating density (ECD) by 0.06 g/cm³. Furthermore, under idealized conditions, this approach is calculated to enhance the ROP by approximately 26%. The proposed molecular design of a shear-responsive, dual physically crosslinked network provides a viable technical pathway for quantitatively tailoring the shear-responsive properties of while-drilling LCMs. Full article

Liver fibrosis is a critical determinant of the progression of chronic liver disease (CLD). Total flavonoids from Carthamus tinctorius L. (TFCTLs) exhibit diverse pharmacological activities while their effect on liver fibrosis remains incompletely understood. This study aimed to elucidate the effects and mechanisms of TFCTLs on liver fibrosis. To this end, we first established a carbon tetrachloride (CCl₄)-induced liver fibrosis model in mice. Histological analysis demonstrated that TFCTL treatment significantly alleviated CCl₄-induced liver collagen deposition (p < 0.001). Meanwhile, TFCTLs could also downregulate the expression levels of fibrosis markers α-SMA and collagen I in a dose-dependent manner (p < 0.05). In vitro, a cellular model of fibrosis was generated by treating HSC-T6 cells with TGF-β1. EdU incorporation assays revealed that TFCTLs significantly suppressed HSC proliferation (p < 0.05). Furthermore, immunofluorescence staining for α-SMA demonstrated a marked reduction in HSC activation upon TFCTL treatment. The inhibitory effect of TFCTLs on cell migration was confirmed by wound healing and transwell assays, which revealed a substantial decrease in the number of migrated cells (p < 0.001). Additionally, flow cytometric analysis indicated that TFCTL treatment promoted HSC apoptosis (p < 0.05). Further mechanistic investigations revealed that TFCTLs exert their antifibrotic effects by inhibiting Hedgehog pathway and activating autophagy process. The antifibrotic effect of TFCTLs was partially reversed by the autophagy inhibitor 3-MA. Furthermore, the Hedgehog agonist PUR not only counteracted the anti-fibrotic actions of TFCTLs but also suppressed TFCTL-induced autophagy activation. In conclusion, our study demonstrated that TFCTLs attenuate liver fibrosis by inhibiting Hedgehog signaling and subsequently promoting autophagy, highlighting their potential as a therapeutic agent for liver fibrosis. Full article

Gallium (Ga)-based liquid metal (LM) composites, particularly those based on eutectic gallium–indium (EGaIn) and related alloys, have emerged as a promising materials platform for soft and deformable energy storage owing to their unique combination of metallic conductivity, fluidic deformability, and adaptive interfaces. Despite rapid advances in LM-enabled devices, binders remain insufficiently understood and are still commonly regarded as passive structural components. Here, we present a comprehensive binder-centered perspective for LM composites, establishing the binder as a key regulator of electro-chemo-mechanical coupling, interfacial stability, transport behavior, and processability in soft energy systems. We show that tailored binder chemistries in Ga-based LM systems—including stretchable batteries, printable conductors, and soft electrochemical devices—govern LM droplet dispersion, suppress coalescence and leakage, and preserve conductive percolation under large deformation, while enabling room-temperature fabrication and printability through rheological regulation and interfacial wetting. Beyond mechanical confinement, emerging binder functionalities—including dynamic bonding, supramolecular interactions, ionically conductive networks, and reversible polymer architectures—enable self-healing interfaces, adaptive transport pathways, and robust adhesion in deformable devices. By integrating recent advances in stretchable batteries, flexible supercapacitors, printable electronics, and multifunctional soft energy systems, we establish a unified multiscale framework linking binder molecular design to device-level electrochemical and mechanical performance. We further discuss sustainability and manufacturing considerations, including recyclable polymer networks, low-temperature fabrication, and scalable processing strategies. Finally, we outline current challenges and future opportunities toward programmable binder systems with tunable viscoelasticity, interfacial reactivity, and adaptive functionality. This Review establishes binder-centered engineering as a key pathway for transforming LM composites from proof-of-concept materials into resilient, manufacturable, and multifunctional soft energy technologies for wearable, stretchable, and biointegrated electronics. Full article

Collagen is a key structural protein of the skin, essential for maintaining its mechanical strength, elasticity, and hydration. Oral collagen supplementation, particularly in the form of collagen peptides, has recently gained significant interest as a nutritional strategy to support skin health and overall wellbeing. However, the evidence regarding its effectiveness in supporting skin health and improving hair, nail, and wound-healing outcomes remains heterogeneous. The aim of this review is to summarize and critically evaluate the current human evidence on oral collagen supplementation and its potential role in supporting skin health, hair and nail quality, and wound healing. A targeted literature search was conducted using PubMed and Web of Science to identify clinical trials and relevant studies assessing the effects of collagen supplementation on skin aging parameters, including elasticity, wrinkles, hydration, and barrier function, as well as hair loss, nail disorders, and wound healing. Collagen-derived peptide supplementation has been associated with improvements in skin hydration, elasticity, wrinkle appearance, and dermal extracellular matrix organization, while also supporting hair thickness and strength, modestly enhancing nail growth, and promoting wound healing. Benefits are most consistent with low-molecular-weight hydroxyproline-rich peptides, with peptide characteristics appearing more important than collagen source. Evidence is limited by short study durations, heterogeneous designs, multi-ingredient formulations, and industry funding, which reduce confidence in the magnitude and consistency of the reported effects. Nevertheless, high-quality, long-term, independently funded trials with standardized outcomes are still required to confirm these findings. Full article

Osteoarthritis (OA) is a disabling joint disease characterised by cartilage degradation, synovial inflammation, and subchondral bone remodelling. Furthermore, catabolic inflammatory processes as well as dysregulated cellular signalling and oxidative stress are central to OA pathogenesis. Despite its growing global burden, currently available therapies primarily provide symptomatic relief and fail to target underlying molecular mechanisms and halt disease progression. Cold atmospheric plasma (CAP), a partially ionised, non-thermal gas that generates controlled reactive oxygen and nitrogen species (RONS), has emerged as a promising therapeutic modality capable of modulating redox-sensitive signalling pathways. CAP has demonstrated the capacity to suppress pro-inflammatory cytokine expression, enhance antioxidant defence mechanisms, influence macrophage polarisation, and stimulate tissue repair processes in rheumatoid arthritis, diabetic and dermal wound healing models. However, its potential as a disease-modifying therapy for the treatment of OA is not yet fully understood and warrants further experimental investigation. This review explores current pre-clinical evidence from different disease models, which may have implications for the potential application of CAP as a therapeutic intervention for OA, either as a disease-modifying therapy or as an adjuvant therapy for intra-articular drug delivery. Furthermore, key translational challenges including plasma parameter standardisation, interactions with synovial fluid and optimisation of joint-specific delivery strategies are discussed, identifying gaps that require further experimental investigation. Collectively, the findings of this review highlight CAP as a promising multimodal therapy with translational potential for the treatment of OA warranting further experimental validation and may open innovative avenues for future research. Full article

Corrosion-protective coatings have progressed from passive barrier systems and chromate-based technologies toward multifunctional materials that integrate barrier durability, interfacial adhesion, active inhibition, electrochemical response, and self-healing capabilities. However, the intellectual framework connecting these technological developments remains fragmented, as most reviews focus on specific material families rather than on the broader evolution of the field. This study examines technological paradigms in corrosion-protective coatings through a citation network analysis of highly cited publications retrieved from Web of Science and processed with CitNetExplorer. The most influential publications were thematically reviewed to identify dominant materials, coating architectures, protection mechanisms, seminal contributions, and bridge articles. Four principal paradigms were identified: smart and self-healing coatings based on nanocontainers, layered double hydroxides, mesoporous silica, halloysite, zeolites, hydroxyapatite reservoirs, and microcapsules; chromate-free sol–gel and silane pretreatments based on organic–inorganic hybrid matrices, organosilanes, rare-earth inhibitors, and oxide nanoparticles; graphene and graphene oxide-based nanocomposite coatings in which two-dimensional fillers enhance tortuosity, reduce water uptake, and reinforce polymer matrices and coating–substrate interfaces; and electroactive coatings based mainly on polyaniline and polypyrrole, where protection is associated with passivation, redox mediation, and dopant-controlled inhibition. The findings indicate that corrosion-protective coatings have evolved through partially overlapping and increasingly integrated paradigms rather than through a single technological trajectory. This citation network analysis clarifies the transition from chromate replacement toward active, nanostructured, electroactive, and self-healing corrosion-protective systems. Full article