Search Results (559)

Tendon injuries, whether resulting from trauma, repetitive strain, or degenerative conditions, present a considerable clinical challenge. The natural healing process, which involves inflammatory, proliferative, and remodeling phases, is often inefficient and leads to excessive scar tissue formation, ultimately compromising the mechanical properties of the tendon compared to its native state. This highlights the critical need for innovative approaches to enhance tendon repair and regeneration. Leveraging the regenerative properties of human amniotic membrane (HAM) and electrospun PCL/gelatin nanofibers, this study aims to develop and assess a novel composite scaffold in a rodent model to facilitate improved tendon healing. This prospective experimental study involved 12 male Sprague Dawley rats (250–300 g), randomly assigned to three groups: Group A (No Treatment/No HAM), Group B (HAM-treated), and Group C (HAM with electrospun nanofibers, HAM-NF). A surgically induced tendon injury was created in the left hind limb, while the right limb served as a control. Following surgery, HAM and HAM-NF (0.5 cm²) were applied to the respective treatment groups, and tendon healing was assessed after six weeks. Gait analysis, including stride length and toe-out angle, was conducted both pre-operatively and six weeks post-operatively. Macroscopic and microscopic evaluations were performed on harvested tendons to assess regeneration, comparing treated groups to the controls. Gait analysis demonstrated that the HAM-NF group showed a significant increase in stride length from 11.70 ± 1.50 cm to 12.79 ± 1.71 cm (p < 0.05), with only a modest change in toe-out angle (14.58 ± 2.96° to 16.27 ± 2.20°). In contrast, the No Treatment group exhibited reduced stride length (10.27 ± 2.17 cm to 8.40 ± 1.67 cm) and a marked increase in toe-out angle (16.33 ± 4.51° to 26.47 ± 5.81°, p < 0.05), while the HAM-only group showed mild changes in both parameters. Macroscopic evaluation showed a significant difference in tendon healing. HAM-NF group had the highest score that indicates more rapid tissue regeneration. Histological analysis after 6 weeks showed that tendons treated with HAM-NF achieved a mean histological score of 5.54 ± 4.14, closely resembling the uninjured tendon (6.67 ± 1.63), indicating substantial regenerative potential. The combination of human amniotic membrane (HAM) and electrospun nanofibers presents significant potential as an effective strategy for tendon regeneration. The HAM/NF group exhibited consistent improvements in gait parameters and histological outcomes, closely mirroring those of uninjured tendons. These preliminary results indicate that this biomaterial-based approach can enhance both functional recovery and structural integrity, providing a promising pathway for advanced tendon repair therapies. Full article

Background: Vesicoureteral reflux (VUR) contributes significantly to recurrent childhood urinary tract infections and renal scarring, yet predicting which patients will develop adverse outcomes or benefit from specific investigations or treatments remains challenging. Numerous prognostic tools have been proposed, but none have achieved widespread adoption. Methods: A comprehensive search of the literature available on MEDLINE, PUBMED, Embase, Emcare, CINAHL, and Google Scholar was performed to identify combinations of factors, scoring systems, ratios, models, and tools relating to VUR. This included predicting the spontaneous resolution of established vesicoureteral reflux, the risk of breakthrough urinary tract infections (UTIs), and guiding clinical decision making regarding the need for VCUG in patients with UTIs, continuous antibiotic prophylaxis (CAP), or surgical intervention in patients with confirmed VUR. Articles were included if they either described or validated a predictive tool that was designed to aid clinical decision making in patients with either suspected or confirmed VUR with regards to investigation or management strategies. All the studies included were then analysed, and the predictive tools have been summarised in a narrative format. Results: Seventeen predictive tools developed over thirty-nine years were identified: six predicting spontaneous resolution, four predicting breakthrough urinary tract infection (BTUTI) on CAP, two determining which children benefit from CAP, and five estimating the probability of VUR or high-grade VUR after a first febrile UTI. Approaches ranged from radiological ratios to multifactorial clinical–radiological scores and machine-learning models. Only five tools had any external validation, and none demonstrated sufficient reliability for universal clinical use. Significant heterogeneity in design, imaging interpretation, inclusion criteria, and outcome definitions limited comparison and wider applicability. Conclusions: This atlas provides the first consolidated overview of prognostic tools in paediatric VUR. Future development should prioritise multicentre, prospectively validated models that integrate established clinical and radiological predictors with transparent computational methods to create practical, generalisable risk-stratification frameworks for routine care. Full article

The stability of nanolubricants is critical for ensuring effective performance under extreme pressure (EP) conditions, where severe boundary lubrication governs friction and wear behaviour. This study examines palm kernel oil (PKO)-based nanolubricants enhanced with carbon graphene (CG), hexagonal boron nitride (hBN), and molybdenum disulfide (MoS₂), with and without oleic acid (OA) as a surfactant. OA incorporation improved CG dispersion stability, reducing agglomerate size by 30.4% (17.61 μm to 12.23 μm) and increasing the viscosity index from ~176 to 188, compared to 152 for the commercial hydrogen engine oil baseline. Under EP conditions, PKO + CG + OA achieved a 51.7% reduction in the coefficient of friction (0.58 to 0.28) and 18.2% improvement in weld load resistance, while wear scar diameter decreased by 13.4%. Surface and elemental analyses indicated the formation of a composite tribofilm containing oxide species, graphene platelets, and carboxylate-derived compounds from OA, consistent with iron–oleate-like chemistry that enhances load-carrying capacity and wear protection. These findings demonstrate the potential of OA-assisted PKO nanolubricants as sustainable, high-performance formulations for extreme pressure boundary lubrication, contributing to the advancement of green tribology. Full article

Background and Objectives: Corneal opacity is the fifth global cause of blindness and moderate-to-severe visual impairment due to scar tissue formation. The purpose of this study is to provide an integrated overview of the current state of corneal engineering strategies focused on the comparison with healthy corneas. It aims to identify engineering strategies that would result in functional corneas, providing real alternatives to donor corneal transplants. Materials and Methods: systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and according to the protocol with the ID: CRD420250654641 at the PROSPERO database. The focus question, prompted by considering the shortage of human corneal grafts, was: what is the performance of bioengineered corneal grafts in experimental animal models when compared with healthy eyes in the restoration of corneal anatomy and function? Results: Incorporating human corneal epithelial cells w/ or w/o human corneal stromal stem cells into a gelatin methacrylate and polyethylene glycol diacrylate matrix emerges as the leading option for epithelial layer regeneration. Human and bovine decellularized corneas, porcine corneal ECM in Gelatin methacrylate, dual layered collagen vitrigel and tissue-engineered human anterior hemi-corneas have shown promise for simultaneous regeneration of the corneal stromal and epithelial layers. Corneal stromal tissue regeneration could be positively impacted by transplantation with grafts derived from aligned self-lifting analogous tissue equivalents and collagen-based hydrogels. Finally, scaffolds of silk fibroin and human purified type I collagen represent promising approaches for corneal endothelial regeneration, though their effectiveness is contingent upon integration with endothelial cells. Conclusions: Collectively, these findings contribute to the growing body of evidence supporting the potential of tissue-engineered corneal substitutes as viable therapeutic options for corneal blindness and vision impairment. Assessing the optical and functional properties of the regenerated cornea should be a cornerstone in all studies aiming to evaluate their clinical effectiveness. Full article

This review summarizes a growing collection of data on adult neurogenesis in various vertebrate species, with a focus on teleost fish and mammals. Teleost fish serve as exceptional models for studying the dynamics of the cell cycle and the functions of adult neural stem progenitor cells (aNSPCs) throughout the central nervous system (CNS). New information about the characteristics of cells in various areas of the telencephalon of non-model objects—juvenile masu salmon Oncorhynchus masou and chum salmon Oncorhynchus keta—during postembryonic ontogenesis and after traumatic injury expands the current understanding of the issue. The expression of molecular markers of adult-type glial precursors in the model zebrafish and non-model objects, juveniles O. masou and O. keta, was presented. Immunohistochemical (IHC) verification of BrdU and PCNA made it possible to identify a population of rapidly and slowly proliferating cells in the pallium of intact O. masou and after traumatic brain injury (TBI). In salmonids, unlike in mammals, progenitor cells are able to differentiate into neurons after injury. The expression of vimentin and GFAP in the aNSCPs has functional specificity. A comparative analysis of the expression of Pax transcription factors in various vertebrates and juveniles O. masou is presented. Pax genes maintain cells in an undifferentiated state and ensure the spatiotemporal formation of mature cell types in changing developing neurogenic niches. The functions of glutamine synthetase (GS) and H₂S in the brains of vertebrates and juvenile chum salmon under intact conditions and after TBI are characterized. In fish, unlike mammals, as a result of TBI, neuronal conduction is restored in the injury area, whereas in mammals the regenerative process is complicated by neuroinflammation and culminates in the formation of a glial scar. Full article

Background: Facial atrophic acne scars have a significant impact on patients’ psychosocial well-being and remain a therapeutic challenge. Existing treatments options are frequently limited by modest efficacy and adverse effects. The combination of Polynucleotide High-Purification Technology (PN HPT™) and hyaluronic acid (HA) represents a novel bioregenerative strategy aimed at improving dermal remodelling and overall skin quality. Methods: This six-month, prospective, real-world study evaluated the efficacy and safety of Newest^® (Mastelli S.r.l., Sanremo, Italy), a sterile intradermal gel containing highly purified polynucleotides (10 mg/mL) and HA (10 mg/mL). Eligible participants, aged 20–60 years with moderate-to-severe atrophic facial post-acne scars, underwent four treatment sessions in two-week intervals. Efficacy was assessed using the Acne Scar Assessment Scale (ASAS) and Global Aesthetic Improvement Scale (GAIS) at three and six months, while safety was monitored throughout the study. Results: A total of 62 patients (32 Caucasian, 30 Asian; 19 males, 43 females; mean age: 36.6 years) completed the study. At three and six months, 46.8% showed at least a one-grade reduction in ASAS score with respect to the baseline. Patient-reported GAIS indicated that 54.8% perceived an improvement in scar appearance, aligning with investigator assessments. Only one mild, transient adverse event (wheal formation) occurred, which resolved spontaneously without intervention. Conclusions: In this real-world study, treatment with Polynucleotide High-Purification Technology (10 mg/mL) combined with HA (10 mg/mL) was associated with observable improvementin atrophic facial acne scars, with an excellent safety and tolerability profile. These findings support the potential of polynucleotide-based therapies for use as well-tolerated options for managing moderate-to-severe atrophic acne scarring, while the need for further controlled studies to confirm efficacy is also acknowledged. Full article

Current wound-healing strategies still fall short in achieving scarless regeneration. Adult wounds often heal in the form of scars, leading to functional impairment and aesthetic concerns. In contrast, fetal wounds exhibit a remarkable capacity for scarless regeneration due to their unique immune environment and regenerative cellular responses. This review systematically elucidates the key mechanisms underlying scarring and contrasts them with the hallmarks of fetal scarless healing. We then comprehensively explore engineering strategies to minimize scar formation in adults, with a focus on the combined application of regenerative biomaterials, bioactive factors, and cell therapies. Particularly emphasis is placed on novel intelligent biomaterials for reprogramming wound immune microenvironment and precise delivery strategies of “spatiotemporal sequential” or “on-demand”. These innovations signify a shift toward precise and controlled therapeutic intervention, offering new pathways for skin regeneration that enhances both functionality and aesthetics. Full article

Astrocytes and microglia constitute nearly half of all central nervous system cells and are indispensable for its proper function. Both exhibit striking morphological and functional heterogeneity, adopting either neuroprotective (A2, M2) or proinflammatory (A1, M1) phenotypes in response to cytokines, pathogen-associated molecular patterns (PAMPs)/damage-associated molecular patterns (DAMPs), toll-like receptor 4 (TLR4) activation, and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling. Crucially, many of these phenotypic transitions arise during the earliest stages of neurodegeneration, when glial dysfunction precedes overt neuronal loss and may act as a primary driver of disease onset. This review critically examines glial-centered hypotheses of neurodegeneration, with emphasis on their roles in early disease phases: (i) microglial polarization from an M2 neuroprotective state to an M1 proinflammatory state; (ii) NLRP3 inflammasome assembly via P2X purinergic receptor 7 (P2X7R)-mediated K⁺ efflux; (iii) a self-amplifying astrocyte–microglia–neuron inflammatory feedback loop; (iv) impaired microglial phagocytosis and extracellular-vesicle–mediated propagation of β-amyloid (Aβ) and tau; (v) astrocytic scar formation driven by aquaporin-4 (AQP4), matrix metalloproteinase-9 (MMP-9), glial fibrillary acidic protein (GFAP)/vimentin, connexins, and janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling; (vi) cellular reprogramming of astrocytes and NG2 glia into functional neurons; and (vii) mitochondrial dysfunction in glia, including Dynamin-related protein 1/Mitochondrial fission protein 1 (Drp1/Fis1) fission imbalance and dysregulation of the sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Sirt1/PGC-1α) axis. Promising therapeutic strategies target pattern-recognition receptors (TLR4, NLRP3/caspase-1), cytokine modulators (interleukin-4 (IL-4), interleukin-10 (IL-10)), signaling cascades (JAK2–STAT, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphoinositide 3-kinase–protein kinase B (PI3K–AKT), adenosine monophosphate-activated protein kinase (AMPK)), microglial receptors (triggering receptor expressed on myeloid cells 2 (TREM2)/spleen tyrosine kinase (SYK)/ DNAX-activating protein 10 (DAP10), siglec-3 (CD33), chemokine C-X3-C motif ligand 1/ CX3C motif chemokine receptor 1 (CX3CL1/CX3CR1), Cluster of Differentiation 200/ Cluster of Differentiation 200 receptor 1 (CD200/CD200R), P2X7R), and mitochondrial biogenesis pathways, with a focus on normalizing glial phenotypes rather than simply suppressing pathology. Interventions that restore neuroglial homeostasis at the earliest stages of disease may hold the greatest potential to delay or prevent progression. Given the complexity of glial phenotypes and molecular isoform diversity, a comprehensive, multitargeted approach is essential for mitigating Alzheimer’s disease and related neurodegenerative disorders. This review not only synthesizes pathogenesis but also highlights therapeutic opportunities, offering what we believe to be the first concise overview of the principal hypotheses implicating glial cells in neurodegeneration. Rather than focusing on isolated mechanisms, our goal is a holistic perspective—integrating diverse glial processes to enable comparison across interconnected pathological conditions. Full article

Wound coatings in the form of sponge plates were obtained based on hydrogels of cod collagen (CC) copolymers. The synthesis of CC copolymers with pectin was carried out in the presence of a triethylbor–hexamethylenediamine (TEB-HMDA) complex, which forms free radicals under reaction conditions, and with polyethylene glycol (PEG) during photocatalysis in the presence of RbTe_1.5W_0.5O₆ oxide under visible-light irradiation with a LED lamp. Evaluation of their effectiveness and safety for rapid healing of wounds and burn surfaces has been conducted on small animals (rats). It has shown significantly higher efficiency in comparison with commercial collagen sponges based on bovine collagen. Coatings based on cod collagen contributed to the normalization of microcirculation levels according to the results of laser Doppler flowmetry and a high rate of reduction in the area of the scalped burn wound according to planimetry. The morphological studies indicate complete epithelialization with the formation of scar tissue in all studied groups of animals. The dynamics of microcirculation parameters indicate the repair of thermal burns during local treatment with wound-healing coatings against the background of normalization of the functioning of the microcirculatory system. It is advisable to use new collagen-based polymer sponge plates to increase the effectiveness of wound treatment of various origins, shorten recovery time, and optimize the course of typical physiological reactions during the wound process in order to accelerate tissue regeneration, as well as reduce mortality. Full article

Background/Objectives: Hypertrophic scar (HS) is a fibroproliferative disorder characterized by excessive fibroblast activation and collagen deposition. The role of PIWI-interacting RNAs (piRNAs) in HS pathogenesis has not been defined. This study aimed to identify HS-related piRNAs, clarify their molecular mechanisms, and evaluate their therapeutic potential. Methods: High-throughput piRNA sequencing was performed on hypertrophic scar and matched normal tissues, followed by validation in patient-derived samples and dermal fibroblasts using quantitative reverse transcription PCR. Functional assays, including proliferation, apoptosis, migration, and invasion assays, were conducted after transfection with piRNA mimics or inhibitors. RNA sequencing, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, as well as dual-luciferase reporter and rescue assays, were used to identify and confirm molecular targets. Results: Sequencing revealed piR-hsa-022095 as one of the most significantly upregulated piRNAs in HS. Its inhibition suppressed fibroblast viability, migration, and invasion while inducing apoptosis and G₀/G₁ arrest. Transcriptomic profiling identified cell-cycle–related genes as major downstream targets, with KLF11 emerging as the principal effector. piR-hsa-022095 targets the 3′ UTR of KLF11, repressing its expression and thereby facilitating fibroblast proliferation. Restoration of KLF11 reversed the pro-fibrotic effects of piR-hsa-022095, confirming its functional role in HS pathogenesis. Conclusions: This study identifies piR-hsa-022095 as a novel regulator implicated in HS formation through repression of KLF11. The piR-hsa-022095–KLF11 axis may represent a previously unrecognized regulatory pathway involved in hypertrophic scar formation, providing new insights into the molecular mechanisms underlying HS pathogenesis. Full article

When blood flow to a part of the myocardial muscle is reduced or blocked, it leads to tissue ischemia in that region. Myocardial infarction (MI) occurs when the ischemic insult is of sufficient duration in time to induce cardiomyocyte death and subsequent activation of the innate immune response. MI initiates a complex cascade of cellular and molecular events within the left ventricle. Inflammatory cells rapidly infiltrate the infarcted area to remove necrotic tissue, setting the stage for reparative wound healing processes. Over the ensuing days, various cell populations—including leukocytes, fibroblasts, and endothelial cells—are attracted to the infarcted site by inflammatory cytokines and chemokines. The activated cells at the site of injury contribute to tissue remodeling and scar formation through the deposition of extracellular matrix components, particularly collagen. While scar formation is essential for structural stabilization of the infarct region to replace the loss of cardiomyocytes, scar tissue also increases myocardial stiffness and impairs cardiac contractile function. This review summarizes our knowledge regarding cellular dynamics, inflammatory signaling, and cardiac remodeling that govern MI healing. We identify the current gaps in the field and provide a foundational resource for those seeking to understand the biological underpinnings of cardiac repair following MI. Full article

To elucidate the corrosion mechanism of orthodontic archwire in fluoride-containing environments, the friction and wear behavior of archwires following corrosion in fluoride-containing oral care products was investigated. Stainless steel archwires were soaked in solutions of fluoride-free toothpaste, fluoride toothpaste, fluoride-free mouthwash, fluoride mouthwash, and sodium monofluorophosphate, followed by friction testing against brackets. The average friction coefficient of the archwire–bracket tribopair increased gradually from 0.17 to 0.28 with prolonged immersion time in the fluoride-containing solution, accompanied by a progressive increase in the wear scar area on the archwire surface. In the fluoride toothpaste solution, the archwire exhibited a corrosion potential and current density of –301.8 mV and 0.348 μA/cm², respectively, indicating a higher susceptibility to corrosion. Analysis of wear debris revealed significant enrichment of fluorine and oxygen elements on the archwire surface after exposure to fluoride-containing solutions, consistent with pronounced corrosion damage. Integration of friction results and surface characterization elucidated the corrosion mechanism in fluoride-containing environments. It was proposed that fluoride ions facilitated the formation of micro-batteries, while active fluoride species accelerated the dissolution of nickel from the archwire surface and promoted oxygen accumulation, thus driving sustained electrochemical corrosion. This progressive surface degradation ultimately exacerbated the friction and wear of the archwire–bracket tribopair. Full article

Background: To compare the histological and histomorphometrical outcomes after sinus floor elevation using an anorganic bovine bone biomaterial or a biphasic calcium phosphate biomaterial. Material and Methods: Patients who needed maxillary sinus elevation were included in this study. A total of 68 implant sites were evaluated from a total of 42 patients. Twenty patients were treated with anorganic bovine bone, while 22 were treated with biphasic calcium phosphate biomaterial. Morphological and morphometrical studies were performed on the bone samples collected during implant placement. Results: Both biomaterials induced similar relative areas of mineralized tissue overall, particularly if only the area of grafted bone was considered. In turn, a higher proportion of non-mineralized tissue was observed in cases of biphasic calcium phosphate biomaterial with less area of remnant biomaterial particles. None of the implants failed at one year of follow-up. Conclusions: Although both biomaterials induce a similar amount of bone formation, the histopathological characteristics of the grafts are different, with a greater proportion of scar connective tissue with the biphasic calcium phosphate biomaterial. Full article

(1) Background: Proliferative vitreoretinopathy (PVR) is the most common cause of failure in retinal detachment surgery and often leads to blindness. Oxidative stress is known to contribute to scar formation; therefore, reducing oxidative stress may protect against PVR development. This study investigated the therapeutic effects of the antioxidant 3′,4′-dihydroxyflavonol (DiOHF) in two preclinical models of PVR. (2) Methods: A retinal pigment epithelial cell line (ARPE-19) was used to investigate the anti-fibrotic effects of DiOHF. PVR was induced in one eye of each animal using dispase. Animals then received either vehicle or DiOHF eye drops in both eyes for 28 days. Eyes were harvested for mass spectrometry to perform proteomic analysis or to quantify tissue accumulation of DiOHF. Proteomic analysis was also performed in ARPE to validate these findings. (3) Results: In DiOHF-treated eyes with induced PVR, proteomic profiles showed reduced fibrosis, inflammation, cell migration, and oxidative stress compared with vehicle-treated PVR eyes. The in vitro studies confirmed that DiOHF inhibited wound healing responses, cell contraction, proliferation, and the generation of reactive oxygen species in ARPE-19 cells. Proteomic analysis in ARPE-19 also showed a similar trend. (4) Conclusions: This study provides compelling evidence that DiOHF eye drops offer protective effects against PVR in preclinical models. Full article

Background: The Orbay approach to volar distal radius described a volar zig-zag incision across the wrist crease, allowing a more distal exposure than traditional approaches. This adaptation enhances mobilization of the proximal radial fragment and improves visualization of both the articular surface and dorsally displaced distal radius fractures. Methods: In the present paper, we propose a further modification of the volar zig-zag approach, positioning the apex of the incision at the level of the radial styloid. Results: This modification aims to improve visualization of the radial styloid, the articular comminution, and the dorsal aspect of the distal radius, thereby optimizing fracture exposure and reduction. Conclusions: The principal advantage lies in the reduced need for traction along the radial margin of the incision to achieve adequate visualization and the avoidance of crossing the wrist crease, thereby preventing the formation of unsightly or adherent scars. Full article