Search Results (3,525)

Background/Objectives: Proximal phalangeal fractures account for 38% of all phalangeal fractures, with unstable patterns requiring surgical intervention. Various modalities have been explored, including open reduction and internal fixation, percutaneous K-wire fixation, and intramedullary techniques. This study explores the technical nuances, indication, and outcomes of antegrade cannulated compressive screw (CCS) fixation of proximal phalangeal fractures. Methods: This retrospective case series involved 18 closed proximal phalangeal fractures in 16 patients who underwent intramedullary headless screw fixation between January 2018 and December 2023. Records were reviewed for demographics, fracture characteristics, and screw type. With the metacarpophalangeal joint flexed at 60–75°, a 1 cm longitudinal incision was made, the extensor tendon split, and a 0.9 mm guidewire advanced anterogradely along the phalangeal axis under fluoroscopy. A 2.2 mm or 3.0 mm SpeedTip CCS was selected based on phalanx size and advanced until fully buried below the cartilage line. Postoperatively, patients were immobilized in a volar intrinsic-plus splint, transitioned to a gutter splint within five to seven days, and commenced on range of motion (ROM) exercises within one week. Primary outcomes included radiographic union, Total Active Motion (TAM), QuickDASH scores, and postoperative complications. Results: All fractures were healed within acceptable radiological parameters and with no postoperative complications. Mean TAM was measured to be 216.0° (SD 7.7°, range 200–230°) and mean QuickDASH was 10.1 (SD 2.8, range 5–16). Conclusions: Antegrade intramedullary headless screw fixation demonstrates feasibility, short-term safety, and excellent early functional outcomes for carefully selected unstable proximal phalanx fractures, supporting its role as a minimally invasive alternative in appropriately indicated cases. Full article

Chondrosarcoma (CHS), the second most common primary malignant cartilage tumor, is largely resistant to conventional therapies, making surgical resection the standard treatment. Proton therapy offers a physical advantage through the Bragg peak, enabling targeted irradiation while sparing surrounding tissues. However, differential biological responses between malignant and normal cartilage cells remain poorly understood. In this study, CHS SW1353 cells and normal chondrocytes (MC615) were exposed to proton irradiation. Biological responses were assessed via clonogenic survival, cell viability, apoptosis (caspase 3/7), micronucleus formation, cell cycle profiling, and oxidative stress markers. Proteomic changes were analyzed using mass spectrometry and bioinformatics. CHS cells exhibited higher radioresistance (D₁₀ = 6.45 Gy) than normal chondrocytes (D₁₀ = 5.08 Gy), oxidative stress adaptation, G1 arrest and proteomic plasticity, whereas normal chondrocytes displayed increased oxidative stress, extracellular matrix fragility and impaired integrin signaling. Notably, the tumor-specific increased levels of Tyrosine-protein kinase Fyn and Yes1-associated transcriptional regulator (YAP1) signaling suggest molecular drivers of radioresistance. Overall, proton irradiation elicits distinct biological and proteomic responses in malignant versus normal cartilage cells. These findings highlight potential radiosensitization targets, including Fyn/Src and YAP1/Hippo pathways, while underscoring the need to optimize proton therapy to enhance tumor control while minimizing damage to healthy cartilage. Full article

Background: Eyelid reconstruction is particularly challenging because of the delicate anatomy and its critical functional and aesthetic roles. Although various methods have been described for anterior and posterior lamellar repairs, no standardized approach has been established. We developed a single-stage technique integrating reconstruction of both lamellae. Methods: This retrospective case series included seven consecutive patients who underwent full-thickness eyelid reconstruction between 2012 and 2024. Patients were included if they had full-thickness defects requiring reconstruction of both lamellae, underwent reconstruction using a nasal septal chondromucosal graft combined with a large local flap, and had at least 12 months of follow-up. The posterior lamella was reconstructed using nasal septal chondromucosal grafts, and the anterior lamella using large local flaps. Donor sites were managed using various methods. Results: All patients (7/7) achieved complete graft survival without partial or total graft loss. All patients achieved complete eyelid closure without lagophthalmos, and no cases of ectropion, corneal complications, or graft failure were observed. Buccal mucosal grafting demonstrated the most favorable donor-site outcomes, with uneventful healing and no septal perforation or airway-related complications. Conclusions: This single-stage approach combining chondromucosal grafts and local flaps is a feasible and reproducible option for selected patients, providing reliable structural support and satisfactory functional outcomes. Full article

The increase in older adults and active lifestyles has made chondral and osteochondral lesions common in the population, making them one of the central challenges in orthopedics. Although hydrogel-based regenerative medicine offers an encouraging therapeutic option for these lesions, important obstacles still prevent these therapies from reaching the clinic. In view of these factors, we adopted a risk-based approach for this review, in line with the current legislative requirements in clinical translation and clinical trials. We identified the factors that could undermine patient safety or lead to poor outcomes. Then, we outlined solutions to remedy these problems that integrate hydrogel technology, clinical/pharmaceutical/surgical protocols, and post-operative follow-up. Upcoming studies should give priority to the development of hydrogel scaffolds modified to mimic cartilage’s mechanical and physicochemical properties, together with patient-specific features. Other crucial characteristics are host-tissue integration, long-lasting cartilage tissue regeneration, and a positive outcome. In parallel, to scale complex and costly innovations, efforts should focus on a harmonized, simplified legislative landscape, optimized standards, and established follow-up protocols. Getting through this “valley of death” between research and innovation is strategic for reaching the clinics and the largest number of patients. Full article

Temporomandibular disorders (TMDs) are the prevalent causes of orofacial pain and dysfunction of the temporomandibular joint (TMJ) and masticatory muscles. Previous studies have revealed that proinflammatory cytokines play a key role in promoting inflammation, pain, and degeneration within the TMJ. In this context, the present systematic review synthesizes current evidence on various cytokines involved in the pathophysiology of TMDs and evaluates their associations with clinical signs and structural TMJ damage. A PRISMA-guided search (PROSPERO: CRD420251163290) was conducted in PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library to identify human-based, in vivo, and in vitro studies (January 2014 to September 2025) that assessed the roles of proinflammatory cytokines in TMDs. The following data were extracted from the identified studies: cytokine profiles, sampling methods, clinical outcomes, and TMJ structural changes. Study quality and risk of bias were systematically evaluated. A total of 15 studies (clinical, animal, and mechanistic) were included in the review. Tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) consistently emerged as the major contributors to synovitis, cartilage degradation, nociceptive sensitization, and bone resorption. Human studies showed that high levels of TNF-α, IL-1β, and IL-6 and chemokines such as C-C motif chemokine ligand 2 (CCL2) and regulated on activation, normal T-cell expressed and secreted (RANTES) were associated with TMJ pain, restricted mandibular motion, crepitus, malocclusion, and erosive changes on imaging. An increased ratio of TNF to soluble TNF receptor in synovial fluid correlated with both pain and condylar damage, suggesting that loss of cytokine control contributes to progressive joint destruction. TMDs, particularly inflammatory and degenerative subtypes, are cytokine-driven pathologies rather than purely mechanical disorders. TNF-α, IL-1β, and IL-6 are the promising candidate biomarkers of local inflammation and structural joint pathology. Standardized longitudinal studies are required to validate cytokine-based diagnostics and develop anti-cytokine therapeutics. Full article

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative maxillofacial disorder marked by progressive cartilage degradation and subchondral bone resorption, severely compromising patients’ quality of life. Intra-articular injection (IA), a standard route for conservative therapy, offers clinical advantages in safety and efficacy; however, outcomes remain limited due to short drug retention, poor tissue penetration, and variable agent efficacy, necessitating repeated administration. To overcome these limitations, fisetin-loaded poly (lactic-co-glycolic acid) nanoparticles (FST-PNP) were developed as a localized drug delivery system (DDS) for TMJOA treatment. Physicochemical analyses showed FST-PNP had uniform spherical morphology, excellent dispersibility, stability, high encapsulation efficiency, and substantial drug loading capacity. An in vitro study demonstrated more sustained and stable release from FST-PNP than free fisetin. The in vivo IA administration of FST-PNP preserved mandibular condylar osteochondral structures in TMJOA models. Notably, FST-PNP suppressed the expression of metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS5) as catabolic enzymes and downregulated p16 and p21 as senescence markers, indicating synergistic anti-inflammatory and anti-senescent effects. These findings highlight FST-PNP as a DDS integrating controlled-release with multifaceted therapeutic actions, providing a promising strategy for IA therapy of TMJOA. Full article

Mechano-sorptive phenomena (MSP) refer to the coupled mechanical response of polymers under simultaneous mechanical stress and fluid sorption. The most researched MSP are environmental stress cracking (ESC) and mechano-sorptive creep (MSC). ESC initiates at regions of localized stress and solvent sorption, presenting as brittle fracture, while MSC is characterized by large, time-dependent, and partially recoverable creep associated with transient bulk sorption. ESC experiments can however also result in significant plastic deformation, in which case the term environmental stress yielding (ESY) has been used. Similarly, MSC can evolve into tertiary creep followed by rupture, in which case the phenomenon is termed mechano-sorptive creep rupture (MSCR). Both behaviors originate from solvent diffusion into the amorphous phase, leading to disruption of non-covalent interactions between polymer chains. This review bridges seemingly disconnected research to illustrate that ESC and MSC represent extremes on a continuum of MSP, rather than disparate phenomena. We identify the principles of polymer thermodynamics and experimental methods necessary to separate polymer deformation under MSC into reversible stress-induced swelling and irreversible non-equilibrium deformation. Finally, we illustrate how MSP underline the functionality of several biomimetic materials including dentin adhesives, mutable collagenous tissue, spider silk, tendons, and articular cartilage, as well the synthesis of biomimetic materials by solvent vapor annealing assisted by soft shear. Full article

Articular cartilage has a limited capacity for self-repair, and effective strategies for its regeneration remain a major clinical challenge. Full-thickness cartilage defects extending to the subchondral bone induce an enhanced inflammatory response and impair spontaneous healing. This study aimed to evaluate the regenerative potential of autologous chondrocyte transplantation using an insoluble polyethersulfone (PES) scaffold in a rabbit model of grade III articular cartilage lesions. Chondrocytes were isolated and expanded in vitro and subsequently seeded onto PES membranes. Sixty-two rabbit knees with defects extending to the subchondral bone were divided into three groups: group I received chondrocyte-seeded PES scaffolds (n = 25), group II received cell-free PES scaffolds (n = 25), and group III served as an untreated control (n = 12). Cartilage regeneration was evaluated macroscopically and histologically over 52 weeks. In addition, the chondrogenic differentiation potential of cells cultured on PES scaffolds was assessed. This study extends our previous investigations of PES scaffolds in grade IV cartilage defects to a clinically relevant grade III lesion model, enabling evaluation of regenerative outcomes at an earlier stage of cartilage degeneration. The results demonstrated superior tissue regeneration in defects treated with chondrocyte-seeded PES scaffolds compared to both control groups. These findings indicate that synthetic PES scaffolds support cartilage repair and represent a promising biomaterial for the development of cell-based therapies in articular cartilage regeneration. Full article

Background: Immediate loading of dental implants shortens treatment time and improves early function, but it also exposes the healing peri-implant tissue to a critical mechanical environment. This study compared the biomechanical and mechanobiological response of a conventional threaded implant and a porous scaffold-based implant under immediate and delayed loading conditions. Methods: A three-dimensional finite element model of a bone block with a 0.2 mm peri-implant callus was developed in ABAQUS/Standard. Model A was a threaded Ti-6Al-4V implant, while Model B was a porous implant with 64.26% porosity. Bone tissues were modeled as poroelastic materials. Immediate and delayed loading were simulated through frictional and tied bone-implant interfaces, respectively. Mechanobiological predictions were performed using the Prendergast-Huiskes stimulus. Results: Under immediate loading, the porous implant reduced cortical bone stress (32.5 MPa vs. 88 MPa) and markedly increased callus stimulation (20.5–31.6 MPa vs. about 2.5 MPa) compared with the threaded implant. Mechanobiological analysis showed that Model B promoted higher fractions of immature and mature bone and lower fractions of cartilage and fibrous tissue. In all cases, implant stresses remained below the yield strength of the corresponding materials. Conclusions: The porous implant provided a more favorable mechanical environment for early peri-implant healing, particularly under immediate loading, and may be a promising strategy to enhance callus maturation and reduce stress shielding. Full article

Juvenile idiopathic arthritis (JIA) represents the most common cause of chronic arthritis in childhood; however, not all early-onset arthropathies are inflammatory in origin. We report the case of a 4-year-old girl initially diagnosed with oligoarticular JIA and treated with methotrexate followed by a tumor necrosis factor inhibitor, without significant clinical improvement and despite persistently normal inflammatory markers. Clinical reassessment raised suspicion of a non-inflammatory arthropathy, supported by characteristic radiographic findings including metaphyseal flaring of the distal femora and proximal tibiae. Genetic analysis identified compound heterozygous pathogenic variants in the PRG4 gene, confirming the diagnosis of camptodactyly–arthropathy–coxa vara–pericarditis (CACP) syndrome (OMIM #208250). PRG4 encodes lubricin, a mucin-like glycoprotein essential for boundary lubrication of articular cartilage and maintenance of synovial joint homeostasis. Loss-of-function variants disrupt joint lubrication, leading to mechanical synovial hyperplasia and chronic non-inflammatory joint effusion. This case highlights common diagnostic pitfalls in pediatric rheumatology and underscores the importance of considering genetic causes of chronic arthropathy when clinical and laboratory features are atypical for inflammatory disease. Early molecular diagnosis prevents unnecessary immunosuppressive therapy and enables appropriate multidisciplinary management. Full article

In this research article, we introduce and develop the notion of complex-valued b-suprametric spaces as a natural generalization of existing metric-type structures. Fundamental concepts, including convergence, Cauchy sequences, and completeness, are examined in this new setting. We establish new common fixed point theorems for generalized and cyclic rational contractive mappings. The obtained results extend and unify various known fixed point theorems available in the current literature. To demonstrate the applicability and effectiveness of our theoretical findings, illustrative nontrivial examples are provided. As an application, we investigate the existence and uniqueness of solutions for Caputo fractional differential equations, which naturally arise in systems with hereditary and memory effects, particularly in biomedical modeling of viscoelastic biological tissues such as arteries, cartilage, and brain tissue. This demonstrates both the mathematical strength and the practical relevance of the proposed framework. Full article

Vitamin C, also known as ascorbic acid, plays a pivotal role in forming blood vessels, cartilage, muscles, and collagen in bones. We report a 6-year-old non-verbal female with global developmental delay who presented with complaints of lower limb pain and inability to bear weight. Symptoms started five weeks prior to presentation and had progressed from decreased activity to complete loss of weight-bearing. Physical examination showed gingival hyperplasia, perifollicular petechiae, lower limb edema, and corkscrew hair. Initial radiologic findings raised concerns of osteomyelitis, showing bone marrow edema, periosteal reaction, and cortical irregularity. However, correlation with dietary history limited to flavored milk and yogurt and lacking fruits and vegetables, in conjunction with clinical presentation, suggested vitamin C deficiency, and she was started on ascorbic acid. Vitamin C deficiency was later confirmed on day 7 by a low C deficiency level (<0.1 mg/dL). Treatment with ascorbic acid, multivitamins, and supportive therapy led to gradual recovery, and gastrostomy tube placement facilitated supplementation. This case highlights the importance of detailed dietary history and recognition of clinical signs of vitamin C deficiency. Early dietary assessment and clinical correlation can prevent unnecessary invasive procedures and prolonged antibiotic therapy. Early identification enables timely intervention, reducing morbidity and improving quality of life. Full article

Stromal vascular fraction (SVF) has emerged as a versatile autologous therapeutic strategy across multiple regenerative medicine applications. Derived from adipose tissue, SVF exerts its effects primarily through paracrine, immunomodulatory, pro-angiogenic, and anti-fibrotic mechanisms rather than direct cell differentiation. Potential regenerative outcomes have been reported in bone, cartilage, scar modulation, and neural repair, highlighting a shared pro-regenerative cascade centered on early inflammation control and vascular support. Indeed, increasing evidence suggests that synergy with biomaterials and point-of-care one-step approaches further enhances SVF efficacy. Regarding the real clinical potential, however, transability is still limited due to heterogeneity in isolation methods, lack of standardization, and insufficient large-scale randomized controlled trials. Full article

This study aims to evaluate the therapeutic efficacy of emodin (EMO) in rheumatoid arthritis (RA) and to verify whether its underlying mechanism involves the blockade of pathological angiogenesis via the inhibition of the nuclear factor-kappa B (NF-κB)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling axis. Bovine type II collagen-induced arthritis (CIA) mouse models and lipopolysaccharide (LPS)-stimulated EA.hy926 endothelial cells were utilized in this study. The effects of EMO on joint pathological alterations, the expression of NF-κB/HIF-1α/VEGF axis proteins, inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β)), and angiogenic capacity were assessed using histopathological analysis, Western blotting, immunohistochemistry (IHC), immunofluorescence, and tube formation assays. Furthermore, small interfering RNA (siRNA) interference targeting key molecules was employed to validate the molecular mechanisms underlying the therapeutic effects of EMO. In the CIA model group, the ankle joints of mice exhibited pronounced inflammatory infiltration, synovial hyperplasia, and bone destruction. Compared with the model group, both the EMO and methotrexate (MTX) treatment groups demonstrated attenuated synovial hyperplasia and cartilage destruction, along with significantly downregulated expression levels of key NF-κB pathway proteins, HIF-1α, and VEGF in joint tissues (p < 0.001). In vitro experiments revealed that EMO treatment significantly reduced the LPS-induced secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) (p < 0.001), and decreased both the number and total length of tubular structures formed by endothelial cells compared to the control (p < 0.001). Notably, siRNA-mediated knockdown of p65 resulted in decreased intracellular protein levels of HIF-1α and VEGF, accompanied by a significant reduction in tube formation (p < 0.001). This study demonstrates that EMO alleviates pathological damage in RA by inhibiting the activation of the NF-κB signaling pathway, which subsequently downregulates pathological angiogenesis and inflammatory responses mediated by the HIF-1α/VEGF axis. These findings provide a robust experimental basis for the potential application of EMO as a therapeutic agent for RA. Full article

Background/Objectives: The medial meniscus is crucial for load transmission and knee stability. Meniscal tears disrupt joint biomechanics, increasing the risk of cartilage degeneration. However, few studies have quantitatively compared how different tear types affect stress and contact mechanics using finite element analysis (FEA). This study aims to analyze stress distributions for various meniscal tear types and develop a predictive model for meniscal stress behavior. This study investigates how stress distributions differ between healthy and torn medial menisci under identical loading conditions. The study examines which meniscal tear type produces the highest stress concentrations. The effects of different tear types on penetration, gap formation, pressure distribution, and sliding distance at the meniscus interface are also analysed. Materials and Methods: The FEA model of the knee joint, including femoral and tibial cartilage and the medial meniscus, was developed. Simulations were conducted for a healthy meniscus and for menisci with radial, horizontal and complex tears. Stress, penetration, gap, pressure, and sliding distance were calculated, and a mathematical model describing their relationships was established. Results: All torn menisci exhibited significantly higher stresses than the healthy meniscus (p < 0.001). Radial tears generated the highest stress concentrations (p < 0.001). Pressure was mainly influenced by meniscal geometry, while the gap remained nearly constant. Penetration increased slightly (p < 0.05). The predictive model demonstrated a strong correlation between meniscal stress and interface parameters (R² > 0.9). In a healthy meniscus, stress distribution is homogeneous (≈26 MPa). Stress concentration increases depending on the tear type: limited in a horizontal tear (≈26.5 MPa), significant in a vertical tear (≈30.8 MPa), and highest in a radial tear (≈40.6 MPa). These results indicate that as the tear progresses, the load-bearing capacity of the meniscus decreases, and stresses concentrate at the tear edges. Conclusions: Meniscal tears, especially radial ones, substantially alter knee biomechanics and elevate tissue stress. These biomechanical insights highlight the importance of early diagnosis and targeted rehabilitation strategies to prevent further cartilage damage and osteoarthritis progression. Full article