Search Results (308)

Background: Wugeng San (WGS) is a traditional Tibetan medicinal preparation that has long been used to treat inflammatory and arthritic conditions. However, its contemporary pharmacological validation and the mechanisms underlying its action in rheumatoid arthritis (RA) have not been fully investigated. Objective: For the first time, this study aimed to systematically investigate the therapeutic effects of WGS on RA, identify its potential targets, and elucidate its action mechanisms. Methods: This study, as the first comprehensive investigation of WGS in RA, employed integrated multiple approaches including chemical component identification via UPLC-Q-TOF/MS, network pharmacology, bioinformatics, machine learning, and in vivo efficacy assessment and mechanism verification in a collagen-induced arthritis (CIA) rat model, a widely accepted experimental model that mimics the key pathological features of RA. Results: The results demonstrated that WGS reduced the severity of arthritis in a dose-dependent manner, as evidenced by decreased paw swelling, normalized body weight, and restored levels of pro- and anti-inflammatory cytokines. The high dose of WGS (252 mg/kg) showed an effect comparable to that of methotrexate (0.2 mg/kg). Histological analysis revealed that WGS reduced synovial hyperplasia, cartilage erosion and bone destruction, decreased osteoclast numbers, and promoted osteoblast activity. Eighty-four compounds were identified using UPLC-Q-TOF/MS. Network pharmacology and machine learning analyses indicated SYK as a key target enriched in the NF-κB signaling and osteoclast differentiation pathways. Experimental validation confirmed that WGS suppressed the phosphorylation of SYK and NF-κB pathway components (p65, IκBα, and IKKα/β), decreased MMP1/MMP3 levels, and modulated the Bax/Bcl-2 ratio to promote apoptosis. Conclusions: In conclusion, WGS exhibits strong anti-arthritic effects through “multi-component, multi-target, and multi-pathway” mechanisms, likely attributable to the inhibition of the SYK/NF-κB signaling axis, suppression of matrix degradation, and regulation of cellular apoptosis. This research offers a pharmacological basis for repurposing WGS as a promising natural candidate for RA therapy. Full article

Solution electrospinning (SES) and melt electrowriting (MEW) are complementary fiber-based fabrication platforms extensively investigated in tissue engineering. SES generates fibers typically ranging from the nanometer to the low-micrometer scale, producing fibrous networks that mimic the native extracellular matrix (ECM) and support key cellular functions. MEW, by contrast, operates solvent-free and enables precise, layer-by-layer deposition of microfibers with well-controlled geometry, conferring the mechanical integrity and open-pore architecture that SES constructs inherently lack. Despite growing interest, the body of peer-reviewed literature reporting original hybrid SES–MEW fabrication and biological outcome data remains limited, with no comprehensive cross-tissue synthesis available to date. This narrative review examines the current state of SES–MEW hybrid strategies across five tissue engineering targets selected for their clinical relevance: skin, vascular grafts, bone, cartilage, cardiac valves, and skeletal muscle. For each application, the architectural rationale, the fabrication approach, and the in vitro and in vivo biological outcomes are discussed in an integrated manner, with attention to how the spatial organization of nano- and microfibers translates into tissue-specific functional responses. A comparative analysis across tissue types highlights both the versatility of hybrid constructs and their persistent limitations, including suture retention values that remain below clinically accepted thresholds in vascular applications, incomplete cellular infiltration through dense nanofibrous layers, and the absence of validated, reproducible scale-up protocols compatible with clinical-grade manufacturing. The review concludes by identifying the most critical open questions in the field, encompassing process standardization, regulatory classification, and the emerging role of machine learning in closed-loop MEW process optimization. This work aims to provide an evidence-based perspective on the current state of hybrid SES–MEW scaffold engineering and the key translational gaps limiting clinical application. 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 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

Tissue engineering integrates concepts from medicine, biology, and engineering to create living constructs capable of repairing, replacing, or supporting damaged tissues. This multidisciplinary field relies on the interplay between biomaterials, cellular sources, and bioactive signaling to achieve functional tissue regeneration. This review provides a comprehensive overview of recent advances in scaffold design, highlighting natural, synthetic, and hybrid materials, as well as innovative fabrication techniques such as electrospinning, 3D bioprinting, and smart biomaterials. It discusses the role of stem cells and growth factors in directing regeneration and examines a wide range of clinical applications, including skin regeneration, cartilage repair, bone tissue engineering, dental and periodontal regeneration, nerve repair, cardiac tissue engineering, liver tissue models, and ophthalmic applications. Current challenges, such as immune responses, limited vascularization, scalability, and regulatory barriers, are addressed alongside emerging strategies aimed at improving clinical translation. By integrating diverse tissue types and engineering approaches within a unified framework, this review offers a broad yet detailed perspective on the current state and future directions of regenerative medicine. Full article

Piezoelectric biomaterials have attracted considerable interest in osteochondral tissue engineering owing to their inherent ability to produce electrical signals in response to mechanical stimuli without external power, thereby closely mimicking the physiological electrical microenvironment required for tissue regeneration. This review comprehensively summarizes recent insights into biological piezoelectricity from the molecular to the macroscopic level, highlighting its interplay with streaming potentials and its regulatory roles in bone and cartilage regeneration. We critically analyze recent advances in major piezoelectric material systems, including ceramics, polymers, and composite scaffolds, with emphasis on their structural characteristics, bioactive performance, and suitability for tissue-specific repair. Among them, polymer-based composite and hybrid piezoelectric scaffolds appear particularly promising for the development of flexible, high-performance osteochondral repair platforms, as they offer a more favorable balance between mechanical compliance, electromechanical output, and biological adaptability. Despite encouraging preclinical findings, significant challenges remain, including biocompatibility, controlled degradation kinetics, and the precise modulation of electrical cues for specific biological contexts. To address these barriers, future research should focus on optimizing scaffold design, integrating responsive and multimodal stimulation strategies, and establishing standardized protocols for preclinical evaluation and clinical translation. Overall, piezoelectric biomaterials hold substantial potential for the development of innovative regenerative therapies for complex osteochondral defects. Full article

Background/Objectives: Osteoarthritis is a chronic joint disorder involving the progressive breakdown of articular cartilage, which leads to joint pain and impaired mobility. The present study investigated the effects of curcuminoids phospholipid (CP) on osteoarthritis progression, assessed its cartilage-protective effects, and elucidated the underlying mechanisms. Methods: Male Sprague–Dawley rats were randomly allocated to six experimental groups. One group received an intra-articular saline injection as the normal control (NC), while the remaining five groups were injected with monosodium iodoacetate (MIA) and consisted of an MIA control group (MC), a positive control group treated with celecoxib (PC, 3 mg/kg), and three groups treated with CP (31.25, 62.5, or 125 mg/kg). Results: Compared with the MC group, CP administration significantly improved pain-related behavior, as assessed by weight-bearing measurements. Micro-computed tomography and histological analyses demonstrated that CP administration mitigated subchondral bone erosion and preserved cartilage integrity. Additionally, the CP treatment significantly reduced markers associated with cartilage degradation, including matrix metalloproteinases and cartilage oligomeric matrix proteins; downregulated the expression of matrix-degrading enzymes; and restored aggrecan expression. Serum levels of inflammatory mediators, including nitric oxide; prostaglandin E₂; C-reactive protein; and pro-inflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β, were reduced following CP administration. Furthermore, CP decreased the activation of nuclear factor kappa B (NF-κB) signaling. Conclusions: These findings suggest that CP may be a promising functional agent for osteoarthritis, demonstrating beneficial effects on pain-related outcomes and cartilage integrity, potentially mediated by its anti-inflammatory activity. Full article

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage destruction, and chondrocyte apoptosis plays a critical role in TMJOA progression. As chondrocytes reside in an avascular microenvironment inside the cartilage matrix, energy production via glycolysis is crucial for their survival. This study investigated the role of the key glycolytic enzyme Hexokinase 2 (HK2) in TMJOA pathogenesis and the therapeutic potential of dental pulp stem cell-derived extracellular vesicles (DPSC-EVs). In a rat experimental TMJOA model induced by monosodium iodoacetate (MIA) intra-articular injection, we observed a significantly decreased expression of HK2 along with cartilage matrix degradation. In the in vitro study, MIA induced chondrocyte apoptosis with caspase-3 activation, accompanied by impaired glycolytic function. Intervention with DPSC-EVs effectively rescued the expression of HK2 within chondrocytes, leading to a notable restoration of cellular glycolysis. Consequently, DPSC-EV treatment markedly attenuated the progression of TMJOA by reducing chondrocyte apoptosis and improved cartilage integrity. Our findings demonstrated that DPSC-EVs represent a promising cell-free therapeutic strategy for TMJOA, exerting their protective effects by targeting HK2, thereby preserving chondrocyte viability and attenuating osteoarthritis development. Full article

Reconstruction of the ear and temporal region presents unique challenges due to the complex anatomy of the lateral skull base and the need to restore both structural integrity and auditory function. Historically managed as separate entities, auricular reconstruction and hearing rehabilitation are increasingly approached in an integrated manner, supported by advances in microsurgical techniques and implantable hearing technologies. This narrative review synthesizes contemporary evidence on microsurgical reconstruction of the ear and temporal region in conjunction with hearing rehabilitation, analyzing a wide range of existing surgical techniques in an integrative manner. Reconstructive techniques discussed include local and regional flaps, free tissue transfer, auricular framework reconstruction using autologous cartilage or alloplastic materials, external auditory canal reconstruction, and subtotal petrosectomy. Hearing rehabilitation options reviewed encompass bone-anchored hearing systems, active and passive transcutaneous devices, middle ear implants, and cochlear implantation. Simultaneous reconstruction and implantation may reduce surgical burden and enable earlier hearing restoration in carefully selected patients, while staged approaches remain advantageous in complex or high-risk scenarios, particularly in the presence of chronic infection or extensive temporal bone surgery. Multidisciplinary collaboration, meticulous preoperative planning, and long-term follow-up are essential to optimize outcomes. Full article

Osteoarthritis (OA) is the main degenerative joint disease affecting nearly 7% of world population. OA is a multifactorial pathology due to environmental, inflammatory and genetic causes. Recently, the diet and consumption of specific foods have been associated to onset and progression of OA. Dietary patterns, macronutrients, micronutrients, and bioactive compounds can influence inflammatory pathways, oxidative stress, and cartilage metabolism. These effects are mediated not only by structural support but also through the modulation of gene expression and cellular signaling pathways. The emerging fields of nutrigenomics and nutrigenetics provide a mechanistic framework to explain interindividual variability in dietary responses. Nutrigenomics investigates how nutrients influence gene expression and molecular pathways involved in OA pathophysiology, whereas nutrigenetics examines how genetic polymorphisms affect nutrient metabolism, bioavailability, and biological efficacy. This narrative review critically examines current evidence on the interaction between diet, nutraceuticals, and common non-pathological genetic variants in OA. We discuss whether specific dietary patterns exert genotype-independent effects or require personalized approaches to optimize outcomes. By integrating genetic, metabolic, and nutritional perspectives, this review aims to clarify inconsistent findings in the literature and to outline the potential of precision nutrition as a complementary strategy for OA prevention and management. The integration of these approaches enables the development of personalized nutritional strategies tailored to an individual’s genetic background, metabolic profile, and comorbid conditions such as obesity, cardiovascular disease, and diabetes. Full article

Cartilage is an important yet vulnerable tissue with limited self-healing capacity, where damage often progresses to joint degeneration, which eventually leads to severe osteoarthritis (OA). Current tissue engineering strategies focus on biocompatible scaffolds for cartilage regeneration, particularly amnion (or amniotic membrane), emerging as a promising biomaterial due to its wide availability, low immunogenicity, and naturally derived microenvironment that is advantageous for cartilage regeneration. This systematic review aims to evaluate the existing evidence on the efficacy of amnion as a tissue scaffolding material for cartilage regeneration in both preclinical and clinical studies. Using terms such as “cartilage damage”, “cartilage injuries”, “amnion” and “amniotic membrane”, 19 relevant studies were identified across three major databases (PubMed, Scopus and Web of Science) until 25 December 2025. All preclinical and clinical studies that utilized amnion for cartilage repair or as cartilage tissue engineering scaffolding materials were included. Evidence quality was assessed using the OHAT and MINORS risk of bias tool. This study is prospectively registered in the PROSPERO database under the ID 1178444. The findings consistently indicate that amniotic scaffolds, regardless of processing methods or cell seeding, yield favorable outcomes without adverse effects across different species. In vitro analysis revealed that treatment groups with amnion show better cell attachment, viability, and proliferation, and higher content of cartilage-related markers expressed by the seeded cells, either chondrocyte, bone marrow-derived mesenchymal stem cells (MSCs), adipose tissue-derived MSCs, placenta-derived MSCs, umbilical cord-derived MSCs, amniotic MSCs or amniotic epithelial cells. In in vivo and ex vivo studies, amnion-treated groups demonstrated improved quality of the treated cartilage, with better integration, as indicated by higher histological scores and the presence of type II collagen (COL-II). There was an inconsistency in the reporting of cartilage defect dimensions in the in vivo models across the different studies. Nevertheless, the outcome measurements were consistently reported with histological analysis, with or without International Cartilage Repair Society (ICRS) scoring and immunohistochemistry (IHC) analysis, across the studies. Clinically, most subjects show improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) Sports and Recreation score and KOOS Quality of Life score, as well as reduced Visual Analogue Scale (VAS) average and maximum pain scores. In conclusion, preclinical and clinical studies support amnion as an ideal scaffold material for cartilage tissue engineering and regeneration. Future research should focus on optimizing and standardizing amnion scaffold preparation at a production scale to facilitate the translation of these positive outcomes into clinical applications. This study is funded by the Ministry of Higher Education Malaysia via Prototype Research Grant Scheme (PRGS/1/2021/SKK01/UM/02/1) and UM International Collaboration Grant—2023 SATU Joint Research Scheme Program: ST007-2024. Full article

Background: Post-traumatic osteoarthritis (PTOA) lacks effective disease-modifying therapies that preserve joint structure while promoting tissue repair. This study aimed to evaluate the therapeutic efficacy and underlying mechanism of Biluo Qianyuan Formula (BLQYF), a standardized herbal formulation derived from clinical practice, as a potential disease-modifying alternative to celecoxib in a murine model of PTOA. Methods: A murine PTOA model was established and treated with BLQYF at different doses, with celecoxib serving as a pharmacological comparator. Safety was assessed by hepatic and renal toxicity analyses. Therapeutic effects were evaluated using micro-computed tomography (micro-CT) and histological staining. Network-based integrative analyses were conducted to identify key regulatory targets, followed by experimental validation in fibroblast-like synoviocytes. Results: BLQYF was well tolerated under the experimental conditions, with no detectable hepatic or renal toxicity at therapeutic doses. Micro-CT and histological analyses demonstrated that BLQYF dose-dependently mitigated subchondral bone deterioration, enhanced cartilage regeneration, and restored collagen deposition. At higher doses, BLQYF showed therapeutic efficacy comparable to celecoxib, with superior outcomes regarding cartilage reparation. Mechanistically, integrative analyses identified fibronectin 1 (FN1) as a central regulatory hub. Validation experiments confirmed that BLQYF suppressed FN1, MMP3, and TGF-β expression in fibroblast-like synoviocytes, thereby attenuating inflammation and extracellular matrix degradation. Conclusions: These findings support BLQYF as a promising disease-modifying therapeutic candidate for PTOA and highlight the fibroblast–FN1 axis as a novel pharmacological target for intervention. Full article

This study investigates whether multi-component T₂ mapping, using bi-exponential (BE) and stretched-exponential (SE) models, enhances the early detection of knee osteoarthritis (OA) compared with the conventional mono-exponential (ME) approach. T₂ relaxation maps were derived from 26 patients with early-stage OA and 26 healthy controls. To minimize the influence of age-related cartilage changes, all model-derived parameters were adjusted for age prior to analysis. Quantitative T₂ parameters were extracted from six anatomically defined cartilage sub-regions to capture spatially heterogeneous tissue alterations characteristic of early OA. These parameters were then integrated using linear discriminant analysis to assess combined diagnostic performance. Global whole-cartilage analyses demonstrated limited discriminatory power across all models, with area under the receiver operating characteristic curve (AUC) values not exceeding 0.65, indicating that diffuse averaging obscures subtle, localized degeneration. In contrast, sub-regional analysis improved classification accuracy, highlighting the importance of regional assessment in early disease. Among the evaluated models, the BE-T₂ model showed the highest performance, achieving an AUC of 0.68, and marginally outperforming both the SE model (AUC = 0.60) and the ME model (AUC = 0.51). These findings suggest that multi-component T₂ mapping, particularly when applied at a sub-regional level, may offer improved sensitivity to early cartilage compositional changes. Overall, this approach shows strong potential as a noninvasive imaging biomarker for the early detection of knee OA. Full article

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage degeneration and subchondral bone remodeling, resulting in chronic pain and functional impairment. Although conservative treatments such as physical therapy and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used, their effectiveness is limited due to the poorly understood pathophysiology of TMJOA. Identifying reliable molecular biomarkers is essential to improving early diagnosis and guiding therapeutic development. This proof-of-concept study aims to identify candidate salivary biomarkers for TMJOA using an integrative approach combining clinical validation with in silico analysis. RNA sequencing was performed on saliva samples from TMJOA patients and healthy controls. In parallel, publicly available transcriptomic dataset GSE205389 was analyzed to identify differentially expressed genes (DEGs). DEGs were validated using qRT-PCR. Gene set enrichment analysis (GSEA) and Metascape were used to explore biological pathways associated with TMJOA. Integration of clinical and in silico RNA sequencing datasets identified 2758 and 3548 DEGs, respectively, with 743 overlapping genes. Pathway enrichment analyses highlighted immune-related, metabolic and osteoclast-related pathways. Four genes, CRIP1, PPA1 and TARS1 (statistically significant) and GCLC (non-significant trend), were validated by qRT-PCR in the clinical saliva samples, confirming elevated expression in TMJOA patients. Validation of the in silico dataset showed an upregulation of PTK2B, ABL1, TNF and IL-1B, supporting their relevance as salivary biomarkers in TMJOA. This exploratory study identifies four candidate salivary genes, CRIP1, PPA1, TARS1 and GCLC, as candidate salivary biomarkers for TMJOA, offering insights into disease mechanisms. Larger studies are needed to validate these findings and assess their clinical utility. Full article

Osteoarthritis (OA) is increasingly conceptualized as a whole-joint disorder, in which pathological processes across articular cartilage, subchondral bone, synovium, and periarticular tissues are tightly interconnected. Within this context, miRNAs have emerged as central post-transcriptional regulators capable of integrating mechanical, inflammatory, and metabolic cues at the network level. In human OA, extensive evidence links miRNA dysregulation to cartilage catabolism, impaired stress adaptation, inter-tissue communication, and the emergence of extracellular and circulating miRNA (cmiRNA) signatures with diagnostic and translational relevance. In contrast, miRNA research in canine OA remains limited, despite dogs developing a naturally occurring form of the disease that closely mirrors human OA in clinical presentation, joint pathology, and biomechanical drivers. To date, only a single pilot study has systematically investigated miRNA expression in spontaneous canine OA, underscoring both the feasibility of miRNA profiling and the substantial gaps that persist in tissue validation and functional characterization. This review critically synthesizes miRNA-mediated regulatory mechanisms in human OA and leverages this evidence to define research priorities in canine OA, where experimental validation remains limited. By focusing on shared molecular contexts rather than assumed equivalence, the review defines a comparative framework highlighting cmiRNAs as promising non-invasive translational targets. Full article