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Articular cartilage is the avascular and aneural tissue which is the primary connective tissue covering the surface of articulating bone. Traumatic damage or degenerative diseases can cause articular cartilage injuries that are common in the population. As a result, the demand for new therapeutic options is continually increasing for older people and traumatic young patients. Many attempts have been made to address these clinical needs to treat articular cartilage injuries, including osteoarthritis (OA); however, regenerating highly qualified cartilage tissue remains a significant obstacle. 3D bioprinting technology combined with tissue engineering principles has been developed to create biological tissue constructs that recapitulate the anatomical, structural, and functional properties of native tissues. In addition, this cutting-edge technology can precisely place multiple cell types in a 3D tissue architecture. Thus, 3D bioprinting has rapidly become the most innovative tool for manufacturing clinically applicable bioengineered tissue constructs. This has led to increased interest in 3D bioprinting in articular cartilage tissue engineering applications. Here, we reviewed current advances in bioprinting for articular cartilage tissue engineering. [ABSTRACT FROM AUTHOR]

Inflammation and loss of articular cartilage are considered the major cause of temporomandibular joint osteoarthritis (TMJOA), a painful condition of the temporomandibular joint (TMJ). To determine the cause of TMJ osteoarthritis in these patients, synovial fluid of TMJOA patients was compared prior to and after hyaluronic lavage, revealing substantially elevated levels of interleukin (IL) 1β, reactive oxidative stress (ROS), and an overload of Fe3+ and Fe2+ prior to lavage, indicative of ferroptosis as a mode of chondrocyte cell death. To ask whether prolonged inflammatory conditions resulted in ferroptosis-like transformation in vitro, we subjected TMJ chondrocytes to IL-1β treatment, resulting in a shift in messenger RNA sequencing gene ontologies related to iron homeostasis and oxidative stress–related cell death. Exposure to rat unilateral anterior crossbite conditions resulted in reduced COL2A1 expression, fewer chondrocytes, glutathione peroxidase 4 (GPX4) downregulation, and 4-hydroxynonenal (4-HNE) upregulation, an effect that was reversed after intra-articular injections of the ferroptosis inhibitor ferrostatin 1 (Fer-1). Our study demonstrated that ferroptosis conditions affected mitochondrial structure and function, while the inhibitor Fer-1 restored mitochondrial structure and the inhibition of hypoxia-inducible factor 1α (HIF-1α) or the transferrin receptor 1 (TFRC) rescued IL-1β–induced loss of mitochondrial membrane potential. Inhibition of HIF-1α downregulated IL-1β–induced TFRC expression, while inhibition of TFRC did not downregulate IL-1β–induced HIF-1α expression in chondrocytes. Moreover, inhibition of HIF-1α or TFRC downregulated the IL-1β–induced MMP13 expression in chondrocytes, while inhibition of HIF-1α or TFRC rescued IL-1β–inhibited COL2A1 expression in chondrocytes. Furthermore, upregulation of TFRC promoted Fe2+ entry into chondrocytes, inducing the Fenton reaction and lipid peroxidation, which in turn caused ferroptosis, a disruption in chondrocyte functions, and an exacerbation of condylar cartilage degeneration. Together, these findings illustrate the far-reaching effects of chondrocyte ferroptosis in TMJOA as a mechanism causing chondrocyte death through iron overload, oxidative stress, and articular cartilage degeneration and a potential major cause of TMJOA. [ABSTRACT FROM AUTHOR]

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This review examines the latest advancements in compositional and quantitative cartilage MRI techniques, addressing both their potential and challenges. The integration of these advancements promises to improve disease detection, treatment monitoring, and overall patient care. We want to highlight the pivotal task of translating these techniques into widespread clinical use, the transition of cartilage MRI from technical validation to clinical application, emphasizing its critical role in identifying early signs of degenerative and inflammatory joint diseases. Recognizing these changes early may enable informed treatment decisions, thereby facilitating personalized medicine approaches. The evolving landscape of cartilage MRI underscores its increasing importance in clinical practice, offering valuable insights for patient management and therapeutic interventions. This review aims to discuss the old evidence and new insights about the evaluation of articular cartilage through MRI, with an update on the most recent literature published on novel quantitative sequences. [ABSTRACT FROM AUTHOR]

Functional articular cartilage regeneration remains an unmet medical challenge, increasing the interest for innovative biomaterial-based tissue engineering (TE) strategies. Hydrogels, 3D macromolecular networks with hydrophilic groups, present articular cartilage-like features such as high water content and load-bearing capacity. In this study, 3D porous polyethylene glycol diacrylate (PEGDA) hydrogels were fabricated combining the gas foaming technique and a UV-based crosslinking strategy. The 3D porous PEGDA hydrogels were characterized in terms of their physical, structural and mechanical properties. Our results showed that the size of the hydrogel pores can be modulated by varying the initiator concentration. In vitro cytotoxicity tests showed that 3D porous PEGDA hydrogels presented high biocompatibility both with human chondrocytes and osteoblast-like cells. Importantly, the 3D porous PEGDA hydrogels supported the viability and chondrogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cell (hBM-MSC)-based spheroids as demonstrated by the positive staining of typical cartilage extracellular matrix (ECM) (glycosaminoglycans (GAGs)) and upregulation of chondrogenesis marker genes. Overall, the produced 3D porous PEGDA hydrogels presented cartilage-like mechanical properties and supported MSC spheroid chondrogenesis, highlighting their potential as suitable scaffolds for cartilage TE or disease modelling strategies. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the inhibitory effects of micro-current stimulation (MCS) on inflammatory responses in chondrocytes and degradation of extracellular matrix (ECM) in osteoarthritis (OA). To determine the efficacy of MCS, IL-1β-treated chondrocytes and monosodium iodoacetate (MIA)-induced OA rat model were used. To evaluate the cytotoxicity and nitric oxide (NO) production in SW1353 cells, the presence or absence of IL-1β treatment or various levels of MCS were applied. Immunoblot analysis was conducted to evaluate whether MCS can modulate IL-1R1/MyD88/NF-κB signaling pathway and various indicators involved in ECM degradation. Additionally, to determine whether MCS alleviates subchondral bone structure destruction caused by OA, micro-CT analysis, immunoblot analysis, and ELISA were conducted using OA rat model. 25 and 50 µA levels of MCS showed effects in cell proliferation and NO production. The MCS group with IL-1β treatment lead to significant inhibition of protein expression levels regarding IL-1R1/MyD88/NF-κB signaling and reduction of the nucleus translocation of NF-κB. In addition, the protein expression levels of MMP-1, MMP-3, MMP-13, and IL-1β decreased, whereas collagen II and aggrecan increased. In animal results, morphological analysis of subchondral bone using micro-CT showed that MCS induced subchondral bone regeneration and improvement, as evidenced by increased thickness and bone mineral density of the subchondral bone. Furthermore, MCS-applied groups showed decreases in the protein expression of MMP-1 and MMP-3, while increases in collagen-II and aggrecan expressions. These findings suggest that MCS has the potential to be used as a non-pharmaceutical method to alleviate OA. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether intra‐articular injections of peripheral blood stem cells (PBSC) with hyaluronan (HA)‐based scaffold improve articular cartilage regeneration in chondral injuries caused by mixed‐femoroacetabular impingement syndrome (FAIS) over a period longer than 24 months post‐hip arthroscopy. Methods: In this prospective cohort study, patients with mixed‐FAIS and chondral injury ≥ IIIB according to the International Cartilage Regeneration and Joint Preservation Society grade or III/IV of Konan/Haddad classification underwent intra‐articular injection of PBSC with an HA‐based scaffold and micro‐drillings during hip arthroscopy. The degree of chondral repair was measured at baseline and 5 years using the International Cartilage Repair Society morphologic score system (MSS) as the primary outcome. Pain was measured at baseline and 5 years using the Visual Analogue Scale for Pain (VAS Pain), and hip functionality was measured at baseline (presurgery), 6 months, 1 year, and 5 years using the Hip Outcome Score (HOS). The largest diameter of injury, median follow‐up, side effects, complications, and improvements were described. T‐test, ANOVA with multiple comparisons, and statistical power were estimated. Results: From initially 34 cases, 25 patients were enrolled. The median follow‐up was 5.1 ± 0.3 years. One patient (4%) reported a few side effects with filgrastim administration. No infection, tumours, or synovitis was reported. The largest diameters in zones two, three, and four were 12.4 ± 3.1 mm (n = 8), 13.5 ± 2.8 mm (n = 14), and 11.4 ± 1.9 mm (n = 3), respectively. Ninety‐two percent (23/25) of patients improved their outcomes. The MSS and HOS increased from 3.8 ± 1.1 to 9.6 ± 1.5 pts (p < 0.001) and from 65.5 ± 13.0 to 93.9 ± 2.4 pts (p < 0.001), respectively. The VAS‐Pain decreased from 5.3 ± 0.7 to 1.3 ± 0.6 mm (p < 0.001). The obtained a posteriori power‐size was 0.99. Conclusion: The intervention suggests a favourable impact on articular cartilage regeneration and clinical outcomes for hip chondral lesions in mixed‐FAIS injuries after a median follow‐up of 5.1 ± 0.3 years. Level of Evidence: Level IV. [ABSTRACT FROM AUTHOR]

BACKGROUND: With the deepening of the aging of the world population, the prevalence rate of osteoarthritis is increasing. In recent years, more and more attention has been paid to the study of osteoarthritis. Studies have shown that autophagy and apoptosis are strongly associated with the occurrence and development of osteoarthritis, and play an important role in it. OBJECTIVE: To review the molecular mechanisms of the interaction between autophagy and apoptosis in osteoarthritis, aiming to explore the relationship between autophagy and apoptosis in osteoarthritis and the coupling mechanism of the two to mediate the occurrence and development of osteoarthritis, so as to provide new ideas for the treatment of osteoarthritis. METHODS: The Chinese and English key words “osteoarthritis, autophagy, apoptosis” were searched in the CNKI and PubMed. After screening by reading the title, abstract and key words, the relevant literature was carefully read. After excluding studies unrelated to the content of the paper and repetitive studies, 68 articles were finally included for the summary. RESULTS AND CONCLUSION: (1) The occurrence and development of osteoarthritis are related to autophagy and apoptosis of chondrocytes. Autophagy protects chondrocytes from stress damage, but excessive autophagy also induces or promotes chondrocyte apoptosis and reduces the survival rate of chondrocytes. The two perturb each other to regulate the degeneration of articular cartilage. (2) miRNA, Beclin-1 and oxidative stress are all involved in the regulation of autophagy and apoptosis on osteoarthritis, and affect the development of osteoarthritis. [ABSTRACT FROM AUTHOR]

Tissue regeneration technology has been rapidly developed and widely applied in tissue engineering and repair. Compared with traditional approaches like surgical treatment, the rising gene therapy is able to have a durable effect on tissue regeneration, such as impaired bone regeneration, articular cartilage repair and cancer-resected tissue repair. Gene therapy can also facilitate the production of in situ therapeutic factors, thus minimizing the diffusion or loss of gene complexes and enabling spatiotemporally controlled release of gene products for tissue regeneration. Among different gene delivery vectors and supportive gene-activated matrices, advanced gene/drug nanocarriers attract exceptional attraction due to their tunable physiochemical properties, as well as excellent adaptive performance in gene therapy for tissue regeneration, such as bone, cartilage, blood vessel, nerve and cancer-resected tissue repair. This paper reviews the recent advances on nonviral-mediated gene delivery systems with an emphasis on the important role of advanced nanocarriers in gene therapy and tissue regeneration. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to provide a comprehensive review of the existing literature regarding the treatment of osteochondral lesions of the talus (OLT) using autologous matrix-induced chondrogenesis (AMIC), while also discussing the mid-long term functional outcomes, complications, and surgical failure rate. Methods: We searched Embase, PubMed, and Web of Science for studies on OLT treated with AMIC with an average follow-up of at least 2 years. Publication information, patient data, functional scores, surgical failure rate, and complications were extracted. Results: A total of 15 studies were screened and included, with 12 case series selected for meta-analysis and 3 non-randomized controlled studies chosen for descriptive analysis. The improvements in the Visual Analog Scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot, and Tegner scores at the last follow-up were (SMD = − 2.825, 95% CI − 3.343 to − 2.306, P < 0.001), (SMD = 2.73, 95% CI 1.60 to 3.86, P < 0.001), (SMD = 0.85, 95% CI 0.5 to 1.2, P < 0.001) respectively compared to preoperative values. The surgery failure rate was 11% (95% CI 8–15%), with a total of 12 patients experiencing complications. Conclusion: The use of AMIC demonstrates a positive impact on pain management, functional improvement, and mobility enhancement in patients with OLT. It is worth noting that the choice of stent for AMIC, patient age, and OLT size can influence the ultimate clinical outcomes. This study provides evidences supporting the safety and efficacy of AMIC as a viable treatment option in real-world medical practice. [ABSTRACT FROM AUTHOR]

Objectives. Osteochondral defects (OCDs) are localized areas of damaged cartilage and underlying subchondral bone that can produce pain and seriously impair joint function. Literature reports indicated that icariin (ICA) has the effect of promoting cartilage repair. However, its mechanism remains unclear. Here, we explored the effects of icariin and extracellular vesicles (EVs) from rabbit synovial‐derived mesenchymal stem cells (rSMSCs) on repairing of OCDs. Materials and Methods. Rabbit primary genicular chondrocytes (rPGCs), knee skeletal muscle cells (rSMCKs), and rSMSCs, and extracellular vesicles derived from the latter two cells (rSMCK‐EVs and rSMSC‐EVs) were isolated and identified. The rPGCs were stimulated with ICA, rSMSC‐EVs either separately or in combination. The rSMCK‐EVs were used as a control. After stimulation, chondrogenic‐related markers were analyzed by quantitative RT‐PCR and western blotting. Cell proliferation was determined by the CCK‐8 assay. The preventative effects of ICA and SMSC‐EVs in vivo were determined by H&E and toluidine blue staining. Immunohistochemical analyses were performed to evaluate the levels of COL2A1 and β‐catenin in vivo. Results. In vitro, the proliferation of rPGCs was markedly increased by ICA treatment in a dose‐dependent manner. When compared with ICA or rSMSC‐EVs treatment alone, combined treatment with ICA and SMSC‐EVs produced stronger stimulative effects on cell proliferation. Moreover, combined treatment with ICA and rSMSC‐EVs promoted the expression of chondrogenic‐related gene, including COL2A1, SOX‐9, and RUNX2, which may be via the activation of the Wnt/β‐catenin pathway. In vivo, combined treatment with rSMSC‐EVs and ICA promoted cartilage repair in joint bone defects. Results also showed that ICA or rSMSC‐EVs both promoted the COL2A1 and β‐catenin protein accumulation in articular cartilage, and that was further enhanced by combined treatment with rSMSC‐EVs and ICA. Conclusion. Our findings highlight the promising potential of using combined treatment with ICA and rSMSC‐EVs for promoting osteochondral repair. [ABSTRACT FROM AUTHOR]

Background: Mechanical unloading of the knee articular cartilage results in cartilage matrix atrophy, signifying the osteoarthritic-inductive potential of mechanical unloading. In contrast, mechanical loading stimulates cartilage matrix production. However, little is known about the response of meniscal fibrocartilage, a major mechanical load-bearing tissue of the knee joint, and its functional matrix-forming fibrochondrocytes to mechanical unloading events. Methods: In this study, primary meniscus fibrochondrocytes isolated from the inner avascular region of human menisci from both male and female donors were seeded into porous collagen scaffolds to generate 3D meniscus models. These models were subjected to both normal gravity and mechanical unloading via simulated microgravity (SMG) for 7 days, with samples collected at various time points during the culture. Results: RNA sequencing unveiled significant transcriptome changes during the 7-day SMG culture, including the notable upregulation of key osteoarthritis markers such as COL10A1, MMP13, and SPP1, along with pathways related to inflammation and calcification. Crucially, sex-specific variations in transcriptional responses were observed. Meniscus models derived from female donors exhibited heightened cell proliferation activities, with the JUN protein involved in several potentially osteoarthritis-related signaling pathways. In contrast, meniscus models from male donors primarily regulated extracellular matrix components and matrix remodeling enzymes. Conclusion: These findings advance our understanding of sex disparities in knee osteoarthritis by developing a novel in vitro model using cell-seeded meniscus constructs and simulated microgravity, revealing significant sex-specific molecular mechanisms and therapeutic targets. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (OA) and obesity are major public health concerns that are closely intertwined. This intimate relationship was documented by considering obesity as the most significant preventable risk factor associated with knee OA. To date, however, the effects of obesity on the knee joint's passive-active structure and cartilage loading have been inconclusive. Hence, this study investigates the intricate relationship between obesity and knee OA, centering on the biomechanical changes in knee joint active and passive reactions during the stance phase of gait. Using a subject-specific musculoskeletal and finite element approach, muscle forces, ligament stresses, and articular cartilage contact stresses were analyzed among 60 individuals with different body mass indices (BMI) classified under healthy weight, overweight, and obese categories. Our predicted results showed that obesity significantly influenced knee joint mechanical reaction, increasing muscle activations, ligament loading, and articular cartilage contact stresses, particularly during key instances of the gait cycle—first and second peak loading instances. The study underscores the critical role of excessive body weight in exacerbating knee joint stress distribution and cartilage damage. Hence, the insights gained provide a valuable biomechanical perspective on the interaction between body weight and knee joint health, offering a clinical utility in assessing the risks associated with obesity and knee OA. [ABSTRACT FROM AUTHOR]

Although the moderate thermal stimulation of articular cartilage exerts chondroprotective effects, it is difficult to effectively heat deep articular cartilage with conventional methods. Photosensitizers increase the ambient temperature using near-infrared (NIR) radiation, which has high tissue permeability. We hypothesized that the intra-articular administration of photosensitizers and NIR irradiation would exert a greater heating effect on articular cartilage. We aimed to evaluate the heating effect of this method on cultured chondrocytes and rat knee cartilage. In vitro, we irradiated a photosensitizer-containing medium with NIR and measured changes in the medium temperature, cytotoxicity, and gene expression of heat shock protein (HSP) 70 and aggrecan (ACAN). In vivo, the knee joints of rats treated with photosensitizers were irradiated with NIR, and changes in intra-articular temperature and gene expression were measured, alongside histological analysis. The results showed that the medium and intra-articular temperature were raised to approximately 40 °C with no apparent disruption to articular cartilage or the immunohistochemically enhanced staining of HSP70 in chondrocytes. The gene expression of HSP70 and ACAN was increased in both cultured and articular cartilage. In summary, this method can safely heat joints and enhance cartilage metabolism by inducing HSP70 expression in articular cartilage. It presents a new hyperthermia therapy with effective cartilage protection. [ABSTRACT FROM AUTHOR]

Angiogenesis and vascular endothelial growth factor (VEGF) are involved in osteoarthritis (OA). We previously reported the inhibitory effect of bevacizumab in a rabbit model of OA. In the current study, we investigated the effects of lenvatinib, an angiogenesis inhibitor targeting the VEGF and fibroblast growth factor receptors, on synovitis, osteophyte formation, and cartilage degeneration in a rabbit OA model. Posttraumatic OA was induced by anterior cruciate ligament transection (ACLT) on one knee of each rabbit. Rabbits were placed into four groups according to the following lenvatinib doses: untreated control (n = 12), L0.3: 0.3 mg/kg/day (n = 15), L1.0: 1.0 mg/kg/day (n = 14), and L3.0: 3.0 mg/kg/day (n = 13) groups. We evaluated limb pain using the weight distribution ratio measured with an incapacitance tester, macroscopic osteophyte formation, and femoral condyle synovium and cartilage histology. For cartilage evaluation, the following distal sites of the femur were evaluated separately: femoral–tibial (FT), femoral–patellar (FP), and femoral corner (between FP and FT). The weight distribution ratio at 12 weeks after surgery was higher in the L0.3 and L1.0 groups than in the control group. Osteophyte formation and synovitis scores were significantly lower in the L0.3, L1.0, and L3.0 groups than in the control group. The Osteoarthritis Research Society International scores of the FT, corner, and FP sites in the L0.3 group were lower than in the control group. The cartilage thickness ratio at the FT and corner sites was significantly lower in the L0.3 group than in the control group. Krenn's grading system of cartilage synovitis showed that all lenvatinib-administered groups had significantly lower scores than the control group. MMP3 expression level in cartilage tissue was significantly lower in the L3.0 group compared with the other three groups. ADAMTS5 expression was lower in the L3.0 group compared with the control and L0.3 groups. Oral administration of lenvatinib inhibited synovitis, osteophyte formation, and cartilage degeneration and reduced pain in a rabbit ACLT model. Lenvatinib is an oral VEGF inhibitor that is easier to administer than other VEGF inhibitors and may have potential as a treatment of posttraumatic OA. [ABSTRACT FROM AUTHOR]

Purpose: Facet joint degeneration (FJD) is a major cause of low back pain. Parathyroid hormone (PTH) (1–34) is commonly used to treat osteoporosis. However, little is known about its effects on FJD induced by estrogen deficiency. This study aims to investigate the effects of PTH (1–34) on FJD induced by estrogen deficiency and the underlying pathogenesis of the disease. Methods: Forty 3-month-old female Sprague-Dawley rats were randomly divided into four groups: 30 received bilateral ovariectomy (OVX) followed by 12 weeks of treatment with normal saline, PTH (1–34) or 17β-estradiol (E2), and 10 received sham surgery followed by administration of normal saline. Status and Wnt/β-catenin signaling activity in the cartilage and subchondral bone of the L4–L5 FJs and serum biomarkers were analyzed. Results: Administration of PTH (1–34) and E2 ameliorated cartilage lesions, and significantly decreased MMP-13 and caspase-3 levels and chondrocyte apoptosis. PTH (1–34) but not E2 significantly increased cartilage thickness, number of chondrocytes, and the expression of aggrecan. PTH (1–34) significantly improved microarchitecture parameters of subchondral bone, increased the expression of collagen I and osteocalcin, and decreased RANKL/OPG ratio. E2 treatment significantly increased the OPG level and decreased the RANKL/OPG ratio in the subchondral bone of ovariectomized rats, but it did not significantly improve the microarchitecture parameters of subchondral bone. Wnt3a and β-catenin expression was significantly reduced in the articular cartilage and subchondral bone in OVX rats, but PTH (1–34) could increase the expression of these proteins. E2 significantly increased the activity of Wnt/β-catenin pathway only in cartilage, but not in subchondral bone. The restoration of Wnt/β-catenin signaling had an obvious correlation with the improvement of some parameters associated with the FJs status. Conclusion: Wnt/β-catenin signaling may be a potential therapeutic target for FJD induced by estrogen deficiency. PTH (1–34) is effective in treating this disease with better efficacy than 17β-estradiol, and the efficacy may be attributed to its restoration of Wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]

Suitable hydrogel materials for cartilage tissue repair should exhibit high strength and toughness, and excellent biocompatibility. However, the mechanical properties of most hydrogels cannot meet the complex mechanical requirements of articular cartilage tissues. Given this situation, we have adopted a chemical cross-linking method using hexafluoro isopropanol to mediate the cross-linking of Silk Fibroin (SF) and deionized water (DI), which promoted the formation of ß-sheets, generating "high-toughness" Silk Fibroin hydrogels. The introduction of Gelatin (Gel) served to increase the content of ß-sheets and increase the tensile modulus from 24.51 ± 2.07 MPa to 39.75 ± 6.54 MPa, which significantly enhanced the flexibility of the hydrogel and meets the mechanical requirements of cartilage tissue. In addition, in vitro biological experiments have shown that the introduction of Gel promotes cell proliferation and enhances the production of cartilage extracellular matrix by chondrocytes. In vivo experiments have demonstrated that SF/Gel hydrogel promotes articular cartilage regeneration more effectively than SF hydrogel, as evidenced by improvements in gross appearance, imaging, and histology. This study has established that high-strength SF/Gel hydrogel prepared by applying the binarysolvent-induced conformation transition strategy has potential applications in cartilage tissue repair and regeneration and is a feasible biomaterial for osteochondral regeneration. [ABSTRACT FROM AUTHOR]

Articular cartilage and meniscus transfer and distribute mechanical loads in the knee joint. Degeneration of these connective tissues occurs during the progression of knee osteoarthritis, which affects their composition, microstructure, and mechanical properties. A deeper understanding of disease progression can be obtained by studying them simultaneously. Time‐resolved synchrotron‐based X‐ray phase‐contrast tomography (SR‐PhC‐µCT) allows to capture the tissue dynamics. This proof‐of‐concept study presents a rheometer setup for simultaneous in situ unconfined compression and SR‐PhC‐µCT of connective knee tissues. The microstructural response of bovine cartilage (n = 16) and meniscus (n = 4) samples under axial continuously increased strain, or two steps of 15% strain (stress–relaxation) is studied. The chondrocyte distribution in cartilage and the collagen fiber orientation in the meniscus are assessed. Variations in chondrocyte density reveal an increase in the top 40% of the sample during loading, compared to the lower half. Meniscus collagen fibers reorient perpendicular to the loading direction during compression and partially redisperse during relaxation. Radiation damage, image repeatability, and image quality assessments show little to no effects on the results. In conclusion, this approach is highly promising for future studies of human knee tissues to understand their microstructure, mechanical response, and progression in degenerative diseases. [ABSTRACT FROM AUTHOR]

The incidence of large bone and articular cartilage defects caused by traumatic injury is increasing worldwide; the tissue regeneration process for these injuries is lengthy due to limited self‐healing ability. Endogenous bioelectrical phenomenon has been well recognized to play an important role in bone and cartilage homeostasis and regeneration. Studies have reported that electrical stimulation (ES) can effectively regulate various biological processes and holds promise as an external intervention to enhance the synthesis of the extracellular matrix, thereby accelerating the process of bone and cartilage regeneration. Hence, electroactive biomaterials have been considered a biomimetic approach to ensure functional recovery by integrating various physiological signals, including electrical, biochemical, and mechanical signals. This review will discuss the role of endogenous bioelectricity in bone and cartilage tissue, as well as the effects of ES on cellular behaviors. Then, recent advances in electroactive materials and their applications in bone and cartilage tissue regeneration are systematically overviewed, with a focus on their advantages and disadvantages as tissue repair materials and performances in the modulation of cell fate. Finally, the significance of mimicking the electrophysiological microenvironment of target tissue is emphasized and future development challenges of electroactive biomaterials for bone and cartilage repair strategies are proposed. [ABSTRACT FROM AUTHOR]

Introduction: Pathological changes in the articular cartilage (AC) and synovium are major manifestations of osteoarthritis (OA) and are strongly associated with pain and functional limitations. Exosome-derived microRNAs (miRNAs) are crucial regulatory factors in intercellular communication and can influence the progression of OA by participating in the degradation of chondrocytes and the phenotypic transformation in the polarization of synovial macrophages. However, the specific relationships and pathways of action of exosomal miRNAs in the pathological progression of OA in both cartilage and synovium remain unclear. Methods: This study evaluates the effects of fibroblast-like synoviocyte (FLS)- derived exosomes (FLS-Exos), influenced by miR-146a, on AC degradation and synovial macrophage polarization. We investigated the targeted relationship between miR-146a and TRAF6, both in vivo and in vitro, along with the involvement of the NF-κB signaling pathway. Results: The expression of miR-146a in the synovial exosomes of OA rats was significantly higher than in healthy rats. In vitro, the upregulation of miR-146a reduced chondrocyte apoptosis, whereas its downregulation had the opposite effect. In vivo, exosomes derived from miR-146a-overexpressing FLSs (miR- 146a-FLS-Exos) reduced AC injury and chondrocyte apoptosis in OA. Furthermore, synovial proliferation was reduced, and the polarization of synovial macrophages shifted from M1 to M2. Mechanistically, the expression of TRAF6 was inhibited by targeting miR-146a, thereby modulating the Toll-like receptor 4/TRAF6/NF-κB pathway in the innate immune response. Discussion: These findings suggest that miR-146a, mediated through FLS-Exos, may alleviate OA progression by modulating cartilage degradation and macrophage polarization, implicating the NF-κB pathway in the innate immune response. These insights highlight the therapeutic potential of miR-146a as a protective agent in OA, underscoring the importance of exosomal miRNAs in the pathogenesis and potential treatment of the disease. [ABSTRACT FROM AUTHOR]

Introduction: Charcot arthropathy is a progressive disorder of the ankle and foot joints that can lead to foot deformity and instability. Surgical intervention is often necessary for deformity and ulcer management during the chronic phase. The device used for arthrodesis remains a challenge. Methods: This clinical trial study included diabetic patients aged 40 years or older with Charcot foot. Lateral approach with lateral malleolar osteotomy was used to access the ankle joints and remove the cartilage. A small incision was made on the plantar aspect of the foot to pass an appropriately sized intramedullary nail. Demographic information, medical history, surgical details and Clinical data were collected at 2-week and 1-year follow-ups using the Ankle-Hindfoot Scale (AOFAS) score and the EuroQol 5-Dimensional 5-Level (EQ-5D-5L) health utility score. Results: Twenty-six patients with a mean age of 63 ± 0.23 years were included in the study. The findings showed significant improvements in AOFAS questionnaire items related to pain score, length of the walk, walking surfaces, walking disorders, sagittal alignment, back leg alignment, sustainability, alignment and the total score (P value < 0.001). The EQ-5D-5L questionnaire also showed a significant improvement in the total score (P value = 0.002). Conclusion: This study provides evidence supporting the effectiveness of tibiotalocalcaneal arthrodesis by hindfoot nailing in diabetic patients with Charcot foot joints and demonstrated comparable and superior outcomes in terms of patient satisfaction and complication rate when compared to previous studies. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Toevaluate theeffects of a gene transfer approach to IL-12 inhibition inan equineosteochondral chip fragment model of joint injury using a self-complementaryadeno-associated virus with interleukin receptorantagonist transgene cassette (scAAVIL-lra), as posttraumatic osteoarthritis in horses, similar to people, is a significant clinical problem. ANIMALS: 16 horses were utilized for the study. METHODS All horses had an osteochondral chip fragment induced arthroscopically in one middle carpal joint while the contralateral joint was sham operated. Eight horses received either scAAVIL-lra or saline in the osteoarthritis joint. Horses were evaluated over 70 days clinically (lameness, imaging, and biomarker analysis) and euthanized at 70 days and evaluated grossly, with imaging and histopathology. RESULTS: The following findings were statistically significant. Injection of scAAVIL-lra resulted in high synovial fluid levels of IL-lra (0.5 to 9 Ug/mL) throughout the duration of the experiment (70 days). Over the duration, we observed scAAVIL-lra to improve lameness (lameness score relative improvement of 1.2 on a scale of 0 to 5), cause suppression of prostaglandin E2 (a relative decline of 30 pg/mL), and result in histological improvement in articular cartilage (decreased chondrocyte loss and chondrone formation) and subchondral bone (less osteochondral splitting and osteochondral lesions). Within the synovial membrane of scAAVIL-lra-treated joints, we also observed perivascular infiltration with CD3-positive WBCs, suggesting Iymphocytic T-cell perivascular infiltration commonly observed with viral transduction. CLINICAL RELEVANCE: These data provide support for further evaluation and optimization of scAAVIL-lra gene therapy to treat equine osteoarthritis. [ABSTRACT FROM AUTHOR]

Purpose: Idiopathic chondrolysis of the hip is characterized by the loss of the articular cartilage of the hip joint with spectrum ranging from full recovery to fibrous ankylosis. Study assessed outcomes following intra-articular steroid injections, joint manipulation and traction immobilization. Methods: Retrospective (2012–2021) review of 41 cases treated for idiopathic chondrolysis of hip, assessed pre-operatively and post-operatively (minimum 2-year follow-up) using Children's Hospital Oakland Hip Evaluation Score (CHOHES), visual analogue scale (VAS) and range of motion measurements. Results: Twenty-five patients (62%) achieved painless mobility, 6 (14%) had hip stiffness without pain and 10 (24%) had painful and stiff hips at final follow-up. They had a mean age of 12.49 ± 2.4 years and a mean follow-up duration of 33.15 ± 13.1 months. Range of motion improved significantly (p < 0.05). VAS improved to 3.93 ± 1.3 from 7.8 ± 0.7. CHOHES improved from 29.12 ± 9.9 to 56.37 ± 17.6. Conclusion: Intra-articular steroid injection, manipulation and traction immobilization may effectively treat idiopathic chondrolysis of the hip by enhancing patient function and reducing the need for further surgical intervention. [ABSTRACT FROM AUTHOR]

Articular cartilage lesions are a common injury that have become increasingly treatable with joint preservation procedures. Well-documented allograft and cellular treatments for these lesions are detailed elsewhere in this volume. This article discusses three new unique options for addressing these defects taking three different paths to address these complex injuries. Agili-C is an existing FDA- and EMEA-approved option using an acellular aragonitebased scaffold to treat both chondral and osteochondral lesions, with or without concurrent arthritis. Cartistem is a stem-cell-based product composed of culture-expanded allogeneic human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel, which is in its final clinical trial stages in the United States, but already has regulatory approval in Korea. IMPACT and RECLAIM studies have shown the safety and efficacy of a new onestage procedure utilizing autologous chondrons combined with allogeneic mesenchymal stem cells (MSCs) that can provide another effective single-stage treatment option. [ABSTRACT FROM AUTHOR]

Articular cartilage defects in the glenohumeral joint may be found in laborers, the elderly, and young athletes, among others. Various factors can contribute to cartilage damage, including prior surgery, trauma, avascular necrosis, inflammatory arthritis, joint instability, and osteoarthritis. There is a wide variety of treatment options, from conservative treatment, injections, and surgical options, including arthroscopic debridement, microfracture, osteochondral autograft transfer, osteochondral graft transplantation, autologous chondrocyte implantation, and the newly emerging techniques such as biologic augmentation. There is a challenge to determine the optimal treatment options, especially for young athletes, due to limited outcomes in the literature. However, there are many options which are viable to address osteochondral defects of the glenohumeral joint. [ABSTRACT FROM AUTHOR]

Articular cartilage defects in the knee are common in athletes who have a variety of loading demands across the knee. Athletes of different sports may have different baseline risk of injury. The most studied sports in terms of prevalence and treatment of cartilage injuries include soccer (football), American football, and basketball. At this time, the authors do not specifically treat patients by their sport; however, return to sports timing may be earlier in sports with fewer demands on the knee based on the rehabilitation protocol. If conservative management is unsuccessful, the authors typically perform a staging arthroscopy with chondroplasty, followed by osteochondral allograft transplantation with possible additional concomitant procedures, such as osteotomies or meniscal transplants. Athletes in a variety of sports and at high levels of competition can successfully return to sports with the appropriate considerations and treatment. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine whether regular running distance and biomechanics are related to medial central femur cartilage (MCFC) structure. Methods: The cross-sectional study sample consisted of 1164 runners and nonrunners aged 18-65 yr. Participants completed questionnaires on physical activity and their running history. We performed quantitative magnetic resonance imaging of knee cartilage--T2 relaxation time (T2) mapping (high T2 indicates cartilage degeneration)--and a running biomechanical analysis using a three-dimensional motion capture system. A 14-d monitoring of the physical activity was conducted. Results: Those aged 35-49 yr were at 84% higher odds of having MCFC T2 in the highest level (85th percentile, P < 0.05) compared with youngest adults indicating that MCFC structures may be altered with aging. Being male was associated with 34% lower odds of having T2 at the highest level (P < 0.05) compared with females. Nonrunners and runners with the highest weekly running distance were more likely to have a high T2 compared with runners with running distance of 6-20 km⋅wk-1 (P < 0.05). In addition, the maximal knee internal adduction moment was associated with a 19% lower odds of having T2 at the highest level (P < 0.05). Conclusions: Females compared with males and a middle-aged cohort compared with the younger cohort seemed to be associated with the degeneration of MCFC structures. Runners who ran 6-20 km⋅wk-1 were associated with a higher quality of their MCFC compared with highly active individuals and nonrunners. Knee frontal plane biomechanics was related to MCFC structure indicating a possibility of modifying the medial knee collagen fibril network through regular running. [ABSTRACT FROM AUTHOR]

Degenerative joint disease is a dynamic pathological process characterised by a destabilisation of the degradation and synthesis processes of articular cartilage and subchondral bone layer. Studies suggest that individuals with gonarthrosis experience deficits in proprioception, in addition to changes within their joints, which directly affects their ability to maintain posture and increases their risk of falling. Objectives: The aim of this study was to assess the functional status of patients with gonarthrosis through a posturographic examination conducted on a stabilometric platform (force plate) and a functional clinical examination. Methods: Participants were divided into two groups—a control group (n = 125) and a study group (n = 125). During the qualification process, subjective and objective examinations were conducted, including a functional assessment by means of such tests as the "Up and Go" Test, Functional Reach Test, Five Time Sit to Stand Test, and the Step Test. Subsequently, an assessment was conducted on the force plate by means of a posturographic test—the Romberg test performed with open and closed eyes in a standing position—and balance was evaluated using the Berg Balance Scale. The obtained data were analysed with the use of the IBM SPSS Statistics software version 27.0, by means of the Mann–Whitney test, and correlations were determined by means of Spearman's test. A significance level of p = 0.05 was adopted. Results: Statistically significant differences were observed among the assessed groups as a result of both functional and posturographic examinations, along with positive correlations for disease duration, age, and BMI index. Conclusions: Patients with gonarthrosis exhibited disturbances in balance, functionality, and posture compared to healthy individuals in the control group. [ABSTRACT FROM AUTHOR]

With rates growing quickly with age, osteoarthritis (OA) is the most common cause of chronic disability in aging persons. The discomfort and reduced motion associated with osteoarthritis have a significant impact on quality of life, and there is no known solution. Runt-related transcription factor 1(Runx1) has been shown to play a protective role in the development of osteoarthritis by promoting chondrogenesis. We had created models of ageing mice with osteoarthritis by anterior cruciate ligament transection (ACLT) and analyzed the effects of intra-articular injection of adeno-associated virus/Runx1 (AAV/Runx1) on the models. The results showed that the AAV/Runx1-group maintained better articular cartilage integrity and retained more proteoglycan than the OA group after injection of AAV-Runx1. The markers related to pathological changes in cartilage were downregulated, while the markers related to physiological changes in cartilage were upregulated. This suggests that Runx1 may impede OA progression on the knee joint of ageing mice, potentially playing a protective role in OA and becoming a probable treatment target for osteoarthritis among ageing patients in the future. [ABSTRACT FROM AUTHOR]

Objective: Early articular cartilage lesion (CL) is a vital sign in the onset of posttraumatic knee osteoarthritis (PTOA) in patients with anterior cruciate ligament deficiency (ACLD). Researchers have suggested that altered kinematics could accelerate CLs and, therefore, lead to the onset of PTOA. However, little is known about whether specific knee kinematics exist that lead to early CL in chronic ACLD knees. Level walking is the most frequent and relevant in vivo activity, which greatly impacts knee health. We hypothesized that the knee kinematics during level walking in chronic ACLD knees with early tibiofemoral CL would significantly differ from those of chronic ACLD knees without early tibiofemoral CL. Methods: Thirty patients with a chronic ACLD history, including 18 subjects with CLs and 12 subjects without CLs, and 35 healthy control subjects were recruited for the study from July 2020 to August 2022. The knee kinematic data during level walking were collected using a three‐dimensional motion analysis system. The kinematic differences between groups were compared using statistical parametric mapping with one dimension for One‐Way ANOVA. The cartilage statuses of the ACLD knees were assessed via MRI examination. The CLs distribution of subjects was evaluated using a modified Noyes scale and analyzed by chi‐square tests. Results: ACLD knees with CLs had significantly greater posterior tibial translation (7.7–8.0mm, 12%–18% gait cycle GC, p = 0.014) compared to ACLD knees without CLs during level walking. ACLD knees with CLs had greater posterior tibial translation (4.6–5.5mm, 0%–23% GC, p < 0.001; 5.8–8.0mm, 86%–100% GC, p < 0.001) than healthy controls during level walking. In the group of ACLD knees with CLs, CL is mainly located in the back of the tibia plateau and front of load bearing area of the medial femoral condyle (p < 0.05). Conclusion: Chronic anterior cruciate ligament deficient knees with cartilage lesions have increased posterior tibial translation compared to anterior cruciate ligament deficient knees without cartilage lesions and healthy subjects. The posterior tibial translation may play an important role in knee cartilage degeneration in ACLD knees. The increased posterior tibial translation and cartilage lesion characteristics may improve our understanding of the role of knee kinematics in cartilage degeneration and could be a helpful potential reference for anterior cruciate ligament deficient therapy, such as physical training to improve abnormal kinematic behavior. [ABSTRACT FROM AUTHOR]

Articular cartilage was expected to be one of the first successfully engineered tissues, but today, cartilage repair products are few and they exhibit considerable limitations. For example, of the cell-based products that are available globally, only one is marketed for non-knee indications, none are indicated for severe osteoarthritis or rheumatoid arthritis, and only one is approved for marketing in the USA. However, advances in cartilage tissue engineering might now finally lead to the development of new cartilage repair products. To understand the potential in this field, it helps to consider the current landscape of tissue-engineered products for articular cartilage repair and particularly cell-based therapies. Advances relating to cell sources, bioactive stimuli and scaffold or scaffold-free approaches should now contribute to progress in therapeutic development. Engineering for an inflammatory environment is required because of the need for implants to withstand immune challenge within joints affected by osteoarthritis or rheumatoid arthritis. Bringing additional cartilage repair products to the market will require an understanding of the translational vector for their commercialization. Advances thus far can facilitate the future translation of engineered cartilage products to benefit the millions of patients who suffer from cartilage injuries and arthritides. In this Review, the current landscape of tissue engineering for repair of articular cartilage is discussed, with reference to advances in cell sources, bioactive stimuli and the use of scaffolds, and with consideration of the challenges that result from the inflammatory articular environments in osteoarthritis and rheumatoid arthritis. Key points: Of the cell-based articular cartilage products available globally, only one is marketed for non-knee indications, none are marketed for severe osteoarthritis and none are marketed for rheumatoid arthritis. Cartilage tissue engineering advances include making scaffold-based and scaffold-free cartilage with robust mechanical properties that might enable implants to survive in the loaded-joint environment. Tissue engineering cartilage implants to survive the inflammatory environment through the use of immunomodulatory biomaterials and synthetic biology is a current research highlight. Most large-animal studies for cartilage tissue engineering in the knee use porcine, caprine and ovine models, whereas porcine models are used for temporomandibular joint studies. Several tissue-engineered cartilage products in clinical development use allogeneic cell sources; the use of cell banks that employ allogeneic cells can improve reproducibility and consistency. Owing to the arduous nature of translating biologics, academic researchers should familiarize themselves with the translational vector (including regulatory, manufacturing, funding and intellectual property aspects) to facilitate clinical development. [ABSTRACT FROM AUTHOR]

Background: Although individuals with anterior cruciate ligament reconstruction (ACLR) are at high risk for posttraumatic osteoarthritis, mechanisms underlying the relationship between running and knee cartilage health remain unclear. Objective: We aimed to investigate how 30 min of running influences femoral cartilage thickness and composition and their relationships with running biomechanics in patients with ACLR and controls. Methods: Twenty patients with ACLR (time post‐ACLR: 14.6 ± 6.1 months) and 20 matched controls participated in the study. A running session required both groups to run for 30 min at a self‐selected speed. Before and after running, we measured femoral cartilage thickness via ultrasound imaging. A MRI session consisted of T2 mapping. Results: The ACLR group showed longer T2 relaxation times in the medial femoral condyle at resting compared with the control group (central: 51.2 ± 16.6 vs. 34.9 ± 13.2 ms, p = 0.006; posterior: 50.2 ± 10.1 vs. 39.8 ± 7.4 ms, p = 0.006). Following the run, the ACLR group showed greater deformation in the medial femoral cartilage than the control group (0.03 ± 0.01 vs. 0.01 ± 0.01 cm, p = 0.001). Additionally, the ACLR group showed significant negative correlations between resting T2 relaxation time in the medial femoral condyle and vertical impulse (standardized regression coefficients = −0.99 and p = 0.004) during running. Conclusions: Our findings suggest that those who are between 6 and 24 months post‐ACLR have degraded cartilage composition and their cartilage deforms more due to running vGRF. [ABSTRACT FROM AUTHOR]

Osteoporosis is a chronic disease characterized by reduced bone mass and increased fracture risk, estimated to affect over 10 million people in the United States alone. Drugs used to treat bone loss often come with significant limitations and/or long‐term safety concerns. Proteoglycan‐4 (PRG4, also known as lubricin) is a mucin‐like glycoprotein best known for its boundary lubricating function of articular cartilage. In more recent years, it has been shown that PRG4 has anti‐inflammatory properties, contributes to the maintenance of subchondral bone integrity, and patients with PRG4 mutations are osteopenic. However, it remains unknown how PRG4 impacts mechanical and material properties of bone. Therefore, our objective was to perform a phenotyping study of bone in a Prg4 gene trap (GT) mouse (PRG4 deficient). We found that femurs of Prg4 GT mice have altered mechanical, structural, and material properties relative to wildtype littermates. Additionally, Prg4 GT mice have a greater number of calvarial osteoclasts than wildtype mice, but do not have a notable inflammatory serum profile. Finally, Prg4 GT mice do not have an altered rate of bone formation, and exogenous recombinant human PRG4 (rhPRG4) administration inhibited osteoclastogenesis in vitro, suggesting that the skeletal phenotype may be due to changes in bone resorption. Overall, this work demonstrates that PRG4 deficiency affects several integral properties of bone structure, mechanics, and skeletal cell activity, and provides the foundation and insight toward future work evaluating PRG4 as a potential therapeutic target in treating bone loss. [ABSTRACT FROM AUTHOR]

OBJECTIVE Polyacrylamide hydrogel (4% PAHG) is an inert viscoelastic supplement used to manage osteoarthritis in horses. Even with a prolonged clinical effect, horses may be administered multiple doses during their performance career. The effect of the serial 4% PAHG treatments is not known. The objectives of this study were to evaluate the clinical, histologic, and synovial fluid biomarker effects following serial administration of 4% PAHG in normal equine fetlock joints. ANIMALS 8 healthy horses. METHODS In a blinded, controlled in vivo study, horses received serial intra-articular injections of 4% PAHG (Noltrex Vet; Nucleus ProVets LLC) and contralateral 0.9% saline control on days 0, 45, 90, and 135. Treatment and control joints were randomly assigned. Synovial fluid was collected before administration of 4% PAHG or 0.9% saline on day 0 and at study completion for cellular and biomarker evaluation. Serial physical and lameness examinations were performed throughout the study. On day 240, gross examination and harvest of cartilage and synovial membrane for histology were completed. RESULTS There were no histologic changes in articular cartilage or synovial fluid biomarkers. The 4% PAHG was seen on the surface of the synovium in 5 of 8 treated joints 105 days after the last treatment. There are minimal effects following serial injections of 4% PAHG on normal joints in horses following administration at 0, 45, 90, and 135 days, with final evaluation on day 240. CLINICAL RELEVANCE Serial administration of intra-articular 4% PAHG in horses may provide long-term joint lubrication with no detrimental effects. [ABSTRACT FROM AUTHOR]

Cartilage degeneration is a characteristic of osteoarthritis (OA), which is often observed in aging populations. This degeneration is due to the breakdown of articular cartilage (AC) mechanical and tribological properties primarily attributed to lubrication failure. Understanding the reasons behind these failures and identifying potential solutions could have significant economic and societal implications, ultimately enhancing quality of life. This review provides an overview of developments in the field of AC, focusing on its mechanical and tribological properties. The emphasis is on the role of lubrication in degraded AC, offering insights into its structure and function relationship. Further, it explores the fundamental connection between AC mechano-tribological properties and the advancement of its degradation and puts forth recommendations for strategies to boost its lubrication efficiency. [ABSTRACT FROM AUTHOR]

Background: The addition of an iliotibial band–based lateral extra-articular tenodesis (LET) to anterior cruciate ligament (ACL) reconstruction (ACLR) has been shown to reduce failure rates. However, there are concerns as to the potential overconstraint of tibiofemoral kinematics that may increase the risk of cartilage degradation. To date, no clinical study has investigated the effect of LET on patellofemoral joint articular cartilage health. Hypothesis: It was hypothesized that at 2 years postoperatively, (1) the addition of LET at the time of ACLR would have no effect on cartilage health on magnetic resonance imaging (MRI), and (2) higher cartilage relaxation values would be associated with worse patient-reported and functional outcomes. Study Design: Cohort study; Level of evidence, 3. Methods: A subset of patients from the STABILITY 1 randomized controlled trial were included. All patients underwent primary ACLR with a hamstring autograft. Patients were randomized to either LET augmentation or not. Cartilage status in the patellofemoral joint between the ACLR group and ACLR+LET group was compared using 2-year postoperative quantitative MRI and the ACL osteoarthritis scores of both the surgical and the contralateral nonsurgical knees. Objective functional outcomes and patient-reported outcome measures (PROMs) were attained. Results: A total of 92 patients (43 patients in the ACLR group; mean age, 18.9 ± 3.2 years; 60.5% female; and 49 patients in the ACLR+LET group; mean age, 18.7 ± 3.2 years, 63.3% female) were included. No significant differences were seen in the mean values (ms) for adjusted T1ρ/T2 relaxation times in the medial patella (47.8/42.2 vs 47.3/43.2), central patella (45.5/42.5 vs 44.1/42.7), lateral patella (48.2/43.5 vs 47.3/43.0), medial trochlea (54.7/50.9 vs 56.4/50.9), central trochlea (53.3/51.1 vs 53.1/52.0), and lateral trochlea (54.9/52.1 vs 53.9/52.6) between the ACLR and ACLR+LET groups. No difference in overall ACL osteoarthritis scores was observed (P =.99). An increase in medial patellar T2 relaxation times was associated with a decreasing International Knee Documentation Committee score (P =.046), Knee injury and Osteoarthritis Outcome Score (KOOS) Symptoms subscale score (P =.01), and total KOOS (P =.01). Conclusion: There was no statistical difference in patellofemoral cartilage health between knees 2 years after primary ACLR with hamstring tendon autograft with or without LET. Statistically significant correlations were found between quantitative MRI relaxation times, functional outcome scores, and PROMs; however, the correlations were weak and the clinical significance is unknown. Registration: NCT02018354 (ClinicalTrials.gov identifier). [ABSTRACT FROM AUTHOR]

This article discusses a study that aimed to assess the association between knee cartilage T2 values and age, sex, and cartilage lesions. The study involved 929 subjects aged 28 to 89 years who underwent MRI scans. The results showed that T2 values were significantly higher in subjects with osteoarthritis (OA) risk factors and cartilage lesions compared to those without. The study also found significant variation in T2 values between different joint compartments, with the highest values in femoral cartilage and the lowest in tibial cartilage. Additionally, T2 values increased with age and were higher in women for certain compartments. The study established a reference database of T2 values for subjects with normal cartilage morphology and without evidence of cartilage degeneration or OA risk factors. [Extracted from the article]

This article evaluates the long-term outcomes of matrix-induced autologous chondrocyte implantation (MACI) for knee cartilage injuries. Twenty-six patients were treated with MACI and underwent magnetic resonance (MR) arthrography and clinical examinations at midterm and long term after surgery. The results showed that while imaging studies indicated deterioration of the grafts, the patients did not experience significant clinical deterioration. The decrease in clinical scores was not significant, but modified MOCART scores decreased significantly. Overall, MACI appears to be a viable treatment option for knee cartilage injuries. [Extracted from the article]

Osteoarthritis (OA) is a chronic joint disease characterized by irreversible cartilage degradation. Current clinical treatment options lack effective pharmaceutical interventions targeting the disease's root causes. MMP (matrix metalloproteinase) inhibitors represent a new approach to slowing OA progression by addressing cartilage degradation mechanisms. However, very few drugs within this class are in preclinical or clinical trial phases. Hydrogel-based 3D in vitro models have shown promise as preclinical testing platforms due to their resemblance to native extracellular matrix (ECM), abundant availability, and ease of use. Metalloproteinase-13 (MMP-13) is thought to be a major contributor to the degradation of articular cartilage in OA by aggressively breaking down type II collagen. This study focused on testing MMP-13 inhibitors using a GelMA-alginate hydrogel-based OA model induced by cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α). The results demonstrate a significant inhibition of type II collagen breakdown by measuring C2C concentration using ELISA after treatment with MMP-13 inhibitors. However, inconsistencies in human cartilage explant samples led to inconclusive results. Nonetheless, the study highlights the GelMA-alginate hydrogel-based OA model as an alternative to human-sourced cartilage explants for in vitro drug screening. [ABSTRACT FROM AUTHOR]

Cartilage, a flexible and smooth connective tissue that envelops the surfaces of synovial joints, relies on chondrocytes for extracellular matrix (ECM) production and the maintenance of its structural and functional integrity. Melatonin (MT), renowned for its anti-inflammatory and antioxidant properties, holds the potential to modulate cartilage regeneration and degradation. Therefore, the present study was devoted to elucidating the mechanism of MT on chondrocytes. The in vivo experiment consisted of three groups: Sham (only the skin tissue was incised), Model (using the anterior cruciate ligament transection (ACLT) method), and MT (30 mg/kg), with sample extraction following 12 weeks of administration. Pathological alterations in articular cartilage, synovium, and subchondral bone were evaluated using Safranin O-fast green staining. Immunohistochemistry (ICH) analysis was employed to assess the expression of matrix degradation-related markers. The levels of serum cytokines were quantified via Enzyme-linked immunosorbent assay (ELISA) assays. In in vitro experiments, primary chondrocytes were divided into Control, Model, MT, negative control, and inhibitor groups. Western blotting (WB) and Quantitative RT-PCR (q-PCR) were used to detect Silent information regulator transcript-1 (SIRT1)/Nuclear factor kappa-B (NF-κB)/Nuclear factor erythroid-2-related factor 2 (Nrf2)/Transforming growth factor-beta (TGF-β)/Bone morphogenetic proteins (BMPs)-related indicators. Immunofluorescence (IF) analysis was employed to examine the status of type II collagen (COL2A1), SIRT1, phosphorylated NF-κB p65 (p-p65), and phosphorylated mothers against decapentaplegic homolog 2 (p-Smad2). In vivo results revealed that the MT group exhibited a relatively smooth cartilage surface, modest chondrocyte loss, mild synovial hyperplasia, and increased subchondral bone thickness. ICH results showed that MT downregulated the expression of components related to matrix degradation. ELISA results showed that MT reduced serum inflammatory cytokine levels. In vitro experiments confirmed that MT upregulated the expression of SIRT1/Nrf2/TGF-β/BMPs while inhibiting the NF-κB pathway and matrix degradation-related components. The introduction of the SIRT1 inhibitor Selisistat (EX527) reversed the effects of MT. Together, these findings suggest that MT has the potential to ameliorate inflammation, inhibit the release of matrix-degrading enzymes, and improve the cartilage condition. This study provides a new theoretical basis for understanding the role of MT in decelerating cartilage degradation and promoting chondrocyte repair in in vivo and in vitro cultured chondrocytes. [ABSTRACT FROM AUTHOR]

Post-traumatic osteoarthritis of the ankle (PTOA) is frequently observed following a debilitating consequence of intra-articular ankle fractures. Numerous risk factors contribute to the pathogenesis of PTOA, including articular incongruity, joint malalignment, and concomitant soft tissue damage. Despite attempts to restore joint anatomy and manage soft tissues to avoid long-term complications after intra-articular ankle fractures, the incidence of PTOA remains markedly elevated. Inflammatory processes triggered by intra-articular ankle fractures have emerged as potential instigators that expedite the progression of PTOA. Injury to the articular cartilage and subchondral bone may lead to the release of inflammatory mediators, which can contribute to cartilage degradation and bone resorption. This study provides a narrative review on the current knowledge concerning the association between inflammation and the development of PTOA following intra-articular ankle fractures. We also discuss novel therapeutic agents that target inflammatory pathways to impede the progression of post-traumatic osteoarthritis after intra-articular ankle fractures. These medication and interventions were summarized within this review article. [ABSTRACT FROM AUTHOR]

Articular cartilage is crucial for joint function but its avascularity limits intrinsic repair, leading to conditions like osteoarthritis (OA). Chondromodulin-I (Cnmd) has emerged as a key molecule in cartilage biology, with potential implications for OA therapy. Cnmd is primarily expressed in cartilage and plays an important role in chondrocyte proliferation, cartilage homeostasis, and the blocking of angiogenesis. In vivo and in vitro studies on Cnmd, also suggest an involvement in bone repair and in delaying OA progression. Its downregulation correlates with OA severity, indicating its potential as a therapeutic target. Further research is needed to fully understand the mode of action of Cnmd and its beneficial implications for managing OA. This comprehensive review aims to elucidate the molecular characteristics of Cnmd, from its expression pattern, role in cartilage maintenance, callus formation during bone repair and association with OA. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease commonly found in elderly people and obese patients. Currently, OA treatments are determined based on their condition severity and a medical professional's advice. The aim of this study was to differentiate human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) into chondrocytes for transplantation in OA-suffering guinea pigs. hWJ-MSCs were isolated using the explant culture method, and then, their proliferation, phenotypes, and differentiation ability were evaluated. Subsequently, hWJ-MSCs-derived chondrocytes were induced and characterized based on immunofluorescent staining, qPCR, and immunoblotting techniques. Then, early-OA-suffering guinea pigs were injected with hyaluronic acid (HA) containing either MSCs or 14-day-old hWJ-MSCs-derived chondrocytes. Results showed that hWJ-MSCs-derived chondrocytes expressed specific markers of chondrocytes including Aggrecan, type II collagen, and type X collagen proteins and β-catenin, Sox9, Runx2, Col2a1, Col10a1, and ACAN gene expression markers. Administration of HA plus hWJ-MSCs-derived chondrocytes (HA-CHON) produced a better recovery rate of degenerative cartilages than HA plus MSCs or only HA. Histological assessments demonstrated no significant difference in Mankin's scores of recovered cartilages between HA-CHON-treated guinea pigs and normal articular cartilage guinea pigs. Transplantation of hWJ-MSCs-derived chondrocytes was more effective than undifferentiated hWJ-MSCs or hyaluronic acid for OA treatment in guinea pigs. This study provides a promising treatment to be used in early OA patients to promote recovery and prevent disease progression to severe osteoarthritis. [ABSTRACT FROM AUTHOR]

Joint-resident chondrogenic precursor cells have become a significant therapeutic option due to the lack of regenerative capacity in articular cartilage. Progenitor cells are located in the superficial zone of the articular cartilage, producing lubricin/Prg4 to decrease friction of cartilage surfaces during joint movement. Prg4-positive progenitors are crucial in maintaining the joint's structure and functionality. The disappearance of progenitor cells leads to changes in articular hyaline cartilage over time, subchondral bone abnormalities, and the formation of ectopic ossification. Genetic labeling cell technology has been the main tool used to characterize Prg4-expressing progenitor cells of articular cartilage in vivo through drug injection at different time points. This technology allows for the determination of the origin of progenitor cells and the tracking of their progeny during joint development and cartilage damage. We endeavored to highlight the currently known information about the Prg4-producing cell population in the joint to underline the significance of the role of these cells in the development of articular cartilage and its homeostasis. This review focuses on superficial progenitors in the joint, how they contribute to postnatal articular cartilage formation, their capacity for regeneration, and the consequences of Prg4 deficiency in these cells. We have accumulated information about the Prg4+ cell population of articular cartilage obtained through various elegantly designed experiments using transgenic technologies to identify potential opportunities for further research. [ABSTRACT FROM AUTHOR]

Authors have demonstrated that apoptosis activation is a pathway related to cartilage degradation characteristics of the OA process. Autophagy is an adaptive response to protect cells from various environmental changes, and defects in autophagy are linked to cell death. In this sense, decreased autophagy of chondrocytes has been observed in OA articular cartilage. The aim of this work was to study the role of OA mitochondria in apoptosis, autophagy, and senescence, using OA and Normal (N) transmitochondrial cybrids. Results: OA cybrids incubated with menadione showed a higher percentage of late apoptosis and necrosis than N cybrids. Stimulation of cybrids with staurosporine and IL-1β showed that OA cybrids were more susceptible to undergoing apoptosis than N cybrids. An analysis of the antioxidant response using menadione on gene expression revealed a lower expression of nuclear factor erythroid 2-like 2 and superoxide dismutase 2 in OA than N cybrids. Activation of microtubule-associated protein 1A/1B-light chain 3 was reduced in OA compared to N cybrids. However, the percentage of senescent cells was higher in OA than N cybrids. Conclusion: This work suggests that mitochondria from OA patients could be involved in the apoptosis, autophagy, and senescence of chondrocytes described in OA cartilage. [ABSTRACT FROM AUTHOR]

Regenerative cartilage procedures have become increasingly more important in the reconstructive treatment of acute and chronic chondral and osteochondral lesions in the knee joint. Depending on the size and depth of the defect standard methods with high evidence and potential methods with rather low evidence have been established. Long-term results determine the success and failure of the applied procedures and are being discussed in this CME article. [ABSTRACT FROM AUTHOR]

The case presentation describes a joint-preserving procedure for pre-existing focal cartilage damage to the shoulder joint with the onset of osteoarthritis in a young female patient with high sporting demands. A significant improvement in quality of life was achieved after an observation period of two years. Imaging morphology shows good cartilage regeneration in the PD sequences in the MRI after application of matrix-augmented bone marrow stimulation using a hyaluronic acid matrix. The clinical and morphological results offer hope for future success in delaying shoulder joint replacement. [ABSTRACT FROM AUTHOR]

Modern pre- and post-operative rehabilitation is geared towards structural damage, functional limitations and concomitant comorbidity. In addition, the cognitive-emotional situation of those affected and their life situation (family, work, sport) must be taken into account. In order to meet the requirement of patientcentered rehabilitation, all possible measures should therefore be adapted to the individual based on clinical and functional criteria. Off-the-shelf follow-up treatment is therefore neither realistic nor effective. Nevertheless, phase models have become established in practice. These create a rough time frame that can be seen as a guide for rehabilitation after cartilage regenerative surgery. In addition to preoperative preparation, the focus is on progressively increasing the load and training the main forms of motor basic skills - mobility, endurance, coordination and strength. [ABSTRACT FROM AUTHOR]

The current approach to the clinical management of osteoarthritis is to alleviate symptoms arising from late-stage disease. Early stage or pre-arthritic disease is clinically silent as structural changes typically precede the clinical signs and symptoms of pain, deformity, functional limitations and disability. Biological and surgical therapeutic approaches to this include platelet-rich plasma (PRP), stromal cells or bone marrow aspirates (BMAC) and hyaluronic acid (HA) as a conservative treatment or support of a surgical cartilage procedure to optimize the cartilage regenerate tissue. The following article provides a condensed overview. [ABSTRACT FROM AUTHOR]

General principles of cartilage repair therapies have not changed in the last years. Recommendations for cartilage repair include symptomatic ICRS grade 3 and 4 classified cartilage defects. However, what has changed in the last years is a better understanding of underlying or concomitant pathologies. Since a more precise analysis and stringent therapy of concomitant pathologies has been performed, an increase in success rates especially in formerly difficult entities could be observed. The most important concomitant pathologies in cartilage therapies of the hip-, knee- and ankle joint are axis deviations, instabilities, meniscus pathologies or prearthrotic deformities like hip dysplasia and femuroacetabular impingement syndrome. To increase the efficiency of cartilage repair procedures these pathologies should be corrected either prior to, or at latest concomitant to any cartilage repair surgery. Therefore, this article is intended to give an overview of the most important concomitant pathologies in cartilage repair of the lower extremities and their possibilities of correction. [ABSTRACT FROM AUTHOR]