Search Results (2,888)

This study investigates 3D extrusion bioinks for cartilage tissue engineering by characterizing the physical properties of 3D-printed scaffolds containing varying alginate and polyvinyl alcohol (PVA) concentrations. We systematically investigated the effects of increasing PVA and alginate concentrations on swelling, degradation, and the elastic modulus of printed hydrogels. Swelling decreased significantly with increased PVA concentrations, while degradation rates rose with higher PVA concentrations, underscoring the role of PVA in modulating hydrogel matrix stability. The highest elastic modulus value was achieved with a composite of 5% PVA and 20% alginate, reaching 0.22 MPa, which approaches that of native cartilage. These findings demonstrate that adjusting PVA and alginate concentrations enables the development of bioinks with tailored physical and mechanical properties, supporting their potential use in cartilage tissue engineering and other biomedical applications. Full article

Alkaptonuria (AKU) is a genetically determined disease associated with disorders of tyrosine metabolism. In AKU, the deposition of homogentisic acid polymers contributes to the pathological ossification of cartilage tissue. The controlled use of biomimetics similar to deposits observed in cartilage during AKU potentially may serve the development of new bone regeneration therapy based on the activation of osteoblasts. The proposed biomimetic is pyomelanin (PyoM), a polymeric biomacromolecule synthesized by Pseudomonas aeruginosa. This work presents comprehensive data on the osteoinductive, pro-regenerative, and antibacterial properties, as well as the cytocompatibility, of water-soluble (PyoM_sol) or water-insoluble (PyoM_insol) PyoM. Both variants of PyoM support osteoinductive processes as well as the maturation of osteoblasts in cell cultures in vitro due to the upregulation of bone-formation markers, osteocalcin (OC), and alkaline phosphatase (ALP). Furthermore, the cytokines involved in these processes were elevated in cell cultures of osteoblasts exposed to PyoM: tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10. The PyoM variants are cytocompatible in a wide concentration range and limit the doxorubicin-induced apoptosis of osteoblasts. This cytoprotective PyoM activity is correlated with an increased migration of osteoblasts. Moreover, PyoM_sol and PyoM_insol exhibit antibacterial activity against staphylococci isolated from infected bones. The osteoinductive, pro-regenerative, and antiapoptotic effects achieved through PyoM stimulation prompt the development of new biocomposites modified with this bacterial biopolymer for medical use. Full article

The amount of sphingosine 1-phosphate (S1P) found in the synovial tissue of individuals with rheumatoid arthritis is five times greater than that in those with osteoarthritis. Our study aims to determine whether inhibiting S1P₂ can mitigate collagen-induced rheumatoid arthritis (CIA) by using an S1P₂ antagonist, JTE-013, alongside DBA-1J S1pr2 wild-type (WT) and knock-out (KO) mice. CIA causes increases in arthritis scores, foot swelling, synovial hyperplasia, pannus formation, proteoglycan depletion, cartilage damage, and bone erosion, but these effects are markedly reduced when JTE-013 is administered to S1pr2 WT mice. CIA also elevates mRNA expression levels of pro-inflammatory Th1/Th17 cytokines in the foot and spleen, which are significantly decreased by JTE-013 in S1pr2 WT mice. Additionally, CIA raises Th1/Th17 and Treg cell counts, while JTE-013 reduces these elevations in the spleens of S1pr2 WT mice. Treatment with JTE-013 or the absence of S1pr2 curtails the differentiation of naïve T cells into Th1 and Th17 cells in a dose-dependent manner. In SW982 human synovial cells, JTE-013 lowers LPS-induced increases in pro-inflammatory cytokine levels. Overall, these findings propose that blocking S1P₂ in immune and synovial cells may alleviate rheumatoid arthritis symptoms and offer a potential therapeutic approach. Full article

Campylaephora hypnaeoides (C. hypnaeoides) was extracted using fermented ethanol. The effect of fermented ethanol extract of C. hypnaeoides (FeCH) on chondrocyte viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-iphenyltetrazolium bromide assay, which showed no cytotoxicity at 2 mg/mL. FeCH pretreatment in IL-1β-stimulated chondrocytes significantly inhibited the accumulation of nitric oxide and prostaglandin E₂, which was analyzed using the ELISA assay. In addition, protein expression levels of inflammatory-related factors, such as inducible nitric oxide synthase, cyclooxygenase-2, interleukin-6, tumor necrosis factor-alpha, and cartilage-degrading-related enzymes, such as matrix metalloproteinases-1, -3, and -13, and a disintegrin and metalloproteinase with thrombospondin motifs-4 and -5 were significantly decreased in IL-1β-stimulated chondrocytes pretreated with FeCH, which were analyzed using western blot analysis. In addition, as a result of analyzing the content of collagen type II (Col II) and proteoglycan through western blot analysis and alcian blue staining, FeCH pretreatment prevented the degradation of Col II and proteoglycan. It was analyzed through western blot analysis that the chondroprotective effect of FeCH may be mediated through MAPKs and NF-κB-signaling mechanisms. In an in vivo study, an osteoarthritis experimental animal model with damaged medial meniscus (DMM) was utilized and orally administered daily for 8 weeks after surgery. At the study end point, knee joints were harvested and subjected to histological analysis with safranin O staining. As a result, articular cartilage was significantly protected in the FeCH group compared to the DMM group. These results suggest FeCH as a candidate material for the development of pharmaceutical materials for the treatment or prevention of degenerative arthritis. Full article

Osteoarthritis (OA) is among the most prevalent degenerative joint disorders worldwide, particularly affecting the aging population and imposing significant disability and economic burdens. The disease is characterized by progressive degradation of articular cartilage and chronic inflammation, with no effective long-term treatments currently available to address the underlying causes of its progression. Conventional therapies primarily manage symptoms such as pain and inflammation but fail to repair damaged tissues. Emerging biotherapies and regenerative medicine approaches offer promising alternatives by addressing cartilage repair and inflammation control at the molecular level. This review explores the recent advancements in biotherapeutic strategies, including mesenchymal stem cell (MSC) therapy, growth factors, and tissue engineering, which hold the potential for promoting cartilage regeneration and modulating the inflammatory microenvironment. Additionally, the integration of nanotechnology has opened new avenues for targeted drug delivery systems and the development of innovative nanomaterials that can further enhance the efficacy of biotherapies by precisely targeting inflammation and cartilage damage. This article concludes by discussing the current clinical applications, the ongoing clinical trials, and the future research directions necessary to confirm the safety and efficacy of these advanced therapies for OA management. With these advancements, biotherapies combined with nanotechnology may revolutionize the future of OA treatment by offering precise and effective solutions for long-term disease management and improved patient outcomes. Full article

Background: Femoral head fractures with osteochondral defects are rare injuries often resulting from traumatic hip dislocations. These injuries create a significant risk for post-traumatic osteoarthritis. Various surgical methods for repair have been utilized to restore these osteochondral defects, including mosaicplasty, autologous cartilage implantation, osteochondral allograft transplant (OAT), and demineralized bone matrix (DBM). Methods: We present a case of a 21-year-old male who sustained a fracture-dislocation of the left femoral head with impaction of the weight-bearing surface due to a motor vehicle collision. Due to the patient’s relatively young age, OAT plugs from a fresh-frozen proximal humerus with DBM supplementation during fracture fragment fixation were chosen to reduce the likelihood of post-traumatic arthritis. Results: The patient regained subjective function and full strength on exam with no pain at 2 years postoperatively. Conclusions: We propose that a proximal humerus allograft is a suitable alternative in an urgent setting when a femoral head allograft is not available. Full article

Background: Osteoarthritis is caused by damage to the articular cartilage due to bone-on-bone collisions and friction. The length, width, and thickness of the ligaments are expected to change in order to regulate excessive bone-to-bone movement. We aimed to clarify the relationship between ligament morphology and joint surface degeneration in the ankle joints using macroscopic observations and measurements. Methods: The participants were 50 feet of 45 Japanese cadavers. The lengths, widths, and thicknesses of the tibionavicular, tibiospring, tibiocalcaneal, posterior tibiotalar, anterior tibiotalar, and calcaneofibular ligaments (CFLs) were measured. The degeneration of the talonavicular joint surface was investigated macroscopically and classified into two groups: the Degeneration (+) group and Degeneration (−) group. Unpaired t-tests were performed for each measurement. Logistic regression analysis was performed on the significantly different items to obtain cutoff values, sensitivity, and specificity. Results: Only the width of the CFL differed significantly between the Degeneration (+) (20 feet) and Degeneration (−) groups (p < 0.001). In the logistic regression analysis, the width of the CFL had an R2 of 0.262, sensitivity of 75.0%, and specificity of 83.3%, with a cutoff value of 8.7 mm. Conclusions: A wide CFL indicates a high likelihood of talonavicular articular surface degeneration. Full article

Background: Osteoporosis (OP) is a chronic inflammatory bone disease characterized by reduced bone structure and strength, leading to increased fracture risk. Effective therapies targeting both bone and cartilage are limited. This study compared the therapeutic effects of extracorporeal shockwave therapy (ESWT), bisphosphonate (Aclasta), and human Wharton jelly-derived mesenchymal stem cells (WJMSCs) in a rat model of OP. Methods: Female rats were assigned to four groups: Sham (no surgery or treatment), OP (bilateral ovariectomy, OVX), ESWT (OVX + ESWT on both tibias at 0.25 mJ/mm², 1500 impulses per tibia), Aclasta (OVX + zoledronic acid 0.1 mg/kg via tail vein injection), and WJMSC (OVX + 2 × 10⁶ WJMSCs). Pathological changes, bone microarchitecture (by micro-CT), serum cytokines (by ELISA), and tissue-specific molecular markers (by immunohistochemistry) were evaluated. Results: All treatments improved bone density, preserved cartilage, and modulated cytokines (IL31, IL33, VEGF, and BMP2), with Aclasta showing the greatest improvements in bone parameters and cartilage preservation. ESWT and WJMSC also demonstrated significant effects, with ESWT highlighting non-invasive chondroprotective potential. Conclusions: Aclasta provided the best overall therapeutic response, particularly in bone regeneration. However, ESWT and WJMSC also showed comparable chondroprotective effects. ESWT emerges as a promising non-invasive alternative for OP management when pharmacological or cell-based therapies are not feasible. Full article

Background: Osteoarthritis (OA) of the knee is the most common joint disease, characterized by the degeneration of joint cartilage. Intra-articular hyaluronic acid (IAHA) injections are a well-established non-surgical treatment. Methods: This retrospective study analyzed knee OA patients receiving IAHA combined with niacinamide injections, assessing pain reduction in relation to patient data, the number of injections, and radiological findings. Results: IAHA injections led to significant pain reduction on the numeric rating scale (NRS) (0–10), with a mean decrease of 3.34 ± 1.65. Pain relief was greater with multiple injections. A comparison of subgroups by injection frequency (1, 2, or >2) showed significant pain reduction between 1 and 2 injections (p = 0.027) and between 1 and >2 injections (p = 0.032). The OA grade measured using the Kellgren–Lawrence (p = 0.95) and Vallotton MRI classifications (p = 0.50) did not correlate with pain reduction. However, patients with meniscal damage (p = 0.02) showed a greater benefit. A strong positive correlation was found between baseline pain intensity and pain reduction (p < 0.001; r = 0.61). Conclusions: IAHA with niacinamide significantly reduces knee OA pain, with more injections enhancing pain relief. Greater benefits were observed in patients with higher baseline pain and meniscal damage. The favorable safety profile and potential for repeated treatments make IAHA a valuable option in knee OA management. Full article

Interleukin-6 (IL-6) expression in mesenchymal stem cells (MSCs) has been shown to play a pivotal role in modulating cartilage regeneration and immune responses, particularly in the context of diseases that involve both degenerative processes and inflammation, such as osteoarthritis (OA). However, the precise mechanism through which IL-6 and other immune-regulatory factors influence the therapeutic efficacy of autologous adipose-derived stem cells (ASCs) transplantation in OA treatment remains to be fully elucidated. This study aims to investigate the relationship between IL-6 expression in autologous ASCs isolated from OA patients and their impact on immune modulation, particularly focusing on the regulation of Receptor Activator of Nuclear factor Kappa-Β Ligand (RANKL), a key mediator of immune-driven cartilage degradation in OA. Autologous ASCs were isolated from the stromal vascular fraction (SVF) of adipose tissue obtained from 22 OA patients. The isolated ASCs were cultured and characterized using reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry to the phenotype and immune regulatory factors of MSCs. Based on IL-6 expression levels, ASCs were divided into high and low IL-6 expression groups. These groups were then co-cultured with activated peripheral blood mononuclear cells (PBMCs) to evaluate their immune-modulatory capacity, including the induction of regulatory T cells, inhibition of immune cell proliferation, and regulation of key cytokines, such as interferon-gamma (IFN-γ). Additionally, RANKL expression, a critical factor in osteoclastogenesis and cartilage degradation, was assessed in both ASC groups. High IL-6-expressing ASCs demonstrated a significantly greater capacity to inhibit immune cell proliferation and IFN-γ production compared to their low IL-6-expressing counterparts under co-culture conditions. Moreover, the group of ASCs with high IL-6 expression showed a marked reduction in RANKL expression, suggesting enhanced potential to control osteoclast activity and subsequent cartilage defect in OA. Conclusion: Autologous ASCs with elevated IL-6 expression exhibit enhanced immunomodulatory properties, particularly in regulating over-activated immune response and reducing osteoclastogenesis through RANKL suppression. These findings indicate that selecting ASCs based on IL-6 expression could enhance the therapeutic efficacy of ASC-based treatments for OA by mitigating immune-driven joint inflammation and cartilage degradation, potentially slowing disease progression. Full article

Knee osteoarthritis (OA) is a chronic articular disease characterized by the progressive degeneration of cartilage and bone tissue, leading to the appearance of subchondral cysts, osteophyte formation, and synovial inflammation. Conventional treatments consist of non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, and glucocorticoids. However, the prolonged use of these drugs causes adverse effects. NSAIDs, for instance, are known to be nephrotoxic, increasing the damage to articular cartilage. New therapies capable of accelerating the process of tissue regeneration and repair are being discussed, such as the use of orthobiologics that are naturally found in the body and obtained through minimally invasive collection and/or laboratory manipulations. Bone marrow aspirate (BMA) and bone marrow aspirate concentrate (BMAC) are both rich in hematopoietic stem cells, mesenchymal stem cells (MSCs), and growth factors (GFs) that can be used in the healing process due to their anabolic and anti-inflammatory effects. The aim of this literature review is to assess the efficacy of BMA and BMAC in the treatment of knee OA based on the favorable results that researchers have obtained with the use of both orthobiologics envisaging an accelerated healing process and the prevention of OA progression. Full article

Antlers are the sole mammalian organs capable of continuous regeneration. This distinctive feature has evolved into various biomedical models. Research on mechanisms of antler growth, development, and ossification provides valuable insights for limb regeneration, cartilage-related diseases, and cancer mechanisms. Here, ribonucleic acid sequencing (RNA-seq) and four-dimensional data-independent acquisition (4D DIA) technologies were employed to examine gene and protein expression differences among four tissue layers of the Chinese milu deer antler: reserve mesenchyme (RM), precartilage (PC), transition zone (TZ), cartilage (CA). Overall, 4611 differentially expressed genes (DEGs) and 2388 differentially expressed proteins (DEPs) were identified in the transcriptome and proteome, respectively. Among the 828 DEGs common to both omics approaches, genes from the collagen, integrin, and solute carrier families, and signaling molecules were emphasized for their roles in the regulation of antler growth, development, and ossification. Bioinformatics analysis revealed that in addition to being regulated by vascular and nerve regeneration pathways, antler growth and development are significantly influenced by numerous cancer-related signaling pathways. This indicates that antler growth mechanisms may be similar to those of cancer cell proliferation and development. This study lays a foundation for future research on the mechanisms underlying the rapid growth and ossification of antlers. Full article

Pararamosis, also known as Pararama-associated phalangeal periarthritis, is a neglected tropical disease primarily affecting rubber tappers in the Amazon region. It is caused by contact with the urticating hairs of the Premolis semirufa moth caterpillar, which resides in rubber plantations. The condition is marked by the thickening of the articular synovial membrane and cartilage impairment, features associated with chronic synovitis. Given the significance of synovial inflammation in osteoarticular diseases, in this study, the role of synoviocytes and their interactions with macrophages and chondrocytes are examined when stimulated by Pararama toxins. Synoviocytes and macrophages treated with Pararama hair extract showed an increased production of cytokines IL-6, IL-1β, and TNF-α, indicating a direct effect on these cells. In cocultures, there was a significant rise in inflammation, with levels of IL-1β, IL-6, and chemokines CCL2, CCL5, and CXCL8 increasing up to seven times compared to monocultures. Additionally, matrix-degrading enzymes MMP-1 and MMP-3 were significantly elevated in cocultures. Chondrocytes exposed to the extract also produced IL-6, CCL2, and CCL5, and in cocultures with synoviocytes, there was a notable increase in IL-6, CCL5, and CXCL8, as well as a doubling of MMP-1 and MMP-3 levels. These findings underscore the critical role of cell crosstalk in the inflammatory and catabolic processes associated with pararamosis and demonstrate how Pararama hair extract can influence factors affecting cartilage health, providing valuable insights into this condition. Full article

Background/Objectives: Cuminum cyminum L. has been utilized as a medicinal plant for centuries. This research sought to examine the effects of cumin methanolic extract (CMT) on the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells. Methods: Spheroids were generated using human stem cells and cultured with CMT at concentrations between 0 and 1 µg/mL. Morphological assessments and cell viability tests were conducted on days 1 and 3. Chondrogenic differentiation expression was evaluated through quantitative polymerase chain reaction, Western blot, and RNA sequencing. SOX9, FAM20B, COL2A1, and COL1A1 mRNA expression levels were determined using real-time polymerase chain reaction. Protein expression was analyzed via Western blot. Results: Throughout this study, the spheroids maintained their integrity and shape. No significant variations in spheroid diameter were observed among the groups. CMT treatment enhanced the expression of SOX9 and FAM20B. Conclusions: The methanolic extract of Cuminum cyminum facilitated chondrogenic differentiation in human bone marrow-derived mesenchymal stem cells by modulating SOX9 and FAM20B expression. This indicates its potential application in cartilage tissue engineering. Full article

Background/Objectives: Cartilage injuries and osteoarthritis are prevalent public health problems, due to their disabling nature and economic impact. Mesenchymal stromal cells (MSCs) isolated from different tissues have the immunomodulatory capacity to regulate local joint environment. This translational study aims to compare cartilage restoration from MSCs from the synovial membrane (SM) and dental pulp (DP) by a tissue-engineered construct with Good Manufacturing Practices. Methods: A controlled experimental study was conducted on fourteen miniature pigs, using scaffold-free Tissue Engineering Constructs (TECs) from DP and SM MSCs, with a 6-month follow-up. Total thickness cartilage defects were created in both hind knees; one side was left untreated and the other received a TEC from either DP (n = 7) or SM (n = 7). An MRI assessed the morphology using the MOCART scoring system, T2 mapping evaluated water, and collagen fiber composition, and histological analysis was performed using the ICRS-2 score. Results: The untreated group had a mean MOCART value of 46.2 ± 13.4, while the SM-treated group was 65.7 ± 15.5 (p < 0.05) and the DP-treated group was 59.0 ± 7.9 (n.s.). The T2 mapping indicated a mean value of T2 of 54.9 ± 1.9 for native cartilage, with the untreated group at 50.9 ± 2.4 (p < 0.05). No difference was found between the T2 value of native cartilage and the treated groups. The ICRS-2 mean values were 42.1 ± 14.8 for the untreated group, 64.3 ± 19.0 for SM (p < 0.05), and 54.3 ± 12.2 for DP (n.s.). Conclusion: MRI and histological analysis indicated that TEC treatment led to superior cartilage coverage and quality compared to the defect group. TECs from SM demonstrated better results than the defect group in the histological assessment. Full article