Search Results (722)

Long-term solutions for cartilage repair after injury are currently being investigated, with most research aiming to exploit the regenerative and chondrogenic differentiation potential of stem-cell-based spheroids. The incorporation of the bioactive polymer CTL, a lactose-modified chitosan, into spheroids is a strategy to improve cell viability and accelerate type II collagen gene expression. In this work, the role of CTL in influencing the dynamics of spheroid formation and its interplay with cell membrane adhesion molecules (integrins and cadherins) and cytoskeletal components is elucidated. The results indicate that CTL is actively involved in the reorganization of cells into spheroids. An analysis of the effects of physical form of CTL (rehydrated polymer coating or polymer solution) in stimulating peculiar biological responses indicates that CTL matrix in spheroids facilitates an early phase of chondrogenic differentiation. Once the CTL matrix is included in spheroids, there is an increase in COL2A1 gene expression and matrix deposition, regardless of the initial physical form of CTL. Overall, these results contribute to a better understanding of the dynamics of spheroid formation in the presence of the polymer and on its bioactive role in mesenchymal stem cell spheroids. Full article

Cartilage-derived migratory cells show great potential for autologous use in cartilage repair surgery. However, their collection through arthroscopic biopsy has not been previously reported in individuals without osteoarthritis. This study aimed to characterize migratory cartilage cells isolated from arthroscopic biopsies of volunteers without osteoarthritis and compare them with cells obtained by enzymatic digestion. Cell cultures were successfully established using both methods—enzymatic digestion and cell migration—from cartilage explants, with no significant differences observed in stem cell markers or plasticity between the cell lines. Cells derived from both procedures exhibited characteristics of mesenchymal stem cell, including fibroblast-like morphology, expression of CD29, CD90, and CD105 markers, absence of hematopoietic and endothelial cell markers, and the ability to differentiate into adipocytes, chondrocytes, and osteoblasts under appropriate conditions. Cells obtained by migration showed lower expression of collagen I and II, along with reduce collagen II/collagen I ratio, both positively associated with chondral matrix production, as well as lower RUNX2 expression. However, no differences were found in the levels of SOX9, essential for chondrogenic differentiation, or in the expression of perlecan gene. Syndecan-1 expression was lower in cells obtained by migration. In conclusion, this study demonstrates that cartilage-derived migratory cells can be successfully obtained from arthroscopic biopsies of individuals without osteoarthritis, presenting comparable dedifferentiation and plasticity profiles. Furthermore, these cells express essential chondrogenic markers and proteins. Although further in vivo studies are needed to determine their effective regenerative potential, cartilage-derived migratory cells represent a promising avenue for cartilage repair strategies. Full article

Breast thread lifting is a minimally invasive technique for correcting mild to moderate ptosis, offering aesthetic enhancement with reduced morbidity compared to traditional mastopexy. This review examines the anatomical underpinnings, clinical indications, technical nuances and limitations of breast thread lifting. The breast’s fascial architecture, particularly the role of Cooper’s ligaments and the retromammary space, critically influences thread trajectory and vector planning. Classification systems assist in proper patient selection, highlighting the suitability of thread lifts for Grades I–II ptosis with minimal skin excess. Advances in ultrasonography have improved preoperative planning, thread placement accuracy and postoperative monitoring. Various thread types, including PDO, PLLA, PCL and Silhouette Soft, offer different lifting capacities and collagen-stimulatory properties, necessitating tailored material selection. Although thread lifts offer immediate improvements, their transient nature necessitates careful patient counseling to manage expectations regarding durability and potential maintenance sessions. Innovative techniques, including clavicular anchoring and multi-level subdermal scaffolding, have expanded the procedural repertoire. Despite certain limitations, breast thread lifting remains a valuable tool within the aesthetic surgeon’s armamentarium, particularly for patients seeking minimally invasive options with shortened recovery periods and favorable psychosocial outcomes. Future developments are expected to further enhance safety, reproducibility and long-term results. Full article

Background/Objectives: As the incidence of breast cancer increases, reliable, effective, and innovative solutions are required for breast deformities following breast-conserving surgery. We aimed to evaluate the biocompatibility and efficacy of optimized three-dimensional (3D) micro-nanofiber scaffolds and demonstrate their clinical potential through preclinical experiments. Methods: Seven-week-old male Sprague-Dawley rats were randomized into four groups. Group I (control group) received a 2-dimensional (2D) micro-nanofiber scaffold weighing 0.2 g; Groups II–IV received 3D micro-nanofiber scaffolds weighing 0.2, 0.3, and 0.6 g, respectively. These were subcutaneously implanted into the dorsal region and harvested with the surrounding tissues at 4, 8, and 16 weeks for histological evaluation. Results: The number of inflammatory cells was higher in Group IV than in Groups II and III at 4 weeks, with a significant increase in Group IV (p < 0.01) compared with that in Group I. At 8 weeks, it was significantly increased in Group III compared with that in Group I. Furthermore, at 16 weeks, it was significantly reduced in Group IV (p < 0.05) compared with that in Group I. The fibrosis depth in the 3D scaffolds revealed significant differences in Groups II, III, and IV (p < 0.001) compared with Group I at 4 weeks. The collagen fiber densities in the 3D groups were higher than those in the 2D group at 8 and 16 weeks. There were no statistically significant differences between the 3D groups. Conclusions: Absorbable 3D micro-nanofiber scaffolds enhance tissue integration and extracellular matrix formation following post-mastectomy breast reconstruction. Full article

Background and Objectives: Many middle-aged and older individuals experience shoulder pain, often due to partial-thickness rotator cuff tears (PTRCTs). If conservative treatment fails to relieve symptoms in a patient, surgical intervention may be necessary. In such cases, using a bioinductive collagen implant may offer a viable alternative to conventional rotator cuff repair. Most notably, it offers potential advantages, particularly in reducing postoperative pain and promoting faster recovery. Accordingly, this study aims to evaluate the clinical outcomes of treating bursal-sided partial-thickness rotator cuff tears using bioinductive collagen implants alone, without concurrent rotator cuff repair. Materials and Methods: We followed 32 patients who had bursal-sided partial-thickness rotator cuff tears (Ellman grade I or II) and received conservative care for more than six months but continued to experience symptoms. These patients received surgery using bioinductive collagen implants without rotator cuff repair, and we followed up on their postoperative prognosis for at least one year after surgery. For a more accurate contrast, we performed clinical evaluation preoperatively and at 2 weeks, 6 weeks, 3 months, 6 months, and 12 months postoperatively. Visual Analog Scale (VAS), American Shoulder and Elbow Surgeons (ASES) score, Single Assessment Numeric Evaluation (SANE), and Western Ontario Rotator Cuff (WORC) score were used as assessment tools in this study. As for radiological outcomes, magnetic resonance imaging (MRI) and ultrasonography were helpful. This supported our assessment of graft integration and failure. Results: These 32 patients included 13 with Ellman grade I tear and 19 with grade II tear. In both cases, they underwent surgery only using bioinductive collagen implants, and any anchor-based cuff repair was completely excluded. As for VAS (3.8 ± 2.9), certain statistically significant improvements were found starting at 2 weeks postoperatively. On the other hand, the scores of ASES (58.6 ± 20.3), SANE (60.1 ± 23.2), and WORC (59.8 ± 22.4) began to indicate a significant improvement starting at 6 weeks postoperatively (p < 0.001), showing continuous progress. At each final step, we confirmed that there were no cases of graft failure by radiological evaluation and found successful healing indicators, such as much less pain in all patients. Conclusions: The findings of this study provide the clinical evidence that a surgery using bioinductive collagen implant for bursal-sided partial-thickness rotator cuff tears is a highly effective treatment option in patients unresponsive to conservative therapy. Particularly, its practical clinical effectiveness includes facilitating rapid recovery without a significant risk of complications. Full article

Mucopolysaccharidosis type IVA (MPS IVA, Morquio A syndrome) is a rare inherited disorder characterized by skeletal dysplasia due to deficient N-acetylgalactosamine-6-sulfate sulfatase activity, resulting in glycosaminoglycan (GAG) accumulation. Identifying accurate biomarkers reflecting clinical severity and therapeutic response remains challenging. This study evaluated potential surrogate biomarkers, including N-terminal pro-C-type natriuretic peptide (NT-proCNP), collagen types I and II, mono-sulfated keratan sulfate (KS), di-sulfated KS, and chondroitin-6-sulfate (C6S), in blood and urine samples from 60 patients ranging from 1 to 62 years of age. NT-proCNP levels were significantly elevated in patients of all ages and negatively correlated with growth impairment, especially after 8 years of age. Collagen type I levels significantly increased in adult patients, whereas collagen type II showed age-dependent elevations. Urinary KS, in mono- and di-sulfated forms, demonstrated moderate negative correlations with growth impairment. Moreover, NT-proCNP, mono- and di-sulfated KS in plasma, and urinary di-sulfated KS were not affected by enzyme replacement therapy in patients younger than 12 years, unlike urinary mono-sulfated KS. In conclusion, NT-proCNP has emerged as a promising independent biomarker reflecting the severity of skeletal dysplasia and possibly the near-future growth rate. These findings highlight the potential role of NT-proCNP in clinical assessment and monitoring therapeutic efficacy, addressing current unmet needs in MPS IVA management. Full article

Developing fibrochondrogenic serum-free media is important for regenerating diseased and injured fibrocartilage but no defined protocols exist. Towards this goal, we characterized the effect of four candidate fibrochondrogenic serum-free media containing transforming growth factor beta-3 (TGF-β3), insulin-like growth factor-1 (IGF-1), and fibroblast growth factor-2 (FGF-2) with high/low glucose and with/without dexamethasone on human mesenchymal stem cells (hMSCs) via proliferation and differentiation assays. In Ki67 proliferation assays, serum-free media containing low glucose and dexamethasone exhibited the highest growth. In gene expression assays, serum-free media containing low glucose and commercially available chondrogenic media (COM) induced high fibrochondrogenic transcription factor expression (scleraxis/SCX and SRY-Box Transcription Factor 9/SOX9) and extracellular matrix (ECM) protein levels (aggrecan/ACAN, collagen type I/COL1A1, and collagen type II/COL2A1), respectively. In immunofluorescence staining, serum-free media containing high glucose and COM induced high fibrochondrogenic transcription factor (SCX and SOX9) and ECM protein (COL1A1, COL2A1, and collagen type X/COL10A1) levels, respectively. In cytochemical staining, COM and serum-free media containing dexamethasone showed a high collagen content whereas serum-free media containing high glucose and dexamethasone exhibited high glycosaminoglycan (GAG) levels. Altogether, defined serum-free media containing high glucose exhibited the highest fibrochondrogenic potential. In summary, this work studied conditions conducive for fibrochondrogenesis, which may be further optimized for potential applications in fibrocartilage tissue engineering. Full article

Background/Objectives: Patellofemoral pain (PFP) is considered a risk factor for knee osteoarthritis (OA) onset. The purpose of this study was to compare degenerative biomarkers in females with and without PFP and to determine changes in these levels, along with pain and function, over 6 months. Methods: All subjects received a knee x-ray to ensure that none had degenerative changes. Urine and serum were collected and analyzed for C-telopeptide fragments of type II collagen (CTX-II) and C-propeptide II (CP-II); these were then expressed as a cartilage degradation: cartilage synthesis ratio (CTX-II:CP-II). Subjects with PFP rated pain using a 10 cm visual analog scale, and function using the Knee injury and Osteoarthritis Outcome Scores-Patellofemoral (KOOS-PF) questionnaire. Subjects with PFP were tested at baseline and at 6 months. Results: Females with PFP had higher levels of CTX-II:CP-II than controls (p < 0.001) and these remained elevated at 6 months (p = 0.82). Females with PFP reported similar levels of pain (p = 0.30) but higher function at 6 months (p = 0.002). However, the 9.0-point increase in KOOS-PF values did not exceed the minimum important change. Conclusions: Females with PFP but no evident structural changes had more elevated biomarkers than controls. This finding suggests that this cohort may have excessive cartilage turnover which may contribute to knee OA. Full article

Developing a functional tissue-engineered articular cartilage remains a challenge to improving clinical treatment of cartilage injury and joint-related degenerative disease. The dynamic self-regenerating cartilage (dSRC) approach presented here encourages autologous chondrocytes to generate their own matrix rather than imposing a matrix upon them. dSRC constructs were grown for 12 weeks under hypoxic conditions in reciprocating motion. Biochemical composition was evaluated, specifically water, collagen, and proteoglycan content. Speckle rHEologicAl micRoscopy (SHEAR) was utilized for spatially resolved evaluation of the shear modulus in engineered cartilage. Histological and immunohistochemical analyses of dSRC were also performed. The maturation of the dSRC matrix results in collagen and glycosaminoglycan (GAG) levels around 50% of those in native cartilage. SHEAR images demonstrate an increase in shear modulus of the matrix to ~20% that of native cartilage after 12 weeks. Histological support for excellent collagen and GAG production was evident, and immunohistochemistry showed a high preference for hyaline-like type II collagen in the neomatrix. A decrease in chondrocyte density occurred from an initial hypercellular matrix to that approaching native cartilage by 12 weeks. While this maturation of dSRC in vitro should not be construed as an absolute prediction of in vivo performance, these results are encouraging, representing a potential new cartilage repair and regeneration approach. Full article

Lysophosphatidylinositols are degradation products of phosphatidylinositols within cell membranes and digestive metabolites of a high-fat diet in the gut. G-protein-coupled receptor 55 (GPR55) is a receptor that senses lysophosphatidylinositol and acts as an immune mediator, being primarily upregulated during immune cell activation. This study aimed to investigate the role of GPR55, using its antagonist, CID16020046, in a collagen-induced rheumatoid arthritis mouse model. It was observed that DBA-1J mice develop joint lesions characteristic of rheumatoid arthritis following immunization with bovine type II collagen. The administration of CID16020046 (1 mg/kg, intraperitoneally) alleviated rheumatoid arthritis symptoms and inflammatory responses. Histopathological analysis showed that CID16020046 reduced foot edema, proteoglycan loss, and bone erosion in the joints. CID16020046 also decreased rheumatoid-arthritis-induced serum IgG levels, as measured using enzyme-linked immunosorbent assays. The treatment reduced levels of pro-inflammatory cytokines (IL-1β and IL-6), Th1 cytokine (IFN-γ), and Th17 cytokine (IL-17A), along with matrix metalloproteinase-3 (MMP-3) and the receptor activator of nuclear factor-κB ligand (RANKL) in the feet. A significant reduction in splenomegaly was also observed, along with significant reductions in CD4⁺ T helper 1 (Th1) and Th17 cells in the spleen. Additionally, CID16020046 suppressed the differentiation of naïve T cells into CD4⁺IL-17⁺ Th17 cells. CID16020046 suppressed expression levels of inflammatory cytokine mRNAs in SW982 human synovial cells. In conclusion, blocking GPR55 alleviates collagen-induced rheumatoid arthritis symptoms by suppressing Th1 and Th17 cells in the spleen and pro-inflammatory cytokines in the joints, suggesting that GPR55 is a potential therapeutic target for autoimmune inflammatory diseases. Full article

Benzo[a]pyrene (B[a]P) is a widespread and persistent organic pollutant that poses serious threats to human health. Although its carcinogenic properties have been extensively studied, its developmental toxicity and underlying mechanisms remain poorly understood. In this study, we employed Caenorhabditis elegans (C. elegans) as a model organism to investigate the effects of B[a]P exposure during early developmental stages. To comprehensively assess B[a]P-induced developmental toxicity, we employed high-throughput sequencing along with transgenic and mutant C. elegans strains. Exposure to B[a]P at concentrations exceeding 1 mg/L significantly reduced larval body size, decreased the number of adult worms, and delayed larval-to-adult development. Furthermore, we analyzed the expression of genes involved in cuticle collagen synthesis and key components of the insulin/insulin-like growth factor signaling (IIS) pathway, including daf-2 and daf-16. These findings suggest that B[a]P-induced developmental toxicity may be associated with dysregulation of the IIS pathway. Specifically, B[a]P appears to influence the activity of the downstream transcription factor daf-16, thereby altering the expression of collagen-related genes. This disruption in collagen synthesis may contribute to delayed larval development and impaired maturation. Our study provides new insights into the environmental hazards associated with B[a]P exposure and reveals a potential mechanism underlying its developmental toxicity. Moreover, our findings highlight the critical role of collagen gene regulation during early developmental stages. These genes may serve as potential biomarkers for environmental toxicant exposure, particularly in vulnerable populations such as children undergoing critical periods of development. Full article

Background/Objectives: Immune cells are integral to bone homeostasis, including the repair and remodeling of bone tissue. Chronic dysregulation within this osteoimmune network can lead to bone marrow defects of the jaw (BMDJ), particularly fatty degenerative osteonecrosis of the jaw (FDOJ). These localized pathologies are implicated in systemic immune dysfunctions. Methods: This study is designed to determine whether BMDJ/FDOJ samples are indicative of medullary bone pathology by evaluating FDOJ gene expression patterns using quantitative real-time PCR. Results: Comparative analyses between pathological and healthy samples evaluated the dysregulation of key molecular pathways. BMDJ/FDOJ samples showed significant upregulation of inflammatory mediators, including CCL5/RANTES, VEGF, IGF and KOR, and downregulation of structural proteins, such as collagen types I, II and IV, and osteogenesis-associated factors, such as SP7. Conclusions: The study provides new insights into the molecular mechanisms of BMDJ/FDOJ by identifying potential molecular changes suggesting a pro-inflammatory state in the affected jawbone which may contribute to systemic immune dysregulation. The findings are consistent with morphologic observations of BMDJ/FDOJ in degenerated jawbone and underscore the need for integrative approaches in dentistry and medicine while highlighting BMDJ/FDOJ as a potential target for therapeutic and preventive strategies against systemic diseases and emphasizing its clinical significance. Full article

Given the growing interest in natural compounds for promoting healthy aging, this study aimed to investigate the potential of cod collagen peptides (CCPs), a readily available marine resource, to extend lifespan and improve health. Lifespan assays were performed on C. elegans treated with different concentrations of CCPs. Furthermore, various stress resistance assays, including those evaluating oxidative and thermal stress, were conducted. To elucidate the underlying mechanisms, gene expression analysis of key aging-related genes was performed. The results demonstrated that treatment with 25 mg/mL of CCPs extended the lifespan of C. elegans by 13.2%, increased body length and width by 14.8% and 20.6%, respectively, and enhanced head-swing and body-bending frequencies by 66.9% and 80.4%. Lipofuscin content and apoptosis were reduced by 45.9% and 34.1%, respectively. C. elegans treated with 25 mg/mL of CCPs also showed improved stress resistance, a 90.7% increase in glutathione peroxidase (GPX) activity, and a 147.4% increase in glutathione (GSH) content. Transcriptomic analysis showed that CCPs enhanced anti-aging activity by activating the MAPK pathway and inhibiting the IIS pathway, which was associated with protein aggregation. It also reduced lipid synthesis and regulated lipid metabolism through the fat-6 pathway. The results indicated that CCPs could be employed as a valuable ingredient in the food and pharmaceutical fields. Full article

Multipotent vascular stem cells (MVSCs) are found in the vascular wall and surrounding tissues and possess the ability to differentiate into mesenchymal lineages. Previous studies have shown that MVSCs can be activated in response to vascular injury and differentiate into vascular smooth muscle cells (SMCs), contributing to vascular remodeling and microvessel formation. However, it remains unclear as to whether and how microenvironmental changes in the extracellular matrix, such as substrate stiffness, modulates MVSC differentiation under pathological conditions. This study demonstrated that MVSCs cultured on stiff substrates exhibited increased cell spreading, stronger cell adhesion, and a higher expression of SMC markers, including myosin heavy chain (MHC), myocardin (MYCD), calponin 1 (CNN1), and smooth muscle α-actin (SMA). In contrast, MVSCs on soft substrates showed an elevated expression of the chondrogenic markers aggrecan 1 (AGC1) and collagen-II (COL2A1). The presence of TGF-β1 further increased the expression of SMC markers on stiff substrates and chondrogenic markers on the soft substrates. Collectively, these results establish substrate stiffness as a key regulator of MVSC lineage commitment through cytoskeletal reorganization, with TGF-β1 acting as a biochemical amplifier. Our findings highlight the substrate-stiffness-dependent differentiation of MVSCs and provide mechanistic insights into the role of MVSCs in vascular remodeling during atherosclerosis development and blood vessel regeneration. Full article

Focusing on the anti-aging mechanism and efficient utilization of anti-aging active ingredients in the skin is an excellent strategy to mitigate aging. In this study, ribose/collagen/decarboxylated carnitine hydrochloride/palmitoyl tripeptide-1 composite nanocarriers (RCDP NCs) were synthesized using transdermal drug delivery nanotechnology. The drug delivery of composite nanocarriers and the anti-aging mechanism of RCDP NCs were studied through transdermal behavior, cell uptake, cell proliferation, antioxidant enzyme activity, lipid oxidation product expression, β—galactosidase content, autophagy vesicle number, autophagy-related protein expression, and other indicators. The results showed that the composite nanocarriers on the skin could reach a dermal depth of 460.0 μm (4 h). The uptake of RCDP NCs by keratinocytes and fibroblasts increased by 47.37% and 89.11% (4 h), respectively. RCDP NCs promoted cell proliferation, enhanced the activities of the main antioxidant enzymes, and reduced the production of the lipid oxidation product malondialdehyde (MDA). Sequestosome-1 protein (p62) decreased, whereas both the ratio of microtubule-associated protein light chain 3 II/microtubule-associated protein light chain 3 I (LC3II/LC3I) and the number of autophagosomes increased, indicating that RCDP NCs promoted autophagy. The drug delivery nanotechnology in this study achieved better transdermal application of active ingredients, which could mitigate skin aging faster and more effectively. Full article