Alpha-ketoglutarate ameliorates age-related and surgery induced temporomandibular joint osteoarthritis via regulating IKK/NF-κB signaling.

Recent studies have shed light on the important role of aging in the pathogenesis of joint degenerative diseases and the anti-aging effect of alpha-ketoglutarate (αKG). However, whether αKG has any effect on temporomandibular joint osteoarthritis (TMJOA) is unknown. Here, we demonstrate that αKG administration improves condylar cartilage health of middle-aged/aged mice, and ameliorates pathological changes in a rat model of partial discectomy (PDE) induced TMJOA. In vitro, αKG reverses IL-1ß-induced/H2O2-induced decrease of chondrogenic markers (Col2, Acan and Sox9), and inhibited IL-1ß-induced/ H2O2-induced elevation of cartilage catabolic markers (ADAMTS5 and MMP13) in condylar chondrocytes. In addition, αKG downregulates senescence-associated (SA) hallmarks of aged chondrocytes, including the mRNA/protein level of SA genes (p16 and p53), markers of nuclear disorders (Lamin A/C) and SA-ß-gal activities. Mechanically, αKG decreases the expressions of p-IKK and p-NF-κB, protecting TMJ from inflammation and senescence-related damage by regulating the NF-κB signaling. Collectively, our findings illuminate that αKG can ameliorate age-related TMJOA and PDE-induced TMJOA, maintain the homeostasis of cartilage matrix, and exert anti-aging effects in chondrocytes, with a promising therapeutic potential in TMJOA, especially age-related TMJOA.

Histological and Histopathological Features of the Third Metacarpal/Tarsal Parasagittal Groove and Proximal Phalanx Sagittal Groove in Thoroughbred Horses with Racing History.

Information regarding the histopathology of the proximal phalanx (P1) sagittal groove in racehorses is limited. Twenty-nine cadaver limbs from nine Thoroughbred racehorses in racing/race-training underwent histological examination. Histological specimens of the third metacarpal/metatarsal (MC3/MT3) parasagittal grooves and P1 sagittal grooves were graded for histopathological findings in hyaline cartilage (HC), calcified cartilage (CC), and subchondral plate and trabecular bone (SCB/TB) regions. Histopathological grades were compared between (1) fissure and non-fissure locations observed in a previous study and (2) dorsal, middle, and palmar/plantar aspects. (1) HC, CC, and SCB/TB grades were more severe in fissure than non-fissure locations in the MC3/MT3 parasagittal groove (p < 0.001). SCB/TB grades were more severe in fissure than non-fissure locations in the P1 sagittal groove (p < 0.001). (2) HC, CC, and SCB/TB grades including SCB collapse were more severe in the palmar/plantar than the middle aspect of the MC3/MT3 parasagittal groove (p < 0.001). SCB/TB grades including SCB collapse were more severe in the dorsal and middle than the palmar/plantar aspect of the P1 sagittal groove (p < 0.001). Histopathology in the SCB/TB region including bone fatigue injury was related to fissure locations, the palmar/plantar MC3/MT3 parasagittal groove, and the dorsal P1 sagittal groove.

Favourable clinical outcomes and low revision rate after M-ACI in adolescents with immature cartilage compared to adult controls: Results at 10 years.

PURPOSE: The purpose of this study was to evaluate long-term survival, patient-reported outcomes (PROs) and radiographic results of matrix-associated autologous chondrocyte implantation (M-ACI) in adolescents with immature cartilage and compare them to adult controls. METHODS: A retrospective matched-pair analysis was performed comparing the PRO after M-ACI for focal cartilage defect of the knee in cartilaginous immature adolescents to mature adults. Groups were matched for sex, body mass index, defect site and size, symptom duration and the number of previous knee surgeries. Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART 2.0) scores were assessed at least 60 months postoperatively. Patient acceptable symptomatic state (PASS) and clinical response rate in KOOS and KOOS subscores were calculated. RESULTS: A total of 54 patients were matched. At a mean of 96 months (65-144 months), no surgical complications, graft hypertrophy or reoperations were noted in the cohorts studied. Adolescents showed superior PROs at the final follow-up (76.9 ± 14.1 vs. 66.4 ± 15.0, p = 0.03) and were significantly more likely to achieve PASS (74.1% vs. 55.6%; p = 0.02) compared to the adult cohort. The KOOS subscale analysis showed long-term benefits for adolescents in terms of symptom improvement, pain reduction, activities of daily living, sports and quality of life (p < 0.05). None of the patients in the adolescent group showed graft hypertrophy on magnet resonance imaging or signs of osteoarthritis on radiographs at long-term follow-ups. CONCLUSIONS: M-ACI is an effective treatment for chondral defects of the knee in patients with immature cartilage with low revision rates and high patient satisfaction over the long term. Adolescents showed comparable clinical and radiographic results in the short and medium term, with slightly more favourable, clinically relevant functional results in adolescents in the long term. M-ACI can be safely used in adolescents, and consideration should be given to expanding the indication to include these patients. LEVEL OF EVIDENCE: Level III.

Alendronate treatment rescues the effects of compressive loading of TMJ in osteogenesis imperfecta mice.

BACKGROUND: Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue caused by mutations associated with type I collagen, which results in defective extracellular matrix in temporomandibular joint (TMJ) cartilage and subchondral bone. TMJ is a fibrocartilaginous joint expressing type I collagen both in the cartilage and the subchondral bone. In the present study the effects of alendronate and altered loading of the TMJ was analyzed both in male and female OI mice. MATERIALS AND METHODS: Forty-eight, 10-weeks-old male and female OI mice were divided into 3 groups: (1) Control group: unloaded group, (2) Saline + Loaded: Saline was injected for 2 weeks and then TMJ of mice was loaded for 5 days, (3) alendronate + loaded: alendronate was injected for 2 weeks and then TMJ of mice was loaded for 5 days. Mice in all the groups were euthanized 24-h after the final loading. RESULTS: Alendronate pretreatment led to significant increase in bone volume and tissue density. Histomorphometrically, alendronate treatment led to increase in mineralization, cartilage thickness and proteoglycan distribution. Increased mineralization paralleled decreased osteoclastic activity. Our immunohistochemistry revealed decreased expression of matrix metallopeptidase 13 and ADAM metallopeptidase with thrombospondin type 1 motif 5. CONCLUSION: The findings of this research support that alendronate prevented the detrimental effects of loading on the extracellular matrix of the TMJ cartilage and subchondral bone.

Silencing of CircTRIM25/miR-138-5p/CREB1 axis promotes chondrogenesis in osteoarthritis.

BACKGROUND: Dysregulated circular RNAs (circRNAs) are involved in osteoarthritis (OA) progression. OBJECTIVE: We aimed to explore the effect of hsa_circ_0044719 (circTRIM25) on the ferroptosis of chondrocytes. METHODS: Chondrocytes were treated with interleukin (IL)-1ß to generate cell model. Cellular behaviours were measured using cell counting kit-8, enzyme-linked immunosorbent assay, relevant kits, propidium iodide staining, and immunofluorescence assay. Quantitative real-time polymerase chain reaction was performed to examine the expression of circTRIM25, miR-138-5p, and cAMP responsive element binding protein 1 (CREB1), and their interactions were assessed using luciferase reporter analysis and RNA pull-down assay. RESULTS: CircTRIM25 was upregulated in OA tissues and IL-1ß-stimulated chondrocytes. Knockdown of circTRIM25 facilitated the viability and suppressed ferroptosis and inflammation of IL-1ß-induced cells. CircTRIM25 served as a sponge of miR-138-5p, which directly targets CREB1. Downregulation of miR-138-5p abrogated the effect induced by knockdown of circTRIM25. Furthermore, enforced CREB1 reversed the miR-138-5p induced effect. Moreover, knockdown of circTRIM25 attenuated cartilage injury in vivo. CONCLUSION: Silencing of circTRIM25 inhibited ferroptosis of chondrocytes via the miR-138-5p/CREB axis and thus attenuated OA progression.

Acceleration of chondrogenic differentiation utilizing biphasic core-shell alginate sulfate electrospun nanofibrous scaffold.

Engineering new biomedical materials with tailored physicochemical, mechanical and biological virtues in order to differentiate stem cells into chondrocytes for cartilage regeneration has garnered much scientific interest. In this study, core/shell nanofibrous scaffold based on poly(ɛ-caprolactone) (PCL) as a core material and alginate sulfate (AlgS)-poly(vinyl alcohol) (PVA) blend as shell materials (AlgS-PVA/PCL) was fabricated by emulsion electrospinning. In this vein, the influence of AlgS to PVA ratio (30:70, 50:50), organic to aqueous phase ratio (1:2, 1:3 and 1:5) and acid concentration (0, 10, 20, 30, 40 and 50 %) on nanofibers morphology were investigated. SEM images depicted that AlgS to PVA ratio of 30:70 and 50:50, organic to aqueous phase ratio of 1:3 and 1:5 and acid concentration of 30 % led to uniform, bead-free fibrous mats. AlgS-PVA/PCL scaffolds with AlgS to PVA ratio of 30:70 and organic to aqueous phase ratio of 1:3, showed admirable mechanical features, high porosity (>90 %) with desirable swelling ratio in wet condition. In vitro assays indicated that the AlgS-PVA/PCL scaffold surface had desirable interaction with stem cells and promotes cells attachment, proliferation and differentiation. Thus, we envision that this salient structure could be an intriguing construction as a cartilage tissue-engineered scaffold.

Deletion of vitamin D receptor exacerbated temporomandibular joint pathological changes under abnormal mechanical stimulation.

AIMS: Temporomandibular disorder can cause degenerative pathological changes by aseptic inflammation in the temporomandibular joint (TMJ). Vitamin D (VD) is known for maintaining calcium homeostasis, and recent studies indicated that VD and the vitamin D receptor (VDR) are important in inflammatory responses. In this study, we explored the anti-inflammatory effect of VD-VDR signaling axis in TMJ pathological degeneration. MAIN METHODS: Mice ablated for Vdr (Vdr-/-res) were fed with a rescue diet to avoid hypocalcemia. With abnormal mechanical stimulation, unilateral anterior crossbite (UAC) induced temporomandibular disorders in mice. Histological staining, immunohistochemistry staining, and micro-CT analysis were performed to evaluate TMJ pathological changes. To identify the mechanisms in the aseptic inflammatory process, in vitro experiments were conducted on wild-type (WT) and Vdr-/- chondrocytes with compressive mechanical stress loading, and the related inflammatory markers were examined. KEY FINDINGS: Vdr-/-res mice did not develop rickets with a high calcium rescue diet. The TMJ cartilage thickness in Vdr-/-res mice was significantly decreased with mechanical stress stimulation compared to WT mice. UAC-induced bone resorption was obvious, and the number of osteoclasts significantly increased in Vdr-/-res mice. The proliferation was inhibited and the gene expression of Il1b, Mmp3, and Mmp13 was significantly increased in Vdr-/- chondrocytes. However, WT chondrocytes showed significantly increased Tnfa gene expression as a response to mechanical stress but not in Vdr-/- chondrocytes. SIGNIFICANCE: VD-VDR is crucial in TMJ pathological changes under abnormal mechanical stimulation. Deletion of Vdr exacerbated inflammatory response excluding TNFα, inhibited chondrocyte proliferation, and promoted bone resorption in TMJ.

Osteocyte-derived exosomes regulate the DLX2/wnt pathway to alleviate osteoarthritis by mediating cartilage repair.

BACKGROUND: Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic agents for OA. OBJECTIVE: This study aimed to investigate the role of exosomes derived from osteocytes in OA, particularly focusing on their effects on cartilage repair and molecular mechanisms. METHODS: An injury cell model was established by treating chondrocytes with IL-1ß. Cartilage repair was evaluated using cell counting kit-8, flow cytometry, scratch test, and Western Blot. Molecular mechanisms were analyzed using quantitative real-time PCR, bioinformatic analysis, and Western Blot. An OA mouse model was established to explore the role of exosomal DLX2 in vivo. RESULTS: Osteocyte-released exosomes promoted cell viability and migration, and inhibited apoptosis and extracellular matrix (ECM) deposition. Moreover, exosomes upregulated DLX2 expression, and knockdown of DLX2 activated the Wnt pathway. Additionally, exosomes attenuated OA in mice by transmitting DLX2. CONCLUSION: Osteocyte-derived exosomal DLX2 alleviated IL-1ß-induced cartilage repair and inactivated the Wnt pathway, thereby alleviating OA progression. The findings suggested that osteocyte-derived exosomes may hold promise as a treatment for OA.

Outcomes of dorsal nasal augmentation using costochondral graft.

Objective: To assess functional and aesthetic outcomes in patients having undergone dorsal nasal augmentation with costochondral graft in a tertiary care setting. METHODS: The single-centre, retrospective, observational study was conducted at Shifa International Hospital, Islamabad, Pakistan, and comprised data of patients who underwent dorsal nasal augmentation using costochondral graft between January 1, 2018, and December 31, 2022. Aesthetic outcomes in terms of patient satisfaction were assessed using Facial Appearance, Health-related Quality of Life and Adverse Effects scores. Data was analysed using SPSS 26. RESULTS: Of the 46 patients, 28(61%) were males and 18(39%) were females. The overall mean age was 28.39±9.13 years. Dorsal nasal deficiency occurred secondary to congenital causes in 12(26.1%) patients, trauma 19(41.3%) and prior surgery 15(32.6%). Postoperative complication rate was 7(15%); 3(6.5%) had recipient site infection and 2(4.3%) had rib graft resorption. Besides, 1(2.2%) patient reported pain 2 months postoperatively and 1(2.2%) had hypertrophic scarring. Patient satisfaction with the outcome was noted in all the 10 parameters analysed. Most commonly reported problem was that the nose was 'looking thick/swollen' by 12(26.1%) patients, but the issue resolved during 1-year follow-up. Conclusion: Costochondral graft was found to be an ideal material for dorsal nasal augmentation, with high patient satisfaction rate.

A large, locally aggressive giant cell tumour arising from the laryngeal cartilage: A Rare Case Report.

Giant cell tumour is a growth predominantly found in long bones of the body. Giant cell tumour has a rare occurrence in the head and neck. A case of a 31 year old male with no known comorbidities at the ENT Department, Shifa International Hospital, Islamabad presented with anterior neck swelling and hoarseness of voice. Patient was diagnosed as having Giant Cell Tumour of Larynx (GTCL) proven on FNA cytology and post-operative biopsy. GCTL is an uncommon entity with only 45 reported cases in the world.

Treatment of bone-cartilage defects with dual-layer tissue-engineered scaffolds loaded with icariin and quercetin.

Over the past few decades, significant research has been conducted on tissue-engineered constructs for cartilage repair. However, there is a growing interest in addressing subchondral bone repair along with cartilage regeneration. This study focuses on a bilayer tissue engineering scaffold loaded with icariin (ICA) and quercetin (QU) for simultaneous treatment of knee joint cartilage and subchondral bone defects. The cytotoxicity of dual-layer scaffolds loaded with ICA and QU was assessed through live/dead cell staining. Subsequently, these dual-layer scaffolds loaded with ICA and QU were implanted into cartilage and subchondral bone defects in Sprague-Dawley (SD) rats. The repair effects were evaluated through macroscopic observation, computed tomography, and immunohistochemistry. After 12 weeks of implantation of dual-layer scaffolds loaded with ICA and QU into the cartilage and bone defects of SD rats, better repair effects were observed in both cartilage and bone defects compared to the blank control group. We found that the dual-layer tissue-engineered scaffold loaded with ICA and QU had excellent biocompatibility and could effectively repair articular cartilage and subchondral bone injuries, showing promising prospects for clinical applications.

Autologous bone grafting in combination with autologous chondrocyte implantation yields favourable outcomes in the treatment of osteochondral defects of the knee: A systematic literature review.

PURPOSE: This study addresses the gap in the current literature by evaluating the combined treatment of autologous bone grafting and autologous chondrocyte implantation (ABCI) for osteochondral defects of the knee. It aims to evaluate clinical outcomes against methodological quality and to summarize histological results and surgical techniques. METHODS: A thorough search was conducted across Pubmed, Cochrane and Embase databases. Studies reporting clinical outcomes of ABCI for osteochondral defects of the knee were included. Patient-reported outcome measures (PROMs), failure rates, methodological quality and potential conflicts of interest were evaluated. Histological results and surgical techniques were summarized. RESULTS: Eighteen studies with 344 analyzed patients met the eligibility criteria for inclusion. All studies showed a significant improvement (p < 0.05) across different PROMs (subjective International Knee Documentation Committee score, Cincinnati Knee Rating System, Visual Analogue Scale, Lysholm Score, Tegner Activity Scale, Knee injury and Osteoarthritis Outcome Score and Knee Society Score) compared to the preoperative status. Failure rates ranged from 0% to 17.6%, with a mean follow-up of 73.2 months (range: 9.0-143.6 months). Methodological quality was low to medium, including only one comparative study. Six studies reviewed reported a potential conflict of interest. The histological assessment showed effective bonding between autologous chondrocytes and bone graft. A large degree of variability was observed in the operative technique used. CONCLUSION: The current literature suggests that ABCI yields good clinical outcomes at mid- to long-term follow-up with favourable histological results for osteochondral defects of the knee. However, future research should focus on high-quality comparative studies to better guide treatment choices. Introducing ABCI as the standard abbreviation may enhance clarity in future research. LEVEL OF EVIDENCE: Level IV.

Dextran-tryamine hydrogel maintains position and integrity under simulated loading in a human cadaver knee model.

Objective: This dextran-tyramine hydrogel is a novel cartilage repair technique, filling focal cartilage defects to provide a cell-free scaffold for subsequent cartilage repair. We aim to asses this techniques' operative feasibility in the knee joint and its ability to maintain position and integrity under expected loading conditions. Method: Seven fresh-frozen human cadaver legs (age range 55-88) were used to create 30 cartilage defects on the medial and lateral femoral condyles dependent of cartilage quality, starting with 1.0 â€‹cm2; augmenting to 1.5 â€‹cm2 and eventually 2.0 â€‹cm2. The defects were operatively filled with the injectable hydrogel scaffold. The knees were subsequently placed on a continues passive motion machine for 30 â€‹min of non-load bearing movement, mimicking post-operative rehabilitation. High resolution digital photographs documented the hydrogel scaffold after placement and directly after movement. Three independent observers blinded for the moment compared the photographs on outline attachment, area coverage and hydrogel integrity. Results: The operative procedure was uncomplicated in all defects, application of the hydrogel was straightforward and comparable to common cartilage repair techniques. No macroscopic iatrogenic damage was observed. The hydrogel scaffold remained predominately unchanged after non-load bearing movement. Outline attachment, area coverage and hydrogel integrity were unaffected in 87%, 93% and 83% of defects respectively. Larger defects appear to be more affected than smaller defects, although not statistically significant (p â€‹> â€‹0.05). Conclusion: The results of this study show operative feasibility of this cell-free hydrogel scaffold for chondral defects of the knee joint. Sustained outline attachment, area coverage and hydrogel integrity were observed after non-load bearing knee movement.

Micro-current stimulation could inhibit IL-1ß-induced inflammatory responses in chondrocytes and protect knee bone cartilage from osteoarthritis.

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-1ß-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-1ß 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-1ß 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-1ß 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.

Auricular Chondrocytes as a Cell Source for Scaffold-Free Elastic Cartilage Tissue Engineering.

Current tissue engineering (TE) methods utilize chondrocytes primarily from costal or articular sources. Despite the robust mechanical properties of neocartilages sourced from these cells, the lack of elasticity and invasiveness of cell collection from these sources negatively impact clinical translation. These limitations invited the exploration of naturally elastic auricular cartilage as an alternative cell source. This study aimed to determine if auricular chondrocytes (AuCs) can be used for TE scaffold-free neocartilage constructs and assess their biomechanical properties. Neocartilages were successfully generated from a small quantity of primary neonatal AuCs of three minipig donors (n = 3). Neocartilage constructs had instantaneous moduli of 200.5 kPa ± 43.34 and 471.9 ± 92.8 kPa at 10% and 20% strain, respectively. TE constructs' relaxation moduli (Er) were 36.99 ± 6.47 kPa Er and 110.3 ± 16.99 kPa at 10% and 20% strain, respectively. The Young's modulus was 2.0 MPa ± 0.63, and the ultimate tensile strength was 0.619 ± 0.177 MPa. AuC-derived neocartilages contained 0.144 ± 0.011 µg collagen, 0.185 µg ± 0.002 glycosaminoglycans per µg dry weight, and 1.7e-3 µg elastin per µg dry weight. In conclusion, this study shows that AuCs can be used as a reliable and easily accessible cell source for TE of biomimetic and mechanically robust elastic neocartilage implants.

Triticeal cartilage: a meta-analysis of prevalence and morphologic evaluation.

PURPOSE: The triticeal cartilage, situated within the lateral thyrohyoid membrane, remains elusive in function yet crucial in clinical contexts. Composed of hyaline cartilage, it is prone to ossification, potentially leading to diagnostic challenges such as misidentification with atherosclerosis or fractures. METHODS: This study, aiming to establish its prevalence and highlight clinical relevance, conducted a systematic review across several electronic databases such as Medline, PUBMED, Scopus, Google Scholar, Web of Science, SpringerLink and Sciencedirect using keywords "triticeal cartilage", "triticeous cartilage" or "cartilago triticea". An assurance tool for anatomical investigations was used to assess the quality of the methodology (AQUA). A random effects model was utilized to determine the pooled prevalence. RESULTS: The true prevalence of triticeal cartilage was found to be variable, with an overall pooled proportion of 43% while crude prevalence were 50.6%. Its crude prevalence was notably higher in women compared to men, in contrary true prevalence was higher in men, posing sex-related disparities. It was mostly seen bilaterally. When the morphologic characteristics of the cartilage were evaluated, classification differences were observed in terms of shape, with a mean length of 5.48 mm, a mean width of 3.04 mm and a mean weight of 62.32 mg. The vertebral level at which the TC was located was mostly C4. The degree of calcification of the cartilage was most commonly mild. CONCLUSION: In conclusion, triticeal cartilage holds significant clinical importance, necessitating vigilance during diagnostic evaluations and surgical approaches. Further studies are imperative to elucidate its function comprehensively and refine diagnostic strategies, ensuring optimal patient care in neck-related pathologies.

Zwitterionic Poly-Carboxybetaine Polymers Restore Lubrication of Inflamed Articular Cartilage.

Osteoarthritis is a degenerative joint disease that is associated with decreased synovial fluid viscosity and increased cartilage friction. Though viscosupplements are available for decades, their clinical efficacy is limited and there is ample need for more effective joint lubricants. This study first evaluates the tribological and biochemical properties of bovine articular cartilage explants after stimulation with the inflammatory cytokine interleukin-1ß. This model is then used to investigate the tribological potential of carboxybetaine (CBAA)-based zwitterionic polymers of linear and bottlebrush architecture. Due to their affinity for cartilage tissue, these polymers form a highly hydrated surface layer that decreases friction under high load in the boundary lubrication regime. For linear pCBAA, these benefits are retained over several weeks and the relaxation time of cartilage explants under compression is furthermore decreased, thereby potentially boosting the weeping lubrication mechanism. Bottlebrush bb-pCBAA shows smaller benefits under boundary lubrication but is more viscous than linear pCBAA, therefore providing better lubrication under low load in the fluid-film regime and enabling a longer residence time to bind to the cartilage surface. Showing how CBAA-based polymers restore the lost lubrication mechanisms during inflammation can inspire the next steps toward more effective joint lubricants in the future.

The emerging role of Piezo1 in the musculoskeletal system and disease.

Piezo1, a mechanosensitive ion channel, has emerged as a key player in translating mechanical stimuli into biological signaling. Its involvement extends beyond physiological and pathological processes such as lymphatic vessel development, axon growth, vascular development, immunoregulation, and blood pressure regulation. The musculoskeletal system, responsible for structural support, movement, and homeostasis, has recently attracted attention regarding the significance of Piezo1. This review aims to provide a comprehensive summary of the current research on Piezo1 in the musculoskeletal system, highlighting its impact on bone formation, myogenesis, chondrogenesis, intervertebral disc homeostasis, tendon matrix cross-linking, and physical activity. Additionally, we explore the potential of targeting Piezo1 as a therapeutic approach for musculoskeletal disorders, including osteoporosis, muscle atrophy, intervertebral disc degeneration, and osteoarthritis.

Temporal modulation of inflammation and chondrogenesis through dendritic nanoparticle-mediated therapy with diclofenac surface modification and strontium ion encapsulation.

Cartilage tissue engineering holds great promise for efficient cartilage regeneration. However, early inflammatory reactions to seed cells and/or scaffolds impede this process. Consequently, managing inflammation is of paramount importance. Moreover, due to the body's restricted chondrogenic capacity, inducing cartilage regeneration becomes imperative. Thus, a controlled platform is essential to establish an anti-inflammatory microenvironment before initiating the cartilage regeneration process. In this study, we utilized fifth-generation polyamidoamine dendrimers (G5) as a vehicle for drugs to create composite nanoparticles known as G5-Dic/Sr. These nanoparticles were generated by surface modification with diclofenac (Dic), known for its potent anti-inflammatory effects, and encapsulating strontium (Sr), which effectively induces chondrogenesis, within the core. Our findings indicated that the G5-Dic/Sr nanoparticle exhibited selective Dic release during the initial 9 days and gradual Sr release from days 3 to 15. Subsequently, these nanoparticles were incorporated into a gelatin methacryloyl (GelMA) hydrogel, resulting in GelMA@G5-Dic/Sr. In vitro assessments demonstrated GelMA@G5-Dic/Sr's biocompatibility with bone marrow stem cells (BMSCs). The enclosed nanoparticles effectively mitigated inflammation in lipopolysaccharide-induced RAW264.7 macrophages and significantly augmented chondrogenesis in BMSCs cocultures. Implanting BMSCs-loaded GelMA@G5-Dic/Sr hydrogels in immunocompetent rabbits for 2 and 6 weeks revealed diminished inflammation and enhanced cartilage formation compared to GelMA, GelMA@G5, GelMA@G5-Dic, and GelMA@G5/Sr hydrogels. Collectively, this study introduces an innovative strategy to advance cartilage regeneration by temporally modulating inflammation and chondrogenesis in immunocompetent animals. Through the development of a platform addressing the temporal modulation of inflammation and the limited chondrogenic capacity, we offer valuable insights to the field of cartilage tissue engineering.

Reconstruction of Palatal Defects Using a Composite Chondromucosal Nasoseptal Flap and Comparative Analysis.

OBJECTIVE: The use of composite chondromucosal nasal septal flaps (ccNSF) has been demonstrated to be effective in cadaveric studies for the anterior skull base and the orbit. However, their application in the clinical setting remains unexplored. Our study aims to introduce a new method for treating palatal defects using ccNSF. Additionally, we studied the average NSF area and compared it to the average palate area. METHODS: We collected 108 CT scans from the medical records of patients without head and neck pathologies from a tertiary medical institution. We quantified the quadrangular (septal) cartilage and palate areas. Furthermore, we included a clinical case in which we used the ccNSF for the palatal defect reconstruction. This was to compare the mean area between the palate and the septal cartilage. RESULTS: The ccNSF covered the palatal defect without any significant complications for the first 9 months of follow-up. A total of 102 CT scans met the inclusion criteria and were measured. We found that the mean quadrangular cartilage had a length of 2.50 (±0.52) cm, a width of 2.28 (±0.51) cm, and an area of 5.43 (±1.68) cm2. The mean palate length was 2.73 (±0.44) cm, with a width of 3.13 (±0.34) cm, and area of 7.87 (±1.43) cm2. CONCLUSIONS: The ccNSF proved successful in palatal defect reconstruction, resulting in positive outcomes and no major complications until the 9-month follow-up. The ccNSF is a useful flap that avoids the use of free flap transfer and its associated morbidities. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.