HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-ß/Smad2/3 axis mediated by microfractures.

The current first-line treatment for repairing cartilage defects in clinical practice is the creation of microfractures (MF) to stimulate the release of mesenchymal stem cells (MSCs); however, this method has many limitations. Recent studies have found that MSC-derived extracellular vesicles (MSC-EVs) play an important role in tissue regeneration. This study aimed to verify whether MSC-EVs promote cartilage damage repair mediated by MFs and to explore the repair mechanisms. In vitro experiments showed that human umbilical cord Wharton's jelly MSC-EVs (hWJMSC-EVs) promoted the vitality of chondrocytes and the proliferation and differentiation ability of bone marrow-derived MSCs. This was mainly because hWJMSC-EVs carry integrin beta-1 (ITGB1), and cartilage and bone marrow-derived MSCs overexpress ITGB1 after absorbing EVs, thereby activating the transforming growth factor-ß/Smad2/3 axis. In a rabbit knee joint model of osteochondral defect repair, the injection of different concentrations of hWJMSC-EVs into the joint cavity showed that a concentration of 50 µg/ml significantly improved the formation of transparent cartilage after MF surgery. Extraction of regenerated cartilage revealed that the changes in ITGB1, transforming growth factor-ß, and Smad2/3 were directly proportional to the repair of regenerated cartilage. In summary, this study showed that hWJMSC-EVs promoted cartilage repair after MF surgery.

Skeletal interoception in osteoarthritis.

The interoception maintains proper physiological conditions and metabolic homeostasis by releasing regulatory signals after perceving changes in the internal state of the organism. Among its various forms, skeletal interoception specifically regulates the metabolic homeostasis of bones. Osteoarthritis (OA) is a complex joint disorder involving cartilage, subchondral bone, and synovium. The subchondral bone undergoes continuous remodeling to adapt to dynamic joint loads. Recent findings highlight that skeletal interoception mediated by aberrant mechanical loads contributes to pathological remodeling of the subchondral bone, resulting in subchondral bone sclerosis in OA. The skeletal interoception is also a potential mechanism for chronic synovial inflammation in OA. In this review, we offer a general overview of interoception, specifically skeletal interoception, subchondral bone microenviroment and the aberrant subchondral remedeling. We also discuss the role of skeletal interoception in abnormal subchondral bone remodeling and synovial inflammation in OA, as well as the potential prospects and challenges in exploring novel OA therapies that target skeletal interoception.

Reciprocal negative feedback between Prrx1 and miR-140-3p regulates rapid chondrogenesis in the regenerating antler.

During growth phase, antlers exhibit a very rapid rate of chondrogenesis. The antler is formed from its growth center reserve mesenchyme (RM) cells, which have been found to be the derivatives of paired related homeobox 1 (Prrx1)-positive periosteal cells. However, the underlying mechanism that drives rapid chondrogenesis is not known. Herein, the miRNA expression profiles and chromatin states of three tissue layers (RM, precartilage, and cartilage) at different stages of differentiation within the antler growth center were analyzed by RNA-sequencing and ATAC-sequencing. We found that miR-140-3p was the miRNA that exhibited the greatest degree of upregulation in the rapidly growing antler, increasing from the RM to the cartilage layer. We also showed that Prrx1 was a key upstream regulator of miR-140-3p, which firmly confirmed by Prrx1 CUT&Tag sequencing of RM cells. Through multiple approaches (three-dimensional chondrogenic culture and xenogeneic antler model), we demonstrated that Prrx1 and miR-140-3p functioned as reciprocal negative feedback in the antler growth center, and downregulating PRRX1/upregulating miR-140-3p promoted rapid chondrogenesis of RM cells and xenogeneic antler. Thus, we conclude that the reciprocal negative feedback between Prrx1 and miR-140-3p is essential for balancing mesenchymal proliferation and chondrogenic differentiation in the regenerating antler. We further propose that the mechanism underlying chondrogenesis in the regenerating antler would provide a reference for helping understand the regulation of human cartilage regeneration and repair.

Efecto de la resección de la grasa del paquete infrapatelar de la rodilla en el desarrollo de la artrosis. Estudio experimental en ovejas / Infrapatellar Fat Pad resection effect on the osteoarthritis development: Experimental study in sheep

Introducción: La grasa de las articulaciones sinoviales puede servir para el mantenimiento de la estructura articular. Nuestro objetivo es analizar la evolución de la degeneración articular en rodillas con y sin paquete adiposo. Material y metodología: En 6 ovejas se efectuó la sección del ligamento cruzado anterior en ambas rodillas, para provocar una artrosis. En un grupo se preservó el paquete adiposo y en otro grupo se extirpó completamente. Realizamos un estudio histológico y de biología molecular analizando la expresión, en la membrana sinovial, el hueso subcondral, cartílago, grasa, menisco y líquido sinovial, de RUNX2, PTHrP, catepsina-K y MCP1. Resultados: No encontramos diferencias morfológicas. Encontramos aumento de la expresión de RUNX2 en membrana sinovial, PTHrP y Catepsina K en líquido sinovial en el grupo sin grasa y aumento de la expresión RUNX2 en el menisco y MCP1 en líquido sinovial en el grupo con grasa. Conclusión: La grasa infrapatelar participa en el proceso inflamatorio que acompaña en la artrosis, pues la resección de la grasa de Hoffa altera los marcadores proinflamatorios, mientras que el modelo con la grasa intacta incrementa el marcador proinflamatorio MCP1 en líquido sinovial.(AU)

Introduction: The fat of the synovial joints can be used to maintain the joint structure. Our objective is to analyze the evolution of joint degeneration in knees with and without adipose pack. Material and methodology: In six sheep, the anterior cruciate ligament was sectioned in both knees, to cause osteoarthritis. In one group the fat pack was preserved and in another group it was completely removed. We performed a histological and molecular biology study analyzing the expression, in the synovial membrane, subchondral bone, cartilage, fat, meniscus, and synovial fluid, of RUNX2, PTHrP, cathepsin-K, and MCP1. Results: We did not find morphological differences. We found increased expression of RUNX2 in synovial membrane, PTHrP and Cathepsin K in synovial fluid in the group without fat, and increased expression of RUNX2 in the meniscus and MCP1 in synovial fluid in the group with fat. Conclusion: Infrapatellar fat participates in the inflammatory process that accompanies osteoarthritis, since Hoffa fat pad resection alters pro-inflammatory markers, while the model with intact fat increases the pro-inflammatory marker MCP1 in synovial fluid.(AU)

[Translated article] Infrapatellar fat pad resection effect on the osteoarthritis development: Experimental study in sheep / Efecto de la resección de la grasa del paquete infrapatelar de la rodilla en el desarrollo de la artrosis. Estudio experimental en ovejas

Introducción: La grasa de las articulaciones sinoviales puede servir para el mantenimiento de la estructura articular. Nuestro objetivo es analizar la evolución de la degeneración articular en rodillas con y sin paquete adiposo. Material y metodología: En 6 ovejas se efectuó la sección del ligamento cruzado anterior en ambas rodillas, para provocar una artrosis. En un grupo se preservó el paquete adiposo y en otro grupo se extirpó completamente. Realizamos un estudio histológico y de biología molecular analizando la expresión, en la membrana sinovial, el hueso subcondral, cartílago, grasa, menisco y líquido sinovial, de RUNX2, PTHrP, catepsina-K y MCP1. Resultados: No encontramos diferencias morfológicas. Encontramos aumento de la expresión de RUNX2 en membrana sinovial, PTHrP y Catepsina K en líquido sinovial en el grupo sin grasa y aumento de la expresión RUNX2 en el menisco y MCP1 en líquido sinovial en el grupo con grasa. Conclusión: La grasa infrapatelar participa en el proceso inflamatorio que acompaña en la artrosis, pues la resección de la grasa de Hoffa altera los marcadores proinflamatorios, mientras que el modelo con la grasa intacta incrementa el marcador proinflamatorio MCP1 en líquido sinovial.(AU)

Introduction: The fat of the synovial joints can be used to maintain the joint structure. Our objective is to analyze the evolution of joint degeneration in knees with and without adipose pack. Material and methodology: In six sheep, the anterior cruciate ligament was sectioned in both knees, to cause osteoarthritis. In one group the fat pack was preserved and in another group it was completely removed. We performed a histological and molecular biology study analyzing the expression, in the synovial membrane, subchondral bone, cartilage, fat, meniscus, and synovial fluid, of RUNX2, PTHrP, cathepsin-K, and MCP1. Results: We did not find morphological differences. We found increased expression of RUNX2 in synovial membrane, PTHrP and Cathepsin K in synovial fluid in the group without fat, and increased expression of RUNX2 in the meniscus and MCP1 in synovial fluid in the group with fat. Conclusion: Infrapatellar fat participates in the inflammatory process that accompanies osteoarthritis, since Hoffa fat pad resection alters pro-inflammatory markers, while the model with intact fat increases the pro-inflammatory marker MCP1 in synovial fluid.(AU)

Scutellarein Ameliorated Chondrocyte Inflammation and Osteoarthritis in Rats.

OBJECTIVE: Osteoarthritis (OA) is a degenerative joint disorder characterized by the gradual degradation of joint cartilage and local inflammation. This study aimed to investigate the anti-OA effect of scutellarein (SCU), a single-unit flavonoid compound obtained from Scutellaria barbata D. Don, in rats. METHODS: The extracted rat chondrocytes were treated with SCU and IL-1ß. The chondrocytes were divided into control group, IL-1ß group, IL-1ß+SCU 50 µmol/L group, and IL-1ß+SCU 100 µmol/L group. Morphology of rat chondrocytes was observed by toluidine blue and safranin O staining. CCK-8 method was used to detect the cytotoxicity of SCU. ELISA, qRT-PCR, Western blotting, immunofluorescence, SAß-gal staining, flow cytometry, and bioinformatics analysis were applied to evaluate the effect of SCU on rat chondrocytes under IL-1ß intervention. Additionally, anterior cruciate ligament transection (ACL-T) was used to establish a rat OA model. Histological changes were detected by safranin O/fast green, hematoxylin-eosin (HE) staining, and immunohistochemistry. RESULTS: SCU protected cartilage and exhibited anti-inflammatory effects via multiple mechanisms. Specifically, it could enhance the synthesis of extracellular matrix in cartilage cells and inhibit its degradation. In addition, SCU partially inhibited the nuclear factor kappa-B/mitogen-activated protein kinase (NF-κB/MAPK) pathway, thereby reducing inflammatory cytokine production in the joint cartilage. Furthermore, SCU significantly reduced IL-1ß-induced apoptosis and senescence in rat chondrocytes, further highlighting its potential role in OA treatment. In vivo experiments revealed that SCU (at a dose of 50 mg/kg) administered for 2 months could significantly delay the progression of cartilage damage, which was reflected in a lower Osteoarthritis Research Society International (OARSI) score, and reduced expression of matrix metalloproteinase 13 (MMP13) in cartilage. CONCLUSION: SCU is effective in the therapeutic management of OA and could serve as a potential candidate for future clinical drug therapy for OA.

Patella Cartilage Status Does Not Affect the Clinical Outcomes of Non-resurfaced Patella in Mobile-Bearing Total Knee Arthroplasty.

Background: During total knee arthroplasty (TKA), patellar retention is performed when the cartilage is fairly well preserved and the thickness of the patella is relatively thin. However, clinical outcomes of the non-resurfaced patella in TKA according to the cartilage status are lacking in the literature. The purpose of this study was to compare patient-reported outcome measures (PROMs) according to the grade and location of the patellar cartilage lesion in TKA patients. Methods: The outcomes of 165 osteoarthritis patients (186 knees) who underwent cemented mobile-bearing TKA without patellar resurfacing were assessed and classified according to the grade and location of the patellar cartilage lesion. PROMs using the Western Ontario and MacMaster Universities Osteoarthritis index, the Knee Society Score (Knee Society Function Score and Knee Society Knee Score), and the Hospital for Special Surgery score were evaluated preoperatively and at postoperative 2, 4, 6, and 8 years. The correlations between PROMs and the grade and location of the cartilage lesion were assessed. Additionally, radiologic outcomes including the patellar tilt angle and patellar height were assessed and their correlation with the grade of cartilage lesion was analyzed. Analysis of variance was used to determine statistical significance. Results: There was no significant difference between PROMs according to the grades and locations of cartilage lesions at any postoperative follow-up. Radiologic parameters also showed no significant differences according to the grades of patellar cartilage lesions. Conclusions: The grade and location of the patellar cartilage lesion had no influence on clinical outcomes in mobile-bearing TKA with patellar retention at short- and long-term follow-up.

[Neonatal cervical chondromesenchymal hamartoma: a case report and literature review].

Cartilage mesenchyme hamartoma originates from the mesoderm and contains a blend of interstitium and cartilage, which is mostly benign tumor and is a non-neoplastic cartilage lesion with self-limiting hyperplasia. This article reports a infant with cervical chondromesenchymal hamartoma in the neck, the main clinical manifestations of which are asphyxia and acute respiratory distress, and the imaging features are often similar to those of malignant tumors.Radical resection operation under general anesthesia is the main treatment method, and the postoperative pathological diagnosis was cartilage mesenchyme, and immunohistochemistry showed Catenin（-）,MDM2（+）,CDK4（-）,H3K36M（+）,Myogenin （-）,SMA （-）.The clinical characteristics and diagnosis and treatment process of this case are reported and related literature is reviewed.

Role of Galectin-3 in intervertebral disc degeneration: an experimental study.

BACKGROUND: This study investigated the role of Galectin-3 in the degeneration of intervertebral disc cartilage. METHODS: The patients who underwent lumbar spine surgery due to degenerative disc disease were recruited and divided into Modic I, Modic II, and Modic III; groups. HE staining was used to detect the pathological changes in endplates. The changes of Galectin-3, MMP3, Aggrecan, CCL3, and Col II were detected by immunohistochemistry, RT-PCR, and Western blot. MTT and flow cytometry were used to detect cartilage endplate cell proliferation, cell cycle, and apoptosis. RESULTS: With the progression of degeneration (from Modic I to III), the chondrocytes and density of the cartilage endplate of the intervertebral disc decreased, and the collagen arrangement of the cartilage endplate of the intervertebral disc was broken and calcified. Meanwhile, the expressions of Aggrecan, Col II, Galectin-3, Aggrecan, and CCL3 gradually decreased. After treatment with Galectin-3 inhibitor GB1107, the proliferation of rat cartilage end plate cells was significantly reduced (P < 0.05). GB1107 (25 µmol/L) also significantly promoted the apoptosis of cartilage endplate cells (P < 0.05). Moreover, the percentage of cartilage endplate cells in the G1 phase was significantly higher, while that in the G2 and S phases was significantly lower (P < 0.05). Additionally, the mRNA and protein expression levels of MMP3, CCL3, and Aggrecan in rat cartilage end plate cells were lower than those in the control group. CONCLUSIONS: Galectin-3 decreases with the progression of the cartilage endplate degeneration of the intervertebral disc. Galectin-3 may affect intervertebral disc degeneration by regulating the degradation of the extracellular matrix.

The Two-Stage Folded Paramedian Forehead Flap Without Cartilage Grafts for Full Thickness Distal Nasal Defects: A Review of 35 Patients.

BACKGROUND: Full thickness defects of the ala, soft triangle, and nasal tip involving the nasal lining have traditionally been repaired with the three-stage folded paramedian forehead flap (FPFF), with a cartilage graft for support. For similar defects, the authors utilize the two-stage FPFF without cartilaginous support which provides reproducible functional and aesthetic results.  Objective: To describe the authors’ experience with the two-stage FPFF, including outcomes, complications, and design modifications to enhance functional and aesthetic success.  Methods: An IRB-approved retrospective database review of FPFF was performed at two sites. Using postoperative photographs, outcomes were assessed by blinded non-investigator dermatologist raters using a modified observer scar assessment scale. RESULTS: Thirty-five patients were reconstructed using the two-stage FPFF without cartilage grafts. Subjective assessment of scar vascularity, pigment, relief, and thickness by 3 independent reviewers yielded an overall cosmesis score of 8.4±1.9 (out of 40). CONCLUSION: The two-stage FPFF without cartilage grafts is a reliable, cosmetically elegant repair that can provide optimal functional and aesthetic results for complex unilateral distal nose defects.J Drugs Dermatol. 2024;23(4): doi:10.36849/JDD.7358.

Expression levels and DNA methylation profiles of the growth gene SHOX in cartilage tissues and chondrocytes.

All attempts to identify male-specific growth genes in humans have failed. This study aimed to clarify why men are taller than women. Microarray-based transcriptome analysis of the cartilage tissues of four adults and chondrocytes of 12 children showed that the median expression levels of SHOX, a growth gene in the pseudoautosomal region (PAR), were higher in male samples than in female samples. Male-dominant SHOX expression was confirmed by quantitative RT-PCR for 36 cartilage samples. Reduced representation bisulfite sequencing of four cartilage samples revealed sex-biased DNA methylation in the SHOX-flanking regions, and pyrosequencing of 22 cartilage samples confirmed male-dominant DNA methylation at the CpG sites in the SHOX upstream region and exon 6a. DNA methylation indexes of these regions were positively correlated with SHOX expression levels. These results, together with prior findings that PAR genes often exhibit male-dominant expression, imply that the relatively low SHOX expression in female cartilage tissues reflects the partial spread of X chromosome inactivation into PAR. Altogether, this study provides the first indication that sex differences in height are ascribed, at least in part, to the sex-dependent epigenetic regulation of SHOX. Our findings deserve further validation.

Compensatory growth and recovery of cartilage cytoarchitecture after transient cell death in fetal mouse limbs.

A major question in developmental and regenerative biology is how organ size and architecture are controlled by progenitor cells. While limb bones exhibit catch-up growth (recovery of a normal growth trajectory after transient developmental perturbation), it is unclear how this emerges from the behaviour of chondroprogenitors, the cells sustaining the cartilage anlagen that are progressively replaced by bone. Here we show that transient sparse cell death in the mouse fetal cartilage is repaired postnatally, via a two-step process. During injury, progression of chondroprogenitors towards more differentiated states is delayed, leading to altered cartilage cytoarchitecture and impaired bone growth. Then, once cell death is over, chondroprogenitor differentiation is accelerated and cartilage structure recovered, including partial rescue of bone growth. At the molecular level, ectopic activation of mTORC1 correlates with, and is necessary for, part of the recovery, revealing a specific candidate to be explored during normal growth and in future therapies.

ICA/SDF-1α/PBMSCs loaded onto alginate and gelatin cross-linked scaffolds promote damaged cartilage repair.

A three-dimensional alginate-coated scaffold (GAIS) was constructed in the present study to showcase the multidifferentiation potential of peripheral blood mesenchymal stem cells (PBMSCs) and to investigate the role and mechanism by which Icariin (ICA)/stromal cell-derived factor (SDF-1α)/PBMSCs promote damaged articular repair. In addition, the ability of ICA, in combination with SDF-1α, to promote the migration and proliferation of stem cells was validated through the utilization of CCK-8 and migration experiments. The combination of ICA and SDF-1α inhibited the differentiation of PBMSCs into cartilage, as demonstrated by in vivo experiments and histological staining. Both PCR and western blot experiments showed that GAIS could upregulate the expression of particular genes in chondrocytes. In comparison to scaffolds devoid of alginate (G0), PBMSCs seeded into GAIS scaffolds exhibited a greater rate of proliferation, and the conditioned medium derived from scaffolds containing SDF-1α enhanced the capacity for cell migration. Moreover, after a 12-week treatment period, GAIS, when successfully transplanted into osteochondral defects of mice, was found to promote cartilage regeneration and repair. The findings, therefore, demonstrate that GAIS enhanced the in vitro capabilities of PBMSCs, including proliferation, migration, homing and chondrogenic differentiation. In addition, ICA and SDF-1α effectively collaborated to support cartilage formation in vivo. Thus, the ICA/SDF-1α/PBMSC-loaded biodegradable alginate-gelatin scaffolds showcase considerable potential for use in cartilage repair.

Magnetic Resonance Imaging in Pediatric Acetabulum Fractures with Open Triradiate Cartilage-A Report of 3 Cases.

We present three cases of posterior wall acetabulum fractures occurring in pediatric patients with open triradiate cartilage for whom preoperative magnetic resonance imaging was obtained and open reduction and internal fixation was done. All patients had excellent outcomes at an average of 68-week follow-up. Failure to adequately recognize the severity of pediatric acetabulum fractures can lead to detrimental long-term sequelae in acetabular development when treated nonsurgically. Management of this rare injury is not well reported in the literature. We highlight the utility of MRI in evaluating potential nonosseous injury and examining the articular surface to guide surgical management.

Isolation and Culturing of Primary Murine Chondroprogenitor Cells: A Mammalian Model of Chondrogenesis.

Embryonic limb bud-derived micromass cultures are valuable tools for investigating cartilage development, tissue engineering, and therapeutic strategies for cartilage-related disorders. This collection of fine-tuned protocols used in our laboratories outlines step-by-step procedures for the isolation, expansion, and differentiation of primary mouse limb bud cells into chondrogenic micromass cultures. Key aspects covered in these protocols include synchronized fertilization of mice (Basic Protocol 1), tissue dissection, cell isolation, micromass formation, and culture optimization parameters, such as cell density and medium composition (Basic Protocol 2). We describe techniques for characterizing the chondrogenic differentiation process by histological analysis (Basic Protocol 3). The protocols also address common challenges encountered during the process and provide troubleshooting strategies. This fine-tuned comprehensive protocol serves as a valuable resource for scientists working in the fields of developmental biology, cartilage tissue engineering, and regenerative medicine, offering an updated methodology for the study of efficient chondrogenic differentiation and cartilage tissue regeneration. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Synchronized fertilization of mice Basic Protocol 2: Micromass culture of murine embryonic limb bud-derived cells Basic Protocol 3: Qualitative assessment of cartilage matrix production using Alcian blue staining.

Chitin: A versatile biopolymer-based functional therapy for cartilage regeneration.

Chitin is the second most abundant biopolymer and its inherent biological characteristics make it ideal to use for tissue engineering. For many decades, its properties like non-toxicity, abundant availability, ease of modification, biodegradability, biocompatibility, and anti-microbial activity have made chitin an ideal biopolymer for drug delivery. Research studies have also shown many potential benefits of chitin in the formulation of functional therapy for cartilage regeneration. Chitin and its derivatives can be processed into 2D/3D scaffolds, hydrogels, films, exosomes, and nano-fibers, which make it a versatile and functional biopolymer in tissue engineering. Chitin is a biomimetic polymer that provides targeted delivery of mesenchymal stem cells, especially of chondrocytes at the injected donor sites to accelerate regeneration by enhancing cell proliferation and differentiation. Due to this property, chitin is considered an interesting polymer that has a high potential to provide targeted therapy in the regeneration of cartilage. Our paper presents an overview of the method of extraction, structure, properties, and functional role of this versatile biopolymer in tissue engineering, especially cartilage regeneration.

Engineering sulfated polysaccharides and silk fibroin based injectable IPN hydrogels with stiffening and growth factor presentation abilities for cartilage tissue engineering.

The extracellular matrix (ECM) presents a framework for various biological cues and regulates homeostasis during both developing and mature stages of tissues. During development of cartilage, the ECM plays a critical role in endowing both biophysical and biochemical cues to the progenitor cells. Hence, designing microenvironments that recapitulate these biological cues as provided by the ECM during development may facilitate the engineering of cartilage tissue. In the present study, we fabricated an injectable interpenetrating hydrogel (IPN) system which serves as an artificial ECM and provides chondro-inductive niches for the differentiation of stem cells to chondrocytes. The hydrogel was designed to replicate the gradual stiffening (as a biophysical cue) and the presentation of growth factors (as a biochemical cue) as provided by the natural ECM of the tissue, thus exemplifying a biomimetic approach. This dynamic stiffening was achieved by incorporating silk fibroin, while the growth factor presentation was accomplished using sulfated-carboxymethyl cellulose. Silk fibroin and sulfated-carboxymethyl cellulose (s-CMC) were combined with tyraminated-carboxymethyl cellulose (t-CMC) and crosslinked using HRP/H2O2 to fabricate s-CMC/t-CMC/silk IPN hydrogels. Initially, the fabricated hydrogel imparted a soft microenvironment to promote chondrogenic differentiation, and with time it gradually stiffened to offer mechanical support to the joint. Additionally, the presence of s-CMC conferred the hydrogel with the property of sequestering cationic growth factors such as TGF-ß and allowing their prolonged presentation to the cells. More importantly, TGF-ß loaded in the developed hydrogel system remained active and induced chondrogenic differentiation of stem cells, resulting in the deposition of cartilage ECM components which was comparable to the hydrogels that were treated with TGF-ß provided through media. Overall, the developed hydrogel system acts as a reservoir of the necessary biological cues for cartilage regeneration and simultaneously provides mechanical support for load-bearing tissues such as cartilage.

Recent advances on biomedical applications of gellan gum: A review.

Gellan gum (GG) has attracted considerable attention as a versatile biopolymer with numerous potential biological applications, especially in the fields of tissue engineering, wound healing, and cargo delivery. Due to its distinctive characteristics like biocompatibility, biodegradability, nontoxicity, and gel-forming ability, GG is well-suited for these applications. This review focuses on recent research on GG-based hydrogels and biocomposites and their biomedical applications. It discusses the incorporation of GG into hydrogels for controlled drug release, its role in promoting wound healing processes, and its potential in tissue engineering for various tissues including bone, retina, cartilage, vascular, adipose, and cardiac tissue. It provides an in-depth analysis of the latest findings and advancements in these areas, making it a valuable resource for researchers and professionals in these fields.

Topological defects in self-assembled patterns of mesenchymal stromal cells in vitro are predictive attributes of condensation and chondrogenesis.

Mesenchymal stromal cells (MSCs) are promising therapeutic agents for cartilage regeneration, including the potential of cells to promote chondrogenesis in vivo. However, process development and regulatory approval of MSCs as cell therapy products benefit from facile in vitro approaches that can predict potency for a given production run. Current standard in vitro approaches include a 21 day 3D differentiation assay followed by quantification of cartilage matrix proteins. We propose a novel biophysical marker that is cell population-based and can be measured from in vitro monolayer culture of MSCs. We hypothesized that the self-assembly pattern that emerges from collective-cell behavior would predict chondrogenesis motivated by our observation that certain features in this pattern, namely, topological defects, corresponded to mesenchymal condensations. Indeed, we observed a strong predictive correlation between the degree-of-order of the pattern at day 9 of the monolayer culture and chondrogenic potential later estimated from in vitro 3D chondrogenic differentiation at day 21. These findings provide the rationale and the proof-of-concept for using self-assembly patterns to monitor chondrogenic commitment of cell populations. Such correlations across multiple MSC donors and production batches suggest that self-assembly patterns can be used as a candidate biophysical attribute to predict quality and efficacy for MSCs employed therapeutically for cartilage regeneration.

The FTO-CMPK2 Pathway in Fibroblast-like Synoviocytes Modulates Rheumatoid Arthritis Synovial Inflammation and Cartilage Homeostasis via mtDNA Regulation.

In rheumatoid arthritis (RA), a debilitating autoimmune disorder marked by chronic synovial inflammation and progressive cartilage degradation, fibroblast-like synoviocytes (FLS) are key pathogenic players. Current treatments targeting these cells are limited. Our study focused on the Fat Mass and Obesity-associated protein (FTO), known for its roles in cell proliferation and inflammatory response modulation, and its involvement in RA. We specifically examined the inflammatory regulatory roles of FTO and CMPK2, a mitochondrial DNA synthesis protein, in FLS. Utilizing a combination of in vitro and in vivo methods, including FTO inhibition and gene knockdown, we aimed to understand FTO's influence on RA progression and chondrocyte functionality. Our findings showed that increased FTO expression in RA synovial cells enhanced their proliferation and migration and decreased senescence and apoptosis. Inhibiting FTO significantly slowed the disease progression in our models. Our research also highlighted that the FTO-CMPK2 pathway plays a crucial role in regulating synovial inflammation through the mtDNA-mediated cGAS/STING pathway, affecting chondrocyte homeostasis. This study indicates that targeting the FTO-CMPK2 axis could be a promising new therapeutic strategy for managing RA.