scholarly journals Ex Vivo Systems to Study Chondrogenic Differentiation and Cartilage Integration

2021 ◽  
Vol 6 (1) ◽  
pp. 6
Author(s):  
Graziana Monaco ◽  
Alicia J. El Haj ◽  
Mauro Alini ◽  
Martin J. Stoddart
Keyword(s):  
Articular Cartilage ◽  
Chondrogenic Differentiation ◽  
Ex Vivo ◽  
Cartilage Regeneration ◽  
Therapeutic Interventions ◽  
Surrounding Tissue ◽  
Self Healing ◽  
Culture Models ◽  
Articular Cartilage Injury ◽  
Cartilage Integration

Articular cartilage injury and repair is an issue of growing importance. Although common, defects of articular cartilage present a unique clinical challenge due to its poor self-healing capacity, which is largely due to its avascular nature. There is a critical need to better study and understand cellular healing mechanisms to achieve more effective therapies for cartilage regeneration. This article aims to describe the key features of cartilage which is being modelled using tissue engineered cartilage constructs and ex vivo systems. These models have been used to investigate chondrogenic differentiation and to study the mechanisms of cartilage integration into the surrounding tissue. The review highlights the key regeneration principles of articular cartilage repair in healthy and diseased joints. Using co-culture models and novel bioreactor designs, the basis of regeneration is aligned with recent efforts for optimal therapeutic interventions.

scholarly journals A Comprehensive Analysis of SE-lncRNA/mRNA Differential Expression Profiles During Chondrogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Yu Jiang ◽  
Chen Zhang ◽  
Lujue Long ◽  
Lihua Ge ◽  
Jing Guo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Articular Cartilage ◽  
Signaling Pathways ◽  
Differential Expression ◽  
Signaling Pathway ◽  
Chondrogenic Differentiation ◽  
Cartilage Regeneration ◽  
Bioinformatic Analysis ◽  
Super Enhancer ◽  
Articular Cartilage Injury

Objective: Articular cartilage injury is common and difficult to treat clinically because of the characteristics of the cartilage. Bone marrow-derived mesenchymal stem cell (BMSC)-mediated cartilage regeneration is a promising therapy for treating articular cartilage injury. BMSC differentiation is controlled by numerous molecules and signaling pathways in the microenvironment at both the transcriptional and post-transcriptional levels. However, the possible function of super enhancer long non-coding RNAs (SE-lncRNAs) in the chondrogenic differentiation of BMSCs is still unclear. Our intention was to explore the expression profile of SE-lncRNAs and potential target genes regulated by SE-lncRNAs during chondrogenic differentiation in BMSCs.Materials and Methods: In this study, we conducted a human Super-Enhancer LncRNA Microarray to investigate the differential expression profile of SE-lncRNAs and mRNAs during chondrogenic differentiation of BMSCs. Subsequent bioinformatic analysis was performed to clarify the important signaling pathways, SE-lncRNAs, and mRNAs associated with SE-lncRNAs regulating the chondrogenic differentiation of BMSCs.Results: A total of 77 SE-lncRNAs were identified, of which 47 were upregulated and 30 were downregulated during chondrogenic differentiation. A total of 308 mRNAs were identified, of which 245 were upregulated and 63 were downregulated. Some pathways, such as focal adhesion, extracellular matrix (ECM)–receptor interaction, transforming growth factor-β (TGF-β) signaling pathway, and PI3K–Akt signaling pathway, were identified as the key pathways that may be implicated in the chondrogenic differentiation of BMSCs. Moreover, five potentially core regulatory mRNAs (PMEPA1, ENC1, TES, CDK6, and ADIRF) and 37 SE-lncRNAs in chondrogenic differentiation were identified by bioinformatic analysis.Conclusion: We assessed the differential expression levels of SE-lncRNAs and mRNAs, along with the chondrogenic differentiation of BMSCs. By analyzing the interactions and co-expression, we identified the core SE-lncRNAs and mRNAs acting as regulators of the chondrogenic differentiation potential of BMSCs. Our study also provided novel insights into the mechanism of BMSC chondrogenic and cartilage regeneration.

scholarly journals Ganglioside GM3 Up-Regulate Chondrogenic Differentiation by Transform Growth Factor Receptors

2020 ◽  
Vol 21 (6) ◽  
pp. 1967 ◽  
Author(s):  
Jae-Sung Ryu ◽  
Sang Young Seo ◽  
Eun-Jeong Jeong ◽  
Jong-Yeup Kim ◽  
Yong-Gon Koh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Chondrogenic Differentiation ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Cartilage Regeneration ◽  
Ganglioside Gm3

Mesenchymal stem cells, also known as multipotent stromal progenitor cells, can differentiate into cells of mesodermal lineage. Gangliosides are sialic acid-conjugated glycosphingolipids that are believed to regulate cell differentiation and several signaling molecules. These molecules are localized in glycosphingolipid-enriched microdomains on the cell surface and are regulated by glycosphingolipid composition. Transforming growth factor-beta (TGF-β) signaling plays a critical role in chondrogenic differentiation. However, the role of gangliosides in chondrogenesis is not understood. In this study, the relationship between the ganglioside GM3 and TGF-β activation, during chondrogenic differentiation, was investigated using an aggregate culture of human synovial membrane-derived mesenchymal stem cells. We showed that the gangliosides GM3 and GD3 were expressed after the chondrogenic differentiation of hSMSC aggregates. To test whether GM3 affected the chondrogenic differentiation of hSMSC aggregates, we used GM3 treatment during chondrogenic differentiation. The results showed that the group treated with 5 μM GM3 had higher expression of chondrogenic specific markers, increased toluidine blue, and safranin O staining, and increased accumulation of glycosaminoglycans compared with the untreated group. Furthermore, GM3 treatment enhanced TGF-β signaling via SMAD 2/3 during the chondrogenic differentiation of hSMSC aggregates. Taken together, our results suggested that GM3 may be useful in developing therapeutic agents for cell-based articular cartilage regeneration in articular cartilage disease.

scholarly journals Dual Delivery of TGF-β3 and Ghrelin in Microsphere/Hydrogel Systems for Cartilage Regeneration

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5732
Author(s):  
Jianjing Lin ◽  
Li Wang ◽  
Jianhao Lin ◽  
Qiang Liu
Keyword(s):  
Growth Factors ◽  
Chondrogenic Differentiation ◽  
Transforming Growth Factor ◽  
Double Emulsion ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Self Healing ◽  
Tissue Formation ◽  
Extraction Technology

Articular cartilage (AC) damage is quite common, but due to AC’s poor self-healing ability, the damage can easily develop into osteoarthritis (OA). To solve this problem, we developed a microsphere/hydrogel system that provides two growth factors that promote cartilage repair: transforming growth factor-β3 (TGF-β3) to enhance cartilage tissue formation and ghrelin synergy TGF-β to significantly enhance the chondrogenic differentiation. The hydrogel and microspheres were characterized in vitro, and the biocompatibility of the system was verified. Double emulsion solvent extraction technology (w/o/w) is used to encapsulate TGF-β3 and ghrelin into microspheres, and these microspheres are encapsulated in a hydrogel to continuously release TGF-β3 and ghrelin. According to the chondrogenic differentiation ability of mesenchymal stem cells (MSCs) in vitro, the concentrations of the two growth factors were optimized to promote cartilage regeneration.

scholarly journals Exploratory Full-Field Mechanical Analysis across the Osteochondral Tissue—Biomaterial Interface in an Ovine Model

Materials ◽  
2020 ◽  
Vol 13 (18) ◽  
pp. 3911
Author(s):  
Jeffrey N. Clark ◽  
Agathe Heyraud ◽  
Saman Tavana ◽  
Talal Al-Jabri ◽  
Francesca Tallia ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Cartilage Regeneration ◽  
Mechanical Analysis ◽  
Surrounding Tissue ◽  
Micro Computed Tomography ◽  
Full Field ◽  
Surgical Interventions ◽  
Osteochondral Injuries ◽  
Osteochondral Tissue

Osteochondral injuries are increasingly prevalent, yet success in articular cartilage regeneration remains elusive, necessitating the development of new surgical interventions and novel medical devices. As part of device development, animal models are an important milestone in illustrating functionality of novel implants. Inspection of the tissue-biomaterial system is vital to understand and predict load-sharing capacity, fixation mechanics and micromotion, none of which are directly captured by traditional post-mortem techniques. This study aims to characterize the localised mechanics of an ex vivo ovine osteochondral tissue–biomaterial system extracted following six weeks in vivo testing, utilising laboratory micro-computed tomography, in situ loading and digital volume correlation. Herein, the full-field displacement and strain distributions were visualised across the interface of the system components, including newly formed tissue. The results from this exploratory study suggest that implant micromotion in respect to the surrounding tissue could be visualised in 3D across multiple loading steps. The methodology provides a non-destructive means to assess device performance holistically, informing device design to improve osteochondral regeneration strategies.

scholarly journals Click chemistry-based pre-targeting cell delivery for cartilage regeneration

2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Cynthia M Co ◽  
Samira Izuagbe ◽  
Jun Zhou ◽  
Ning Zhou ◽  
Xiankai Sun ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Click Chemistry ◽  
Ex Vivo ◽  
Cartilage Regeneration ◽  
Cartilage Injury ◽  
Cell Delivery ◽  
Polymer Carrier ◽  
Human Cartilage ◽  
Joint Injury ◽  
Cell Based Therapy

Abstract A fraction of the OA patient population is affected by post-traumatic osteoarthritis (PTOA) following acute joint injuries. Stopping or reversing the progression of PTOA following joint injury could improve long-term functional outcomes, reduced disability, and medical costs. To more effectively treat articular cartilage injury, we have developed a novel cell-based therapy that involves the pre-targeting of apoptotic chondrocytes and the delivery of healthy, metabolically active chondrocytes using click chemistry. Specifically, a pre-targeting agent was prepared via conjugating apoptotic binding peptide (ApoPep-1) and trans-cyclooctene (TCO) onto polyethylene glycol (PEG) polymer carrier. The pre-targeting agent would be introduced to injured areas of articular cartilage, leading to the accumulation of TCO groups on the injured areas from actively binding to apoptotic chondrocytes. Subsequently, methyltetrazine (Tz)-bearing chondrocytes would be immobilized on the surface of TCO-coated injured cartilage via Tz-TCO click chemistry reaction. Using an ex vivo human cartilage explant PTOA model, the effectiveness of this new approach was evaluated. Our studies show that this novel approach (Tz-TCO click chemistry) significantly enhanced the immobilization of healthy and metabolically active chondrocytes to the areas of apoptotic chondrocytes. Histological analyses demonstrated that this treatment regimen would significantly reduce the area of cartilage degeneration and enhance ECM regeneration. The results support that Tz-TCO click chemistry-mediated cell delivery approach has great potential in clinical applications for targeting and treatment of cartilage injury.

scholarly journals Biofunctionalized Structure and Ingredient Mimicking Scaffolds Achieving Recruitment and Chondrogenesis for Staged Cartilage Regeneration

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhen Yang ◽  
Hao Li ◽  
Yue Tian ◽  
Liwei Fu ◽  
Cangjian Gao ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Growth Factor ◽  
Chondrogenic Differentiation ◽  
Cartilage Regeneration ◽  
Recruitment Strategy ◽  
Prolonged Release ◽  
Cell Recruitment ◽  
Articular Cartilage Regeneration

It remains scientifically challenging to regenerate injured cartilage in orthopedics. Recently, an endogenous cell recruitment strategy based on a combination of acellular scaffolds and chemoattractants to specifically and effectively recruit host cells and promote chondrogenic differentiation has brought new hope for in situ articular cartilage regeneration. In this study, a transforming growth factor-β3 (TGF-β3)-loaded biomimetic natural scaffold based on demineralized cancellous bone (DCB) and acellular cartilage extracellular matrix (ECM) was developed and found to improve chondral repair by enhancing cell migration and chondrogenesis. The DCB/ECM scaffold has porous microstructures (pore size: 67.76 ± 8.95 μm; porosity: 71.04 ± 1.62%), allowing the prolonged release of TGF-β3 (up to 50% after 42 days in vitro) and infrapatellar fat pad adipose-derived stem cells (IPFSCs) that maintain high cell viability (>96%) and favorable cell distribution and phenotype after seeding onto the DCB/ECM scaffold. The DCB/ECM scaffold itself can also provide a sustained release system to effectively promote IPFSC migration (nearly twofold in vitro). Moreover, TGF-β3 loaded on scaffolds showed enhanced chondrogenic differentiation (such as collagen II, ACAN, and SOX9) of IPFSCs after 3 weeks of culture. After implanting the composite scaffold into the knee joints of rabbits, enhanced chondrogenic differentiation was discovered at 1, 2, and 4 weeks post-surgery, and improved repair of cartilage defects in terms of biochemical, biomechanical, radiological, and histological results was identified at 3 and 6 months post-implantation. To conclude, our study demonstrates that the growth factor (GF)-loaded scaffold can facilitate cell homing, migration, and chondrogenic differentiation and promote the reconstructive effects of in vivo cartilage formation, revealing that this staged regeneration strategy combined with endogenous cell recruitment and pro-chondrogenesis is promising for in situ articular cartilage regeneration.

Polycaprolactone Based Biomaterials and Sodium Hyaluronate Nanoreservoirs for Cartilage Regeneration

2021 ◽  
Author(s):  
Rana Smaida ◽  
Henri Favreau ◽  
Moustafa Naja ◽  
Guoqiang Hua ◽  
Florence Fioretti ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Chondrogenic Differentiation ◽  
Sodium Hyaluronate ◽  
Cartilage Regeneration ◽  
Vinyl Pyrrolidone ◽  
Cartilage Defects ◽  
Treatment And Prevention ◽  
Poly Vinyl Pyrrolidone ◽  
Articular Cartilage Defects

Obstacles persist in the treatment and prevention of articular cartilage defects. Polycaprolactone (PCL) and poly(vinyl-pyrrolidone) (PVP) biomaterials were obtained by electrospinning and electrospraying to inspect their potential application for cartilage regeneration. Sodium hyaluronate (SH) was then added into nanofibers of PCL and particles of PVP. The aim of incorporating sodium hyaluronate to this polymer is to enhance the capacity of articular cartilage to regenerate. Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) were seeded onto these tissue engineering (TE) products. The cell viability in vitro and the ability of biomaterials to support the chondrogenic differentiation of hBM-MSCs have been assessed. We report here that hBM-MSCs on these biomaterials were not able to regenerate articular cartilage mainly due to unsuitable culture environment.

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