Accelerating bone healing in vivo by harnessing the age-altered activation of c-Jun N-terminal kinase 3

González-Vázquez, Arlyng; Raftery, Rosanne M.; Gunbay, Suzan; Chen, Gang; Murray, Dylan J.; O’Brien, Fergal J.

doi:10.1016/j.biomaterials.2020.120540

Cited by 8 publications

(6 citation statements)

References 87 publications

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“…MSCs were isolated from the bone‐marrow of adults (donor age range: 20–30 years old) (purchased from Lonza (Switzerland) using standard protocols including a stringent analysis of cell phenotype as previously described. [ 37 ] The cells were incubated with low‐glucose Dulbecco's modified Eagle's medium (DMEM) (Sigma‐Aldrich, Ireland) supplemented with 10% fetal bovine serum (ThermoFisher Scientific, Ireland) and 1% penicillin/streptomycin (ThermoFisher Scientific, Ireland). Cells were passaged by trypsinization once confluent, and replated onto T‐175 (175 cm 2 growth area) flasks under normoxic cell culture conditions (37 °C, 5% CO 2 , 21% O 2 ).…”

Section: Methodsmentioning

confidence: 99%

An Innovative miR‐Activated Scaffold for the Delivery of a miR‐221 Inhibitor to Enhance Cartilage Defect Repair

Intini

Ferreras

Casey

et al. 2023

Advanced Therapeutics

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The development of treatments to restore damaged cartilage that can provide functional recovery with minimal risk of revision surgery remains an unmet clinical need. Gene therapy shows increased promise as an innovative solution for enhanced tissue repair. Within this study a novel microRNA (miR)-activated scaffold is developed for enhanced mesenchymal stem/stromal cells (MSC) chondrogenesis and cartilage repair through the delivery of an inhibitor to microRNA-221 (miR-221), which is known to have a negative effect of chondrogenesis. To fabricate the miR-activated scaffolds, composite type II collagen-containing scaffolds designed specifically for cartilage repair are first manufactured by lyophilization and then functionalized with glycosaminoglycan-binding enhanced transduction (GET) system nanoparticles (NPs) encapsulating the miR-221 inhibitor. Subsequently, scaffolds are cultured with human-derived MSCs in vitro under chondrogenic conditions for 28 days. The miR-activated scaffolds successfully transfect human MSCs with the miR-221 cargo in a sustained and controlled manner up to 28 days. The silencing of miR-221 in human MSCs using the miR-activated scaffold promotes an improved and more robust cell-mediated chondrogenic response with repressed early-stage events related to MSC hypertrophy. Taken together, this innovative miR-activated scaffold for the delivery of a miR-221 inhibitor demonstrates capability to improve chondrogenesis with promise to enhance cartilage defect repair.

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Section: Methodsmentioning

confidence: 99%

An Innovative miR‐Activated Scaffold for the Delivery of a miR‐221 Inhibitor to Enhance Cartilage Defect Repair

Intini

Ferreras

Casey

et al. 2023

Advanced Therapeutics

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“…To obtain a sufficient quantity of human bone-marrow MSCs, cells were first expanded in monolayer prior to seeding on the scaffolds. MSCs were either purchased from Lonza (Basel, Switzerland) or isolated from the iliac crest of adults (donor age range: 20–30 years old) using standardised protocols and including a stringent analysis of cell phenotype as previously described [ 31 ]. Cells were incubated with low-glucose Dulbecco’s modified Eagle’s medium (DMEM) (Sigma-Aldrich, Arklow, Ireland) supplemented with 10% fetal bovine serum (ThermoFisher Scientific, Dublin, Ireland) and 1% penicillin/streptomycin (ThermoFisher Scientific, Dublin, Ireland).…”

Section: Methodsmentioning

confidence: 99%

Highly Porous Type II Collagen-Containing Scaffolds for Enhanced Cartilage Repair with Reduced Hypertrophic Cartilage Formation

et al. 2022

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The ability to regenerate damaged cartilage capable of long-term performance in an active joint remains an unmet clinical challenge in regenerative medicine. Biomimetic scaffold biomaterials have shown some potential to direct effective cartilage-like formation and repair, albeit with limited clinical translation. In this context, type II collagen (CII)-containing scaffolds have been recently developed by our research group and have demonstrated significant chondrogenic capacity using murine cells. However, the ability of these CII-containing scaffolds to support improved longer-lasting cartilage repair with reduced calcified cartilage formation still needs to be assessed in order to elucidate their potential therapeutic benefit to patients. To this end, CII-containing scaffolds in presence or absence of hyaluronic acid (HyA) within a type I collagen (CI) network were manufactured and cultured with human mesenchymal stem cells (MSCs) in vitro under chondrogenic conditions for 28 days. Consistent with our previous study in rat cells, the results revealed enhanced cartilage-like formation in the biomimetic scaffolds. In addition, while the variable chondrogenic abilities of human MSCs isolated from different donors were highlighted, protein expression analysis illustrated consistent responses in terms of the deposition of key cartilage extracellular matrix (ECM) components. Specifically, CI/II-HyA scaffolds directed the greatest cell-mediated synthesis and accumulation in the matrices of type II collagen (a principal cartilage ECM component), and reduced deposition of type X collagen (a key protein associated with hypertrophic cartilage formation). Taken together, these results provide further evidence of the capability of these CI/II-HyA scaffolds to direct enhanced and longer-lasting cartilage repair in patients with reduced hypertrophic cartilage formation.

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“…For example, the application of highly versatile functionalized scaffolds, which have previously demonstrated success in modulating c-Jun N-terminal kinase 3 (JNK3) for enhancing the osteogenic potential of mesenchymal stem cells, might provide the basis as a platform for targeted regulation of MAPK signaling pathways in other tissues such as cartilage. 122…”

Section: The Mitogen-activated Protein Kinase (Mapk) Pathwaymentioning

confidence: 99%

Mechanosignalling in cartilage: an emerging target for the treatment of osteoarthritis

et al. 2021

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 Mechanical forces are a critical environmental factor in maintaining joint homeostasis, determining cell phenotype, inflammatory responses and a tightly regulated anabolic-catabolic signaling axis essential to cartilage homeostasis. Chondrocytes sense their mechanical environment through numerous direct and indirect mechanisms that regulate cell function in health and degenerative diseases, such as osteoarthritis. Targeted inhibition of mechano-inflammatory signalling pathways or restoration of functional chondroprotective extracellular matrix environments in OA may prevent ECM degradation and promote reparative anabolic processes. Development of self-regulating and mechanically responsive biomaterials and drug delivery systems offer advanced 'on-demand' therapeutic approaches for the treatment of OA.

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Accelerating bone healing in vivo by harnessing the age-altered activation of c-Jun N-terminal kinase 3

Cited by 8 publications

References 87 publications

An Innovative miR‐Activated Scaffold for the Delivery of a miR‐221 Inhibitor to Enhance Cartilage Defect Repair

An Innovative miR‐Activated Scaffold for the Delivery of a miR‐221 Inhibitor to Enhance Cartilage Defect Repair

Highly Porous Type II Collagen-Containing Scaffolds for Enhanced Cartilage Repair with Reduced Hypertrophic Cartilage Formation

Mechanosignalling in cartilage: an emerging target for the treatment of osteoarthritis

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