Differential response of inner and outer zone meniscal cells to tensile load under non-inflammatory and inflammatory conditions

Irwin, Rebecca M.; Puranam, Ishaan; Hoffman, Brenton D.; McNulty, Amy L.

doi:10.1016/j.joca.2021.05.011

Cited by 3 publications

(5 citation statements)

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“…In the inner zone only, 10% loading increased the expression level of COL1A1 and decreased that of NOS2. This study indicates that mechanical stimulation may be advantageous in treating meniscus injuries by counteracting inflammation-induced damage [63].…”

Section: Mechanical Loading and Hypoxiamentioning

confidence: 71%

“…McNulty [62] Mechanical compression Irwin [63] Dynamic loading, IL-1 Szojka [64] Mechanical loading, hypoxia Millar [65] Hypoxia…”

Section: Author Investigationmentioning

confidence: 99%

“…McNulty [62] Mechanical compression Irwin [63] Dynamic loading, IL-1 Szojka [64] Mechanical loading, hypoxia Millar [65] Hypoxia Promising preclinical studies, both in vitro using explant models and in vivo on animal models, have demonstrated the potential for meniscus healing at the molecular level. However, there is a notable gap in clinical trials from phases I to IV in this area.…”

Section: Author Investigationmentioning

confidence: 99%

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Molecular Biology of Meniscal Healing: A Narrative Review

Tramś,

Kamiński

2024

IJMS

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This review provides insights at the molecular level into the current and old methods for treating meniscal injuries. Meniscal injuries have been found to have a substantial impact on the progression of osteoarthritis. In line with the “save the meniscus” approach, meniscectomy is considered a last-resort treatment. Nevertheless, it is important to note that mechanical repair alone may not achieve the complete restoration of the meniscus. A deep understanding of the healing pathways could lead to future improvements in meniscal healing. The inclusion of cytokines and chemokines has the potential to facilitate the process of tear repair or impede the inflammatory catabolic cascade. MicroRNA (miRNA) could serve as a potential biomarker for meniscal degeneration, and RNA injections might promote collagen and growth factor production. The critical aspect of the healing process is angiogenesis within the inner zone of the meniscus. The use of collagen scaffolds and the implantation of autologous meniscus fragments have been successfully integrated into clinical settings. These findings are encouraging and underscore the need for well-designed clinical trials to explore the most effective factors that can enhance the process of meniscal repair.

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Section: Mechanical Loading and Hypoxiamentioning

confidence: 71%

“…McNulty [62] Mechanical compression Irwin [63] Dynamic loading, IL-1 Szojka [64] Mechanical loading, hypoxia Millar [65] Hypoxia…”

Section: Author Investigationmentioning

confidence: 99%

Section: Author Investigationmentioning

confidence: 99%

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Molecular Biology of Meniscal Healing: A Narrative Review

Tramś,

Kamiński

2024

IJMS

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“…[13][14][15] In thin film collagen hydrogels, both inner and outer MFCs responded to dynamic strain by regulating the production of a known mechanotransducive calcium channel receptor, transient receptor potential vanilloid 4 (TRPV4), illustrating the mechanosensitivity of MFCs. 16 Further, tuning the equilibrium modulus of PEGDA:GelMA hydrogels to $30 kPa resulted in a recovery of both inner and outer MFC phenotype after many passages of culture on rigid tissue culture polystyrene. 17 Taken together, tuning the mechanical properties of 3D hydrogels is critical to promote the cell behavior necessary for meniscus regeneration.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, MFCs embedded in high‐density collagen hydrogels and clamped to provide mechanical boundary constraints produced large collagen fibers with diameters mimicking native tissue, highlighting the role of the microenvironment and mechanical cues on neotissue formation 13–15 . In thin film collagen hydrogels, both inner and outer MFCs responded to dynamic strain by regulating the production of a known mechanotransducive calcium channel receptor, transient receptor potential vanilloid 4 (TRPV4), illustrating the mechanosensitivity of MFCs 16 . Further, tuning the equilibrium modulus of PEGDA:GelMA hydrogels to ~30 kPa resulted in a recovery of both inner and outer MFC phenotype after many passages of culture on rigid tissue culture polystyrene 17 .…”

Section: Introductionmentioning

confidence: 99%

Modulating pentenoate‐functionalized hyaluronic acid hydrogel network properties for meniscal fibrochondrocyte mechanotransduction

Burkey

Castillo

Elrod

et al. 2023

J Biomedical Materials Res

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Knee meniscus tears are one of the most common musculoskeletal injuries. While meniscus replacements using allografts or biomaterial‐based scaffolds are available, these treatments rarely result in integrated, functional tissue. Understanding mechanotransducive signaling cues that promote a meniscal cell regenerative phenotype is critical to developing therapies that promote tissue regeneration rather than fibrosis after injury. The purpose of this study was to develop a hyaluronic acid (HA) hydrogel system with tunable crosslinked network properties by modulating the degree of substitution (DoS) of reactive‐ene groups to investigate mechanotransducive cues received by meniscal fibrochondrocytes (MFCs) from their microenvironment. A thiol‐ene step‐growth polymerization crosslinking mechanism was employed using pentenoate‐functionalized hyaluronic acid (PHA) and dithiothreitol to achieve tunability of the chemical crosslinks and resulting network properties. Increased crosslink density, reduced swelling, and increased compressive modulus (60–1020 kPa) were observed with increasing DoS. Osmotic deswelling effects were apparent in PBS and DMEM+ compared to water; swelling ratios and compressive moduli were decreased in the ionic buffers. Frequency sweep studies showed storage and loss moduli of hydrogels at 1 Hz approach reported meniscus values and showed increasing viscous response with increasing DoS. The degradation rate increased with decreasing DoS. Lastly, modulating PHA hydrogel surface modulus resulted in control of MFC morphology, suggesting relatively soft hydrogels (E = 60 ± 35 kPa) promote more inner meniscus phenotype compared to rigid hydrogels (E = 610 ± 66 kPa). Overall, these results highlight the use of ‐ene DoS modulation in PHA hydrogels to tune crosslink density and physical properties to understand mechanotransduction mechanisms required to promote meniscus regeneration.

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Current advances in engineering meniscal tissues: insights into 3D printing, injectable hydrogels and physical stimulation based strategies

Bandyopadhyay,

Ghibhela,

Mandal

2024

Biofabrication

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Knee meniscus is the cushioning fibro-cartilage tissue present in between the femoral condyles and tibial plateau of knee joint. It is largely avascular in nature and suffers from a wide range of tears and injuries caused by accidents, trauma, active lifestyle of the populace and old age of individuals. Healing of meniscus is especially difficult due to their avascularity and hence requires invasive arthroscopic approaches such as surgical resection, suturing or implantation. Though various tissue engineering approaches are proposed for treatment of meniscus tears, 3D printing/bioprinting, injectable hydrogels and physical stimulation involving modalities are gaining forefront in the past decade. A plethora of new printing approaches such as direct light photopolymerization and volumetric printing, injectable biomaterials loaded with growth factors and physical stimulation such as low intensity ultrasound approaches are being added to the treatment portfolio along with the contemporary tear mitigation measures. This review discusses on the necessary design considerations, approaches for 3D modeling and design practices for meniscal tear treatments within the scope of tissue engineering and regeneration. Also, the suitable materials, cell sources, growth factors, mechanical stimulation approaches, 3D printing strategies and injectable hydrogels for meniscal tear management have been elaborated. We have also summarized potential technologies and the potential framework that could be the herald of future of meniscus tissue engineering and repair approaches.

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Differential response of inner and outer zone meniscal cells to tensile load under non-inflammatory and inflammatory conditions

Cited by 3 publications

References 0 publications

Molecular Biology of Meniscal Healing: A Narrative Review

Molecular Biology of Meniscal Healing: A Narrative Review

Modulating pentenoate‐functionalized hyaluronic acid hydrogel network properties for meniscal fibrochondrocyte mechanotransduction

Current advances in engineering meniscal tissues: insights into 3D printing, injectable hydrogels and physical stimulation based strategies

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