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"Slow walk" mimetic tensile loading maintains human meniscus tissue resident progenitor cells homeostasis in photocrosslinked gelatin hydrogel.

ABSTRACT: Meniscus, the cushion in knee joint, is a load-bearing tissue that transfers mechanical forces to extracellular matrix (ECM) and tissue resident cells. The mechanoresponse of human tissue resident stem/progenitor cells in meniscus (hMeSPCs) is significant to tissue homeostasis and regeneration but is not well understood. This study reports that a mild cyclic tensile loading regimen of ∼1800 loads/day on hMeSPCs seeded in 3-dimensional (3D) photocrosslinked gelatin methacryloyl (GelMA) hydrogel is critical in maintaining cellular homeostasis. Experimentally, a "slow walk" biomimetic cyclic loading regimen (10% tensile strain, 0.5 Hz, 1 h/day, up to 15 days) is applied to hMeSPCs encapsulated in GelMA hydrogel with a magnetic force-controlled loading actuator. The loading significantly increases cell differentiation and fibrocartilage-like ECM deposition without affecting cell viability. Transcriptomic analysis reveals 332 mechanoresponsive genes, clustered into cell senescence, mechanical sensitivity, and ECM dynamics, associated with interleukins, integrins, and collagens/matrix metalloproteinase pathways. The cell-GelMA constructs show active ECM remodeling, traced using a green fluorescence tagged (GFT)-GelMA hydrogel. Loading enhances nascent pericellular matrix production by the encapsulated hMeSPCs, which gradually compensates for the hydrogel loss in the cultures. These findings demonstrate the strong tissue-forming ability of hMeSPCs, and the importance of mechanical factors in maintaining meniscus homeostasis.

SUBMITTER: Sun J

PROVIDER: S-EPMC9941420 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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"Slow walk" mimetic tensile loading maintains human meniscus tissue resident progenitor cells homeostasis in photocrosslinked gelatin hydrogel.

Sun Jing J Chan Yau Tsz YT Ho Ki Wai Kevin KWK Zhang Li L Bian Liming L Tuan Rocky S RS Jiang Yangzi Y

Bioactive materials 20230208

Meniscus, the cushion in knee joint, is a load-bearing tissue that transfers mechanical forces to extracellular matrix (ECM) and tissue resident cells. The mechanoresponse of human tissue resident stem/progenitor cells in meniscus (hMeSPCs) is significant to tissue homeostasis and regeneration but is not well understood. This study reports that a mild cyclic tensile loading regimen of ∼1800 loads/day on hMeSPCs seeded in 3-dimensional (3D) photocrosslinked gelatin methacryloyl (GelMA) hydrogel i ...[more]

PMID: 36825224

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Project description:Tendon pathology is associated with damage. While tendon damage is likely initiated by mechanical loading, little is known about the specific etiology. Damage is defined as an irreversible change in the microstructure that alters the macroscopic mechanical parameters. In tendon, the link between mechanical loading and microstructural damage, resulting in macroscopic changes, is not fully elucidated. In addition, tendon damage at the macroscale has been proposed to initiate when tendon is loaded beyond a strain threshold, yet the metrics to define the damage threshold are not determined. We conducted multi-scale mechanical testing to investigate the mechanism of tendon damage by simultaneously quantifying macroscale mechanical and microstructural changes. At the microscale, we observe full recovery of the fibril strain and only partial recovery of the interfibrillar sliding, indicating that the damage initiates at the interfibrillar structures. We show that non-recoverable sliding is a mechanism for tendon damage and is responsible for the macroscale decreased linear modulus and elongated toe-region observed at the fascicle-level, and these macroscale properties are appropriate metrics that reflect tendon damage. We concluded that the inflection point of the stress-strain curve represents the damage threshold and, therefore, may be a useful parameter for future studies. Establishing the mechanism of damage at multiple length scales can improve prevention and rehabilitation strategies for tendon pathology.Statement of significanceTendon pathology is associated with mechanically induced damage. Damage, as defined in engineering, is an irreversible change in microstructure that alters the macroscopic mechanical properties. Although microstructural damage and changes to macroscale mechanics are likely, this link to microstructural change was not yet established. We conducted multiscale mechanical testing to investigate the mechanism of tendon damage by simultaneously quantifying macroscale mechanical and microstructural changes. We showed that non-recoverable sliding between collagen fibrils is a mechanism for tendon damage. Establishing the mechanism of damage at multiple length scales can improve prevention and rehabilitation strategies for tendon pathology.

Dataset Information

"Slow walk" mimetic tensile loading maintains human meniscus tissue resident progenitor cells homeostasis in photocrosslinked gelatin hydrogel.

Publications

"Slow walk" mimetic tensile loading maintains human meniscus tissue resident progenitor cells homeostasis in photocrosslinked gelatin hydrogel.

Similar Datasets

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