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Engineered human meniscus’ matrix-forming phenotype is unaffected by low strain dynamic compression under hypoxic conditions
Author(s) -
Alexander R A Szojka,
Colleen N. Moore,
Yan Liang,
Stephen H. J. Andrews,
Melanie Kunze,
Aillette MuletSierra,
Nadr M. Jomha,
Adetola B Adesida
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0248292
Subject(s) - scaffold , oxygen tension , biophysics , hypoxia (environmental) , matrix (chemical analysis) , microbiology and biotechnology , meniscus , phenotype , biomedical engineering , chemistry , extracellular matrix , materials science , oxygen , biochemistry , biology , composite material , medicine , physics , organic chemistry , incidence (geometry) , optics , gene
Low oxygen and mechanical loading may play roles in regulating the fibrocartilaginous phenotype of the human inner meniscus, but their combination in engineered tissues remains unstudied. Here, we investigated how continuous low oxygen (“hypoxia”) combined with dynamic compression would affect the fibrocartilaginous “inner meniscus-like” matrix-forming phenotype of human meniscus fibrochondrocytes (MFCs) in a porous type I collagen scaffold. Freshly-seeded MFC scaffolds were cultured for 4 weeks in either 3 or 20% O 2 or pre-cultured for 2 weeks in 3% O 2 and then dynamically compressed for 2 weeks (10% strain, 1 Hz, 1 h/day, 5 days/week), all with or without TGF-β3 supplementation. TGF-β3 supplementation was found necessary to induce matrix formation by MFCs in the collagen scaffold regardless of oxygen tension and application of the dynamic compression loading regime. Neither hypoxia under static culture nor hypoxia combined with dynamic compression had significant effects on expression of specific protein and mRNA markers for the fibrocartilaginous matrix-forming phenotype. Mechanical properties significantly increased over the two-week loading period but were not different between static and dynamic-loaded tissues after the loading period. These findings indicate that 3% O 2 applied immediately after scaffold seeding and dynamic compression to 10% strain do not affect the fibrocartilaginous matrix-forming phenotype of human MFCs in this type I collagen scaffold. It is possible that a delayed hypoxia treatment and an optimized pre-culture period and loading regime combination would have led to different outcomes.

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