Abstract
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% O2 or pre-cultured for 2 weeks in 3% O2 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% O2 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.
Funder
Natural Sciences and Engineering Research Council of Canada
Canadian Institutes of Health Research
Edmonton Civic Employees Charitable Assistance Fund
Canada Foundation for Innovation
University Hospital of Alberta Foundation
Edmonton Orthopaedic Research Committee
Government of Alberta
Faculty of Medicine and Dentistry, University of Alberta
Faculty of Graduate Studies and Research, University of Alberta
Alexander Graham Bell Scholarship, NSERC
President’s Doctoral Prize of Distinction, University of Alberta
Queen Elizabeth II Scholarship program, Alberta Government
Alberta Graduate Scholarship, Student Aid Alberta
Alberta Innovates Health Solutions
Li Ka Shing Sino-Canadian Exchange Program
Alberta Cancer Foundation-Mickleborough Interfacial Biosciences Research Program
University of Alberta
Publisher
Public Library of Science (PLoS)
Cited by
5 articles.
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