Authors
Zhiyao Ma, Liam McEachern, Xiaoyi Lan, David Xinzheyang Li, Aahil A Ansari, Ivan Au, Madeline Barker, Melanie Kunze, Aillette Mulet-Sierra, Adetola B Adesida
Published in
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. Volume 40. Issue 18. Pages e72309. Sep 30, 2026.
Abstract
Chondrocytes and mesenchymal stromal cells (MSC) metabolism shapes cartilage matrix quality, but cartilage engineering lacks a non-destructive, time-resolved readout that links oxygen uses to matrix assembly and mechanics under standard culture conditions. We continuously recorded oxygen-consumption rate (OCR) in nasal chondrocyte (NC), MSC, and NC-MSC co-culture pellets cultured for 27 days under normoxia, and integrated OCR trajectories with time-resolved gene expression, matrix histology, glycosaminoglycan (GAG)/DNA, and unconfined compression mechanics across defined NC:MSC ratios (monocultures; 3:1, 2:1, 1:1, 1:2, 1:3). OCR trajectories were reproducibly tri-phasic-(I) condensation/priming (Days 0-9), (II) differentiation/matrix synthesis (Days 9-21/24), and (III) maturation/remodeling (Days 24-27)-and strongly composition dependent. NC-rich mixtures exhibited an earlier hypoxic tone with transient HIF-1α, accelerated SOX9 followed by ACAN and COL2A1 induction, and marked GAG synergy peaking at 3:1. MSC-rich mixtures sustained late respiration with higher PGC-1α, elevated COL10A1 and MMP13, and achieved the highest equilibrium modulus at 1:3 despite lower GAG/DNA. An OCR downshift near Day 24 marked metabolic settling in most groups, whereas 1:3 pellets maintained or increased respiration, consistent with continued oxidative remodeling. Correlation analyses linked OCR features to hyaline anabolism in NC-rich pellets and to remodeling/hypertrophy in MSC-rich pellets, indicating ratio-specific coordination between respiratory and matrix-associated signatures. These findings support OCR monitoring as a sensitive, non-destructive process metric associated with chondrogenic stage transitions, provide guidance for selecting NC-rich ratios to maximize hyaline fidelity and GAG productivity, and MSC-rich ratios to increase stiffness while managing hypertrophic risk, and offer a generalizable framework for in-process bioenergetic control across tissue-engineering contexts.
PMID:
42750492
Bibliographic data and abstract were imported from PubMed on 17 Sep 2026.
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