Recapitulating hypoxic metabolism in cartilaginous organoids via adaptive cell-matrix interactions enhances histone lactylation and cartilage regeneration.

ABSTRACT: Mesenchymal condensation, characterized by rapid proliferation and aggregation of precursor cells within a restructured mesodermal extracellular matrix, is critical for skeletal tissue development, including articular cartilage. This process establishes a hypoxic microenvironment that drives metabolic shifts and epigenetic modifications essential for cartilage development. To replicate this, we engineer a cell-adaptable supramolecular hydrogel that accommodates the extensive volumetric and morphological changes of encapsulated mesenchymal stromal cells, facilitating the rapid formation of large multicellular cartilaginous organoids. This adaptation fosters a hypoxic environment and induces metabolic shifts toward glycolysis, increasing lactate accumulation and histone lysine lactylation. E

SUBMITTER: Yang B 

PROVIDER: S-EPMC11923171 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature