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Chemical Engineering Journal

Chemical Engineering Journal

IF: 13.3
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Constructing bone organoids based on endochondral ossification model via endogenous enzyme-induced mineralization

Published:22 November 2024 DOI: 10.1016/j.cej.2024.157930
Li Dong, Weiguo Chen, Song Chen

Abstract

Regenerative strategies based on the utilization of bone organoids have been effective. The mineralization of bone organoids, in particular, is a crucial step that not only validates their functionality but also their potential for clinical applications in bone regeneration and disease modeling. However, the mechanisms underlying mineralization in bone organoids is unclear. Here, we recapitulated the differentiation and mineralization processes of natural bone development, through the mineralization of cartilaginous pellets (CPs) by utilizing the concept of endogenous enzyme-induced mineralization. An endogenous enzyme-induced mineralization system based on the encapsulation of CPs, calcium glycerophosphate (CaGP), and 6,8-dimethyl-3-(4-phenyl-1H-imidazol-5-yl)-quinolin-2(1H)-one (DIPQUO) in a methacrylated gelatin (GelMA) hydrogel was reconstructed. DIPQUO significantly enhanced the expression of alkaline phosphatase (ALP) in CPs, hydrolyzed CaGP to provide calcium and phosphate ions, and synchronously accelerated the mineralization of CPs and the hydrogel. The mineralization of CPs exhibited a stage-specific gene expression pattern highly consistent with the process of endochondral ossification, which was mediated by the Wnt/β-catenin and MAPK/ERK signaling pathways confirmed by RNA sequencing. Electron microscopy-based ultrastructural analysis showed that the number of mitochondria, lysosomes, and vesicles increased markedly during mineralization. Furthermore, bone organoids constructed via endogenous enzyme-induced mineralization led to rapid bone healing within 4?weeks in a rat model with a distal femoral condyle defect. Our findings have important implications for elucidating the bone formation process and bone-defect regeneration.

Substances (6)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Ascorbic Acid 50-81-7 C6H8O6 1625 suppliers $6.00-$2170.00
Ethylenediaminetetraacetic acid 60-00-4 C10H16N2O8 1170 suppliers $10.00-$6397.62
Dexamethasone 50-02-2 C22H29FO5 781 suppliers $20.00-$5210.50
Sodium pyruvate 113-24-6 C3H5NaO3 666 suppliers $13.00-$884.00
FETUIN 9014-81-7 NULL 66 suppliers $37.07-$4380.00
L-Lysine, L-asparaginyl-L-histidyl-L-alanyl-L-seryl-L-seryl-L-valyl-L-prolyl-L-arginyl-L-seryl-L-lysyl-L-isoleucyl-L-leucyl-L-threonyl-L-valyl-L-arginyl-L-valyl-L-isoleucyl-L-leucyl-L-alanyl-L-prolyl-L-tryptophyl-L-lysyl- 161374-99-8 C119H202N36O29 9 suppliers Inquiry

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