A single-cell transcriptome of mesenchymal stromal cells to fabricate bioactive hydroxyapatite materials for bone regeneration

ABSTRACT: The osteogenic microenvironment of bone-repairing materials plays a key role in accelerating bone regeneration but remains incompletely defined, which significantly limits the application of such bioactive materials. Here, the transcriptional landscapes of different osteogenic microenvironments, including three-dimensional (3D) hydroxyapatite (HA) scaffolds and osteogenic medium (OM), for mesenchymal stromal cells (MSCs) in vitro were mapped at single-cell resolution. Our findings suggested that an osteogenic process reminiscent of endochondral ossification occurred in HA scaffolds through sequential activation of osteogenic-related signaling pathways, along with inflammation and angiogenesis, but inhibition of adipogenesis and fibrosis. Moreover, we revealed the mechanism during OM-mediated osteogenesis involves the ZBTB16 and WNT signaling pathways. Heterogeneity of MSCs was also demonstrated. In vitro ossification of LRRC75A+ MSCs was shown to have better utilization of WNT-related ossification process, and PCDH10+ MSCs with superiority in hydroxyapatite-related osteogenic process. These findings provided further understanding of the cellular activity modulated by OM conditions and HA scaffolds, providing new insights for the improvement of osteogenic biomaterials. This atlas provides a blueprint for research on MSC heterogeneity and the osteogenic microenvironment of HA scaffolds and a database reference for the application of bioactive materials for bone regeneration. Graphical abstract Image 1 Highlights • A single-cell transcriptome of stem cells is mapped for bone regeneration.• PCDH10+ cells accelerate hydroxyapatite-related osteogenesis.• Osteogenic medium shows adverse effects on hydroxyapatite-related osteogenesis.• A time window for cell modification of hydroxyapatite in vitro is critical.• The hypoxic and inflammatory microenvironment of biomaterials deserves attention.

SUBMITTER: Guo P 

PROVIDER: S-EPMC8586438 | biostudies-literature |

REPOSITORIES: biostudies-literature