Transcriptomic and cellular decoding of scaffolds-induced suture mesenchyme regeneration

作者：Jiayi Wu, Feifei Li, Peng Yu, Changhao Yu, Chuyi Han, Yitian Wang, Fanyuan Yu, Ling Ye · 发表于：International Journal of Oral Science · 年份：2024 · DOI：10.1038/s41368-024-00295-y · 被引用次数：7 · 研究领域：Bone Tissue Engineering Materials、Bone fractures and treatments、Reconstructive Surgery and Microvascular Techniques

Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal regeneration. Despite extensive studies on mineralized parenchymal tissue rebuilding, regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances yet. Current knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic damage. But to date, the absence of promising therapeutic biomaterials/scaffolds remains. The reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of scaffolds. To address these issues, in this study, we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial scaffolds. Our data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses. A feasible scaffold, polylactic acid electrospinning membrane (PLA), was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center, meanwhile supporting proper osteointegration with defect bony edges. Especially, transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were deciphered. This study for the first time cellularly de...