Transcriptomic profiling of BMSCs and VECs treated with GelMA-HIF-1alpha composite hydrogels reveals mechanisms of osteogenesis-angiogenesis coupling in bone regeneration

Bone regeneration requires coordinated osteogenesis and angiogenesis; however, the molecular mechanisms underlying their coupling remain incompletely understood. In this study, we constructed a GelMA-HIF-1alpha composite hydrogel via EDC/NHS-mediated covalent conjugation to achieve sustained release of HIF-1alpha and enhance bone defect repair.To investigate the transcriptional mechanisms underlying osteogenesis-angiogenesis coupling, RNA sequencing (RNA-seq) was performed on bone marrow stromal cells (BMSCs) and vascular endothelial cells (VECs) cultured with GelMA-HIF-1alpha composite hydrogels and corresponding control groups. Differential gene expression analysis, Gene Ontology (GO), KEGG pathway enrichment, and Gene Set Enrichment Analysis (GSEA) were conducted to identify key signaling pathways involved in angiogenesis, osteogenesis, extracellular matrix remodeling, hypoxic response, and energy metabolism.Transcriptomic profiling revealed significant enrichment of HIF-1 signaling, Rap1 signaling, PI3K-Akt pathway, cell adhesion molecules (CAMs), mineral absorption, and MAPK signaling pathways, supporting a bidirectional positive feedback mechanism between BMSCs and VECs. These findings provide molecular evidence that GelMA-HIF-1alpha hydrogels promote coordinated osteogenesis and angiogenesis during bone defect repair.This dataset contributes to understanding the transcriptomic regulation of bone-vascular coupling and provides a valuable resource for biomaterial-mediated bone regeneration research.