Platelet-Rich Fibrin Potentiates Dental Pulp Stem Cell Angiogenesis through Mitochondrial Transfer-Meditated Metabolic-Signaling Integration

Therapeutic angiogenesis in inflammatory microenvironments is constrained by mitochondrial dysfunction in mesenchymal stem cells (MSCs). This study demonstrates that platelet-rich fibrin (PRF) serves as a mitochondrial reservoir that transfers functional mitochondria to dental pulp stem cells (DPSCs) via extracellular vesicle-dependent mechanisms. Multi-omics analyses revealed that PRF-derived mitochondria activated the tricarboxylic acid (TCA) cycle in DPSCs, driving concurrent fatty acid biosynthesis and JAK2/STAT4-mTOR pathway activation. This metabolic-signaling integration enhanced VEGF secretion and cell migration under inflammatory conditions. PRF’s fibrin matrix further sustained mitochondrial release while providing topological guidance for DPSC recruitment. In vivo, PRF-DPSC composites significantly accelerated wound closure and neovascularization compared to controls, supported by histomorphometric and molecular analyses. Beyond cytokine delivery, this work establishes PRF as a mitochondrial-augmented biomaterial to reverse MSC metabolic insufficiency, offering a translatable strategy for vascular regeneration in hostile microenvironments.