Advances in research on ferroptosis in jaw bone augmentation

Ferroptosis, an iron-dependent form of regulated cell death (RCD) driven by lipid peroxidation, has emerged as a critical regulatory mechanism in jawbone augmentation, which addresses a major barrier to successful dental implants: insufficient jawbone volume. This review summarizes the molecular basis of ferroptosis and jaw-specific features that regulate it (high mitochondrial density, PUFA enrichment, and GPX4 dependency in jawbone osteoblasts), with a focus on core regulatory networks (namely, the system xc⁻/GSH/GPX4 axis, lipid metabolism pathways, Nrf2/p53 transcriptional regulation, and non-coding RNAs). We highlight that jawbone osteoblasts are more sensitive to ferroptosis than to other RCD pathways (apoptosis, necroptosis, pyroptosis) due to their intrinsic biological properties. Importantly, modulation of ferroptosis exhibits substantial translational value in bone-related diseases, including osteoporosis (through alleviating osteoblast loss) and bone defect repair (via optimizing regenerative niche formation). We analyze ferroptosis's context-dependent dual effects—moderate activation promotes regeneration by clearing senescent cells and modulating inflammation, while excessive activation impairs functional cells and vascularization—and position these effects as the central theme. Preclinical data validate ferroptosis-modulating biomaterials (e.g., PDA/β-TCP scaffolds, tFNA, selenium-doped substitutes) as effective strategies to overcome limitations of traditional techniques (donor site morbidity, microbial rejection, degradation-osteogenesis mismatch). Finally, we discuss clinical translation priorities and challenges, highlighting ferroptosis as a promising target for optimizing jawbone augmentation and thereby improving dental implant success.