Rat Calvarial Guided Bone Regeneration Model: Preclinical Insights into Biomaterials, Barrier Design, and Systemic Modulators

Guided bone regeneration (GBR) plays a key role in alveolar ridge augmentation and implant therapy, but the biological mechanisms governing its outcomes are not fully understood. Preclinical animal models provide critical insights that cannot be obtained in early human studies. Over the past 15 years, our group has developed and optimized a standardized rat calvarial GBR model using plastic caps, enabling reproducible and quantitative evaluation of bone regeneration through micro-computed tomography and histomorphometry. The present narrative review synthesizes the findings from our body of work. Our studies demonstrated that advanced substitutes such as hydroxyapatite/collagen composites and carbonate apatite provide favorable outcomes, indicating that local and systemic application of growth factors or parathyroid hormone can markedly enhance augmentation, and that barrier permeability critically modulates angiogenesis and osteogenesis. Moreover, systemic conditions such as nicotine exposure and estrogen deficiency profoundly compromise regenerative outcomes but can be partly mitigated by pharmacological interventions. Finally, regenerated bone within GBR spaces is biologically competent, although it remains less mature than native cortical bone. Together, these insights highlight the translational value of our GBR model and indicate the integration of spatial omics for the elucidation of the cellular mechanisms that will guide future regenerative strategies.