Effect of surface area and pore size on long-term bone regeneration: dynamic changes in geometric characteristics, mass transport, and mechanobiology

The specific surface area (S_S) and pore size (D) exhibit an inherent trade-off in the microscale design of bone implants: larger pores typically correlate with reduced surface area and vice versa. This relationship has attracted notable attention because of its critical role in the regulation of cell adhesion and osteogenesis. However, it remains largely unclear how S_S and D affect the generated bone tissue and dynamically change during long-term osteogenesis. Herein, by applying rigorous geometric mapping to minimal surfaces, we constructed precisely partitioned and layer-by-layer thickened tissue models to simulate osteogenesis across different temporal scales and thereby track the dynamic evolution of geometric characteristics, permeability, and mechanobiological tissue differentiation. The high-S_S samples were found to facilitate the rapid formation of new bone tissue in the early stages. However, their smaller pores tended to cause occlusions, hindering further tissue development. In contrast, low-S_S samples showed slower bone regeneration, but their larger pores provided adequate physical space for tissue regeneration and mass transport, ultimately promoting bone formation in the long term. Mechanobiological regulation suggests that fibrous tissue formation inhibits additional bone formation, establishing a dynamic equilibrium between osteogenesis and pore space to sustain nutrient/waste exchange throughout the regenerative process. Overall, smaller pores are preferable in implants for minimally loaded osteoplasty procedures focused on early-stage bone consolidation, whereas larger pores are preferable in dynamically loaded implants requiring prolonged mechanical stability.