Confinement-Controlled Formation of Calcium Phosphate Clusters within Iron Porphyrin-Functionalized Oriented Mesoporous Silica Nanospaces

Calcium phosphate (CP), a principal component of hard tissues in the human body, exhibits excellent biocompatibility. In vivo, CP exists as aggregates composed of nanoscale clusters. However, reproducing and controlling such a hierarchical structure under in vitro conditions have remained challenging. In this study, we aimed to utilize the three-dimensionally confined mesoporous space of uniaxially oriented mesoporous silica films (OMPS) as a reaction field to stably induce the nucleation and growth of CP clusters and aggregates. For this purpose, we prepared the OMPS functionalized with iron(III)-containing cationic porphyrin (FeTM) to simultaneously stabilize the mesoporous structure and provide nucleation sites for the CP cluster formation. The OMPS possessed highly oriented mesoporous cylinders (orientation degree: 97%, pore diameter: 4.8 nm), which are expected to serve as a nanoscale confinement template for CP cluster and aggregate formation. Furthermore, the UV–vis absorption spectra of OMPS-FeTM showed a distinct blue shift in the Q-band, suggesting that the porphyrin ring was electronically localized through electrostatic interactions between the Fe³⁺ center and phosphate ions. In the CP precipitation, the Q-band exhibited an additional blue shift. This spectral change is attributed to the electronic density alteration of the Fe³⁺ center due to further interaction with phosphate ions, indicating that the Fe³⁺ ions act as nucleation triggers for the formation of CP clusters and aggregates within the mesopores. The mesostructural stability was also evaluated after CP precipitation. OMPS-FeTM maintained its ordered mesoporous structure, exhibiting higher structural stability as compared to the case in the OMPS without FeTM. The field-emission scanning electron microscopy (FE-SEM) observations revealed that, after the CP precipitation, OMPS exhibited the widespread and dense precipitation of amorphous CP aggregates on its surface. In contrast, OMPS-FeTM clearly suppressed the CP precipitation on the external surface. Moreover, the cross-sectional transmission electron microscopy (TEM) observations demonstrated that, in OMPS, the mesostructure collapsed after the CP formation, accompanied by the precipitation of amorphous CP particles with diameters of 5–30 nm. On the other hand, OMPS-FeTM retained its mesoporous structure, and the CP clusters and aggregates of approximately 4–7 nm were successfully formed within the confined mesopores. These results clearly indicate that the mesoporous confinement strategy enables the controlled precipitation of CP clusters and aggregates within the mesopores of OMPS-FeTM.