Background: Understanding the interfacial reactions to synthetic bone regenerative scaffolds in vivo is fundamental for improving osseointegration and osteogenesis. Using transmission electron microscopy, it is possible to study the biological response of hydroxyapatite (HA) and zirconia (ZrO₂) scaffolds at the nanometer scale. Purpose: In this study, the bone-bonding abilities of HA and ZrO₂ scaffolds produced by free-form fabrication were evaluated in the human maxilla at 3 months and 7 months. Materials and Methods: HA and ZrO₂ scaffolds (ø: 3mm) were implanted in the human maxilla, removed with surrounding bone, embedded in resin, and sectioned. A novel focused ion beam (FIB) sample preparation technique enabled the production of thin lamellae for study by scanning transmission electron microscopy. Results: Interface regions were investigated using high-angle annular dark-field imaging and energy-dispersive X-ray spectroscopy analysis. Interfacial apatite layers of 80nm and 50nm thickness were noted in the 3- and 7-month HA samples, respectively, and bone growth was discovered in micropores up to 10μm into the samples. Conclusions: The absence of an interfacial layer in the ZrO₂ samples suggest the formation of a direct contact with bone, while HA, which bonds through an apatite layer, shows indications of resorption with increasing implantation time. This study demonstrates the potential of HA and ZrO₂ scaffolds for use as bone regenerative materials.