Interface-programmed regeneration of segmental bone defects with biomimetic mineral-coated β-TCP microparticles

Large segmental bone defects remain difficult to treat: autografts are limited by supply and morbidity, while calcium-phosphate substitutes often deliver inconsistent outcomes. This inconsistency largely originates at the early post-implantation interface, where protein adsorption and Ca²⁺/PO₄^3- flux are unpredictable and lack a scalable solution. We therefore engineered mineral-coated microparticles (MCM) by growing a conformal, low-crystallinity apatite nanolayer on porous β-TCP under aqueous, protein-compatible conditions, preserving interconnected porosity. The coating establishes a uniform, stable protein corona and attenuates burst while smoothing ion release; in a rabbit mandibular critical-size model, MCM achieved more complete bridging, denser μCT infill, and higher bone mineral density than β-TCP and β-TCP/HA. Collectively, these data support a growth-factor-free, interface-first design that delivers more consistent regeneration and is readily translatable as an off-the-shelf particulate filler.