Osseointegration enhancement by controlling dispersion state of carbonate apatite in polylactic acid implant

Osteoconductive ceramics (OCs) are often used to endow polylactic acid (PLA) with osseointegration ability. Conventionally, OC powder is dispersed in PLA. However, considering cell attachment to the implant, OCs may be more favorable when they exist in the form of aggregations, such as granules, and are larger than the cells rather than being dispersed like a powder. In this study, to clarify the effects of the dispersion state of OCs on the osseointegration ability, carbonate apatite (CAp), a bone mineral analog that is osteoconductive and bioresorbable, powder-PLA (P-PLA), and CAp granule-PLA (G-PLA) composite implants were fabricated via thermal pressing. The powder and granule sizes of CAp were approximately 1 and 300-600 µm, respectively. G-PLA exhibited a higher water wettability and released calcium and phosphate ions faster than P-PLA. When cylindrical G-PLA, P-PLA, and PLA were implanted in rabbit tibial bone defects, G-PLA promoted bone maturation compared to P-PLA and pure PLA. Furthermore, G-PLA bonded directly to the host bone, whereas P-PLA bonded across the osteoid layers. Consequently, the bone-to-implant contact of G-PLA was 1.8- and 5.6-fold higher than those of P-PLA and PLA, respectively. Furthermore, the adhesive shear strength of G-PLA was 1.9- and 3.0-fold higher than those of P-PLA and PLA, respectively. Thus, G-PLA achieved earlier and stronger osseointegration than P-PLA or PLA. The findings of this study highlight the significance of the state of dispersion of OCs in implants as a novel strategy for material development.