Bone regenerative efficacy of binder-jet fabricated hydroxyapatite granules with and without biomimetic octacalcium phosphate-coated modification in a rat critical-sized calvarial defect model

Bone substitutes fabricated via additive manufacturing offer promising solutions for bone grafting. This study investigated the bone regeneration potential of binder-jet fabricated hydroxyapatite (HA) and biomimetic octacalcium phosphate (OCP)-coated binder-jet fabricated HA (HA-B) granules in a rat critical-sized calvarial defect model. Bone graft in the form of granules was produced via binder jet 3D printing combined with a phase transformation process and implanted into 5 mm defects for 4 and 12 weeks, with empty defects as controls. New bone formation, mechanical integration and cellular responses were assessed using micro-computed tomography, histology, histomorphometry, push-out testing and immunohistochemistry. Both HA and HA-B supported bone formation without local or systemic adverse effects. Osteoblast, osteoclast and osteocyte counts indicated active remodeling in bone graft implanted groups. Micro-CT showed significantly higher bone volume in HA-B than HA and Empty at 12 weeks, while histomorphometry showed differences only between HA-B and Empty. HA-B also exhibited the highest push-out force, indicating superior mechanical integration. These results demonstrate that binder-jet fabricated HA and OCP-coated HA granules are safe, osteoconductive, and effective for bone repair, with OCP coating further enhancing bone formation and material-host integration.