Cranial Defect Reconstruction With Custom 3D-Printed Hydroxyapatite Scaffolds Augmented With rhBMP-2 or Dipyridamole in a Nonhuman Primate Model.

Objective: Reconstruction of critical-sized bone defects, particularly in the cranio-maxillofacial region, presents unique challenges due to the need for integration with adjacent well-vascularized tissue and the absence of significant load-bearing requirements. This study evaluated the clinical readiness of bone tissue engineering (BTE) for critically sized cranial defects using custom 3D-printed hydroxyapatite scaffolds augmented with either recombinant human bone morphogenetic protein-2 (rhBMP-2) or dipyridamole (DIPY) in a highly translational nonhuman primate model. Methods: Identical 5 × 5-cm vertex guided craniotomies were created in 12 macaques: Three cynomolgus macaques served as negative controls to validate the critical size nature of the defect, while nine rhesus macaques underwent scaffold reconstruction. Subjects were divided into three groups: uncoated scaffolds ( Results: Negative control subjects did not demonstrate new bone formation, confirming the critical defect model. Subjects treated with scaffolds through all treatment groups remained intact throughout the 12-month follow-up. The rhBMP-2-treated group exhibited bridging, ∼90% circumferentially, significantly greater than DIPY (∼9%) or the uncoated scaffold (10%) ( Conclusions: Reconstructing critically sized cranial defects with custom 3D-printed hydroxyapatite scaffolds was successful and yielded favorable results in this model. Scaffolds augmented with rhBMP-2 demonstrated superior bone ingrowth, integration, and mechanical properties, highlighting their potential as a viable alternative to autografts and allograft materials for cranioplasty.