Geometric Mismatch Promotes Anatomic Repair in Periorbital Bony Defects in Skeletally Mature Yucatan Minipigs.

Porous tissue-engineered 3D-printed scaffolds are a compelling alternative to autografts for the treatment of large periorbital bone defects. Matching the defect-specific geometry has long been considered an optimal strategy to restore pre-injury anatomy. However, studies in large animal models have revealed that biomaterial-induced bone formation largely occurs around the scaffold periphery. Such ectopic bone formation in the periorbital region can affect vision and cause disfigurement. To enhance anatomic reconstruction, we introduced geometric mismatches in the scaffolds used to treat full thickness zygomatic defects created bilaterally in adult Yucatan minipigs. We used 3D-printed, anatomically-mirrored scaffolds in combination with autologous stromal vascular fraction of cells (SVF) for treatment. We developed an advanced image-registration workflow to quantify the post-surgical geometric mismatch and correlate it with the spatial pattern of the regenerating bone. Osteoconductive bone growth on the dorsal and ventral aspect of the defect enhanced scaffold integration with the native bone while medio-lateral bone growth led to failure of the scaffolds to integrate. We found a strong positive correlation between geometric mismatch and orthotopic bone deposition at the defect site. The data suggested that strategic mismatch >20% could improve bone scaffold design to promote enhanced regeneration, osseointegration and long-term scaffold survivability. This article is protected by copyright. All rights reserved.