Icariin-Releasing 3-Dimensionally Printed Scaffolds for Alveolar Cleft Reconstruction

Each year, 1 in every 700 babies is born with an orofacial cleft in the USA. Despite a well-established protocol for early cleft repair, the alveolar cleft persists during craniofacial growth. Current surgical treatments with bone grafts for alveolar cleft often provide inadequate nasal base support and insufficient alveolar bone volume for permanent tooth eruption. Here, we developed 3-dimensionally printed polycaprolactone scaffolds with controlled delivery of icariin (ICA) to facilitate bone reconstruction. After establishing a reliable fabrication process, we determined the optimal loading dose and release kinetics of ICA for induced osteogenic differentiation of bone marrow mesenchymal stem/progenitor cells and mineralized tissue formation in vitro. Then, the ICA-releasing polycaprolactone scaffolds with the preoptimized dose were implanted into rats with full-thickness maxillary defects. Up to 8 weeks, micro-computed tomography analyses demonstrated significantly accelerated bone healing and defect closure with an ICA-releasing scaffold compared to scaffold alone and defect controls. Histology consistently confirmed the formation of dense woven bone with ICA-releasing scaffolds in contrast to unclosed gaps and soft tissue infiltration in controls. Our findings suggest the significant potential of ICA-releasing 3-dimensionally printed scaffolds to serve as a patient-focused and custom-built bone graft to improve the clinical outcome of alveolar cleft reconstruction.