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

This study presents a 3D-printed polycaprolactone (PCL) scaffold incorporating controlled release of icariin (ICA), a plant-derived osteogenic flavonoid, for alveolar cleft reconstruction. ICA was embedded in PCL at 0.1–0.6 wt%, achieving sustained release for up to 28 days. The optimal formulation (0.3 wt% ICA/PCL) enhanced osteogenic differentiation of mesenchymal stem cells in vitro, with elevated expression of COL1A1, IBSP, and BGLAP, and demonstrated significant in vivo bone regeneration in a rat alveolar defect model. Micro‑CT and histological analyses confirmed nearly complete defect closure and mature woven bone formation at 8 weeks, surpassing PCL‑only controls. The ICA/PCL scaffold offers a growth factor‑free, translationally viable approach for craniofacial bone reconstruction.