RESOURCES

Abstract
In this study, a novel hybrid scaffold comprising 3D-printed porous polyhydroxybutyrate (PHB), dextran (Dex), and magnesium-doped whitlockite (WL) nanoparticles was developed, which were further enhanced with an electrospun nanofibrous coating composed of Dex and Pluronic F127 (F127) loaded with Sildenafil (Sil) for use in craniofacial regeneration. This design was intended to improve the solubility of sildenafil and enable controlled release. Scanning electron microscopy (SEM) revealed a well-integrated structure between the 3D-printed strands and electrospun nanofibers. The scaffold exhibited sustained release of Sil over 28 days, with mechanical testing showing a compressive strength of 3.70 ± 0.33 MPa and an elastic modulus of 49.04 ± 4.62 MPa. Non-toxicity was confirmed via MTT assay on the MG63 cell line, and qRT-PCR results indicated significantly higher expression levels of collagen I, RUNX2, osteocalcin, VEGF, and CD31 markers associated with osteogenesis and angiogenesis. Following implantation in a rat calvarial defect model, the scaffold demonstrated robust osteogenic activity and new bone tissue formation over an eight-week period. This innovative scaffold design offers a promising solution for overcoming the challenges in craniofacial defect repair by integrating bioactive materials with advanced drug delivery systems, leading to more effective tissue regeneration strategies.