Pcl/Zif-8@Ris Scaffolds For Bone Defect Regeneration

This study aims to develop a novel drug delivery system by encapsulating sodium risedronate (RIS) within zeolitic imidazolate framework-8 (ZIF-8), and integrating this complex (ZIF-8@RIS) into polycaprolactone (PCL) scaffolds using 3D printing technology, thereby enhancing bone regeneration in maxillofacial defects. The nanoZIF-8, ZIF-8@RIS, and PCL/ZIF-8@RIS scaffolds were characterized for their structural properties, porosity, mechanical strength, and zinc ion release. In vitro studies assessed cytocompatibility, osteogenic differentiation, and molecular pathways using MC3T3-E1 cells, employing immunofluorescence, genomic sequencing, qRT-PCR, and Western blot. In vivo, a rabbit calvarial defect model was used to evaluate bone regeneration, with outcomes analyzed through micro-CT, histology, and immunohistochemistry. Osteogenic pathways, including Wnt/β-catenin, P38 MAPK, and NF-κB signaling, were also investigated. The PCL/ZIF-8@RIS scaffolds exhibited excellent biocompatibility, enhancing cell adhesion and osteogenic differentiation in vitro. The PCL/ZIF-8@RIS-5 group showed significantly higher osteogenic activity, with mechanical properties resembling cancellous bone. In vivo, the scaffolds promoted bone regeneration in an osteoporotic defect model, with optimal outcomes in micro-CT and histological analysis. The scaffolds activated the MAPK/Akt signaling pathway, contributing to substantial bone regeneration. The PCL/ZIF-8@RIS scaffold, incorporating a drug delivery system through 3D printing, shows promising potential for enhancing bone regeneration in maxillofacial defects, offering a novel approach in bone tissue engineering.