Three‐Dimensional‐Printed Polylactic Acid Scaffolds Coated With a Paeonol‐Incorporated Gelatin/Bioactive Glass Composite Layer for Enhanced Osteogenic Performance

Customizable three-dimensional (3D)-printed scaffolds in bone tissue engineering (BTE) are considered promising alternatives to conventional grafting techniques. Polylactic acid (PLA), an FDA-approved biodegradable synthetic polymer, is widely used in 3D printing owing to its excellent mechanical strength, particularly at load-bearing sites. However, its inherent hydrophobicity impedes tissue regeneration. Paeonol (PN) is a naturally occurring phenolic compound with diverse therapeutic properties, but its osteogenic potential remains largely unexplored, and its poor aqueous solubility and low bioavailability necessitate an efficient delivery system. Hence, to enhance the bioactivity of PLA and PN, the 3D-printed PLA scaffolds coated with gelatin (GEL)/bioactive glass (BG) containing PN (PLA/GEL/BG-PN) were developed to achieve sustained and localized delivery of PN for potential bone regeneration. The primary objective of this study was to evaluate the osteogenic potential of the developed scaffolds. Comprehensive analyses revealed that the incorporation of GEL/BG significantly enhanced swelling, degradation behavior, and protein adsorption of the 3D-printed PLA scaffolds, whereas the inclusion of PN did not significantly alter these characteristics. Furthermore, these scaffolds were biocompatible with mouse mesenchymal stem cells and significantly promoted osteoblastic differentiation, as evidenced by cellular and molecular studies. Therefore, these findings suggest that PLA/GEL/BG-PN scaffolds are promising materials for BTE applications.