Manganese-doped oleic acid functionalized whitlockite/polycaprolactone nanocomposite scaffolds enhance bone regeneration through improved dispersibility and antioxidative capacity

Bone defects present significant clinical challenges due to the complexities of healing. While polycaprolactone (PCL) scaffolds offer promising mechanical support for bone tissue engineering, their limited bioactivity and dispersibility issues with bioactive fillers restrict their effectiveness. Here, we develop manganese-doped oleic acid-functionalized whitlockite (Mn-OAWH) nanoparticles designed to enhance both the mechanical and biological properties of PCL scaffolds. The nanoparticles were synthesized via a hydrothermal approach using oleic acid as both solvent and surface ligand, enabling superior dispersibility in dichloromethane and uniform integration with PCL. Characterization of the resulting 3D printed Mn-OAWH/PCL composite scaffolds confirmed enhanced compressive strength, supported by both mechanical testing and finite element analysis. In vitro studies demonstrated that the release of Mn 2+ , Mg 2+ , and Ca 2+ ions significantly promoted osteogenic proliferation, exhibited strong antioxidative properties, and accelerated osteogenic differentiation. Furthermore, in vivo implantation in a rat critical-sized cranial defect model revealed significantly improved bone formation compared to undoped and PCL-only controls. These findings establish Mn-OAWH/PCL composite scaffolds as a promising platform for bone tissue engineering, offering both enhanced mechanical support and biological functionality through improved nanoparticle dispersibility, strong antioxidative properties and osteogenic activity.