Surface Decoration of Redox-Modulating Nanoceria on 3D-Printed Tissue Scaffolds Promotes Stem Cell Osteogenesis and Attenuates Bacterial Colonization.

Abstract

Oxidative stress at the bone defect site delays the bone regeneration process. Increased level of reactive oxygen species (ROS) is the primary cause of oxidative stress at the damaged site. Bone tissue scaffolds that scavenge ROS offer a potential and yet unexplored route for faster bone healing. Cerium oxide (ceria) is known for its redox-modulating behavior. Three-dimensional (3D)-printed porous scaffolds fabricated from degradable polymers provide a physical microenvironment but lack the bioactivity for tissue regeneration. In this work, porous poly(lactic acid) (PLA) scaffolds were prepared by 3D printing and modified with poly(ethylene imine) and citric acid to decorate with ceria nanoparticles. Scanning electron micrographs revealed a macroporous architecture decorated with ceria particles. The compressive modulus of 27 MPa makes them suitable for trabecular bone. The scaffolds supported human mesenchymal stem cell growth, confirming cytocompatibility. The ability to scavenge ROS confirmed that surface functionalization with ceria could reduce oxidative stress levels in the cells. Stem cell osteogenesis was enhanced after ceria decoration of the PLA scaffolds. Transcriptional profiling studied by sequencing revealed changes in the expression of genes associated with inflammation and cell-material interactions. The ceria-functionalized scaffolds show enhanced antibacterial activity against both Gram-negative and Gram-positive bacterial strains. These results demonstrate that surface decoration with nanoceria offers a viable route for enhancing the bioactivity of 3D-printed PLA scaffolds for bone tissue regeneration with ROS scavenging and antibacterial capability.