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. Threedimensional (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.

Targeting Endogenous Reactive Oxygen Species Removal and Regulating Regenerative Microenvironment at Annulus Fibrosus Defects Promote Tissue Repair

“…CeNPs can improve the local microenvironment of AF defects, and TGF-β3 can continuously promote cell recruitment, where a good microenvironment is the foundation for tissue repair and regeneration. CeNPs have attracted much attention because of their favorable biological characteristics, such as antioxidant, anti-inflammatory, antibacterial, and angiogenesis potential. , Previous studies have failed to regulate the local microenvironment after AF injury, but in this study, CeNPs were used to eliminate ROS and regulate immune responses. Immunohistochemical staining showed decreased expression of pro-inflammatory TNF-α in the C-MSN/G-H and C-MSN-T/G-H hydrogel groups, and increased expression of the anti-inflammatory factor, IL-10, was observed in the C-MSN/G-H and C-MSN-T/G-H hydrogel groups (Figure E,F).…”

PgC3Mg metal–organic cages functionalized hydrogels with enhanced bioactive and ROS scavenging capabilities for accelerated bone regeneration

“…56 In addition, the bioactive components such as bone morphogenetic protein-2 (BMP-2)-associated peptide, ursodeoxycholic acid, smoothened agonist, or inorganic materials combined with antioxidant agents in bone tissue scaffolds can promote osteogenesis and bone formation by regulating antioxidant and osteogenic pathways. 20,28,57,58 However, a general and efficient approach for the development of highly bioactive and robust antioxidant scaffolds with biocompatible and biodegradable properties to promote bone tissue regeneration is lacking. Herein, the versatile PgC 3 Mg particles endow the conventional GelMA hydrogels with ROS scavenging ability and osteogenesis in critical cranial bone defects, suggesting tremendous translational potential as bone regenerative grafts.…”

3D Printed Hierarchical Porous Poly(ε-caprolactone) Scaffolds from Pickering High Internal Phase Emulsion Templating

“…20−22 On the other hand, electrospun scaffolds can mimic the native ECM topologically, chemically, mechanically, and biologically with their interconnected porosity; however, they are unable to produce mechanically stable 3D scaffolds with the hierarchical porous architecture needed for 3D organ regeneration, 6 whereas 3D printing enables the fabrication of hierarchical porous scaffolds with precise control over the shape, size, and pore morphology, simulating the desired application. 21 Consequently, it is essential to incorporate microporous architectures within hierarchical porous scaffolds produced by 3D printing, which can be achieved through using the inks, which contain a large number of sacrificial templates for the development of micropores. Among various ink precursor materials, hydrogel, emulsion, and polymer solution are the most widely explored to date.…”

“…Macroporous scaffolds can easily be obtained using porogen leaching, gas foaming, and solvent casting, but they lack uniformly designed interconnected porous structures. Also, the simultaneous incorporation of cells with high spatial control in these methods is not possible. − On the other hand, electrospun scaffolds can mimic the native ECM topologically, chemically, mechanically, and biologically with their interconnected porosity; however, they are unable to produce mechanically stable 3D scaffolds with the hierarchical porous architecture needed for 3D organ regeneration, whereas 3D printing enables the fabrication of hierarchical porous scaffolds with precise control over the shape, size, and pore morphology, simulating the desired application …”