Osteogenesis of Iron Oxide Nanoparticles-Labeled Human Precartilaginous Stem Cells in Interpenetrating Network Printable Hydrogel

Abstract

Smart biomaterials combined with stem cell-based therapeutic strategies have brought innovation in the field of bone tissue regeneration. However, little is known about precartilaginous stem cells (PCSCs), which can be used as seed cells and incorporated with bioactive scaffolds for reconstructive tissue therapy of bone defects. Herein, iron oxide nanoparticles (IONPs) were employed to modulate the fate of PCSCs, resulting in the enhanced osteogenic differentiation potential both in vitro and in vivo. PCSCs were isolated from the ring of La-Croix extracted from polydactylism patient and identified through immunohistochemically staining using anti-FGFR-3 antibodies. Potential toxicity of IONPs toward PCSCs was assessed through cell viability, proliferation, and attachment assay, and the results demonstrated that IONPs exhibited excellent biocompatibility. After that, the effects of IONPs on osteogenic differentiation of PCSCs were evaluated and enhanced ALP activity, formation of mineralized nodule, and osteogenic-related genes expressions could be observed upon IONPs treatment. Moreover, in vivo bone regeneration assessment was performed using rabbit femur defects as a model. A novel methacrylated alginate and 4-arm poly (ethylene glycol)-acrylate (4A-PEGAcr)-based interpenetrating polymeric printable network (IPN) hydrogel was prepared for incorporation of IONPs-labeled PCSCs, where 4A-PEGAcr was the common component for three-dimensional (3D) printing. The implantation of IONPs-labeled PCSCs significantly accelerated the bone formation process, indicating that IONPs-labeled PCSCs could endow current scaffolds with excellent osteogenic ability. Together with the fact that the IONPs-labeled PCSCs-incorporated IPN hydrogel (PCSCs-hydrogels) was biosafety and printable, we believed that PCSCs-hydrogels with enhanced osteogenic bioactivity could enrich the stem cell-based therapeutic strategies for bone tissue regeneration.