Application of 4D-Printed Magnetoresponsive FOGS Hydrogel Scaffolds in Auricular Cartilage Regeneration

Abstract

3D-printed hydrogel scaffolds are widely utilized in auricular cartilage tissue engineering. However, issues such as graft-related inflammation, poor mechanical properties, and the lack of external modulation of 3D-printed scaffolds in vivo have raised significant concerns. To address these challenges, a “fried egg” structure is designed, consisting of chitosan-coated ferroferric oxide magnetic nanoparticles (Fe₃O₄@CS MNPs), which are uniformly incorporated into hydrogel. Through 4D printing technology, magnetoresponsive hydrogel scaffolds are constructed to overcome the aforementioned limitations. The results demonstrated that, compared to 3D printing, 4D-printed magnetic hydrogel scaffolds significantly enhanced cartilage tissue regeneration in both in vitro and in vivo environments when subjected to an external magnetic field (MF). Furthermore, the mechanical strength of regenerated cartilage approached to that of natural cartilage. The chitosan coating on the surface of MNPs exhibited anti-inflammatory and antibacterial properties, promoting M2 polarization of macrophages and suppressing graft-related inflammation and bacteria. Transcriptomic analysis confirmed that MNPs modulate macrophage immunity by activating JAK2/STAT3 signaling pathway. Taken together, a magnetoresponsive multifunctional scaffold is designed that can be externally controlled by magnetic fields to promote ear cartilage tissue regeneration. The regenerated cartilage exhibits excellent biocompatibility, anti-inflammatory, antibacterial properties, and mechanical performance, providing new insights for auricular cartilage tissue engineering.