Development of 4D-bioprinted shape-morphing magnetic constructs for cartilage regeneration using a silk fibroin-gelatin bioink
Juhi Chakraborty, Julia Fernández‐Pérez, Milad Takhsha Ghahfarokhi, Kenny A. van Kampen, Tim ten Brink, Jopeth Ramis, Maria Kalogeropoulou, Riccardo Cabassi, César de Julián Fernández, F. Albertini, Carlos Mota, Sourabh Ghosh, Lorenzo Moroni
Abstract
External magnetic fields can regulate cellular responses when interacting with magnetic nanoparticles (MNPs). Here, we develop a 4D-bioprinted construct by incorporating anisotropic MNPs into a silk fibroin-gelatin bioink with human bone-marrow-derived mesenchymal stromal cells for cartilage regeneration. We measure the magnetic-field-induced temperature response of the acellular construct, determine its mechanical response (actuation), and compare it with the MNPs. Constructs are then magnetically actuated, and their effects on chondrogenesis are investigated. Actuation is induced cyclically every other day (5 min and 30 min/day) for 21 days. Actuation for 30 min exhibits enhanced early (Sox-9 and aggrecan) and late (collagen-II) expression with downregulation of hypertrophic markers (collagen-X and matrix metalloproteinase-13) and enhanced matrix deposition, total collagen, and glycosaminoglycan compared to the constructs actuated for 5 min, kept static, or with no MNPs. Hence, magnetic field actuation could be a significant strategy to stimulate constructs mechanically for articular cartilage regeneration.