Ferritin Nanocage Conjugated Hybrid Hydrogel for Tissue Engineering and Drug Delivery Applications

Hydrogels have recently been attractive in various drug delivery and tissue engineering applications because of their structural similarities to the natural extracellular matrix. Despite enormous advances in the application of hydrogels, poor mechanical properties and lack of control for the release of drugs and biomolecules act as major barriers for widespread clinical applications. To overcome these challenges, we developed both physically and covalently conjugated nanocage-laden hydrogels between the surface of the nanocage and a gelatin methacryloyl (GelMA) hydrogel matrix. Ferritin and its empty-core equivalent apoferritin were used as nanocages that could be easily incorporated into a GelMA hydrogel via physical bonding. To fabricate covalently conjugated nanocage-laden GelMA hydrogels, ferritin and apoferritin were chemically modified to present the methacryloyl groups, ferritin methacryloyl (FerMA) and apoferritin methacryloyl (ApoMA), respectively. The covalently conjugated FerMA- and ApoMA-GelMA hydrogels offered a better ability to tune mechanical properties compared with those prepared by direct dispersion of ferritin and apoferritin into GelMA hydrogels with physical bonding, without affecting their porosity or cell growth. Furthermore, the ability of the nanocage to release small chemical compounds was confirmed by performing a cumulative release test on fluorescein isothiocyanate (FITC) encapsulated apoferritin and ApoMA incorporated GelMA hydrogels by pH stimulus. Thus, the nanocage incorporated hydrogels have emerged as excellent materials for drug delivery and tissue engineering applications.