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Nanocomposite (NC) hydrogels have been widely studied due to their tunable biochemical/ physical properties for tissue engineering and biomedical applications. Nanoparticles (NPs) that can carry bioactive hydrophilic/hydrophobic molecules and provide sustained release within hydrogels are an ideal all-in-one-platform for local drug delivery applications. Dual delivery of different bioactive molecules is desired to achieve synergetic therapeutic effect in biomedical applications. For example, the co-administration of drug molecules and oxygen (O2) is an ideal choice to improve cell viability, while reducing the harmful effects of hypoxia. Therefore, we prepared drug-loaded O2-carrying periodic mesoporous organosilica (PMO-PFC) NPs and their 3D-printable hydrogel precursors based on gelatin methacryloyl (GelMa) to fabricate 3D-scaffolds to improve cell-viability under both normoxia (21% O2) and hypoxia (1% O2) conditions. We used rutin as the hydrophobic drug molecule to demonstrate that our O2-carrying PMO-PFC NPs can improve hydrophobic drug loading and their sustained delivery over 7 days, while supporting sustained O2-delivery for 14 days under hypoxia conditions. Furthermore, the fibroblast cells were interacted with NC hydrogel scaffolds to test their impact on cell-viability under both normoxia and hypoxia conditions. The improved rheological properties suggest the prepared NC hydrogels can be further tested or used as an injectable hydrogel. The improved mechanical properties and 3D printability of NC hydrogels indicate their potential use as artificial tissue constructs.

3D-Printable Oxygen- and Drug-Carrying Nanocomposite Hydrogels for Enhanced Cell Viability