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Bone defects in patients entail the microenvironment that needs to boost the functions of stem cells (e.g., proliferation, migration, and differentiation) while alleviating severe inflammation induced by high oxidative stress. Biomaterials can help to shift the microenvironment by regulating these multiple events. Here we report multifunctional composite hydrogels composed of photo-responsive Gelatin Methacryloyl (GelMA) and dendrimer (G3)-functionalized nanoceria (G3@nCe). Incorporation of G3@nCe into GelMA could enhance the mechanical properties of hydrogels and their enzymatic ability to clear reactive oxygen species (ROS). The G3@nCe/GelMA hydrogels supported the focal adhesion of mesenchymal stem cells (MSCs) and further increased their proliferation and migration ability (vs. pristine GelMA and nCe/GelMA). Moreover, the osteogenic differentiation of MSCs was significantly stimulated upon the G3@nCe/GelMA hydrogels. Importantly, the capacity of G3@nCe/GelMA hydrogels to scavenge extracellular ROS enabled MSCs to survive against H2O2-induced high oxidative stress. Transcriptome analysis by RNA sequencing identified the genes upregulated and the signalling pathways activated by G3@nCe/GelMA that are associated with cell growth, migration, osteogenesis, and ROS-metabolic process. When implanted subcutaneously, the hydrogels exhibited excellent tissue integration with a sign of material degradation while the inflammatory response was minimal. Furthermore, G3@nCe/GelMA hydrogels demonstrated effective bone regeneration capacity in a rat critical-sized bone defect model, possibly due to an orchestrated capacity of enhancing cell proliferation, motility and osteogenesis while alleviating oxidative stress.

Bioactive phosphate glasses incorporated with Zn2+ (predicted to be useful for bone regeneration applications) were synthesized. Characterization of the bioglasses were done using XRD, FTIR, SEM, and EDS techniques, both prior to and after soaking in simulated body fluid (SBF) solution. The bioactive performance of samples was evaluated by incubated in SBF for different days by means of the pH measuring and comparing the results of XRD and SEM studies. The obtained results show the formation of hydroxyapatite (HAP) layer on the surface of as-developed bioactive glasses. The degradation of the samples evaluated by weight loss and pH of the remnant solution measured as functions of ZnO concentration and immersion time revealed the enhanced formation of HAP layer on the sample surface. The results further indicated the rate of degradation can be monitored by tailoring the concentration of ZnO and immersion time. The studies were also extended to in vitro cytocompatibility and cell proliferation measurements on rMSC using CCK-8 for incubation periods of 24 h and 72 h. These studies have revealed the considerable levels of rMSC proliferation and improved viability within the limits of nontoxic levels. The measurements of antibacterial activity of ZnO-doped phosphate bioactive glasses against E. coli and S. aureus, carried out for 24 h and 48 h have confirmed their potential antibacterial activity. Finally, quantitative analysis of these results confirmed an enhanced in vitro biological and antibacterial activity of the samples due to the ZnO doping and subsequent controlled release of Zn2+ ions in the glass matrix.