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Injectable in situ‐forming scaffolds that induce both angiogenesis and osteogenesis have been proven to be promising for bone healing applications. Here, we report the synthesis of an injectable hydrogel containing cobalt‐doped bioactive glass (BG)‐loaded microspheres. Silk fibroin (SF)/gelatin microspheres containing BG particles were fabricated through microfluidics. The microspheres were mixed in an injectable alginate solution, which formed an in situ hydrogel by adding CaCl2. The hydrogel was evaluated for its physicochemical properties, in vitro interactions with osteoblast‐like and endothelial cells, and bone healing potential in a rat model of calvarial defect. The microspheres were well‐dispersed in the hydrogel and formed pores of >100 μm. The hydrogel displayed shear‐thinning behavior and modulated the cobalt release so that the optimal cobalt concentration for angiogenic stimulation, cell proliferation, and deposition of mineralized matrix was only achieved by the scaffold that contained BG doped with 5% wt/wt cobalt (A‐S‐G5Co). In the scaffold containing higher cobalt content, a reduced biomimetic mineralization on the surface was observed. The gene expression study indicated an upregulation of the osteogenic genes of COL1A1, ALPL, OCN, and RUNX2 and angiogenic genes of HIF1A and VEGF at different time points in the cells cultured with the A‐S‐G5Co. Finally, the in vivo study demonstrated that A‐S‐G5Co significantly promoted both angiogenesis and osteogenesis and improved bone healing after 12 weeks of follow‐up. These results show that incorporation of SF/gelatin microspheres containing cobalt‐doped BG in an injectable in situ‐forming scaffold can effectively enhance its bone healing potential through promotion of angiogenesis and osteogenesis. [ABSTRACT FROM AUTHOR]

Employing 3D printing bone scaffolds with various polymers is growing due to their biocompatibility, biodegradability, and good mechanical properties. However, their biological properties need modification to have fewer difficulties in clinical experiments. Herein, the fused‐deposition modeling technique is used to design triply‐periodic‐minimal‐surfaces polylactic‐acid scaffolds and evaluate their biological response under static and dynamic cell culture conditions. To enhance the biological response of 3D‐printed bone scaffolds, graphene‐oxide (GO) is coated on the surface of the scaffolds. Fourier‐transform infrared spectroscopy, X‐ray diffraction, and energy‐dispersion X‐ray analysis are conducted to check the GO presence and its effects. Also, computational fluid dynamics analysis is implemented to investigate the shear stress on the scaffold, which is a critical parameter for cell proliferation under dynamic cell culture conditions. Compression tests and contact‐angle measurements are performed to assess the GO effect on mechanical properties and wettability, respectively. Also, it was shown that surface‐treated scaffolds have lower mechanical properties and higher wettability than uncoated scaffolds. A perfusion bioreactor is used to study cell culture. Also, field‐emission‐scanning‐electron‐microscope and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5 diphenyl‐tetrazolium‐bromide (MTT) assay analyses are conducted to observe cell viability and cell attachment. An increase of up to 220% in viability was achieved with GO and dynamic cell culture. [ABSTRACT FROM AUTHOR]