Enhanced Bone Regeneration Using a ZIF‐8‐Loaded Fibrin Composite Scaffold

In the present study, fibrin-based biomaterials made of zeolite imidazole framework-8 (ZIF-8) and fibrin gel (Z-FG) are fabricated with the aim of enhancing skull regeneration. X-ray diffraction (XRD), scanning electron microscopy (SEM), ultraviolet (UV)-vis spectrophotometry, Fourier transform infrared spectroscopy, and rheometry are used to characterize ZIF-8 and Z-FG. The influences of ZIF-8 on the physical properties of fibrin gel (e.g., porosity, modulus, and in vitro biodegradation) are investigated, and the effect of ZIF-8 concentration on fibrin gel properties in vitro is determined by seeding ectomesenchymal stem cells (EMSCs) over Z-FG. EMSC osteogenic differentiation reveals higher expression of bone-related proteins and higher calcium deposition and alkaline phosphatase activity, indicating that Z-FG may be a good osteoinductive biomaterial. Furthermore, these results show that the piezochannel and yes-associated protein (YAP) signaling pathway are involved in the differentiation process. In addition, the in vivo results demonstrate that Z-FG increases bone formation in critical-sized calvarial defects in rats. Thus, the developed composite scaffold may be a suitable biomaterial for skull tissue-engineering applications.