Non-invasive monitoring of in vivo bone regeneration based on alkaline phosphatase-responsive scaffolds

Although numerous biomaterials have been fabricated as scaffolds for the application of tissue engineering, real-time non-invasive monitoring of in vivo bone regeneration is still a big challenge. Particularly, the early osteogenesis is difficult to detect using conventional imaging modalities, such as X-ray computed tomography (CT) and magnetic resonance imaging (MRI) due to the limited amount of neo-bone tissue. Herein we report on alkaline phosphatase (ALP)-responsive scaffolds, which are composed of a turn-on hemicyanine dye (LET-3) and a typical three dimensional (3D) printed bone tissue engineering scaffold (polycaprolactone/calcium silicate, PCL/CS), for real-time non-invasive monitoring of in vivo bone regeneration by near-infrared fluorescence (NIR-FL) and photoacoustic (PA) duplex imaging. ALP, an early-stage biomarker of bone formation, turns “on” the NIR-FL/PA signals of LET-3 in scaffolds both in vitro and in vivo. Thus, the osteogenic-associated bioactivity of LET-3 labeled scaffolds could be visualized by NIR-FL/PA dual-modal imaging. Our results provide a promising strategy for detecting neo-bone formation by the combination of ALP prober and bone tissue engineering scaffolds, which holds great potential for traceable tissue engineering.