NIR-II photothermal-driven pulsatile PTH release for osteoporotic bone repair

Integrating light-controlled intelligent materials into three-dimensional (3D) printing technology holds great promise for bone tissue engineering, enabling spatiotemporal control over in situ drug dosing. However, this integration faces a critical molecular design challenge, as incorporated photoresponsive molecules must simultaneously fulfill the dual demands of high ultraviolet (UV)-stability during UV-mediated photopolymerization, and strong long-wavelength absorption for deep-tissue activation. Here, we report a wavelength-selective quinolinium dye (QC7CN) as photoresponsive 'dye ink' for addressing this dilemma. This dye features high UV transparency that ensures stability during the printing process, while possessing robust second near infrared (NIR-II) absorbance for deep-seated photothermal responsiveness. Leveraging these properties, we engineer an NIR-II light-controlled 3D-printed scaffold, composed of methacryloylated gelatin and calcium phosphate oligomers as a printing matrix, thermosensitive phase-transformable microspheres as a parathyroid hormone (PTH) drug carrier and QC7CN as a photothermal trigger. Upon NIR-II laser irradiation, QC7CN induces localized mild hyperthermia to drive the gel-sol phase transition of microspheres, thereby manipulating pulsatile PTH release for deep-tissue osteoporotic bone repair. As such, our study provides a full demonstration in molecular design and additive manufacturing to push the limits of intelligent materials in precision medicine.