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

Integrating light-controlled intelligent materials into 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 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 printing process, while possessing robust second near infrared (NIR-II) absorbance for deep-seated photothermal responsiveness. Leveraging these properties, we engineer a NIR-II light-controlled 3D-printed scaffold, composed of methacryloylated gelatin and calcium phosphate oligomers as printing matrix, thermosensitive phase-transformable microspheres as parathyroid hormone (PTH) drug carrier, and QC7CN as photothermal trigger. Upon NIR-II laser irradiation, QC7CN induces localized mild hyperthermia to drive 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.