Novel 3D-Printed Biophotonic Scaffold Displaying Luminescence under Near-Infrared Light for Photopharmacological Activation

The development of platforms for precise spatiotemporal control over drug activity remains a central goal in photopharmacology. While photoswitchable compounds offer powerful opportunities for light-mediated modulation of biological systems, their application in deep tissues is limited by poor penetration of activating wavelengths in the UV–visible range. Upconversionbased strategies provide a promising solution by converting tissue-penetrant near-infrared (NIR) light into higher-energy photons capable of triggering photochemical processes locally. Here, we report the design and characterization of 3D-printed, bioresorbable biophotonic scaffolds embedded with upconversion (UC) crystals, enabling localized NIR-to-visible light conversion for on-demand activation of photoswitchable molecules. These scaffolds act as implantable optical transducers, combining structural functionality with remote optical control. We demonstrate that the scaffolds exhibit stable upconversion emission under NIR excitation and maintain chemical integrity in simulated physiological conditions. Importantly, their emission is sufficient to drive biologically relevant photoreactions, including the controlled release of nitric oxide (NO) and the photoisomerization of the muscarinic photoswitchable ligand PhthalimideAzo-Iperoxo (PAI), enabling receptor-level modulation under NIR illumination. This work establishes bioresorbable upconversion scaffolds as a versatile strategy for deep-tissue photopharmacology, enabling minimally invasive, spatially confined, and temporally precise control of drug activity using NIR light.