3D‐Printed Biocompatible Scaffolds with Built‐In Nanoplasmonic Sensors

Abstract 3D printing strategies have acquired great relevance toward the design of 3D scaffolds with precise macroporous structures, for supported mammalian cell growth. Despite advances in 3D model designs, there is still a shortage of detection tools to precisely monitor in situ cell behavior in 3D, thereby allowing a better understanding of the progression of diseases or to test the efficacy of drugs in a more realistic microenvironment. Even if the number of available inks has exponentially increased, they do not necessarily offer the required functionalities to be used as internal sensors. Herein the potential of surface‐enhanced Raman scattering (SERS) spectroscopy for the detection of biorelevant analytes within a plasmonic hydrogel‐based, 3D‐printed scaffold is demonstrated. Such SERS‐active scaffolds allow for the 3D detection of model molecules, such as 4‐mercaptobenzoic acid. Flexibility in the choice of plasmonic nanoparticles is demonstrated through the use of gold nanoparticles with different morphologies, gold nanorods showing the best balance between SERS enhancement and scaffold transparency. Detection of the biomarker adenosine is also demonstrated as a proof‐of‐concept toward the use of these plasmonic scaffolds for SERS sensing of cell‐secreted molecules over extended periods of time.