Biocompliant Composite Au/pHEMA Plasmonic Scaffolds for 3D Cell Culture and Noninvasive Sensing of Cellular Metabolites

The field of 3D printing is an area of active research, with a substantial focus given to the design and construction of customized tools for applications in technology. There exists a particular need in these developing areas of opportunity for new multi‐functional soft materials that are biologically compatible for the growth and directed culturing of cells. Herein, a composite material consisting of gold nanoparticles with useful plasmonic properties embedded within a highly hydrophilic poly‐2‐hydroxyethylmethacrylate matrix is described and characterized. This composite material serves dual functions as both host framework scaffold for cell lines such as pre‐osteoblasts as well as a plasmonic biosensor for in situ measurements of living cells. The plasmonic properties of this system are characterized as a function of the material properties and related to compositional features of the material through a proposed light‐directed mechanism. This chemistry provides a tunable, 3D printable plasmonic composite material of encapsulated gold nanoparticles in a biologically‐compliant, acrylate‐based hydrogel matrix. Surface‐enhanced Raman scattering studies of 3D‐microcultures supported by the scaffolds are carried out and the strong influence of perm‐selective molecular diffusion in its analytical responses is established. Most notably, specific, largely hydrophilic, cellular metabolites are detected within the supported live cultures. A printable plasmonic hydrogel composite material for 3D cell culture and non‐invasive sensing of cellular metabolites is presented. Printability of the material is improved by growing AuNPs post‐printing via an in situ reduction of Au3+ ions. Murine osteoblasts are successfully cultured on the scaffolds and cellular metabolites are detected using surface‐enhanced Raman spectroscopy.