Alveoli‐Like Multifunctional Scaffolds for Optical and Electrochemical In Situ Monitoring of Cellular Responses from Type II Pneumocytes

Abstract

While breathing, alveoli are exposed to external irritants, which contribute to the pathogenesis of lung disease. Therefore, in situ monitoring of alveolar responses to stimuli of toxicants under in vivo environments is important to understand lung disease. For this purpose, 3D cell cultures are recently employed for examining cellular responses of pulmonary systems exposed to irritants; however, most of them have used ex situ assays requiring cell lysis and fluorescent labeling. Here, an alveoli‐like multifunctional scaffold is demonstrated for optical and electrochemical monitoring of cellular responses of pneumocytes. Porous foam with dimensions like the alveoli structure is used as a backbone for the scaffold, wherein electroactive metal–organic framework crystals, optically active gold nanoparticles, and biocompatible hyaluronic acid are integrated. The fabricated multifunctional scaffold allows for label‐free detection and real‐time monitoring of oxidative stress released in pneumocytes under toxic‐conditions via redox‐active amperometry and nanospectroscopy. Moreover, cellular behavior can be statistically classified based on fingerprint Raman signals collected from the cells on the scaffold. The developed scaffold is expected to serve as a promising platform to investigate cellular responses and disease pathogenesis, owing to its versatility in monitoring electrical and optical signals from cells in situ in the 3D microenvironments.

Dynamic 3D in vitro lung models: applications of inorganic nanoparticles for model development and characterization

“…185–187 Especially plasmonic AuNPs find popularity as optical enhancing agents, given their easy surface modification, chemical stability as well as biocompatibility, and have found applications across numerous in vitro lung studies. 188–191 They provide contrast, in the context of surface enhanced Raman spectroscopy (SERS) imaging, a sensitive, label-free, non-invasive characterization technique, 192 as well as in computer tomography (CT). 184 Importantly, they can be combined with fluorescent imaging 193 or additional techniques.…”

“…Based on this concept, and as performed before for an in vitro breast cancer model, 144,204 Eom et al have developed multifunctional alveolar scaffolds coated with AuNPs, to monitor real time alveolar cell responses. 188 The backbone of the scaffolds was based on nickel foam with integrated electroactive metal–organic framework crystals and AuNPs, functionalized with hyaluronic acid and seeded with A549 cells (alveolar epithelial cells) (Fig. 7A).…”