In this work, we report the design and fabrication of a light-addressable, paper-based nanocomposite scaffold for optical pacing and read-out of in vitro grown cardiac tissue. The scaffold consists of paper cellulose microfibers functionalized with gold nanorods (GNRs) and semiconductor quantum dots (QDs), embedded in a cell-permissive collagen matrix. The GNRs enable cardiomyocyte activity modulation through local temperature gradients induced by modulated near-infrared (NIR) laser illumination, with the local temperature changes reported by temperature-dependent QD photoluminescence (PL). The micrometer-sized paper fibers promote the tubular organization of HL-1 cardiac muscle cells, while the NIR plasmonic stimulation modulates reversibly their activity. Given the nanoscale spatial resolution and facile fabrication, paper-based nanocomposite scaffolds with NIR modulation offer excellent alternatives to electrode-based or optogenetic methods for cell activity modulation, at the single cell level, and are compatible with 3D tissue constructs. Such paper-based optical platforms can provide new possibilities for the development of in vitro drug screening assays and heart disease modeling.
Keywords: 3D cardiac construct; cardiomyocyte pacing; paper-based cell scaffold; plasmonic modulation; quantum dot nanothermometer.