Gold Nanoturf-Mediated Wireless Photothermal Upregulation of Human Adipose-Derived Stem Cell Spheroids for Synergistic Skin-Wound Closure.

3D stem cell aggregates at the sub-millimeter feature, known as spheroids, have garnered significant interest for their capability to effectively heal and close wound areas. Nevertheless, further efforts to unlock their maximal therapeutic potential and to address engineering challenges are required for medical/clinical translation. Herein, a wireless skin wound care platform designed for multimodal therapy, combining photothermal, stem cell, and light (PTSCL) effects to enhance therapeutic efficacy, is presented. The synergy is achieved by integrating a wireless LED module that irradiates visible light (630 nm-wavelength) and human adipose-derived stem cells (hADSCs) spheroid-laden polydimethylsiloxane (PDMS) patch embedded with a light-to-heat converting membrane (i.e., Au-coated nanoturf). This wireless platform primarily enables photothermal stimulation at the wound site, facilitating hADSC spheroid formation and upregulation via heat shock protein-mediated mechanism, and effective delivery of spheroids from the patch. Additionally, the photothermal approach, comprising mild hyperthermia and light stimulation, independently utilized to promote wound healing, exhibits a synergistic therapeutic effect. Collected data from visual/computational analysis, in vitro assays, and in vivo experiments in a mouse wound model (2 cm-by-2 cm) provide evidence for the synergistic effect of the proposed PTSCL treatment and suggest its potential to be implemented for tissue regeneration for severe wound patients.