Enhancing Optical Coherence Tomography Contrast of Corneal Stromal Stem Cells Using Gold Nanobipyramids

Gold nanobipyramids (GNBPs) were investigated as near-infrared contrast agents for optical coherence tomography (OCT) tracking of human corneal stromal stem cells (CSSCs). GNBPs with various longitudinal localized surface plasmon resonance peaks were synthesized, and the variant with a peak at 855 nm (GNBPs-1), closest to the central wavelength of the OCT system, exhibited optimal OCT signal enhancement. To improve stability and biocompatibility, GNBPs-1 were PEGylated. In vitro studies confirmed that PEGylated GNBPs were non-toxic to human CSSCs at concentrations up to 1.6 × 10⁷ particles per cell. At a labeling concentration of 2 × 10⁶ particles per cell, the OCT signal intensity increased by approximately threefold and remained detectable for at least 48 h. The OCT signal intensity and the number of detectable cells correlated closely with cell status upon GNBP-labeling, indicating enhanced tracking of intact transplanted cells. Ex vivo experiments using rabbit corneas demonstrated that GNBP-labeled CSSCs embedded in hydrogel exhibited significantly enhanced OCT contrast compared to unlabeled cells, with signal persistence for more than seven days. Overall, these results identify GNBPs as effective, non-toxic, and long-lasting OCT contrast agents for donor corneal stromal stem cell tracking, highlighting their potential for use in corneal regenerative therapies.