An Engineered Living Material With Pro‐Angiogenic Activity Inducible by Near‐Infrared Light

Abstract

Impaired angiogenesis is a central barrier in the treatment of chronic and deep tissue wounds, preventing progression through the normal healing cascade. While the combination of near infrared (NIR) photobiomodulation and pro-angiogenic growth factors has shown synergistic therapeutic benefit, the clinical translation of growth factor therapy is hindered by high cost, instability, and the need for localized dosing to avoid aberrant vasculature. Peptidomimetics such as the VEGF-derived QK peptide offer a more stable and predictable alternative, but still require a means for localized, tunable presentation. Here, we establish an engineered living material-based delivery system that responds to clinically relevant NIR light to produce and release a QK-Fusion protein directly at the target site. The probiotic Escherichia coli Nissle 1917 was engineered with an 800 nm-responsive optogenetic circuit and encapsulated within an optimized alginate core–shell hydrogel that ensures biocontainment while allowing controlled outward diffusion of the secreted peptide. The released peptide remains non-cytotoxic, capable of binding extracellular matrix analogs, and promotes angiogenesis in endothelial cultures and the chick chorioallantoic membrane assay. We thus establish a strategy for developing engineered living materials toward remote-controlled angiogenic stimulation.