The additive manufacturing of stimuli-responsive polymers has gained increasing attention for the development of customized 3D/4D printed scaffolds that respond to biological stimuli for personalized medicine purposes. Among different biological stimuli, reactive oxygen species (ROS) have emerged as powerful cell-signaling agents in disease but also in physiology. ROS effect can vary from beneficial cell survival to non-desirable oxidative stress when they are overproduced, thus causing inflammation, cancer, and age-related diseases.[1] The controlled production of ROS through exogenous stimuli such as light is expected to provide lower invasiveness, relying on wireless stimulation, reversibility, and high spatial selectivity. Semiconducting polymers, originally used in organic electronics, are attracting increasing attention as phototriggers of ROS due to their biocompatibility, intrinsic conductivity and optical properties.[2]

In previous works, we focused on poly(3-hexylthiophene) (P3HT) materials processed in the form of thin films and nanoparticles whose performance was influenced by the π-conjugated semiconducting polymer structure and its 3D confinement during the nanomaterial formation. All those features clearly modulated the photophysical processes and ultimately determined their biophotonic applications.[3, 4] Here, we will present different strategies to modulate the ROS production through the design of 3D/4D tailor-made polymer scaffolds via digital light printing (DLP). To that aim, we designed ROS responsive hydrogels through the use of P3HT semiconducting polymer nanoparticles (SPNs), which acted as both visible-light photoinitiators and photosensitizers in 3D printable acrylic hydrogels. Interestingly, P3HT SPNs retained their photoelectrochemical properties when embedded within the polymer hydrogels, showing photocurrent densities that range from ∼0.2 to ∼1.1 μA cm⁻² depending on the intensity of the visible light-lamp (λ = 467 nm). Second, they can be used as photosensitizers (PS) to generate reactive oxygen species (ROS), 12–15 μM H₂O₂, on demand. The acrylic hydrogels containing P3HT SPNs do not exhibit cytotoxic effects under normal physiological conditions in the darkness against mouse glioma 261 (GL261) cells and S. aureus bacteria. However, they induce a ∼50% reduction GL261 cancer cell viability and a ∼99% S. aureus cell death in contact with them upon illumination (λ = 467 nm) due to the localized overproduction of ROS, which makes them attractive candidates for photodynamic therapies (PDT).[5]