4D‐Printable Poly(Thio)urethane Photoresins With Reactive Oxygen Species Responsiveness and Anti‐Inflammatory Functionality

ABSTRACT Stimuli‐responsive polymers, particularly those sensitive to reactive oxygen and nitrogen species (RONS), are emerging as promising materials for 4D printing in regenerative medicine. Their ability to respond to oxidative stress makes them highly suitable for treating diseases like cancer, diabetes, spinal cord injury, etc., where RONS and inflammation contribute to severe tissue damage. Herein, we report the development of digital light processing (DLP) 3D printable poly(thio)urethane (PSU) thermosets through UV‐light activated click‐reaction between a thiol crosslinker, and difunctional aliphatic isocyanates based on polypropyleneglycol‐di‐isophorone diisocyanate (PPG‐di‐IPDI) or poly(ethylene glycol)‐block‐poly(propylene glycol)‐block‐poly(ethylene glycol)‐di‐isophorone diisocyanate (PluronicL35‐di‐IPDI), containing 50 wt.% of poly(ethylene glycol) (PEG), catalyzed by using a photobase generator system composed of a triazabicyclodecene tetraphenylborate salt (TBD·BPh 4 ) and 2‐isopropylthioxanthone (ITX). The PSU printed materials exhibit ROS‐responsiveness, as they increase their hydrophilicity and flexibility in the presence of 1 mM H 2 O 2 . Finally, the cytotoxicity of PSU materials is evaluated in vitro with human fibroblasts (MRC‐5) and murine microglia (BV‐2). PSU materials containing 100 wt.% PPG in the network (PSU1) are non‐cytotoxic, showing metabolic activities comparable to the control and good cell viability. In contrast, PEG‐containing PSU materials, with 25 and 50 wt.% PEG (PSU2 and PSU3 respectively), exhibit reduced cell compatibility. In addition, PSU1 materials effectively reduce nitric oxide production and TNF‐α levels in LPS‐stimulated BV‐2 cells up to basal levels, ≈ 1 µM nitrites and ≈ 4.8 pg mL − 1 TNF‐α. These findings pave the way for the development of 4D printable scaffolds with built‐in anti‐inflammatory properties for tissue engineering avoiding traditional radical mediated fabrication methods on DLP manufacturing.