Thioketal-Based Polymers for Biomedical Applications: Structure Design, Properties, And Perspectives

Reactive oxygen species (ROS) are highly enriched in pathological microenvironments such as inflammation, tumors, and ischemia-reperfusion, providing an endogenous trigger for on-demand drug release, degradation, and clearance. The thioketal (TK) moiety is stable under normal physiological conditions but undergoes oxidative cleavage in elevated ROS environments, making it a foundational motif for designing ROS-responsive polymers. The TK-based polymers, including linear poly(thioketal) (PTK), polyurethanes, and hyperbranched polymers, enable precise control of degradation kinetics, mechanical properties, and drug-release profiles by adjusting parameters such as TK content, backbone hydrophilic–hydrophobic balance, and branching architecture. These polymers have been fabricated into hydrogels, micro/nanoparticles, electrospun fibers, and porous scaffolds demonstrating synergistic ROS-scavenging and stimulus-responsive release in models of acute lung injury, wound repair, myocardial infarction, spinal cord injury, and neuronal regeneration. This Viewpoint summarizes the design strategies, structure–property relationships, and biomedical applications of TK-based polymers, highlights major challenges including ROS heterogeneity in vivo, biosafety of degradation byproducts, and scalable synthesis, and proposes perspectives to advance the TK-based polymers toward clinical and industrial translation.