Biodegradable hydrogels represent an effective healing biomaterial for wounds. However, the fabrication of smart hydrogels containing unstable hemiaminal structures remains challenging. Here, we report a biodegradable hemiaminal-type polymeric hydrogel with formaldehyde (FA)-fixed (FP-hydrogel), synthesized via a one-pot aldimine condensation of poly(ethylene glycol) diamines (PEG-DAs) and polyformaldehyde (PFA). This design leverages the stable semiclosed eight-membered cyclic hemiaminal structures within the hydrogel network, which confer remarkable mechanical strength, self-healing capability, and plasticity. The FP-hydrogel degrades in response to diverse biological signals, including acidic pH, reactive oxygen species (ROS), and glutathione (GSH). Active FA is released from FP-hydrogel under weakly acidic conditions (pH 6.5) with a release rate of 74% and displays a significant antibacterial effect, which enables the healing of acute bacterial-infected wounds at safer FA concentrations compared to the commercial urotropine. In addition, the hydrogel effectively scavenges overexpressed ROS in chronic diabetic wounds and modulates the wound microenvironment. Consequently, it accelerates the healing processes of both acute bacteria-infected and chronic diabetic wounds in vivo due to the specific responsiveness of hemiaminal structures to multiple physiological signals in the complex wound microenvironment, demonstrating its promising use as versatile and advanced wound dressings.
Yang et al. (2026) studied this question.