Macroporous hydrogel loaded with AIE-photosensitizer for enhanced antibacterial and wounds healing

Effective wound healing requires precise immune regulation, including infection clearance to prevent excessive immune cell activation and polarization of macrophages. Therapeutic systems with combined immunomodulatory effects are crucial. Photodynamic therapy (PDT) is a promising antimicrobial treatment(AIE), with photosensitizers (PSs) playing a central role. The PSs with aggregation-induced emission can efficiently generate reactive oxygen species (ROS) in the aggregated state, making them workable in high concentration. Introduction of a biocompatible carrier is beneficial for the PSs' immobilization and distribution and hydrogels are excellent candidates. It is pursuing to design a PS-hydrogel system with synergetic effect. Type II PSs can generate singlet oxygen under sufficient oxygen. Macroporous hydrogels (MPHs) own superiorities in matter transport and immune cell adhesion reduction. Herein, an AIE-PS, TCSPy⁺ was designed. With its nanoparticles (NPs), an MPH dressing was developed using a facile extrusion-sequential-photo-crosslinking method based on PEGDA and GelMA. In vitro and in vivo studies demonstrated that TCSPy⁺@MPH dressing exhibited superior antibacterial activity compared to non-porous hydrogel-based one, significantly inhibiting excessive immune cell activation and polarization of macrophages. The macroporous structure also facilitated inflammatory exudates removal. The synergetic effect with the combined immunomodulation ability allows the dressing to efficiently treat infected wounds, offering an effective strategy to design advanced therapeutic systems for tissue regeneration and immune regulation.