Redox-Responsive Polymer Dot Nanozymes Coordinate Exosome-Mediated Cutaneous Regeneration via Laser-Modulated Microenvironment Remodeling

Cutaneous wound healing is orchestrated by tightly coordinated biochemical and biomechanical cues that regulate epithelial activation, angiogenesis, and extracellular matrix (ECM) remodeling. However, nanozyme-based biomaterial platforms capable of dynamically regulating the wound microenvironment remain limited. Here, we develop a nanozyme-enabled regenerative platform in which redox-responsive hyperbranched polymer dot nanozymes (PDNs) are integrated with porcine fallopian tube stem cell–derived exosomes and picosecond laser stimulation to modulate phase-specific microenvironmental responses. Unlike conventional carriers, PDNs act as catalytic nanozymes that regulate reactive oxygen species (ROS) dynamics within the wound microenvironment. Using a murine splinted excisional wound model that isolates epithelial-driven regeneration, treatment with exosomes and PDNs (Exo+PDN) significantly accelerated early wound closure and was associated with coordinated activation of the EGF–ERK1/2–AQP3 signaling axis. When combined with picosecond laser stimulation (Exo+Laser+PDN), the platform preferentially enhanced early angiogenic activation, followed by improved epidermal maturation and more organized collagen architecture. Analysis of epithelial plasticity markers revealed maintained E-cadherin expression with concurrent vimentin upregulation in the absence of SLUG induction, indicating a regulated partial epithelial plasticity state rather than a full epithelial–mesenchymal transition. Collectively, these findings demonstrate that PD nanozymes function as active microenvironment-modulating biomaterials that integrate biochemical and physical cues to guide phase-dependent wound regeneration. This work highlights a material-driven strategy for regulating the temporal dynamics of tissue repair beyond conventional delivery-based approaches.