Smart Microneedles Regulate Reactive Oxygen Species and Deliver Matrix Metalloproteinases for Pathological Scar Treatment.

Excessive oxidative stress and abnormal collagen deposition are critical drivers of pathological scar (PS) formation. To investigate the differences between normal and keloid tissues, single-cell sequencing and histological staining were conducted on patient samples, revealing that heightened collagen proliferation and oxidative stress are central to PS. To modulate the oxidative microenvironment and remodel the extracellular matrix (ECM), a smart microneedle capable of regulating reactive oxygen species (ROS) and delivering matrix metalloproteinase (MMP) functions was developed. Composed of methacrylated alginate hydrogel and hollow manganese dioxide nanoparticles, this microneedle not only scavenges ROS but also promotes the expression of genes and proteins associated with antioxidant and anti-inflammatory responses. Furthermore, MMP release from the ROS-responsive hydrogel suppresses transforming growth factor signaling, degrades excessive collagen, and facilitates ECM remodeling. In vivo evaluations in rabbit and porcine PS models demonstrated that this smart microneedle reduces scar thickness and restores skin function, highlighting its promising clinical potential. Overall, this study provides a clinically relevant framework for material design and establishes a closed-loop therapeutic strategy that integrates pathological signal decoding with targeted intervention, offering a approach for PS treatment.