Diamond-Inspired DNA Hydrogel Based on Tetrahedral Framework Nucleic Acids for Burn Wound Healing

Abstract

Burn wounds frequently pose high risks of a prolonged healing process and even death due to the persistent reactive oxygen species (ROS)-mediated inflammatory cascade. There is an urgent requirement for advanced dressings modulating the immune microenvironment surrounding the wound. DNA hydrogels have been preliminarily investigated in tissue regeneration due to their excellent permeability, editability, and biocompatibility. However, their broader applications have been limited by poor mechanical properties, and their roles in tissue regeneration remain insufficiently explored. Inspired by diamond, this study introduces a DNA hydrogel formulated with tetrahedral framework DNA, which exhibits enhanced mechanical strength due to its stable structure. Additionally, it exhibits multiple functionalities, including ROS scavenging, hemostatic performance, adhesion, injectability, shear-thinning behavior, and self-healing capability. Single-cell sequencing analysis indicates that this hydrogel disrupts the ROS-inflammatory cascade and promotes the transformation of pro-inflammatory macrophages into an anti-inflammatory phenotype. This effect promotes extracellular matrix formation and re-epithelialization with changes in the communication between macrophages, fibroblasts, and keratinocytes, ultimately facilitating burn wound healing on the skin of mice. In summary, this study not only presents a novel approach to bolstering the mechanical strength of pure DNA hydrogels but also marks a systematic evaluation of DNA hydrogels in regenerative medicine.

Keywords: DNA hydrogel; macrophage; single‐cell sequencing analysis; skin regeneration; tetrahedral DNA nanostructure.