Self‐Assembled DNA Composite‐Engineered Mesenchymal Stem Cells for Improved Skin‐Wound Repair

Abstract The direct use of mesenchymal stem cells (MSCs) as therapeutics for skin injuries is a promising approach, yet it still faces several obstacles, including limited adhesion, retention, and engraftment of stem cells in the wound area, as well as impaired regenerative and healing functions. Here, DNA‐based self‐assembled composites are reported that can aid the adhesion of MSCs in skin wounds, enhance MSC viability, and accelerate wound closure and re‐epithelialization. Rolling‐circle amplification (RCA)‐derived DNA flowers, equipped with multiple copies of cyclic Arg‐Gly‐Asp (cRGD) peptides and anti‐von Willebrand factor (vWF) aptamers, act as robust scavengers of reactive oxygen species (ROS) and enable synergistic recognition and adhesion to stem cells and damaged vascular endothelial cells. These DNA structure‐aided stem cells are retained at localized wound sites, maintain repair function, and promote angiogenesis and growth factor secretion. In both normal and diabetes‐prone db/db mice models with excisional skin injuries, facile topical administration of DNA flower‐MSCs elicits rapid blood vessel formation and enhances the sealing of the wound edges in a single dose. DNA composite‐engineered stem cells warrant further exploration as a new strategy for the treatment of skin and tissue damage.