Programmable Artificial Skins Accomplish Antiscar Healing with Multiple Appendage Regeneration

Abstract Functional appendage regeneration is essential for skin rehabilitation, but it has always failed by current existing healing approaches, owing to their inefficacy in preventing disfiguring scars. In this study, a novel regeneration‐directing artificial skin (RDAS) system is presented, which is based on the rational design of multi‐layered hydrogels that closely mimic natural skin matrices. By leveraging the programmability and architectural rigidity of DNA components, without the need for exogenous cell transplantation, such RDAS effectively minimizes tissue fibrosis by accurately guiding the regenerative process in wound fibroblasts, enabling rapid scarless wound repair, restoration of dermal function, and successful in situ regeneration of multiple appendages, such as hair follicles (HFs), sebaceous glands (SGs), and sweat glands (SwGs). Therefore, the RDAS offers a cell‐free antiscarring therapeutic strategy for regenerative wound healing, resulting in improved outcomes. This innovative approach holds great potential for future clinical applications and burn rehabilitation.