Multifunctional DNA Hydrogel Enhances Stemness of Adipose‐Derived Stem Cells to Activate Immune Pathways for Guidance Burn Wound Regeneration

Abstract A grade 3 burn is a nonstatic fatal injury, which can lead to complete damage to the skin structure, accompanied by a series of symptoms such as persistent inflammation, pain, pruritus, ulcer, and peripheral neuropathy. Although the primary clinical burn treatment is skin grafting, it cannot comprehensively solve burn symptoms. Here, a multifunctional DNA hydrogel integrated system is conveniently obtained through dynamic cross‐linking of the DNA unit, polyacrylamide, and l‐ascorbate 2‐phosphate (l‐A2P) formation of dense hydrogen bonds. The DNA hydrogel is doped with borneol for pain and itch relief. The obtained DNA hydrogel provides a hotbed similar to the extracellular matrix structure in vivo for the growth and development of stem cells, which can regulate cell proliferation, maintain cell viability, and achieve perfect release in a suitable environment. Additionally, the pharmacological wound dressing shell features excellent mechanical behavior, tissue adhesion, and antibacterial properties. Beyond that, the multifunctional DNA hydrogel integrated system can promote macrophage transformation, angiogenesis, and neurogenesis. Notably, the system activates the phosphatidylinositol 3′‐kinase (PI3K)‐Akt signaling pathway, which helps to promote tissue regeneration. Therefore, the DNA hydrogel integrated system opens the cascade mode of effective integrated treatment of burn wounds, further driving the in‐depth study of clinical transformation mechanisms in the future.