Collagen mRNA‐LNP Accelerates Skin Wound Healing

Abstract Collagen plays a critical role in wound repair. Current recombinant collagen therapies provide exogenous collagen to the wound site; however, they fail to stimulate endogenous collagen production, which is crucial for achieving structurally integrated and durable tissue repair. To overcome this critical limitation, ionizable lipid nanoparticles (LNPs) are engineered containing nucleotide‐modified messenger RNA (mRNA) that encodes collagen. In immortalized human keratinocytes, these mRNA‐LNPs successfully expressed collagen. Functional assays of the mRNA‐LNP‐treated keratinocytes revealed cell migration rates tripled, superoxide dismutase activity increased by 40%, and proliferation is slightly enhanced. In mice, subcutaneous delivery of luciferase mRNA‐LNP showed rapid fluorescence generation (4 h postinjection) with sustained expression up to 144 h. In an 8‐mm full‐thickness wound model, collagen mRNA‐LNP‐treated tissue saw a wound area reduction of 40% at day 3 compared with 10% reduction in the control. A histological evaluation demonstrated a significant increase in neovascularization density and higher collagen depositioncompared to the control. These findings demonstrate that collagen mRNA‐LNPs accelerated wound healing through coordinated mechanisms that enhanced cell migration, oxidative stress resistance, angiogenesis, and extracellular matrix remodeling. The technology overcomes limitations of existing collagen‐based therapies by enabling endogenous protein biosynthesis, offering translational potential for dermatological applications.