Enzyme-Assisted Dendrobium officinale Polysaccharides Enhance Keratinocyte Proliferation and Accelerate Cutaneous Wound Healing

<i>Dendrobium</i> polysaccharides (DOPs) have been demonstrated to possess protective activities against UVB-induced skin damage and oxidative stress, but their role in wound healing remains unexplored. This study employed multiple enzymatic hydrolysis methods to prepare <i>Dendrobium</i> polysaccharide hydrolysates and systematically evaluated their wound-healing activity and molecular mechanisms in an in vitro HaCaT keratinocyte model and an in vivo mouse wound model. In vitro results demonstrated that enzymatically extracted DOPs promoted the proliferation and migration of HaCaT keratinocytes, with the composite enzymatic product (D-ceh) exhibiting optimal efficacy. Mechanistic analyses revealed that D-ceh activated the NF-κB signaling pathway and upregulated pro-inflammatory cytokines, thereby enhancing keratinocyte proliferation and migration. In vivo experiments demonstrated that D-ceh considerably enhanced collagen deposition and extracellular matrix remodeling, accelerating wound closure. These findings reveal that enzymatically processed DOPs have potential therapeutic value in accelerated skin wound healing, and the NF-κB signaling pathway plays a pivotal role in its biphasic regulation, promoting inflammation in the early phase and remodeling in the mid-to-late phase, thereby supporting the clinical development prospects of DOPs as natural wound healing promoters.