Abstract

The skin is a three-dimensional organ composed of multilayered tissues, in which the epidermis, dermis, and subcutaneous adipose layer cooperate to maintain protection, thermoregulation, and repair. Although recent advances in tissue-engineered skin substitutes have improved cutaneous regeneration, strategies that simultaneously promote dermal and adipose restoration remain limited. Here, we developed a bi-layered tissue-engineered skin scaffold with dermal–adipose architecture fabricated by conjugate electrospinning of polycaprolactone solutions containing acellular dermal matrix (ADM) or decellularized adipose tissue (DAT). The construct exhibited dual bioactivity: stimulating fibroblast proliferation and collagen remodeling in the dermal layer, while promoting adipose-derived stem cell proliferation and adipogenesis in the adipose layer. In a full-thickness nude rat wound model, the scaffold enhanced vascularization, modulated inflammation, and accelerated regeneration of both dermal and adipose tissues. These findings demonstrate a versatile platform for multilayered skin tissue engineering and provide new insight into dermal–adipose synergistic regeneration.