ECM-inspired stem cell secretome sustained releasing composite nanofibrous membranes for accelerated wound healing

Designing dressings that mimic the composition, structure, and function of native skin is of great significance. Despite commercial decellularized extracellular matrix (dECM)-based wound dressings promoted skin regeneration process, reconstructing the fibrous microstructure of native dermis remains a significant challenge. In this work, a dECM-based composite nanofibrous membranes loaded with stem cell secretomes (SCS/dECMM) have been developed for accelerating wound repair, which comprehensively mimicked the dermal tissue in terms of composition, structure, and function. In detail, dermal dECM was prepared by eco-friendly supercritical carbon dioxide (SC-CO₂) technology and then mixed with SCS to obtain SCS/dECMM by using electrospinning technology. The resulting nanofibrous membrane with 555.19 nm diameter that maintained SCS bioactivity while enabling sustained SCS release. SCS/dECMM significantly enhanced cell adhesion, proliferation, migration, and angiogenesis, thereby continuously promoting wound repair. <i>In vivo</i> wound healing results revealed that SCS/dECMM accelerated wound healing by promoting re-epithelialization, collagen deposition, and vascularization. SCS/dECMM offered a novel strategy for accelerating wound healing by replicating the composition, structure, and function of native skin.