Effect of Decellularized Extracellular Matrix Bioscaffolds Derived from Fibroblasts on Skin Wound Healing and Remodeling

The mammalian tissue extracellular matrix (ECM) has been used as a scaffold to facilitate the repair and reconstruction of numerous tissues. However, the material properties of decellularized ECM (dECM) from in vitro cell cultures and the effect of these properties on wound remodeling remain unclear. To elucidate its biological activity, we extracted dECM from human lung fibroblasts, fabricated it into a patch, and applied it to a full-thickness skin wound. The fibroblast-derived dECM (fdECM) maintained the content of collagen., collagen., and elastin, and the extraction process did not damage its critical growth factors. The fdECM-conjugated collagen patch (COL-fdECM) facilitated wound contraction and angiogenesis in the proliferative phase when applied to the in vivo full-thickness skin wound model. Moreover, the COL-fdECM treated wound showed increased regeneration of the epidermal barrier function, mature collagen, hair follicle, and subepidermal nerve plexus, suggesting qualitative skin remodeling. This therapeutic efficacy was similarly observed when applied to the diabetic ulcer model. fdECM was shown to help remodel the tissue by regulating fibroblast growth factors, matrix metalloproteinases, and tissue inhibitors of metalloproteinases via the p38 and ERK signaling pathways in an in vitro experiment for understanding the underlying mechanism. These results provide a biological basis for cell-derived ECM as a multifunctional biomaterial applicable to various diseases.

Automated summary

Mammalian tissue extracellular matrix (ECM) has been used as a scaffold for tissue repair. This study investigated the properties and effects of decellularized ECM (dECM) from human lung fibroblasts on wound remodeling. The fibroblast-derived dECM (fdECM) maintained important components and growth factors, and when applied to skin wounds, facilitated wound contraction, angiogenesis, and qualitative skin remodeling. The therapeutic efficacy was also observed in a diabetic ulcer model. In vitro experiments revealed that fdECM helps tissue remodeling by regulating growth factors and signaling pathways.