Given that many people suffer from large‐area skin damage, skin regeneration is a matter of high concern. Here, an available method is developed for the formation of large‐area robust skins through three stages: fabrication of a biodegradable sealant‐loaded nanofiber scaffold (SNS), skin tissue reconstruction, and skin regeneration. First, a microfluidic blow‐spinning strategy is proposed to fabricate a large‐scale nanofiber scaffold with an area of 140 cm × 40 cm, composed of fibrinogen‐loaded polycaprolactone/silk fibroin (PCL/SF) ultrafine core–shell nanofibers with mean diameter of 65 nm. Then, the SNS forms, where the gelling reaction of fibrin sealant occurs in situ between thrombin and fibrinogen on PCL/SF nanofiber surface, to promote the migration and proliferation of fibroblasts, accelerating skin regeneration. Through an in vivo study, it is shown that the SNS can rapidly repair acute tissue damage such as vascular bleeding and hepatic hemorrhage, and also promote angiogenesis, large‐area abdominal wall defect repair, and wound tissue regeneration for medical problems in the world. Besides, it avoids the risk of immune rejection and secondary surgery in clinical applications. This strategy offers a facile route to regenerate large‐scale robust skin, which shows great potential in abdominal wall defect repair.