Skin regeneration is one of the most important issues in tissue engineering. Research on more effective biomaterials that will enhance regeneration while enabling requirements of a healing skin site is an important challenge in skin tissue engineering. In this study, heparin was encapsulated in Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) which were then incorporated into Sericin/Gelatin (Ser/Gel) nanofibers during the electrospinning process in order to develop a combined system that has controlled release approach, besides the ability to help the regeneration of skin tissue by the involvement of biopolymers; gelatin, and sericin. The loading capacity and heparin encapsulation efficiency in the nanoparticles were determined as 30.04 mg/g of polymer and 60%, respectively. Cumulative release of heparin from NPs for 1 week was faster than from NPs loaded gelatin scaffolds and from dual protein (Ser/Gel) scaffolds with ratios: 1/7 and 1/2 (approximately 85%, 65%, 55%, and 40%, respectively). Sericin addition slowed down the degradation properties of the scaffold. The scaffold having a Ser/Gel ratio (1/2) was found as the most promising candidate because of its proper fiber morphology, high water retention, and low degradation degree.