Poly(glycerol sebacate) (PGS) is a biodegradable and biocompatible polyester that is increasingly used in the biomedical field. Herein, a novel ternary poly(ε‐caprolactone)/gelatin/PGS (PCL/gelatin/PGS) blend nanofibers were designed and fabricated with a wide range of chemical compositions, mechanical properties, and modulated degradability levels. PGS blends with gelatin are commonly used for enhancing electrospinability but their low‐mechanical properties, lack of structural stability in an aqueous medium, and unmodulated degradation behavior limited their application. Blending PGS and gelatin with PCL could improve their properties in a ternary structure. In addition, considering ternary blends of PCL/gelatin/PGS, an enhancement of hydrophilicity due to the presence of gelatin in the system is expected, resulting in better biocompatibility and controlled biodegradation. By increasing the polymer concentration, voltage, and distance of the needle to the collector, the bead‐free electrospun nanofibers were obtained. The ternary blend nanofibers with an equal weight ratio of polymers, T33 (containing 33 wt% PGS, 33 wt% gelatin, and 33 wt% PCL), possess more than a 4‐fold increase in tensile strength (7 MPa) and 89‐fold increase in elongation at break (1760.6%) compared to gelatin/PGS binary nanofibers. In vitro studies on glioma cells showed well attachment and proliferation of C6 glioma cells. The obtained results demonstrated the potential of these scaffolds for nerve tissue engineering applications.

In this study, different polycaprolactone (PCL) soft blocks were incorporated into poly(glycerol sebacate) (PGS) structure to prepare a series of PGS‐based elastomers with a wide range of chemical compositions, mechanical properties, and modulated degradation behavior. The PGS and PGS‐co‐PCL elastomers were prepared under a thermal curing process in the absence of any catalysts. Here, in addition to the effect of different lengths of PCL block, the effect of thermal curing time on the mechanical properties and degradation behavior of the elastomers was investigated. The synthesized PGS‐co‐PCL elastomers exhibited tunable mechanical properties in the range of soft tissues. Moreover, the in vitro degradation study revealed linear degradation kinetics with approximately twofold decrease in the elastomers degradation rate. In vitro study showed that proliferation of human olfactory ecto‐mesenchymal stem cells (OE‐MSCs) was supported on PGS‐co‐PCL elastomer. In addition, in vivo evaluation of PGS‐co‐PCL elastomer confirmed mild tissue response with high angiogenesis, indicating a good candidate in various biomedical applications and soft tissue engineering.