The first line of treatment regime for bone cancers including osteosarcoma is surgical removal of the primary tumor, scaffold and/or bone fillers are required to fill the bone void during the surgery. Development and advancement of adjuvant chemotherapy and immunotherapy promotes tumoricidal activity and improves patients’ survival rate. IL-21 is a recently identified cytokine that has strong effects on both CD8+ and CD4+ cells and could be a good candidate for cancer immune therapy. The current study was to develop and characterize an electro-spun PCL nanofiber membrane with IL-21 plasmid vectors that can be used as a wrapping material on the bone tumor removal surgery, and serves as a gene delivery tool to provide persistent IL-21 expression at the site to promote local immunity.