Controlled release of vancomycin hydrochloride (vanco HCl) in order to enhance therapeutic effects and to reduce toxic effects of systemic administration has received a lot of interest in recent years. In the present study, a hydrogel scaffold of silk fibroin/oxidized pectin (SF/OP) based on Schiff mechanism has been prepared. To prevent bone infection or treat osteomyelitis, vanco HCI was loaded into the scaffolds. For obtaining sustained release of vanco HCl, electrospun fibers of poly (L-lactide) (PLLA)-drug were aminolyzed and then added to the hydrogel. The results of many techniques that assessed on scaffolds demonstrated that incorporation of aminolyzed fibers into the hydrogel resulted in 61% reduction of drug release content. Moreover, 15% decrease in swelling ratio, 52% increase in crosslinking density and 30% increase in compressive modulus were observed. Antibacterial effect of scaffolds against methicillin resistant Staphylococcus areous (MRSA) was proved and also nontoxicity versus human adipose derived mesenchymal stem cells (hAD-MSCs) was confirmed by MTT assay. In conclusion, the presence of aminolyzed PLLA-drug fibers in SF/OP hydrogel made this delivery system very promising in sustained release of vanco HCl.