Abstract: Described herein are biocompatible materials that include a nitric oxide (NO) donor embedded in silk fibroin nanoparticles. In one aspect, the nitric oxide donor is present in the hydrophobic core of the silk fibroin nanoparticles such that the nitric oxide donor is encapsulated. The biocompatible materials described herein serve as a biocompatible and inexpensive nitric oxide delivery platform that provide sustained release of nitric oxide. The biocompatible materials are non-toxic and can be used in biomedical applications such as wound healing, where a combination of therapeutic and antibacterial properties of silk and nitric oxide are desired. Additionally, described herein are methods of making the biocompatible materials.