A delivery platform was developed using silk-based hydrogels, and sustained delivery of the cationic chemokine CXCL12 at therapeutically relevant doses is demonstrated. Hydrogels were prepared from plain silk and silk that had been chemically modified with sulfonic acid groups. CXCL12 was mixed with the silk solution prior to gelation, resulting in 100% encapsulation effitiency, and both hydrated and lyophilized gels were compared. By attaching a fluorescein tag to CXCL12 using a site-specific sortase-mediated enzymatic ligation, release was easily quantified in a high throughput manner using fluorescence spectroseopy. CXCL12 continually eluted from both plain and acid modified silk hydrogels for more than 5 Weeks at concentrations ranging from 10 to 160 ng per day, depending on the gel preparation method. Notably, acid modified silk hydrogels displayed minimal: burst release yet had higher long term release rates compared to those of plain silk hydrogels. Similar release profiles were observed over a range of loading capacities, allowing dosage to be easily varied,