Affibody-mediated controlled release of fibroblast growth factor 2

Protein therapeutics possess high target affinity and specificity, yet short residence times, which limit their broad utility. To overcome this challenge, we used affinity interactions to modulate protein release from a hydrogel delivery vehicle thereby prolonging therapeutic availability. Specifically, we designed an affibody-modified hyaluronan (HA)-based hydrogel as a delivery platform for fibroblast growth factor 2 (FGF2), a neuroprotective and neuroregenerative factor in the central nervous system (CNS). We identified a highly specific affibody binding partner with moderate affinity for FGF2 using yeast surface display and flow cytometry-based screening. Importantly, we demonstrated controlled release of bioactive FGF2 from the hydrogel by varying the ratio of affibody to protein and showed increased thermal stability of FGF2 in the presence of affibody. This versatile delivery platform will allow the distinct, simultaneous release of multiple proteins based on specific affinity interactions.