Heparin is a glycosaminoglycan that can regulate and interact with a variety of proteins. In particular, its non-covalent interactions with heparin-binding motifs on proteins have been shown to be critical for protein stabilization. Yet despite its potential to aid in the delivery of proteins for various therapeutic applications, the heparin/protein complex is soluble in water, thereby rendering it ineffective for controlled delivery purposes. To utilize the benefits of heparin for controlled delivery applications, we take inspiration from the interaction between proteins of the FGF family with its receptor and heparin. We mimic the interactions between these three components – protein, heparin, receptor – by substituting the heparin-binding sequence of the receptor with various synthetic polycations. The resulting ternary complex is stabilized via polyvalent ionic interactions and forms a complex coacervate phase. Utilizing this controlled release platform, we demonstrate applications in angiogenesis, myocardial regeneration, wound healing, and cancer.
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