A Heparin-Mimicking Polymer Conjugate Stabilizes Basic Fibroblast Growth Factor (bFGF)

Basic fibroblast growth factor (bFGF) plays a crucial role in diverse cellular functions from wound healing to bone regeneration. However, a major obstacle to the widespread application of bFGF is its inherent instability during storage and delivery. Herein, we describe stabilization of bFGF by covalent conjugation of a heparin-mimicking polymer, a copolymer consisting of styrene sulfonate units and methyl methacrylate units bearing poly(ethylene glycol) side chains. The bFGF conjugate of this polymer retained bioactivity after synthesis and was stable to a variety of environmentally and therapeutically relevant stressors such as heat, mild and harsh acidic conditions, storage, and proteolytic degradation, compared to native bFGF. After applied stress, the conjugate was also significantly more active than the control conjugate system where the styrene sulfonate units were omitted from the polymer structure. This research has important implications for the clinical use of bFGF and for stabilization of heparin-binding growth factors in general.