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A heparin-mimicking polymer conjugate stabilizes basic fibroblast growth factor
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Journal Article
A heparin-mimicking polymer conjugate stabilizes basic fibroblast growth factor
2013
Overview
Basic fibroblast growth factor (bFGF) is a protein that 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. Here, we describe the stabilization of bFGF by covalent conjugation with 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—unlike native bFGF. Following the application of stress, the conjugate was also significantly more active than the control conjugate system in which the styrene sulfonate units were omitted from the polymer structure. This research has important implications for the clinical use of bFGF and for the stabilization of heparin-binding growth factors in general.
Basic fibroblast growth factor (bFGF) is crucial for a range of diverse cellular processes, from wound healing to bone regeneration, yet is inherently unstable. This important biologic has now been covalently linked to a polymer that mimics the polysaccharide heparin to produce a conjugate that shows remarkable stability to a wide range of therapeutically and environmentally relevant stressors.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Biomimetic Materials - chemical synthesis
/ Biomimetic Materials - chemistry
/ Biomimetic Materials - pharmacology
/ Fibroblast Growth Factor 2 - analogs & derivatives
/ Fibroblast Growth Factor 2 - chemistry
/ Fibroblast Growth Factor 2 - pharmacology
/ Humans
/ Methacrylates - chemical synthesis
/ Methacrylates - pharmacology
/ Polyethylene Glycols - chemical synthesis
/ Polyethylene Glycols - chemistry
/ Polyethylene Glycols - pharmacology
/ Polymers
/ Polystyrenes - chemical synthesis
/ Proteins
/ Receptor, Fibroblast Growth Factor, Type 1 - antagonists & inhibitors
/ Styrene
