Structure-Guided PEGylated Fibroblast Growth Factor 2 Variants Accelerate Wound Healing With Improved Stability

The study investigated PEGylated variants of fibroblast growth factor 2 (FGF2) to enhance its stability and efficacy in wound healing. By modifying FGF2 based on its crystal structure, researchers aimed to improve its short in vivo half-life. The PEGylated FGF2 variants demonstrated significantly improved stability in plasma and wound fluid compared to native FGF2. Among the variants, Compound 6 showed superior performance in promoting cell proliferation, migration, angiogenesis, and wound healing in vitro and in vivo. However, PEGylation near the receptor and heparin binding regions reduced bioactivity, particularly near the heparin binding domain. The study concluded that the heparin binding domain is crucial for FGF2 activity, and Compound 6 emerged as a promising candidate for therapeutic wound healing applications.