Fibroblast growth factors: properties, biosynthesis, biological functions, therapeutic applications and engineering

Abstract

Fibroblast Growth Factors (FGFs) function as signaling molecules within various signaling pathways, regulating the proliferation, migration, and differentiation of soft connective tissues, nerves, epithelial tissue, and bone. The FGF family comprises 22 members, with acidic Fibroblast Growth Factor (aFGF/FGF-1) and basic Fibroblast Growth Factor (bFGF/ FGF-2) being of primary significance. This article explores the biochemical and biological properties of different FGFs, elucidating their roles in various biological processes. Additionally, it delves into the interactions between FGFs and Receptor tyrosine kinases (RTKs), which activate several cell signaling cascades, such as the RAS/MAPK (Mitogen-activated Protein Kinase) pathway, PI3K (phosphoinositide 3-kinase)/AKT (v-akt murine thymoma viral oncogene homolog) pathway, PLC-γ (Phospholipase C-γ) pathway, and Signal Transducer and Activator of Transcription (STAT) pathway, to facilitate diverse cellular functions. The article also examines methods for engineering FGFs, including N-terminal truncation, point mutations, or combinations thereof, for therapeutic applications in tissue regeneration, angiogenesis, and repairing damaged tissues such as cartilage, bone, ligaments, and skin. Finally, it concludes with a discussion of the delivery systems for FGFs, encompassing scaffolds, hydrogels, as well as nano- and micro-particulate methods.