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

G rowth factors are among the most studied and ex- plored proteins of the human body.They have been in the limelight since the 1980s and have shown tremendous scope in therapeutics over the last few decades.They regulate cellular functions such as stem cell differentiation [1], cell proliferation [2], growth of cells, migration of cells, angiogenesis [3], adhesion in the epithelium, cartilage, bone, some soft connective tissues, nerve cells, and maintaining the stemness of stem cells [4].They can also be modified genetically or structurally following their use in therapeutics and their commercial production.Growth factors are named based on their tissue of origin, such as the Cartilage-Derived Growth Factor (CDGF), Retina-Derived Growth Factor (RDGF), Astroglial Growth Factors (AGF), and Eye-Derived Growth Factor (EDGF); while some are named according to the tissue they stimulate, like endothelial cell growth factor (ECGF) [5], fibroblast growth factors (FGFs), and vascular endothelial growth factors (VEGFs).Among these, this review paper will emphasize Fibroblast growth factor and their therapeutic applications, structural modifications, and binding aspects of FGFs with FGFRs.The first-ever discovered Fibroblast growth factor was bFGF.It was initially referred to as a polypeptide that acted 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.