The FGFs include a family of polypeptides growth factors which have been demonstrated to have considerable capability in tissue repair and regeneration. It was originally identified to induce proliferation and differentiation in various types of the cell [82]. The interaction of FGFs with their receptor tyrosine kinases (FGFRs) in the presence of heparin/heparan sulfate (HS) proteoglycans (HSPG) as a cofactor results in activation of FGFRs by phosphorylation of tyrosine residues [83]. Activated FGFRs lead to triggering a number of signaling pathways such as the RAS/MAP kinase pathway, PI3 kinase/AKT pathway, and PLCγ pathway, resulting in specific cellular responses [84]. Regeneration is controlled by a different type of growth factors among which FGFs are the key players in tissue regeneration, including the neural, liver, bone, skin, intestine, cardiac, and muscle [85]. According to the amino acid sequence, the FGF family is divided into seven subfamilies [86]. However, FGF2 (basic FGF) is indicated to be widely applied for scarless wound healing and skin wound regenerative therapy [87]. It has been reported that the sustained release of basic FGF from a chitosan film as a delivery vehicle could accelerate wound healing in full-thickness skin wounds made on the backs of genetically diabetic mice and promote proliferation of fibroblasts and granulation tissue formation [52]. In another study, incorporation of bFGF with gelatin microspheres significantly accelerated dermal tissue regeneration [88]. Furthermore, studies have identified that FGFs are key regulators of keratinocyte migration in wounded skin, as the loss of FGFR1 and FGFR2 in keratinocytes results in a wound-healing defect [89].
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