Fibroblast growth factors (FGFs) that signal through FGF receptors (FGFRs) regulate a broad spectrum of biological functions, including cellular proliferation, survival, migration, and differentiation. The FGF signal pathways are the RAS/MAP kinase pathway, PI3 kinase/AKT pathway, and PLCγ pathway, among which the RAS/MAP kinase pathway is known to be predominant. Several studies have recently implicated the in vitro biological functions of FGFs for tissue regeneration. However, to obtain optimal outcomes in vivo, it is important to enhance the half-life of FGFs and their biological stability. Future applications of FGFs are expected when the biological functions of FGFs are potentiated through the appropriate use of delivery systems and scaffolds. This review will introduce the biology and cellular functions of FGFs and deal with the biomaterials based delivery systems and their current applications for the regeneration of tissues, including skin, blood vessel, muscle, adipose, tendon/ligament, cartilage, bone, tooth, and nerve tissues.

Growth factors (GFs) such as BMPs, FGFs, VEGFs and IGFs have significant impacts on osteoblast behavior, and thus have been widely utilized for bone tissue regeneration. Recently, securing biological stability for a sustainable and controllable release to the target tissue has been a challenge to practical applications. This challenge has been addressed to some degree with the development of appropriate carrier materials and delivery systems. This review highlights the importance and roles of those GFs, as well as their proper administration for targeting bone regeneration. Additionally, the in vitro and in vivo performance of those GFs with or without the use of carrier systems in the repair and regeneration of bone tissue is systematically addressed. Moreover, some recent advances in the utility of the GFs, such as using fusion technology, are also reviewed.

Fibroblast growth factor18 (FGF18) belongs to the FGF family and is a pleiotropic protein that stimulates proliferation in several tissues. Bone marrow mesenchymal stem cells (BMSCs) participate in the normal replacement of damaged cells and in disease healing processes within bone and the haematopoietic system. In this study, we constructed FGF18 and investigated its effects on rat BMSCs (rBMSCs). The proliferative effects of FGF18 on rBMSCs were examined using an MTS assay. To validate the osteogenic differentiation effects of FGF18, ALP and mineralization activity were examined as well as osteogenic differentiation-related gene levels. FGF18 significantly enhanced rBMSCs proliferation (p<0.001) and induced the osteogenic differentiation by elevating ALP and mineralization activity of rBMSCs (p<0.001). Furthermore, these osteogenic differentiation effects of FGF18 were confirmed via increasing the mRNA levels of collagen type I (Col I), bone morphogenetic protein 4 (BMP4), and Runt-related transcription factor 2 (Runx2) at 3 and 7 days. These results suggest that FGF18 could be used to improve bone repair and regeneration.

Fibroblast growth factor 2 (FGF2) protein plays important roles in wound healing and tissue regeneration. Collagen is clinically used for wound care applications. We investigated the potential value of FGF2-functionalized collagen matrices for skeletal muscle tissue engineering. When C2C12 cells were treated with FGF2, cell adhesion increased after 3 and 5 days compared to the control (P < 0.05). Wound healing activity of FGF2 was slightly higher than the control through cell migration. Cell proliferation activity of FGF2-functionalized collagen matrices on C2C12 cells also increased. Taken together, FGF2 stimulated C2C12 myoblast growth by promoting cell adhesion, proliferation and wound healing activity after injury. The potential effect of FGF2-functionalized collagen matrices was also observed. Thus FGF2 stimulates skeletal muscle development and regeneration, thereby leading to potential utility for skeletal muscle tissue engineering.

The sustained release of growth factors plays a critical role in therapeutic applications because of the instability of these factors in the body. Here, we designed a fibroblast growth factor 2 (FGF2) fused with a collagen-binding domain (rhCBD-FGF2) for collagen-based sustained release of FGF2.The release profile of rhCBD-FGF2 showed sustained release from collagen matrices. Further, rhCBD-FGF2 also stimulated adhesion of the MC3T3-E1 cells to the collagen matrices. In addition, rhCBD-FGF2 increased the cell proliferation activity at 3 and 5 days in the MC3T3-E1 cells attached to the collagen matrices compared to that in the control. Further, rhCBD-FGF2 significantly induced the osteogenic differentiation of MC3T3-E1 cells on collagen matrices by up-regulating the alkaline phosphatase activity at 7 days. These osteogenic differentiation activities were confirmed in gene expression of MC3T3-E1 cell. Taken together, rhCBD-FGF2 could specifically bind with collagen matrices, which indicates important advancements in bone tissue engineering.