Growth factor mediated wound healing

Growth factors' roles in tissue regeneration

Growth factors are naturally-occurring polypeptides capable of stimulating cellular proliferation, differentiation, and maturation through signal transduction. Of significant importance to wound healing are fibroblast growth factor 2 (FGF-2) and vascular endothelial growth factor (VEGF); both have been shown to promote angiogenesis, the formation of new blood vessels from pre-existing vessels, and to stimulate wound healing in animal models 1,2.

<box 500px green>:labmembers:mdr_gfs.jpg</box|Figure 1. FGF-2 and VEGF stimulate cellular proliferation, differentiation, and maturation. A) VEGF ligands, shown in purple boxes, bind to their associated receptors, leading to receptor dimerization and subsequent signal transduction (www.researchvegf.com). B) FGF-2 binds to its transmembrane cell surface receptor to initiate angiogenesis (www.cellml.org).>

<box 260px right green> :labmembers:mdr_mc.jpg</box|Figure 2. A) Digital and B) scanning electron microscope images of maleic chitosan hydrogels (myip.cctec.cornell.edu).

Growth factor delivery

For this study, we are utilizing a novel platform for growth factor delivery, maleic chitosan hydrogel, that was developed by the Chu Lab. Chosen for its attractive biomaterial attributes, which include hydrophilicity, biocompatibility, biodegradability, high protein and fat affinity, and antibacterial properties, chitosan is the N-deacetylated form of chitin, the second most abundant polysaccharide 3. Chemical modification of chitosan by maleic acid grafting improves both solubility and reactivity, yielding a material that is highly suited for biomedical applications. By photopolymerizing maleic chitosan with polyethylene diacrylate (PEGDA) in the presence of growth factor, we can produce flexible, natural scaffolds capable of extended growth factor release for wound healing therapy. Individuals to benefit from this biomaterial include those experiencing compromised healing processes, such as diabetic patients, and full-thickness burn victims.

Ongoing research

Our in vitro studies have confirmed the proliferative effects of FGF-2 on human dermal fibroblasts and human umbilical vein endothelial cells (HUVECS). Dose-dependent increases in both metabolic activity and proliferation exhibited by cells in the presence of FGF-2 are essential to design consideration. Further evaluation of the effects of PEGDA molecular weight and glycosaminoglycan incorporation on hydrogel growth factor release will lead to product optimization and in vivo analysis.

<box 500px green>:labmembers:mdr_cell_prolif.jpg</box|Figure 3. Effects of FGF-2 on cell proliferation. A) Human dermal fibroblasts stained with crystal violet after 5 days of culture in 0ng/ml and B) 10ng/ml FGF-2. C) Human umbilical vein endothelial cells (HUVECs) after 5 days of culture in 0ng/ml and D) 10ng/ml FGF-2.

References

1. Pike, D.B., Cai, S., Pomraning, K.R., Firpo, M.A., Fisher, R.J., Shu, X.Z., Prestwich, G.D., Peattie, R.A. Heparin-regulated release of growth factors in vitro and angiogenic response in vivo to implanted hyaluronan hydrogels containing VEGF and bFGF. Biomaterials 2007; 27: 5242-5251

2. Liu, Y., Cai, S., Shu, X.Z., Shelby, J. Release of basic fibroblast growth factor from a crosslinked glycosaminoglycan hydrogel promotes wound healing. Wound Rep Reg 2007; 15: 245-251

3. Hasipoglu, H.N., Yilmaz, E., Yilmaz, O., Caner, H. Preparation and characterization of maleic acid grafted chitosan. International Journal of Polymer Anal. Charact. 2005; 10:313-327