Self-assembling elastin-like peptides growth factor chimeric nanoparticles for the treatment of chronic wounds

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 3; pp. 1034 - 1039
• Main Authors: Koria, Piyush, Yagi, Hiroshi, Kitagawa, Yuko, Megeed, Zaki, Nahmias, Yaakov, Sheridan, Robert, Yarmush, Martin L., Langer, Robert
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 18-01-2011; National Acad Sciences
• Subjects: Analysis of Variance; Animals; Biological Sciences; Blotting, Western; Cell growth; Data processing; Diabetes; Diabetes complications; Diabetes mellitus; Elastin; Elastin - chemistry; Epithelial cells; Escherichia coli; Fibroblast Growth Factor 7 - chemistry; Fibroblasts; Fusion protein; Gels; Keratinocyte growth factor; Keratinocytes; Male; Mice; Microscopy, Electron, Transmission; Multiprotein Complexes - chemistry; Multiprotein Complexes - pharmacology; Multiprotein Complexes - therapeutic use; nanoparticles; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Nanoparticles - ultrastructure; peptide growth factors; Peptides; Physical Sciences; Proteins; Skin; Temperature effects; Transition temperature; Wound healing; Wound Healing - drug effects; Wounds and Injuries - drug therapy
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1009881108

Chronic wounds are associated with poor epidermal and dermal remodeling. Previous work has shown the efficacy of keratinocyte growth factor (KGF) in reepithelialization and elastin in dermal wound healing. Here we demonstrate the fabrication of a fusion protein comprising of elastin-like peptides and KGF. This fusion protein retains the performance characteristics of KGF and elastin as evidenced by its enhancement of keratinocyte and fibroblast proliferation. It also preserved the characteristic elastin-like peptides inverse phase transitioning allowing the recombinant protein to be expressed in bacterial hosts (such as Escherichia coli) and purified rapidly and easily using inverse temperature cycling. The fusion protein self-assembled into nanoparticles at physiological temperatures. When applied to full thickness, wounds in Lepr db diabetic mice these particles enhanced reepithelialization and granulation, by 2- and 3-fold respectively, when compared to the controls. The data strongly suggests that these self-assembled nanoparticles may be beneficial in the treatment of chronic wounds resulting from diabetes or other underlying circulatory conditions.