title: Self-assembling elastin-like peptides growth factor chimeric nanoparticles for the treatment of chronic wounds.
abstract: 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.
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital, Boston, MA 02129, USA.
authors.forename: Piyush
authors.initials: P
authors.lastname: Koria
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Zaki
authors.initials: Z
authors.lastname: Megeed
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Nahmias
authors.forename: Robert
authors.initials: R
authors.lastname: Sheridan
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D004549:Elastin / Q000737:chemistry*; D051523:Fibroblast Growth Factor 7 / Q000737:chemistry*; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D046912:Multiprotein Complexes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use* / Q000648:ultrastructure; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000188:drug therapy*
chemical_list: D046912:Multiprotein Complexes; D051523:Fibroblast Growth Factor 7; D004549:Elastin