Delivery of a growth factor fusion protein having collagen-binding activity to wound tissues.
Recently, we established a collagen-binding growth factor consisting of epidermal growth factor and the fibronectin collagen-binding domain (FNCBD-EGF). FNCBD-EGF is a biologically active fusion protein that could stably bind to collagen materials, and exert its growth factor activity even after collagen binding. In this study, we investigated the concept that FNCBD moiety with high collagen affinity may enhance the effective local concentration of EGF at the site of administration in the following tissues: skin wounds, catheter-injured arteries, and hind limb muscles. In an animal model of impaired wound healing, application of FNCBD-EGF in combination with collagen gel induced granulation tissue formation in the wounds due to its sustained retention. In the injured artery, infused FNCBD-EGF remained bound to collagen exposed on the injured tissues even after blood circulation was restored. Injection of the fusion protein into the hind limbs revealed that our delivery system was effective for direct administration to muscular tissue.
Ishikawa
Tetsuya
T
Terumo Corporation R&D Center, 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan. tetsuya_ishikawa@terumo.co.jp
Terai
Hiroshi
H
Yamamoto
Takashi
T
Harada
Kazumichi
K
Kitajima
Takashi
T
D000287:Administration, Topical; D000818:Animals; D020212:Carotid Artery Injuries / Q000628:therapy; D003094:Collagen / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D016503:Drug Delivery Systems; D004815:Epidermal Growth Factor / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D005353:Fibronectins / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D005782:Gels; D006614:Hindlimb; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014945:Wound Healing / Q000187:drug effects*
D005353:Fibronectins; D005782:Gels; D018809:Proliferating Cell Nuclear Antigen; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor; D003094:Collagen