Improved neovascularization and wound repair by targeting human basic fibroblast growth factor (bFGF) to fibrin.
Targeted therapy is a new generation of therapeutics, where two critical factors are involved. One is the particular molecular target, and the other is the specific target-binding drug. In this work, the fibrin, a main component of plasma clot at wound sites, was used as the target for human bFGF, aiming to improve therapeutic neovascularization and wound repair. To endow bFGF with fibrin-targeting ability, a fibrin-binding peptide Kringle1 (K1), derived from human plasminogen, was fused to human bFGF. The recombinant K1bFGF showed high fibrin and plasma-clot-binding ability. When applied to the wound sites with plasma clots, K1bFGF induced robust neovascularization and improved wound healing. To extend the application of K1bFGF to other cases where no plasma clots exist, we developed a fibrin-scaffold/K1bFGF system. This system could induce localized neovascularization by delivery of K1bFGF in a sustained and site-targeting manner, and provide a microenvironment promoting cell growth and tissue regeneration. In summary, we successfully used the pathologic environment fibrin clot as the target for bFGF, and based on which bFGF was designed into a targeting agent by introduction of a fibrin-binding peptide. This provides a potential approach to improve therapeutic neovascularization and wound repair.
Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Wenxue
W
Zhao
Qianqian
Q
Han
Hang
H
Lin
Yuan
Y
Gao
Wenjie
W
Sun
Yannan
Y
Zhao
Bin
B
Wang
Bing
B
Chen
Zhifeng
Z
Xiao
Jianwu
J
Dai
D000818:Animals; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005337:Fibrin / Q000378:metabolism* / Q000648:ultrastructure; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018082:Kringles / Q000235:genetics / Q000502:physiology*; D008297:Male; D008855:Microscopy, Electron, Scanning; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2; D005337:Fibrin