Human basic fibroblast growth factor fused with Kringle4 peptide binds to a fibrin scaffold and enhances angiogenesis.
Appropriate three-dimensional (3D) scaffolds and signal molecules could accelerate tissue regeneration and wound repair. In this work, we targeted human basic fibroblast growth factor (bFGF), a potent angiogenic factor, to a fibrin scaffold to improve therapeutic angiogenesis. We fused bFGF to the Kringle4 domain (K4), a fibrin-binding peptide from human plasminogen, to endow bFGF with specific fibrin-binding ability. The recombinant K4bFGF bound specifically to the fibrin scaffold so that K4bFGF was delivered in a site-specific manner, and the fibrin scaffold provided 3D support for cell migration and proliferation. Subcutaneous implantation of the fibrin scaffolds bound with K4bFGF but not with bFGF induced neovascularization. Immunohistochemical analysis showed significantly more proliferation cells in the fibrin scaffolds incorporated with K4bFGF than in those with bFGF. Moreover, the regenerative tissues were integrated well with the fibrin scaffolds, suggesting its good biocompatibility. In summary, targeted delivery of K4bFGF could potentially improve therapeutic angiogenesis.
Zhao
Wenxue
W
Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Han
Qianqian
Q
Lin
Hang
H
Sun
Wenjie
W
Gao
Yuan
Y
Zhao
Yannan
Y
Wang
Bin
B
Wang
Xia
X
Chen
Bing
B
Xiao
Zhifeng
Z
Dai
Jianwu
J
D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D005337:Fibrin / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D018082:Kringles / Q000235:genetics; D008855:Microscopy, Electron, Scanning; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D017510:Protein Folding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D023822:Tissue Engineering; D054457:Tissue Scaffolds
D017931:DNA Primers; D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2; D005337:Fibrin