title: Human basic fibroblast growth factor fused with Kringle4 peptide binds to a fibrin scaffold and enhances angiogenesis.
abstract: 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.
authors.affiliation: Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Wenxue
authors.initials: W
authors.lastname: Zhao
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Han
authors.forename: Hang
authors.initials: H
authors.lastname: Lin
authors.forename: Wenjie
authors.initials: W
authors.lastname: Sun
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Yannan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Xiao
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
mesh_terms: 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
chemical_list: D017931:DNA Primers; D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2; D005337:Fibrin