Vascularization and cellularization of collagen scaffolds incorporated with two different collagen-targeting human basic fibroblast growth factors.
To develop a collagen-based wound targeting repair system, we introduced two collagen-binding domains (CBDs) into the human basic fibroblast growth factor (bFGF). Three expression vectors were constructed: the first one (named V-bFGF) contained bFGF and the CBD WREPSFCALS derived from von Willeband's factor (vWF); the second (named C-bFGF) contained bFGF and the CBD TKKTLRT derived from collagenase; the third (named bFGF) was bFGF as a control. The recombinant proteins of V-bFGF and C-bFGF were demonstrated to retain both growth factor activity and collagen-binding activity. We found that C-bFGF possessed higher collagen-binding ability than V-bFGF. The targeted repair systems consisting of collagen scaffolds and CBD-bFGFs were assembled in vitro and then implanted subcutaneously. Results showed that C-bFGF promoted vascularization at the implanted sites more effectively than V-bFGF. Histological analysis showed more cells migrated into collagen scaffolds incorporated with C-bFGF than those with V-bFGF. These data suggested that the higher collagen-binding ability the CBD-bFGF possessed, the more significant vascularization, and cellularization were observed. In summary, CBD-bFGF/collagen system could be used as a targeted repair system with beneficial effects of the restriction of bFGF diffusion, the prolonging of bFGF activity, and the targeted promotion of vascularization and cellularization.
Zhao
Wenxue
W
Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100080, China.
Chen
Bing
B
Li
Xiaodong
X
Lin
Hang
H
Sun
Wenjie
W
Zhao
Yanhong
Y
Wang
Bin
B
Zhao
Yannan
Y
Han
Qianqian
Q
Dai
Jianwu
J
D001665:Binding Sites; D002460:Cell Line; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010446:Peptide Fragments / Q000235:genetics; D011485:Protein Binding; D015202:Protein Engineering / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects; D014841:von Willebrand Factor / Q000235:genetics
D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014841:von Willebrand Factor; D016222:Fibroblast Growth Factor 2; D003094:Collagen; D017364:Collagenases