Development of functional fibrous matrices for the controlled release of basic fibroblast growth factor to improve therapeutic angiogenesis.
In this study, novel fibrous matrices were developed as a depot to store and liberate growth factors in a controlled manner. Specifically, heparin was covalently conjugated onto the surface of fibrous matrices (composites of poly[caprolactone] and gelatin crosslinked with genipin), and basic fibroblast growth factor (bFGF) was then reversibly immobilized. The immobilization of bFGF was controlled as a function of the amount of conjugated heparin. The sustained release of bFGF from the fibrous matrices was successfully achieved over 4 weeks whereas physical adsorption of bFGF released quickly. The bFGF released from the fibrous matrices significantly enhanced in vitro proliferation of human umbilical vein endothelial cells. From the in vivo study, the group implanted with a higher amount of immobilized bFGF significantly facilitated neo-blood vessel formation as compared with other implantation groups. These results indicate that the sustained release of bFGF is important for the formation of blood vessels and that our fibrous matrices could be useful for regulation of tissue damage requiring angiogenesis. Further, our system can be combined with other growth factors with heparin binding domains, representing a facile depot for spatiotemporal control over the delivery of bioactive molecules in regenerative medicine.
Kim
Min Sup
MS
Department of Biomedical Engineering, Hanyang University, Seoul, Korea.
Bhang
Suk-Ho
SH
Yang
Hee Seok
HS
Rim
Nae Gyune
NG
Jun
Indong
I
Kim
Sun I
SI
Kim
Byung-Soo
BS
Shin
Heungsoo
H
D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005780:Gelatin / Q000737:chemistry; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011091:Polyesters / Q000737:chemistry; D014471:Umbilical Veins / Q000166:cytology
D011091:Polyesters; D016222:Fibroblast Growth Factor 2; C016240:polycaprolactone; D005780:Gelatin