TY - JOUR
T1 - Type I collagen can function as a reservoir of basic fibroblast growth factor
AU - Kanematsu, Akihiro
AU - Marui, Akira
AU - Yamamoto, Shingo
AU - Ozeki, Makoto
AU - Hirano, Yoshiaki
AU - Yamamoto, Masaya
AU - Ogawa, Osamu
AU - Komeda, Masashi
AU - Tabata, Yasuhiko
N1 - Funding Information:
This work was supported in part by a Grant for Scientific Research from the Japanese Ministry of Education and Science, and 21st Century COE Program (Integration of Transplantation Therapy and Regenerative Medicine), Kyoto University.
PY - 2004/9/30
Y1 - 2004/9/30
N2 - Storage and release of endogenous growth factors by the extracellular matrix (ECM) are important biological events that control tissue homeostasis and regeneration. The interaction between basic fibroblast growth factor (bFGF) and heparan sulfate proteoglycans has been extensively studied and used as a prototype model of such a system, while the lower affinity of fibrillar type I collagen for bFGF has generally been considered biologically insignificant. However, our present investigation revealed that bFGF spontaneously interacts with type I collagen solution and sponges under in vitro and in vivo physiological conditions, and is protected from the proteolytic environment by the collagen. bFGF incorporated in a collagen sponge sheet was sustainedly released in the mouse subcutis according to the biodegradation of the sponge matrix, and exhibited local angiogenic activity in a dose-dependent manner. Intramuscular injection of collagen microsponges incorporating bFGF induced a significant increase in the blood flow in the murine ischemic hindlimb, which could never have been attained by bolus injection of bFGF. These results suggest the significance and therapeutic utility of type I collagen as a reservoir of bFGF.
AB - Storage and release of endogenous growth factors by the extracellular matrix (ECM) are important biological events that control tissue homeostasis and regeneration. The interaction between basic fibroblast growth factor (bFGF) and heparan sulfate proteoglycans has been extensively studied and used as a prototype model of such a system, while the lower affinity of fibrillar type I collagen for bFGF has generally been considered biologically insignificant. However, our present investigation revealed that bFGF spontaneously interacts with type I collagen solution and sponges under in vitro and in vivo physiological conditions, and is protected from the proteolytic environment by the collagen. bFGF incorporated in a collagen sponge sheet was sustainedly released in the mouse subcutis according to the biodegradation of the sponge matrix, and exhibited local angiogenic activity in a dose-dependent manner. Intramuscular injection of collagen microsponges incorporating bFGF induced a significant increase in the blood flow in the murine ischemic hindlimb, which could never have been attained by bolus injection of bFGF. These results suggest the significance and therapeutic utility of type I collagen as a reservoir of bFGF.
KW - Basic fibroblast growth factor
KW - Reservoir
KW - Type I collagen
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U2 - 10.1016/j.jconrel.2004.07.008
DO - 10.1016/j.jconrel.2004.07.008
M3 - Article
C2 - 15380637
AN - SCOPUS:4544340505
VL - 99
SP - 281
EP - 292
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 2
ER -