Type I collagen can function as a reservoir of basic fibroblast growth factor.
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.
Kanematsu
Akihiro
A
Department of Biomaterial, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawara-cho, Sakyo, Kyoto 606-8507, Japan.
Marui
Akira
A
Yamamoto
Shingo
S
Ozeki
Makoto
M
Hirano
Yoshiaki
Y
Yamamoto
Masaya
M
Ogawa
Osamu
O
Komeda
Masashi
M
Tabata
Yasuhiko
Y
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002942:Circular Dichroism / Q000379:methods; D003094:Collagen / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D024042:Collagen Type I / Q000138:chemical synthesis / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005346:Fibroblast Growth Factors / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics*; D006614:Hindlimb / Q000033:anatomy & histology; D007456:Iodine Isotopes; D007564:Japan; D035002:Lower Extremity / Q000098:blood supply; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
D024042:Collagen Type I; D004337:Drug Carriers; D007456:Iodine Isotopes; D005346:Fibroblast Growth Factors; D003094:Collagen; D014357:Trypsin