Novel functional biodegradable polymer IV: pH-sensitive controlled release of fibroblast growth factor-2 from a poly(gamma-glutamic acid)-sulfonate matrix for tissue engineering.
The acidic pH-sensitive controlled release of fibroblast growth factor-2 (FGF-2) from a biodegradable hydrogel without any denaturation of the FGF-2 was successfully performed by a combination of FGF-2 activity and acidic pH-sensitivity. We prepared semi-interpenetrating polymer network like hetero-gels (S72-netgels) composed of poly(gamma-glutamic acid) (gamma-PGA) and 72% sulfonated gamma-PGA (gamma-PGA-S72). S72-netgels including 36 mol % sulfonic acid (S72-netgel-36) showed wide acidic pH-sensitive deswelling properties at pH = 2.0-6.0, corresponding to the isoelectric point of carboxylic acid, because of the concentration of protons due to the neighboring sulfonic acids from the carboxylic acids. The S72-netgel-36 (the volume of hydrogel is 7.85 x 10(-2) cm3) can incorporate 280 ng of FGF-2 after 24 h immersion in Tris-HCl buffer (pH = 7.4), including 1.0 microg of FGF-2. The S72-netgel-36 still retained about 60% of the FGF-2 even after 15 days of incubation in fresh Tris-HCl buffer at 37 degrees C because of the stable interaction of FGF-2 with gamma-PGA-S72 in S72-netgel-36. The release of FGF-2 from the S72-netgel-36 was successfully controlled by alternating immersion in pH = 7.4 and acidic pH buffers. Furthermore, the FGF-2 released from the S72-netgel-36 retained its activity without denaturation because the gamma-PGA-S72 in S72-netgel-36 has a protective activity. The acidic pH-sensitive FGF-2 release property of the S72-netgel-36 without denaturation of the FGF-2 may be useful for tissue engineering fields such as neovascular treatment for ischemia and inflammation.
Matsusaki
Michiya
M
Center of Excellence (COE) Program for 21st Century, and Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita 565-0871, Japan.
Akashi
Mitsuru
M
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001673:Biodegradation, Environmental; D002264:Carboxylic Acids / Q000737:chemistry; D002448:Cell Adhesion; D002460:Cell Line; D049109:Cell Proliferation; D016895:Culture Media, Serum-Free; D016503:Drug Delivery Systems; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000378:metabolism*; D018698:Glutamic Acid / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007249:Inflammation; D007511:Ischemia; D046911:Macromolecular Substances / Q000737:chemistry*; D051379:Mice; D008956:Models, Chemical; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry; D011485:Protein Binding; D013451:Sulfonic Acids / Q000737:chemistry; D013696:Temperature; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*
D001672:Biocompatible Materials; D002264:Carboxylic Acids; D016895:Culture Media, Serum-Free; D046911:Macromolecular Substances; D011108:Polymers; D013451:Sulfonic Acids; C451199:poly(glutamic acid)sulfonate; D016222:Fibroblast Growth Factor 2; D011099:Polyglutamic Acid; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D018698:Glutamic Acid