%0 Journal Article %J J Control Release %D 2007 %T Rescue of SCID murine ischemic hindlimbs with pH-modified rhbFGF/poly(DL-lactic-co-glycolic acid) implants %A Zhong, Yanqiang %A Zhang, Li %A Ding, Amy G %A Shenderova, Anna %A Zhu, Gaozhong %A Pei, Ping %A Chen, Ruth R %A Mallery, Susan R %A Mooney, David J %A Schwendeman, Steven P %K Angiogenesis Inducing Agents %K Animals %K Disease Models, Animal %K Drug Carriers %K Fibroblast Growth Factors %K Hindlimb %K Humans %K Hydrogen-Ion Concentration %K Ischemia %K Lactic Acid %K Male %K Mice %K Mice, SCID %K Necrosis %K Neovascularization, Physiologic %K Polyglycolic Acid %K Polymers %K Recombinant Proteins %K Regional Blood Flow %X Site-specific controlled release of biologically active angiogenic growth factors such as recombinant human basic fibroblast growth factor (rhbFGF) is a promising approach to improve collateral circulation in patients suffering from ischemic heart disease or peripheral vascular disease. Previously, we demonstrated stabilization of rhbFGF encapsulated in injectable poly(DL-lactic-co-glycolic acid) (PLGA) millicylindrical implants upon co-incorporation of Mg(OH)2 to raise the microclimate pH in the polymer. The purpose of this study was to compare stabilized (S; +Mg(OH)2+other stabilizers), partially stabilized (PS; -Mg(OH)2+other stabilizers), unstabilized (US; no stabilizers), and blank (B) PLGA-encapsulated rhFGF formulations to promote angiogenesis in SCID mice. Following 4 weeks subcutaneous implantation at a 0.1 microg dose in healthy animals, the S group exhibited significantly higher blood vessel density (62+/-17 vessels/mm2) compared with PS, US, and B groups (11+/-2*, 17+/-7*, and 3+/-1** respectively) (* p<0.05; ** p<0.01). Furthermore, the S group developed a thicker granulation layer at the tissue/implant interface relative to the other groups (39+/-7 vs 25+/-2**, 21+/-1***, and 12+/-1 microm*** respectively) (*** p<0.001). After 6 weeks implantation in mice with ischemic hindlimbs, the S group implants also markedly augmented both limb reperfusion (87+/-14%) and limb survival (5/5), whereas ischemic limbs did not recover in PS, US and B groups. Stabilized rhbFGF incorporated in pH modified PLGA millicylinders effectively promotes site-directed in vivo angiogenesis and also enables preservation of ischemic hindlimb function. %B J Control Release %V 122 %P 331-7 %8 2007 Oct 08 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/17706831?dopt=Abstract %R 10.1016/j.jconrel.2007.05.016