Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1427121 | Journal of Controlled Release | 2007 | 7 Pages |
Abstract
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; â 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 μg 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 ± 2â, 17 ± 7â, and 3 ± 1ââ respectively) (âp < 0.05; ââp < 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 ± 2ââ, 21 ± 1âââ, and 12 ± 1 μmâââ respectively) (âââp < 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.
Related Topics
Physical Sciences and Engineering
Materials Science
Biomaterials
Authors
Yanqiang Zhong, Li Zhang, Amy G. Ding, Anna Shenderova, Gaozhong Zhu, Ping Pei, Ruth R. Chen, Susan R. Mallery, David J. Mooney, Steven P. Schwendeman,