title: Sustained delivery of FGF-1 increases vascular density in comparison to bolus administration.
abstract: The use of growth factors for the therapeutic stimulation of neovascularization in regenerative medicine has been extensively investigated, but the inability to control their temporal delivery may limit clinical success. A strategy that delivers continuous therapeutic concentrations of growth factors may increase the protein's efficacy. The present study investigates the ability of sustained delivery of fibroblast growth factor-1 (FGF-1), to induce neovascularization in vivo. Alginate microbeads were synthesized to release active FGF-1 for three weeks. Microbeads loaded with FGF-1 (total amount 150 ng) were implanted into a surgically created omentum pouch in rats and were compared to control empty microbead implants and a single bolus injection of 150 ng of FGF-1 with empty microbead implant. Animals were sacrificed at either 3 or 6 weeks post implantation and omenta were analyzed for vascular density and mural cell interactions. Vascular area for bolus FGF-1 and FGF-1 loaded microbeads was higher than control at 3 weeks. At 6 weeks, vascular density in the group with FGF-1 loaded microbeads was significantly higher than the group with bolus administration of FGF-1, primarily due to an increase in the number of vessels less than 20 microm in diameter. Vascular density in omenta of the group receiving the bolus FGF-1 returned to control levels by 6 weeks. Staining for smooth muscle actin showed that 50% of vessels had associated mural cells. There was a trend of increased mural cell staining at 6 weeks for the FGF-1 loaded beads compared to bolus FGF-1 and control levels. Results in these studies suggest that sustained release of FGF-1 increases the duration of the vascular response in contrast to a bolus injection of FGF-1.
authors: Pritzker Institute of Biomedical Science and Engineering, Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL 60616, USA. moyamon@iit.edu
authors: Monica L
authors: ML
authors: Moya
authors: Stephanie
authors: S
authors: Lucas
authors: Megan
authors: M
authors: Francis-Sedlak
authors: Xiang
authors: X
authors: Liu
authors: Marc R
authors: MR
authors: Garfinkel
authors: Jung-Ju
authors: JJ
authors: Huang
authors: Ming-Huei
authors: MH
authors: Cheng
authors: Emmanuel C
authors: EC
authors: Opara
authors: Eric M
authors: EM
authors: Brey
mesh_terms: D000199:Actins / Q000378:metabolism; D000464:Alginates / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D016503:Drug Delivery Systems; D016220:Fibroblast Growth Factor 1 / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*; D020723:Glucuronic Acid / Q000138:chemical synthesis / Q000737:chemistry; D006603:Hexuronic Acids / Q000138:chemical synthesis / Q000737:chemistry; D007150:Immunohistochemistry; D008863:Microspheres; D018919:Neovascularization, Physiologic / Q000235:genetics*; D009852:Omentum / Q000098:blood supply / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D013997:Time Factors
chemical_list: D000199:Actins; D000464:Alginates; D006603:Hexuronic Acids; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016220:Fibroblast Growth Factor 1; D020723:Glucuronic Acid; D051496:Receptor, Fibroblast Growth Factor, Type 1