Sustained Release of Multiple Growth Factors from Injectable Polymeric System as a Novel Therapeutic Approach Towards Angiogenesis
The aim was to investigate that a bio-degradable alginate and poly lactide-co-glycolide (PLG) system capable of delivering growth factors sequentially would be superior to single growth factor delivery in promoting neovascularization and improving perfusion.
Three groups of apoE null mice underwent unilateral hindlimb ischemia surgery and received ischemic limb intramuscular injections of alginate (Blank), alginate containing VEGF165 (VEGF), or alginate containing VEGF165 combined with PLG microspheres containing PDGF-BB (VEGF/PDGF). Vascularity in the ischemic hindlimb was assessed by morphologic and immunohistochemical end-points, while changes in blood flow were assessed by Laser Doppler Perfusion Index. Muscle VEGF and PDGF content was assessed at multiple time points.
In the VEGF/PDGF group, local tissue VEGF and PDGF levels peaked at week 2 and 4, respectively, with detectable PDGF levels at week 6. At week 6, mean vessel mean diameter was significantly greater in the VEGF/PDGF group compared to the VEGF or Blank groups with evidence of well-formed smooth muscle-lined arterioles.
Sequential delivery of VEGF and PDGF using an injectable, biodegradable platform resulted in stable and sustained improvements in perfusion. This sustained, control-released, injectable alginate polymer system is a promising approach for multiple growth factor delivery in clinical application.
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- Sustained Release of Multiple Growth Factors from Injectable Polymeric System as a Novel Therapeutic Approach Towards Angiogenesis
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Volume 27, Issue 2 , pp 264-271
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- 1. Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio, 43210-1252, USA
- 2. Division of Cardiovascular Medicine, College of Medicine, The Ohio State University, Columbus, Ohio, 43210-1252, USA
- 3. Davis Heart & Lung Research Institute, College of Medicine, The Ohio State University, 460W 12th Avenue, Room 398, Columbus, Ohio, 43210-1252, USA
- 4. School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA
- 5. New York Center for Biomedical Engineering, The City University of New York, New York, New York, USA
- 6. Division of Cardiovascular Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, 48109-0306, USA