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Sustained release of multiple growth factors from injectable polymeric system as a novel therapeutic approach towards angiogenesis.

Sun Q, Silva EA, Wang A, Fritton JC, Mooney DJ, Schaffler MB, Grossman PM, Rajagopalan S - Pharm. Res. (2009)

Bottom Line: 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.This sustained, control-released, injectable alginate polymer system is a promising approach for multiple growth factor delivery in clinical application.

View Article: PubMed Central - PubMed

Affiliation: Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio 43210-1252, USA. sun.224@osu.edu

ABSTRACT

Purpose: 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.

Methods: Three groups of apoE mice underwent unilateral hindlimb ischemia surgery and received ischemic limb intramuscular injections of alginate (Blank), alginate containing VEGF(165) (VEGF), or alginate containing VEGF(165) 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.

Results: 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.

Conclusions: 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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Related in: MedlinePlus

Representative images of micro-CT after 5 weeks intramuscular injections of alginate (Blank), alginate containing VEGF165 (VEGF), or alginate containing VEGF165 combined with PLG microspheres containing PDGF-BB (VEGF/PDGF).
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Fig4: Representative images of micro-CT after 5 weeks intramuscular injections of alginate (Blank), alginate containing VEGF165 (VEGF), or alginate containing VEGF165 combined with PLG microspheres containing PDGF-BB (VEGF/PDGF).

Mentions: Blood flow was reduced to less than 20% of the baseline following ligation surgery. There was no significant difference in limb perfusion between groups in the first 2 weeks after the operation. The blood flow remained severely impaired and showed delayed recovery after vessel ligation in the group that received blank alginate solution containing no growth factor. The VEGF/PDGF group of 3 µg VEGF165 with 3 µg PDGFBB recovered significantly faster than the blank or the VEGF group of 3 µg VEGF165 and achieved more than 80% of the initial value by the end of the experiment. VEGF showed a positive effect on the recovery of perfusion from week 3 to week 6 compared to the blank group, but weaker than the VEGF/PDGF group (Fig. 3). Micro-CT scanning showed clear restoration of blood flow in the previously ligated vessels and the filling of collateral vessels by the VEGF or VEGF/PDGF treatment, compared to the blank (Fig. 4).Fig. 3


Sustained release of multiple growth factors from injectable polymeric system as a novel therapeutic approach towards angiogenesis.

Sun Q, Silva EA, Wang A, Fritton JC, Mooney DJ, Schaffler MB, Grossman PM, Rajagopalan S - Pharm. Res. (2009)

Representative images of micro-CT after 5 weeks intramuscular injections of alginate (Blank), alginate containing VEGF165 (VEGF), or alginate containing VEGF165 combined with PLG microspheres containing PDGF-BB (VEGF/PDGF).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2812420&req=5

Fig4: Representative images of micro-CT after 5 weeks intramuscular injections of alginate (Blank), alginate containing VEGF165 (VEGF), or alginate containing VEGF165 combined with PLG microspheres containing PDGF-BB (VEGF/PDGF).
Mentions: Blood flow was reduced to less than 20% of the baseline following ligation surgery. There was no significant difference in limb perfusion between groups in the first 2 weeks after the operation. The blood flow remained severely impaired and showed delayed recovery after vessel ligation in the group that received blank alginate solution containing no growth factor. The VEGF/PDGF group of 3 µg VEGF165 with 3 µg PDGFBB recovered significantly faster than the blank or the VEGF group of 3 µg VEGF165 and achieved more than 80% of the initial value by the end of the experiment. VEGF showed a positive effect on the recovery of perfusion from week 3 to week 6 compared to the blank group, but weaker than the VEGF/PDGF group (Fig. 3). Micro-CT scanning showed clear restoration of blood flow in the previously ligated vessels and the filling of collateral vessels by the VEGF or VEGF/PDGF treatment, compared to the blank (Fig. 4).Fig. 3

Bottom Line: 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.This sustained, control-released, injectable alginate polymer system is a promising approach for multiple growth factor delivery in clinical application.

View Article: PubMed Central - PubMed

Affiliation: Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio 43210-1252, USA. sun.224@osu.edu

ABSTRACT

Purpose: 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.

Methods: Three groups of apoE mice underwent unilateral hindlimb ischemia surgery and received ischemic limb intramuscular injections of alginate (Blank), alginate containing VEGF(165) (VEGF), or alginate containing VEGF(165) 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.

Results: 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.

Conclusions: 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.

Show MeSH
Related in: MedlinePlus