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Uncoupling angiogenesis and inflammation in peripheral artery disease with therapeutic peptide-loaded microgels.
- Source :
-
Biomaterials [Biomaterials] 2014 Dec; Vol. 35 (36), pp. 9635-48. Date of Electronic Publication: 2014 Aug 22. - Publication Year :
- 2014
-
Abstract
- Peripheral artery disease (PAD) is characterized by vessel occlusion and ischemia in the limbs. Treatment for PAD with surgical interventions has been showing limited success. Moreover, recent clinical trials with treatment of angiogenic growth factors proved ineffective as increased angiogenesis triggered severe inflammation in a proportionally coupled fashion. Hence, the overarching goal of this research was to address this issue by developing a biomaterial system that enables controlled, dual delivery of pro-angiogenic C16 and anti-inflammatory Ac-SDKP peptides in a minimally-invasive way. To achieve the goal, a peptide-loaded injectable microgel system was developed and tested in a mouse model of PAD. When delivered through multiple, low volume injections, the combination of C16 and Ac-SDKP peptides promoted angiogenesis, muscle regeneration, and perfusion recovery, while minimizing detrimental inflammation. Additionally, this peptide combination regulated inflammatory TNF-α pathways independently of MMP-9 mediated pathways of angiogenesis in vitro, suggesting a potential mechanism by which angiogenic and inflammatory responses can be uncoupled in the context of PAD. This study demonstrates a translatable potential of the dual peptide-loaded injectable microgel system for PAD treatment.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Subjects :
- Angiogenesis Inducing Agents therapeutic use
Animals
Anti-Inflammatory Agents therapeutic use
Cell Line
Human Umbilical Vein Endothelial Cells
Inflammation complications
Inflammation immunology
Injections
Matrix Metalloproteinase 9 immunology
Matrix Metalloproteinase Inhibitors administration & dosage
Matrix Metalloproteinase Inhibitors therapeutic use
Mice
Oligopeptides therapeutic use
Peripheral Arterial Disease complications
Peripheral Arterial Disease immunology
Polyesters chemistry
Tumor Necrosis Factor-alpha antagonists & inhibitors
Tumor Necrosis Factor-alpha immunology
Angiogenesis Inducing Agents administration & dosage
Anti-Inflammatory Agents administration & dosage
Drug Carriers chemistry
Inflammation drug therapy
Neovascularization, Physiologic drug effects
Oligopeptides administration & dosage
Peripheral Arterial Disease drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5905
- Volume :
- 35
- Issue :
- 36
- Database :
- MEDLINE
- Journal :
- Biomaterials
- Publication Type :
- Academic Journal
- Accession number :
- 25154665
- Full Text :
- https://doi.org/10.1016/j.biomaterials.2014.08.011