Hak-Joon Sung
Assistant Professor of Biomedical Engineering, Assistant Professor of Medicine-Cardiovascular Medicine
Last active: 2/12/2015

Uncoupling angiogenesis and inflammation in peripheral artery disease with therapeutic peptide-loaded microgels.

Zachman AL, Wang X, Tucker-Schwartz JM, Fitzpatrick ST, Lee SH, Guelcher SA, Skala MC, Sung HJ
Biomaterials. 2014 35 (36): 9635-48

PMID: 25154665 · PMCID: PMC4164579 · DOI:10.1016/j.biomaterials.2014.08.011

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.

Copyright © 2014 Elsevier Ltd. All rights reserved.

MeSH Terms (16)

Angiogenesis Inducing Agents Animals Anti-Inflammatory Agents Cell Line Drug Carriers Human Umbilical Vein Endothelial Cells Inflammation Injections Matrix Metalloproteinase 9 Matrix Metalloproteinase Inhibitors Mice Neovascularization, Physiologic Oligopeptides Peripheral Arterial Disease Polyesters Tumor Necrosis Factor-alpha

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