title: Uncoupling angiogenesis and inflammation in peripheral artery disease with therapeutic peptide-loaded microgels.
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.
authors.affiliation: Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Zachman
authors.affiliation: Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Xintong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Tucker-Schwartz
authors.affiliation: Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Sean T
authors.initials: ST
authors.lastname: Fitzpatrick
authors.affiliation: Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Sue H
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Guelcher
authors.affiliation: Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Skala
authors.affiliation: Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA. Electronic address: hak-joon.sung@vanderbilt.edu.
authors.forename: Hak-Joon
authors.initials: HJ
authors.lastname: Sung
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D007267:Injections; D020780:Matrix Metalloproteinase 9 / Q000276:immunology; D061965:Matrix Metalloproteinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009842:Oligopeptides / Q000008:administration & dosage* / Q000627:therapeutic use; D058729:Peripheral Arterial Disease / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D011091:Polyesters / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D043925:Angiogenesis Inducing Agents; D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D061965:Matrix Metalloproteinase Inhibitors; D009842:Oligopeptides; D011091:Polyesters; D014409:Tumor Necrosis Factor-alpha; C016240:polycaprolactone; D020780:Matrix Metalloproteinase 9; C058504:goralatide
keywords: Angiogenesis; Inflammation; Peptide; Polycaprolactone; Polyethylene glycol; Polymer