title: Treatment of hind limb ischemia using angiogenic peptide nanofibers.
abstract: For a proangiogenic therapy to be successful, it must promote the development of mature vasculature for rapid reperfusion of ischemic tissue. Whole growth factor, stem cell, and gene therapies have yet to achieve the clinical success needed to become FDA-approved revascularization therapies. Herein, we characterize a biodegradable peptide-based scaffold engineered to mimic VEGF and self-assemble into a nanofibrous, thixotropic hydrogel, SLanc. We found that this injectable hydrogel was rapidly infiltrated by host cells and could be degraded while promoting the generation of neovessels. In mice with induced hind limb ischemia, this synthetic peptide scaffold promoted angiogenesis and ischemic tissue recovery, as shown by Doppler-quantified limb perfusion and a treadmill endurance test. Thirteen-month-old mice showed significant recovery within 7 days of treatment. Biodistribution studies in healthy mice showed that the hydrogel is safe when administered intramuscularly, subcutaneously, or intravenously. These preclinical studies help establish the efficacy of this treatment for peripheral artery disease due to diminished microvascular perfusion, a necessary step before clinical translation. This peptide-based approach eliminates the need for cell transplantation or viral gene transfection (therapies currently being assessed in clinical trials) and could be a more effective regenerative medicine approach to microvascular tissue engineering.
authors.affiliation: Department of Chemistry and Department of Bioengineering, Rice University, Houston, TX, USA.
authors.forename: Vivek A
authors.initials: VA
authors.lastname: Kumar
authors.affiliation: Department of Molecular Cardiology, Texas Heart Institute, Houston, TX, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Department of Bioengineering, Rice University, Houston, TX, USA.
authors.forename: Navindee C
authors.initials: NC
authors.lastname: Wickremasinghe
authors.affiliation: Department of Chemistry and Department of Bioengineering, Rice University, Houston, TX, USA.
authors.forename: Siyu
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Molecular Cardiology, Texas Heart Institute, Houston, TX, USA.
authors.forename: Toya T
authors.initials: TT
authors.lastname: Cornwright
authors.affiliation: Department of Molecular Cardiology, Texas Heart Institute, Houston, TX, USA.
authors.forename: Yuxiao
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Molecular Cardiology, Texas Heart Institute, Houston, TX, USA.
authors.forename: Alon
authors.initials: A
authors.lastname: Azares
authors.affiliation: Department of Chemistry and Department of Bioengineering, Rice University, Houston, TX, USA.
authors.forename: Amanda N
authors.initials: AN
authors.lastname: Moore
authors.affiliation: Department of Chemistry and Department of Bioengineering, Rice University, Houston, TX, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Acevedo-Jake
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Noel R
authors.initials: NR
authors.lastname: Agudo
authors.affiliation: Department of Molecular Cardiology, Texas Heart Institute, Houston, TX, USA.
authors.forename: Su
authors.initials: S
authors.lastname: Pan
authors.affiliation: Department of Molecular Cardiology, Texas Heart Institute, Houston, TX, USA.
authors.forename: Darren G
authors.initials: DG
authors.lastname: Woodside
authors.affiliation: Department of Molecular Cardiology, Texas Heart Institute, Houston, TX, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Vanderslice
authors.affiliation: Department of Molecular Cardiology, Texas Heart Institute, Houston, TX, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Willerson
authors.affiliation: Department of Molecular Cardiology, Texas Heart Institute, Houston, TX, USA. Electronic address: rdixon@texasheart.org.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Dixon
authors.affiliation: Department of Chemistry and Department of Bioengineering, Rice University, Houston, TX, USA. Electronic address: jdh@rice.edu.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Hartgerink
mesh_terms: D000818:Animals; D006614:Hindlimb / Q000098:blood supply*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000473:pathology; D057139:Nanofibers / Q000627:therapeutic use*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D015424:Reperfusion; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D010455:Peptides
keywords: Hind-limb ischemia; Multi-domain peptide; Peripheral artery disease; Self-assembly; Therapeutic angiogenesis