title: Concurrent and Sustained Delivery of FGF2 and FGF9 from Electrospun Poly(ester amide) Fibrous Mats for Therapeutic Angiogenesis.
abstract: Therapeutic angiogenesis has emerged as a potential strategy to treat ischemic vascular diseases. However, systemic or local administration of growth factors is usually inefficient for maintaining the effective concentration at the site of interest due to their rapid clearance or degradation. In this study, we report a differential and sustained release of an angiogenic factor, fibroblast growth factor-2 (FGF2), and an arteriogenic factor, fibroblast growth factor-9 (FGF9), from α-amino acid-derived biodegradable poly(ester amide) (PEA) fibers toward targeting neovessel formation and maturation. FGF2 and FGF9 were dual loaded using a mixed blend and emulsion electrospinning technique and exhibited differential and sustained release from PEA fibers over 28 days with preserved bioactivity. In vitro angiogenesis assays showed enhanced endothelial cell (EC) tube formation and directed migration of smooth muscle cells (SMCs) to platelet-derived growth factor (PDGF)-BB and stabilized EC/SMC tube formation. FGF2/FGF9-loaded PEA fibers did not induce inflammatory responses in vitro using human monocytes or in vivo after their subcutaneous implantation into mice. Histological examination showed that FGF2/FGF9-loaded fibers induced cell niche recruitment around the site of implantation. Furthermore, controlled in vivo delivery of FGF9 to mouse tibialis anterior (TA) muscle resulted in a dose-dependent expansion of mesenchymal progenitor-like cell layers and extracellular matrix deposition. Our data suggest that the release of FGF2 and FGF9 from PEA fibers offers an efficient differential and sustained growth factor delivery strategy with relevance to therapeutic angiogenesis.
authors.affiliation: 1 Biomedical Engineering Graduate Program, The University of Western Ontario , London, Canada .
authors.forename: Somiraa S
authors.initials: SS
authors.lastname: Said
authors.affiliation: 2 Robarts Research Institute, Schulich School of Medicine and Dentistry, The University of Western Ontario , London, Canada .
authors.forename: Caroline
authors.initials: C
authors.lastname: O'Neil
authors.affiliation: 2 Robarts Research Institute, Schulich School of Medicine and Dentistry, The University of Western Ontario , London, Canada .
authors.forename: Hao
authors.initials: H
authors.lastname: Yin
authors.affiliation: 2 Robarts Research Institute, Schulich School of Medicine and Dentistry, The University of Western Ontario , London, Canada .
authors.forename: Zengxuan
authors.initials: Z
authors.lastname: Nong
authors.affiliation: 2 Robarts Research Institute, Schulich School of Medicine and Dentistry, The University of Western Ontario , London, Canada .|3 Department of Medicine (Cardiology), The University of Western Ontario , London, Canada .|4 Department of Biochemistry, The University of Western Ontario , London, Canada .|5 Department of Medical Biophysics, The University of Western Ontario , London, Canada .
authors.forename: J Geoffrey
authors.initials: JG
authors.lastname: Pickering
authors.affiliation: 1 Biomedical Engineering Graduate Program, The University of Western Ontario , London, Canada .|6 Department of Chemical and Biochemical Engineering, Faculty of Engineering, The University of Western Ontario , London, Canada .
authors.forename: Kibret
authors.initials: K
authors.lastname: Mequanint
mesh_terms: D000577:Amides / Q000737:chemistry*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003692:Delayed-Action Preparations; D004655:Emulsions; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D051525:Fibroblast Growth Factor 9 / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011091:Polyesters / Q000737:chemistry*; D019919:Prosthesis Implantation; D040521:Subcutaneous Tissue / Q000187:drug effects / Q000473:pathology; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D000577:Amides; D003692:Delayed-Action Preparations; D004655:Emulsions; C496459:FGF9 protein, human; D051525:Fibroblast Growth Factor 9; D011091:Polyesters; D016222:Fibroblast Growth Factor 2