title: Heparin mimetic peptide nanofibers promote angiogenesis.
abstract: New blood vessel formation (angiogenesis) is one of the most important processes required for functional tissue formation. Induction of angiogenesis is usually triggered by growth factors released by cells. Glycosaminoglycans (e.g., heparan sulphates) in the extracellular matrix aid in proper functioning of these growth factors. Therefore, exogeneous heparin or growth factors were required for promoting angiogenesis in previous regenerative medicine studies. Here we report for the first time induction of angiogenesis by a synthetic nanofibrous peptide scaffold without the addition of any exogenous growth factors or heparin. We designed and synthesized a self-assembling peptide amphiphile molecule that is functionalized with biologically active groups to mimic heparin. Like heparin, this molecule has the ability to interact with growth factors and effectively enhance their bioactivity. The nanofibers formed by these molecules were shown to form a 3D network mimicking the structural proteins in the extracellular matrix. Because of heparin mimicking capabilities of the peptide nanofibers, angiogenesis was induced without the addition of exogenous growth factors in vitro. Bioactive interactions between the nanofibers and the growth factors enabled robust vascularization in vivo as well. Heparin mimetic peptide nanofibers presented here provide new opportunities for angiogenesis and tissue regeneration by avoiding the use of heparin and exogenous growth factors. The synthetic peptide nanofiber scaffolds enriched with proper chemical functional groups shown in this study can be used to induce various desired physiological responses for tissue regeneration.
authors.affiliation: UNAM-Institute of Materials Science and Nanotechnology, Bilkent University, Ankara 06800, Turkey.
authors.forename: Rashad
authors.initials: R
authors.lastname: Mammadov
authors.forename: Busra
authors.initials: B
authors.lastname: Mammadov
authors.forename: Sila
authors.initials: S
authors.lastname: Toksoz
authors.forename: Bahri
authors.initials: B
authors.lastname: Aydin
authors.forename: Ramazan
authors.initials: R
authors.lastname: Yagci
authors.forename: Ayse B
authors.initials: AB
authors.lastname: Tekinay
authors.forename: Mustafa O
authors.initials: MO
authors.lastname: Guler
mesh_terms: D000818:Animals; D032701:Biomimetics / Q000379:methods*; D049109:Cell Proliferation / Q000187:drug effects; D003315:Cornea / Q000098:blood supply*; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D056965:Injections, Intraocular; D051379:Mice; D057139:Nanofibers / Q000737:chemistry* / Q000627:therapeutic use / Q000648:ultrastructure; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D015202:Protein Engineering / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044968:Regenerative Medicine / Q000379:methods*; D013501:Surface-Active Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D023822:Tissue Engineering / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D010455:Peptides; D013501:Surface-Active Agents; D042461:Vascular Endothelial Growth Factor A; D006493:Heparin