title: Material-mediated proangiogenic factor release pattern modulates quality of regenerated blood vessels.
abstract: Hydrogels designed to sustainably release bioactive molecules are extensively used to enhance tissue repair and regenerative therapies. Along this line, numerous efforts are made to control the molecular release rate and amount. In contrast, few efforts are made to control the molecular release pattern, and, subsequently, modulate the spatial organization of newly forming tissues, including blood vessels. Therefore, using a hydrogel printed to release vascular endothelial growth factor (VEGF) into a pre-defined pattern, this study demonstrates that spatial distribution of VEGF is important in guiding growth direction of new blood vessels, and also in retaining the structural integrity of pre-existing vasculature. Guided by a computational model, we fabricated a patch composed of micro-sized VEGF-releasing poly(ethylene glycol) diacrylate (PEGDA) hydrogel cylinders using an ink-jet printer. Interestingly, hydrogel printed with computationally optimized spacing created anisotropically aligned vasculature exclusively when the printed gel pattern was placed parallel to pre-existing blood vessels. In contrast, vascular sprouting from placing the printed gel pattern perpendicular to pre-existing vessels resulted in deformation and structural disintegration of the original vasculature. We envision that this study will be useful to better understand angiogenesis-modulated neovascularization and further improve the treatment quality for various wounds and tissue defects.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Max H
authors.initials: MH
authors.lastname: Rich
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Lee
authors.affiliation: Department of Material Science & Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Kwanghyun
authors.initials: K
authors.lastname: Baek
authors.affiliation: Department of Chemical Engineering, Soongsil University, Seoul 145-743, South Korea.
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Korea Institute of Industrial Technology, Ansan 426-910, South Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA; Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Millet
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA; Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
authors.forename: Rashid
authors.initials: R
authors.lastname: Bashir
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA. Electronic address: hjkong06@illinois.edu.
authors.forename: Hyunjoon
authors.initials: H
authors.lastname: Kong
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000254:growth & development*; D002626:Chemistry, Pharmaceutical; D002642:Chick Embryo; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000187:drug effects; D020100:Hydrogels; D066298:In Vitro Techniques; D018919:Neovascularization, Physiologic; D011092:Polyethylene Glycols; D011327:Printing; D012038:Regeneration / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D043925:Angiogenesis Inducing Agents; D020100:Hydrogels; D042461:Vascular Endothelial Growth Factor A; C437167:poly(ethylene glycol)diacrylate; D011092:Polyethylene Glycols
keywords: Angiogenesis; Hydrogel; Ink-jet printing; Vascular endothelial growth factor