title: Bioartificial matrices for therapeutic vascularization.
abstract: Therapeutic vascularization remains a significant challenge in regenerative medicine applications. Whether the goal is to induce vascular growth in ischemic tissue or scale up tissue-engineered constructs, the ability to induce the growth of patent, stable vasculature is a critical obstacle. We engineered polyethylene glycol-based bioartificial hydrogel matrices presenting protease-degradable sites, cell-adhesion motifs, and growth factors to induce the growth of vasculature in vivo. Compared to injection of soluble VEGF, these matrices delivered sustained in vivo levels of VEGF over 2 weeks as the matrix degraded. When implanted subcutaneously in rats, degradable constructs containing VEGF and arginine-glycine-aspartic acid tripeptide induced a significant number of vessels to grow into the implant at 2 weeks with increasing vessel density at 4 weeks. The mechanism of enhanced vascularization is likely cell-demanded release of VEGF, as the hydrogels may degrade substantially within 2 weeks. In a mouse model of hind-limb ischemia, delivery of these matrices resulted in significantly increased rate of reperfusion. These results support the application of engineered bioartificial matrices to promote vascularization for directed regenerative therapies.
authors.affiliation: Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Phelps
authors.forename: Natalia
authors.initials: N
authors.lastname: Landázuri
authors.forename: Peter M
authors.initials: PM
authors.lastname: Thulé
authors.forename: W Robert
authors.initials: WR
authors.lastname: Taylor
authors.forename: Andrés J
authors.initials: AJ
authors.lastname: García
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005121:Extremities / Q000098:blood supply; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry; D007511:Ischemia / Q000628:therapy; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D012038:Regeneration / Q000187:drug effects*; D044968:Regenerative Medicine / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D020100:Hydrogels; D009842:Oligopeptides; D014677:Pharmaceutical Vehicles; D042461:Vascular Endothelial Growth Factor A; C437167:poly(ethylene glycol)diacrylate; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid