Bioartificial matrices for therapeutic vascularization.
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.
Phelps
Edward A
EA
Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Landázuri
Natalia
N
Thulé
Peter M
PM
Taylor
W Robert
WR
García
Andrés J
AJ
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
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