title: Sustaining neovascularization of a scaffold through staged release of vascular endothelial growth factor-A and platelet-derived growth factor-BB.
abstract: Tissue regeneration into a three-dimensional scaffold requires the stimulation of blood vessel ingrowth. We have employed a freely interconnecting porous scaffold developed by us to determine the utility of a covalently bound heparin surface coating for the delivery of vascular endothelial growth factor (VEGF) and platelet-derived growth factor BB (PDGF-BB) in vivo. The heparin surface was shown to release VEGF far more rapidly than PDGF-BB in vitro (VEGF: 75 ng/h for 24 h; PDGF-BB: 86 pg/h for >7 days). In rat subcutaneous implants, at 10 days the heparin surface alone increased vessel ingrowth substantially (p<0.05 vs. unmodified scaffold), release of VEGF resulted in a further increase (p<0.05 vs. heparinized scaffold), whereas PDGF-BB had no additional effect. The increase induced by the combination of growth factors was similar to VEGF alone. After 2 months, PDGF-BB, but not VEGF delivery, resulted in a substantial increase in vascularization above that induced by heparin (p<0.05). At the longer time point the combination of growth factors was similar to PDGF-BB. However, only the combination of growth factors significantly elevated the number of ingrowing arterioles (p<0.05 vs. heparinized scaffold). Thus, the covalent modification of a porous scaffold with heparin allows for the differential release of VEGF and PDGF-BB that results in both a rapid and sustained increase in scaffold vascularization.
authors: Cardiovascular Research Unit, University of Cape Town, Cape Town, South Africa. neil.davies@uct.ac.za
authors: Neil H
authors: NH
authors: Davies
authors: Christian
authors: C
authors: Schmidt
authors: Deon
authors: D
authors: Bezuidenhout
authors: Peter
authors: P
authors: Zilla
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000254:growth & development; D000077214:Becaplermin; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011140:Polyurethanes / Q000494:pharmacology; D016062:Porosity / Q000187:drug effects; D019919:Prosthesis Implantation; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D040521:Subcutaneous Tissue / Q000187:drug effects; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D011140:Polyurethanes; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; D000077214:Becaplermin; D006493:Heparin