Engineering vascular networks in porous polymer matrices.
Enhanced vascularization is critical to the treatment of ischemic tissues and the engineering of new tissues and organs. We have investigated whether sustained and localized delivery of vascular endothelial growth factor (VEGF) combined with transplantation of human microvascular endothelial cells (HMVECs) can be used to engineer new vascular networks. VEGF was incorporated and released in a sustained manner from porous poly(lactic-co-glycolic acid) (PLG) matrices to promote angiogenesis at the transplantation site. VEGF could be incorporated and released in a biologically active form from PLG matrices, with the majority of VEGF release (64%) occurring within 2 weeks. These matrices promoted a 260% increase in the density of host SCID mouse-derived capillaries invading the matrices after 7 days of implantation, confirming the activity of the released VEGF. HMVECs were transplanted into SCID mice on PLG matrices, and organized to form immature human-derived vessels within 3 days. Functional vessels were observed within 7 days. Importantly, when HMVECs were transplanted on VEGF-releasing matrices, a 160% increase in the density of human-derived blood vessels was observed after 14 days. These findings suggest that combining elements of vasculogenesis and angiogenesis provides a viable and novel approach to enhancing local vascularization.
Peters
Martin C
MC
Department of Biomedical Engineering, University of Michigan, 5213 Dental School, 1011 North University Avenue, Ann Arbor, Michigan 48109-1078, USA.
Polverini
Peter J
PJ
Mooney
David J
DJ
D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D017690:Cell Transplantation; D016228:Endothelial Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000494:pharmacology; D008222:Lymphokines / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011098:Polyglactin 910 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D001672:Biocompatible Materials; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D011098:Polyglactin 910