Polymeric system for dual growth factor delivery.
The development of tissues and organs is typically driven by the action of a number of growth factors. However, efforts to regenerate tissues (e.g., bone, blood vessels) typically rely on the delivery of single factors, and this may partially explain the limited clinical utility of many current approaches. One constraint on delivering appropriate combinations of factors is a lack of delivery vehicles that allow for a localized and controlled delivery of more than a single factor. We report a new polymeric system that allows for the tissue-specific delivery of two or more growth factors, with controlled dose and rate of delivery. The utility of this system was investigated in the context of therapeutic angiogenesis. We now demonstrate that dual delivery of vascular endothelial growth factor (VEGF)-165 and platelet-derived growth factor (PDGF)-BB, each with distinct kinetics, from a single, structural polymer scaffold results in the rapid formation of a mature vascular network. This is the first report of a vehicle capable of delivery of multiple angiogenic factors with distinct kinetics, and these results clearly indicate the importance of multiple growth factor action in tissue regeneration and engineering.
Richardson
T P
TP
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Peters
M C
MC
Ennett
A B
AB
Mooney
D J
DJ
D000199:Actins / Q000032:analysis; D000818:Animals; D000077214:Becaplermin; D001808:Blood Vessels / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000379:methods*; D004357:Drug Synergism; D016228:Endothelial Growth Factors / Q000008:administration & dosage* / Q000378:metabolism; D007700:Kinetics; D008222:Lymphokines / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008863:Microspheres; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage* / Q000378:metabolism; D011098:Polyglactin 910 / Q000008:administration & dosage*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011917:Rats, Inbred Lew; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000199:Actins; D003692:Delayed-Action Preparations; D016228:Endothelial Growth Factors; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000077214:Becaplermin; D011098:Polyglactin 910