Dose response of angiogenesis to basic fibroblast growth factor in rat corneal pocket assay: II. Numerical simulations.
Angiogenesis involves interactions among various molecules and cells. To understand the complexity of interactions, we developed a mathematical model to numerically simulate angiogenesis induced by basic fibroblast growth factor (bFGF) in the corneal pocket assay. The model considered interstitial transport of bFGF, cellular uptake of bFGF, and dynamics of vessel growth. The model was validated by comparing simulated vascular networks, induced by bFGF at three different doses: 5 ng, 15 ng, and 50 ng, with experimental data obtained in the first part of the study, in terms of migration distance of vascular network, total vessel length, and number of vessels. The model was also used to simulate growth dynamics of vascular networks as well as spatial and temporal distribution of bFGF, which could not be measured experimentally. Taken together, results of the study suggested that the coupling between diffusion and cellular uptake of bFGF was critical for determining structures of vascular networks and that the mathematical model was appropriate for simulation of angiogenesis in the cornea.
Tong
Sheng
S
Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
Yuan
Fan
F
D042501:Angiogenic Proteins / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001681:Biological Assay / Q000379:methods; D001692:Biological Transport; D003198:Computer Simulation; D003315:Cornea / Q000098:blood supply*; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008955:Models, Cardiovascular; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000378:metabolism; D015203:Reproducibility of Results; D013997:Time Factors
D042501:Angiogenic Proteins; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2