RT Journal Article
SR Electronic
T1 Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.12.989053
DO 10.1101/2020.03.12.989053
A1 Pascal R. Buenzli
A1 Matthew Lanaro
A1 Cynthia S. Wong
A1 Maximilian P. McLaughlin
A1 Mark C. Allenby
A1 Maria A. Woodruff
A1 Matthew J. Simpson
YR 2020
UL http://biorxiv.org/content/early/2020/03/13/2020.03.12.989053.abstract
AB Tissue growth in bioscaffolds can be influenced significantly by pore geometry, but how this geometric dependence emerges from dynamic cellular processes such as cell proliferation and cell migration remains poorly understood. Here we investigate the influence of pore size on the time required to bridge pores in a 3D printed scaffold by analysing experiments with a mathematical model. Experimentally, the new tissue infills the pore continually from the pore perimeter under strong curvature control, which leads to rounding off of the initial pore shape. Despite the varied shapes assumed by the tissue during this evolution, we find that time to bridge the pore simply increases linearly with the overall pore size. To disentangle the biological influence of cell behaviour and the mechanistic influence of geometry in this experimental observation, we propose a simple reaction–diffusion model of tissue growth based on Porous-Fisher invasion of cells into the pores. First, this model provides a good qualitative representation of the evolution of the tissue; new cellular tissue in the model grows at a rate that depends on the local curvature of the tissue substrate. Second, the model suggests that a linear dependence of bridging time with pore size arises due to geometric reasons alone, not to differences in cell behaviours across pores of different sizes. Our analysis therefore suggests that tissue growth dynamics in these experimental constructs is dominated by mechanistic cell proliferation and cell diffusion processes. The rates of these processes are unaffected by pore geometry, and can be predicted by simple reaction–diffusion models of cells that have robust, consistent behaviours.