Dynamics of the Self-Assembly of Complex Cellular Aggregates on Micromolded Nonadhesive Hydrogels
Dynamics of the Self-Assembly of Complex Cellular Aggregates on Micromolded Nonadhesive Hydrogels
Summary:
Napolitano, A. P., Chai, P., Dean, D. M., Morgan, J. R. (2007) Dynamics of the Self-Assembly of Complex Cellular Aggregates on Micromolded Nonadhesive Hydrogels. Tissue Engineering, 13(8), 2087-2094. doi:10.1089/ten.2006.0190
Self-assembly of cells has been observed in both embryonic tissues and adult cells. Spheroids are formed that mimic in vivo differentiation and cellular interactions (cell-cell and cell-extracellular matrix (ECM)). Large tissue-engineering structures are partly dependent on self-assembly, so knowing the dynamics of assembly is important.
Napolitano, et al. developed a method to form cellular aggregates on micromolded nonadhesive hydrogels for this purpose. Polyacrylamide hydrogels and agarose gels were cast using a wax mold and incubated in medium. Normal human fibroblasts (NHFs) and human umbilical vein endothelial cells (HUVECs) were cultured in the recesses of the gels.
They found that cells sank into recesses within an hour and spheroids formed within 24 hours. Aggregate geometry and size was dependent on recess geometry as well as density of cells. The spheroids could also be easily removed by inverting and briefly centrifuging. The use of a hydrogel substrate minimized cell-substrate interactions so that the neighboring cells would determine the environment.
Using mixed cell suspensions of NHFs and HUVECs, the researchers were able to demonstrate that not only do the cells self-assemble into layered spheroids but also that mature spheroids can reorganize to incorporate additional cells that are added later to form the same layered spheroids.
The authors indicate that their experimental data supports cytokeleton-mediated (adhesion and interfactial) tension and cell contraction playing a role during self-assembly
Significance:
An understanding of the forces in play when cells aggregate is important for designing tissue-engineered devices. This type of spheroid production has potential for transplantation if it can be scaled up or applied to more complex geometries.
4 comments:
what kinds of hydrogels are used? are they biocompatible and nontoxic?
I'm curious about whether the spheroid formation dependent on the micromold pattern/size. In particular, I wonder if the spheroid would continue even if the cells on the inside begin to die of starvation (or would cell-cell signaling lead to a halt).
Daniel,
Polyacrylamide hydrogels and agarose gels were used in this paper. After a quick search, it seems like the two are both biocompatible.
Is there any control on the geometry? It seems like only spherical shapes would be possible. Also, at a certain size, it may be energetically unfavorable for the cells to form spheroids and would instead prefer to cover the surface in a flat layer (surface energy effects). Would this be a limit to the maximum size the spheroid could grow to?
Also, can this be used as a method of measuring relative surface energies as is done with wet drops on a surface? (contact angle measurements)
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