Document Detail

Effectiveness factor and diffusion limitations in collagen gel modules containing HepG2 cells.
MedLine Citation:
PMID:  20653045     Owner:  NLM     Status:  MEDLINE    
A major obstacle in tissue engineering is overcoming hypoxia in thick, three-dimensional (3D) engineered tissues, which is caused by the diffusional limitations of oxygen and lack of internal vasculature to facilitate mass transfer. Modular tissue engineering is a bio-mimetic strategy that forms scalable, vascularized and uniform 3D constructs by assembling small (sub-mm), cell-containing modules. It was previously assumed that mass transfer resistance within the individual modules was negligible, due to their small size. In the present study, this assumption was tested using theoretical analysis of oxygen transport within the module (effectiveness factor) and experimental studies. Small (400 µm diameter post-contraction) and large (700 µm diameter post-contraction) HepG2-collagen modules were made for a range of seeding densities (2 × 10(6) -1 × 10(7) cells/ml collagen). Cell density, distribution and morphology within the modules showed that the small modules were capable of sustaining high cell densities (8.0 × 10(7) ± 4.4 × 10(7) cells/cm(3) ) with negligible mass transfer inhibition. Conversely, large modules developed a necrotic core and had significantly (p < 0.05) reduced cell densities (1.5 × 10(7) ± 9.2 × 10(6) cells/cm(3) ). It was also observed that the embedded cells responded quickly to the oxygen availability, by proliferating or dying, to reach a sustainable density of approximately 8000 cells/module. Furthermore, a simple effectiveness factor calculation was successful in estimating the maximum cell density per module. The results gathered in this study confirm the previous assumption that the small-diameter modules avoid the internal mass transfer limitations that are often observed in larger constructs.
Lindsay Corstorphine; Michael V Sefton
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of tissue engineering and regenerative medicine     Volume:  5     ISSN:  1932-7005     ISO Abbreviation:  J Tissue Eng Regen Med     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-26     Completed Date:  2011-04-25     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101308490     Medline TA:  J Tissue Eng Regen Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  119-29     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 John Wiley & Sons, Ltd.
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Canada.
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MeSH Terms
Cell Hypoxia
Hep G2 Cells
Tissue Engineering / methods*
Tissue Scaffolds*
Grant Support
Reg. No./Substance:
0/Gels; 9007-34-5/Collagen

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