Document Detail

Design of tissue engineering scaffolds as delivery devices for mechanical and mechanically modulated signals.
MedLine Citation:
PMID:  17822359     Owner:  NLM     Status:  MEDLINE    
New approaches to tissue engineering aim to exploit endogenous strategies such as those occurring in prenatal development and recapitulated during postnatal healing. Defining tissue template specifications to mimic the environment of the condensed mesenchyme during development allows for exploitation of tissue scaffolds as delivery devices for extrinsic cues, including biochemical and mechanical signals, to drive the fate of mesenchymal stem cells seeded within. Although a variety of biochemical signals that modulate stem cell fate have been identified, the mechanical signals conducive to guiding pluripotent cells toward specific lineages are less well characterized. Furthermore, not only is spatial and temporal control of mechanical stimuli to cells challenging, but also tissue template geometries vary with time due to tissue ingrowth and/or scaffold degradation. Hence, a case study was carried out to analyze flow regimes in a testbed scaffold as a first step toward optimizing scaffold architecture. A pressure gradient was applied to produce local (nm-micron) flow fields conducive to migration, adhesion, proliferation, and differentiation of cells seeded within, as well as global flow parameters (micron-mm), including flow velocity and permeability, to enhance directed cell infiltration and augment mass transport. Iterative occlusion of flow channel dimensions was carried out to predict virtually the effect of temporal geometric variation (e.g., due to tissue development and growth) on delivery of local and global mechanical signals. Thereafter, insights from the case study were generalized to present an optimization scheme for future development of scaffolds to be implemented in vitro or in vivo. Although it is likely that manufacture and testing will be required to finalize design specifications, it is expected that the use of the rational design optimization will reduce the number of iterations required to determine final prototype geometries and flow conditions. As the range of mechanical signals conducive to guiding cell fate in situ is further elucidated, these refined design criteria can be integrated into the general optimization rubric, providing a technological platform to exploit nature's endogenous tissue engineering strategies for targeted tissue generation in the lab or the clinic.
Eric J Anderson; Melissa L Knothe Tate
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Tissue engineering     Volume:  13     ISSN:  1076-3279     ISO Abbreviation:  Tissue Eng.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-02     Completed Date:  2007-11-26     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9505538     Medline TA:  Tissue Eng     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2525-38     Citation Subset:  IM    
Department of Mechanical and Aerospace Engineering, Case School of Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
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MeSH Terms
Biomimetic Materials / chemistry*
Cell Physiological Phenomena*
Computer Simulation
Computer-Aided Design
Equipment Design
Equipment Failure Analysis
Extracellular Matrix / chemistry*
Mechanotransduction, Cellular / physiology*
Microfluidics / instrumentation,  methods*
Models, Biological
Models, Chemical*
Tissue Engineering / instrumentation,  methods*
Grant Support
AR049351-01/AR/NIAMS NIH HHS; C06 RR12463-01/RR/NCRR NIH HHS

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