Biomechanics and Modeling in Mechanobiology

, Volume 12, Issue 5, pp 889–899

Scaffold architecture determines chondrocyte response to externally applied dynamic compression

Authors

  • Tariq Mesallati
    • Department of Mechanical and Manufacturing Engineering, School of EngineeringTrinity College Dublin
    • Trinity Centre for Bioengineering, Trinity Biomedical Sciences InstituteTrinity College Dublin
  • Conor T. Buckley
    • Department of Mechanical and Manufacturing Engineering, School of EngineeringTrinity College Dublin
    • Trinity Centre for Bioengineering, Trinity Biomedical Sciences InstituteTrinity College Dublin
  • Thomas Nagel
    • Department of Mechanical and Manufacturing Engineering, School of EngineeringTrinity College Dublin
    • Trinity Centre for Bioengineering, Trinity Biomedical Sciences InstituteTrinity College Dublin
    • Department of Environmental InformaticsHelmholtz Centre for Environmental Research-UFZ
    • Department of Mechanical and Manufacturing Engineering, School of EngineeringTrinity College Dublin
    • Trinity Centre for Bioengineering, Trinity Biomedical Sciences InstituteTrinity College Dublin
Original Paper

DOI: 10.1007/s10237-012-0451-2

Cite this article as:
Mesallati, T., Buckley, C.T., Nagel, T. et al. Biomech Model Mechanobiol (2013) 12: 889. doi:10.1007/s10237-012-0451-2

Abstract

It remains unclear how specific mechanical signals generated by applied dynamic compression (DC) regulate chondrocyte biosynthetic activity. It has previously been suggested that DC-induced interstitial fluid flow positively impacts cartilage-specific matrix production. Modifying fluid flow within dynamically compressed hydrogels therefore represents a promising approach to controlling chondrocyte behavior, which could potentially be achieved by changing the construct architecture. The objective of this study was to first determine the influence of construct architecture on the mechanical environment within dynamically compressed agarose hydrogels using finite element (FE) modeling and to then investigate how chondrocytes would respond to this altered environment. To modify construct architecture, an array of channels was introduced into the hydrogels. Increased magnitudes of fluid flow were predicted in the periphery of dynamically compressed solid hydrogels and also around the channels in the dynamically compressed channeled hydrogels. DC was found to significantly increase sGAG synthesis in solid constructs, which could be attributed at least in part to an increase in DNA. DC was also found to preferentially increase collagen accumulation in regions of solid and channeled constructs where FE modeling predicted higher levels of fluid flow, suggesting that this stimulus is important for promoting collagen production by chondrocytes embedded in agarose gels. In conclusion, this study demonstrates how the architecture of cell-seeded scaffolds or hydrogels can be modified to alter the spatial levels of biophysical cues throughout the construct, leading to greater collagen accumulation throughout the engineered tissue rather than preferentially in the construct periphery. This system also provides a novel approach to investigate how chondrocytes respond to altered levels of biophysical stimulation.

Keywords

Dynamic compressionAgarose hydrogelChondrocytesChanneled constructsBiophysical stimulationNutrient transport

Abbreviations

DC

Dynamic compression

FE

Finite element

sGAG

Sulfated glycosaminoglycan

ECM

Extracellular matrix

PBS

Phosphate-buffered saline

hgDMEM

High-glucose Dulbecco’s modified Eagle’s medium

FBS

Fetal bovine serum

DMSO

Dimethyl sulphoxide

P1

Passage one

FGF-2

Fibroblast growth factor-2

CDM

Chondrogenic medium

PTFE

Polytetrafluoroethylene

PDMS

Polydimethylsiloxane

CNC

Computer numerical controlled

TGF-β 3

Transforming growth factor-beta 3

FS

Free swelling

DCS

Dynamically compressed solid

DCM

Dynamically compressed microchannel

FSM

Free swelling microchannel

FSS

Free swelling solid

Supplementary material

10237_2012_451_MOESM1_ESM.docx (197 kb)
ESM 1 (DOCX 198 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2012